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[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: Neural Network Techniques for Time Series Prediction: A Review \nChapter Title: A. Applications on Physical Time Series Prediction with Neural Networks \n1. Abstract of Cited Paper (BIB001): This paper presents a new type of recurrent neural network, called the Recurrent Pi-Sigma Neural Network (RPSN) and its application to physical time series prediction. The network is constructed of two layers, the sigma and the pi unit layers. The recurrent pi-sigma network calculates the product sum of the weighted inputs and passes the results to a non-linear transfer function. The output of the network is the feedback to its input. The performance of the network is tested in non-linear and non-stationary physical signal prediction. Two popular time series, the mean value of the AE index and the number of sunspots, are used in our studies. The simulation results showed an average improvement in the Signal to Noise Ratio (SNR) of 1.85 dB over the feedforward pi-sigma neural networks. \n2. Abstract of Cited Paper (BIB002): Harmful algal blooms (HABs) have drawn great attention in coastal areas worldwide in the past decades because of their multiple effects on marine ecosystems as well as public health. This study utilized geographic information system (GIS) techniques to analyze the primary data on HABs, as well as shellfish toxins data, in the East China Sea from 2000 to 2006. The frequency of HABs was mapped by kernel density estimation, and the relative risk posed by HABs was assessed based on their physical-chemical characteristics. In addition, the spatial patterns and the trend of HAB events were examined by nearest neighbor analysis and time series analysis, respectively. The results revealed that HAB events not only had an increasing trend and significant seasonality, but also were clustered in space and time. HAB events displayed a higher frequency and a higher risk in Zhejiang coastal waters, particularly in the Zhoushan Archipelago, the largest marine fishery in China. Shellfish toxins were detected in areas with high HAB risk, but were not correlated with the risk. This paper provides a novel method to assess the relative risk caused by HABs and some useful information for HAB monitoring and management and aquaculture development. \n3. Abstract of Cited Paper (BIB003): Travel time prediction for urban networks is an important issue in Advanced Traveler Information Systems (ATIS) since drivers can make individual decisions, choose the shortest route, avoid congestion and improve network efficiency based on the predicted travel time information. In this research, two algorithms are proposed to estimate and predict travel time for urban networks: the simulation-based and time-series models. The simulation-based model, DynaTAIWAN, designed and developed for mixed traffic flows, is adopted to simulate the traffic flow patterns. The Autoregressive Integrated Moving Average (ARIMA) model, calibrated with vehicle detector (VD) data, is integrated with signal delay to predict travel time for arterial streets. In the numerical analysis, an arterial street in Kaohsiung city in Taiwan is conducted to illustrate these two models. The empirical and historical data are used to predict and analyze travel time, including: travel time data from survey and historical speed data from vehicle detectors (VD). \n4. Abstract of Cited Paper (BIB004): Neural networks have been widely used in nonlinear time series prediction. They have generated lot of interest due to their comprehensive adaptive and learning abilities. Neural networks have been used in Medical forecasting, Exchange rate forecasting, stock index prediction, and other areas, which show a practical value of neural networks. This paper presents a novel application of the Self-organised Multilayer perceptrons network that is inspired by the Immune Algorithm (SMIA) in physical time series prediction. The Regularization technique is used with the self-organised multilayer perceptronss network that is inspired by the immune algorithm (R-SMIA). The results of 20 simulations generated from two non-stationary physical time series using various neural networks are demonstrates. The results of R-SMIA were compared with four networks which include the MLP, R-MLP, FLNN, and SMIA networks. \n5. Abstract of Cited Paper (BIB005): Since early ages, people tried to predicate earthquakes using simple observations such as strange or atypical animal behavior. In this paper, we study data collected from past earthquakes to give better forecasting for coming earthquakes. We propose the application of artificial intelligent predication system based on artificial neural network which can be used to predicate the magnitude of future earthquakes in northern Red Sea area including the Sinai Peninsula, the Gulf of Aqaba, and the Gulf of Suez. We present performance evaluation for different configurations and neural network structures that show prediction accuracy compared to other methods. The proposed scheme is built based on feed forward neural network model with multi-hidden layers. The model consists of four phases: data acquisition, pre-processing, feature extraction and neural network training and testing. In this study the neural network model provides higher forecast accuracy than other proposed methods. Neural network model is at least 32% better than other methods. This is due to that neural network is capable to capture non-linear relationship than statistical methods and other proposed methods. \n6. Abstract of Cited Paper (BIB006): Because of the chaotic nature and intrinsic complexity of wind speed, it is difficult to describe the moving tendency of wind speed and accurately forecast it. In our study, a novel EMD-ENN approach, a hybrid of empirical mode decomposition (EMD) and Elman neural network (ENN), is proposed to forecast wind speed. First, the original wind speed datasets are decomposed into a collection of intrinsic mode functions (IMFs) and a residue by EMD, yielding relatively stationary sub-series that can be readily modeled by neural networks. Second, both IMF components and residue are applied to establish the corresponding ENN models. Then, each sub-series is predicted using the corresponding ENN. Finally, the prediction values of the original wind speed datasets are calculated by the sum of the forecasting values of every sub-series. Moreover, in the ENN modeling process, the neuron number of the input layer is determined by a partial autocorrelation function. Four prediction cases of wind speed are used to test the performance of the proposed hybrid approach. Compared with the persistent model, back-propagation neural network, and ENN, the simulation results show that the proposed EMD-ENN model consistently has the minimum statistical error of the mean absolute error, mean square error, and mean absolute percentage error. Thus, it is concluded that the proposed approach is suitable for wind speed prediction. \n7. Abstract of Cited Paper (BIB007): A Markov-switching model in wind speed forecasting is examined in this research. The proposed method employs a regime switching process governed by a discrete-state Markov chain to model the nonlinear evolvement of the wind speed time-series. A Bayesian inference rather than the traditional maximum likelihood estimation is applied to evaluate the parameters of the Markov-switching model. Unlike the traditional point forecast of wind speeds, the Markov-switching model can offer both of the point and interval wind speed forecast. To examine the forecasting performance of the Markov-switching model, four wind speed forecasting models, the persistent model, the autoregressive model, the neural networks model, and the Bayesian structural break model, are employed as baselines. Wind speed data collected from utility-scale wind turbines are utilized for the model development and the computational results demonstrate that the Markov-switching model is promising in wind speed forecasting. \n8. Abstract of Cited Paper (BIB008): The aim of this work is to develop a prediction method for renewable energy sources in order to achieve an intelligent management of a microgrid system and to promote the utilization of renewable energy in grid connected and isolated power systems. The proposed method is based on the multi-resolution analysis of the time-series by means of Wavelet decomposition and artificial neural networks. The analysis of predictability of each component of the input data using the Hurst coefficient is also proposed. In this context, using the information of predictability, it is possible to eliminate some components, having low predictability potential, without a negative effect on the accuracy of the prediction and reducing the computational complexity of the algorithm. In the evaluated case, it was possible to reduce the resources needed to implement the algorithm of about 29% by eliminating the two (of seven) components with lower Hurst coefficient. This complexity reduction has not impacted the performance of the prediction algorithm.\n\nLiterature Review:", "role": "user" }, { "content": "The data that is collected within a specific time period like daily, hourly, monthly or annually is known as time series data. It appears in many different areas like physical time series, economic time series and marketing and sales time series. Physical time series belongs to physical sciences that include the study of natural science and its phenomena. In the analysis of physical time series, the data contain random noise which generally creates the difficulty for a pattern to identify. Therefore, in order to make the pattern more eminent, there is a way to filter out the noise in physical time series techniques. These patterns described by model-based components like trend component, seasonal component, cyclic component and irregular component BIB003 . Basically, physical time series is utilized to study the past behavior of the variable, designing the policy decisions and make a plan for the future operations. Also, to estimate or predict the behavior of phenomena in future that is very necessary for the business planning. The application of physical time series also occurs to predict travel time for urban networks BIB004 . Physical time series are difficult to be determined and predicted among many time series. To resolve the issues related to prediction of physical time series a special kind of spiking neural network called Polychronous Spiking Network was applied to explore the features of the spiking neural network model . RPNN-EF RPNN-EF uses few amounts of weights as compared to other models and it can be efficient way to enhance the performance of forecasting. The proposed network setting may not best for all models. Furthermore, Recurrent Pi-Sigma Neural Network (RPSN) was proposed and its application to the prediction of physical time series is mentioned in BIB002 . This network structure utilized the properties of HONN. The structure of the network is regular and has a recurrent connection between the output layer to input layer employed to store the information for later use. This network provides promising results and has the ability of faster learning as compared to existing feedforward networks. In contrast, the structure of RPSN is not appropriate to forecast the nonstationary and highly nonlinear signals. Meanwhile, some statistical tools like an artificial neural network that get attention to the researchers to predict the seismic events by neural intelligence approach BIB006 . The comparative analysis of different forecasting techniques is shown by the Table 1 . Furthermore, for the better and accurate prediction of non-stationary and physical time-series, another approach was applied called Regularization technique in SMIA network BIB005 . The proposed network provides the promising results for the prediction of nonlinear time series. Besides this, there is a need for some different approaches that would beneficial to find appropriate initial weights for network structure. Moreover, to predict physical time series artificial neural network by combining the wavelet technique is used. In this regard, monthly rainfall time series data set is used to check the performance and it shows that wavelet neural network provides better prediction than ANN . However, to forecast the wind speed another approach Empirical Mode Decomposition (EMD) with Elman Neural Network (ENN) is proposed. The results of EMD-ENN model show lower error as compared to ENN, back-propagation neural network and persistent model BIB007 . Furthermore, artificial wavelet neural network is used to forecast the wind time series. The proposed method also reduced the computational complexity BIB009 . Different models are developed for forecasting of wind speed and power generation. The statistical ARIMA model and linear autoregressive (AR) model were selected for wind speed prediction and also ensure the lowest errors BIB008 BIB001 .", "role": "assistant" } ]

[ { "content": "You will be shown a claim about public health and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: High blood pressure may mean higher risk of hospitalization or severe illness.\n\nAbstract:\nOBJECTIVE: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia.\nMETHODS: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19.\nComposite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest.\nRESULTS: A total of 6560 patients were pooled from 30 studies.\nHypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I2, 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I2, 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I2 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I2,0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I2 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I2 0%, p = 0.55).\nMeta-regression analysis showed that gender (p = 0.013) was a covariate that affects the association.\nThe association was stronger in studies with a percentage of males < 55% compared to ⩾ 55% (RR 2.32 v. RR 1.79).\nCONCLUSION: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"CONCLUSION: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.\"]}", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your response other than the answer.\n\nParagraph: The field of 'virus dynamics' was first developed to describe the mechanistic underpinnings of long-term patterns of steady-state viral load exhibited by patients in chronic phase infections with HIV, who appeared to produce and clear virus at equivalent rates (Nowak and May, 2000; Ho et al., 1995) . Models of simple target cell depletion, in which viral load is dictated by a bottom-eLife digest Bats can carry viruses that are deadly to other mammals without themselves showing serious symptoms. In fact, bats are natural reservoirs for viruses that have some of the highest fatality rates of any viruses that people acquire from wild animals -including rabies, Ebola and the SARS coronavirus. Bats have a suite of antiviral defenses that keep the amount of virus in check. For example, some bats have an antiviral immune response called the interferon pathway perpetually switched on. In most other mammals, having such a hyper-vigilant immune response would cause harmful inflammation. Bats, however, have adapted anti-inflammatory traits that protect them from such harm, include the loss of certain genes that normally promote inflammation. However, no one has previously explored how these unique antiviral defenses of bats impact the viruses themselves. Now, Brook et al. have studied this exact question using bat cells grown in the laboratory. The experiments made use of cells from one bat species -the black flying fox -in which the interferon pathway is always on, and another -the Egyptian fruit bat -in which this pathway is only activated during an infection. The bat cells were infected with three different viruses, and then Brook et al. observed how the interferon pathway helped keep the infections in check, before creating a computer model of this response. The experiments and model helped reveal that the bats' defenses may have a potential downside for other animals, including humans. In both bat species, the strongest antiviral responses were countered by the virus spreading more quickly from cell to cell. This suggests that bat immune defenses may drive the evolution of faster transmitting viruses, and while bats are well protected from the harmful effects of their own prolific viruses, other creatures like humans are not. The findings may help to explain why bats are often the source for viruses that are deadly in humans. Learning more about bats' antiviral defenses and how they drive virus evolution may help scientists develop better ways to predict, prevent or limit the spread of viruses from bats to humans. More studies are needed in bats to help these efforts. In the meantime, the experiments highlight the importance of warning people to avoid direct contact with wild bats. up resource supply of infection-susceptible host cells, were first developed for HIV (Perelson, 2002) but have since been applied to other chronic infections, including hepatitis-C virus (Neumann et al., 1998) , hepatitis-B virus (Nowak et al., 1996) and cytomegalovirus (Emery et al., 1999) . Recent work has adopted similar techniques to model the within-host dynamics of acute infections, such as influenza A and measles, inspiring debate over the extent to which explicit modeling of top-down immune control can improve inference beyond the basic resource limitation assumptions of the target cell model (Baccam et al., 2006; Pawelek et al., 2012; Saenz et al., 2010; Morris et al., 2018) . To investigate the impact of unique bat immune processes on in vitro viral kinetics, we first undertook a series of virus infection experiments on bat cell lines expressing divergent interferon phenotypes, then developed a theoretical model elucidating the dynamics of within-host viral spread. We evaluated our theoretical model analytically independent of the data, then fit the model to data recovered from in vitro experimental trials in order to estimate rates of within-host virus transmission and cellular progression to antiviral status under diverse assumptions of absent, induced, and constitutive immunity. Finally, we confirmed our findings in spatially-explicit stochastic simulations of fitted time series from our mean field model. We hypothesized that top-down immune processes would overrule classical resource-limitation in bat cell lines described as constitutively antiviral in the literature, offering a testable prediction for models fit to empirical data. We further predicted that the most robust antiviral responses would be associated with the most rapid within-host virus propagation rates but also protect cells against virus-induced mortality to support the longest enduring infections in tissue culture. We first explored the influence of innate immune phenotype on within-host viral propagation in a series of infection experiments in cell culture. We conducted plaque assays on six-well plate monolayers of three immortalized mammalian kidney cell lines: [1] Vero (African green monkey) cells, which are IFN-defective and thus limited in antiviral capacity (Desmyter et al., 1968) ; [2] RoNi/7.1 (Rousettus aegyptiacus) cells which demonstrate idiosyncratic induced interferon responses upon viral challenge (Kuzmin et al., 2017; Arnold et al., 2018; Biesold et al., 2011; Pavlovich et al., 2018) ; and [3] PaKiT01 (Pteropus alecto) cells which constitutively express IFN-a (Zhou et al., 2016; Crameri et al., 2009) . To intensify cell line-specific differences in constitutive immunity, we carried out infectivity assays with GFP-tagged, replication-competent vesicular stomatitis Indiana viruses: rVSV-G, rVSV-EBOV, and rVSV-MARV, which have been previously described (Miller et al., 2012; Wong et al., 2010) . Two of these viruses, rVSV-EBOV and rVSV-MARV, are recombinants for which cell entry is mediated by the glycoprotein of the bat-evolved filoviruses, Ebola (EBOV) and Marburg (MARV), thus allowing us to modulate the extent of structural, as well as immunological, antiviral defense at play in each infection. Previous work in this lab has demonstrated incompatibilities in the NPC1 filovirus receptor which render PaKiT01 cells refractory to infection with rVSV-MARV (Ng and Chandrab, 2018, Unpublished results) , making them structurally antiviral, over and above their constitutive expression of IFN-a. All three cell lines were challenged with all three viruses at two multiplicities of infection (MOI): 0.001 and 0.0001. Between 18 and 39 trials were run at each cell-virus-MOI combination, excepting rVSV-MARV infections on PaKiT01 cells at MOI = 0.001, for which only eight trials were run (see Materials and methods; Figure 1 -figure supplements 1-3, Supplementary file 1). Because plaque assays restrict viral transmission neighbor-to-neighbor in two-dimensional cellular space (Howat et al., 2006) , we were able to track the spread of GFP-expressing virus-infected cells across tissue monolayers via inverted fluorescence microscopy. For each infection trial, we monitored and re-imaged plates for up to 200 hr of observations or until total monolayer destruction, processed resulting images, and generated a time series of the proportion of infectious-cell occupied plate space across the duration of each trial (see Materials and methods). We used generalized additive models to infer the time course of all cell culture replicates and construct the multi-trial dataset to which we eventually fit our mechanistic transmission model for each cell line-virus-specific combination ( Figure 1; Figure 1 -figure supplements 1-5). All three recombinant vesicular stomatitis viruses (rVSV-G, rVSV-EBOV, and rVSV-MARV) infected Vero, RoNi/7.1, and PaKiT01 tissue cultures at both focal MOIs. Post-invasion, virus spread rapidly across most cell monolayers, resulting in virus-induced epidemic extinction. Epidemics were less severe in bat cell cultures, especially when infected with the recombinant filoviruses, rVSV-EBOV and rVSV-MARV. Monolayer destruction was avoided in the case of rVSV-EBOV and rVSV-MARV infections on PaKiT01 cells: in the former, persistent viral infection was maintained throughout the 200 hr duration of each experiment, while, in the latter, infection was eliminated early in the time series, preserving a large proportion of live, uninfectious cells across the duration of the experiment. We assumed this pattern to be the result of immune-mediated epidemic extinction (Figure 1) . Patterns from MOI = 0.001 were largely recapitulated at MOI = 0.0001, though at somewhat reduced total proportions (Figure 1-figure supplement 5 ). A theoretical model fit to in vitro data recapitulates expected immune phenotypes for bat cells We next developed a within-host model to fit to these data to elucidate the effects of induced and constitutive immunity on the dynamics of viral spread in host tissue ( Figure 1 ). The compartmental within-host system mimicked our two-dimensional cell culture monolayer, with cells occupying five distinct infection states: susceptible (S), antiviral (A), exposed (E), infectious (I), and dead (D). We modeled exposed cells as infected but not yet infectious, capturing the 'eclipse phase' of viral integration into a host cell which precedes viral replication. Antiviral cells were immune to viral infection, in accordance with the 'antiviral state' induced from interferon stimulation of ISGs in tissues adjacent to infection (Stetson and Medzhitov, 2006) . Because we aimed to translate available data into modeled processes, we did not explicitly model interferon dynamics but instead scaled the rate of cell progression from susceptible to antiviral (r) by the proportion of exposed cells (globally) in the system. In systems permitting constitutive immunity, a second rate of cellular acquisition of antiviral status (\") additionally scaled with the global proportion of susceptible cells in the model. Compared with virus, IFN particles are small and highly diffusive, justifying this global signaling assumption at the limited spatial extent of a six-well plate and maintaining consistency with previous modeling approximations of IFN signaling in plaque assay (Howat et al., 2006) . To best represent our empirical monolayer system, we expressed our state variables as proportions (P S , P A , P E , P I , and P D ), under assumptions of frequency-dependent transmission in a wellmixed population (Keeling and Rohani, 2008) , though note that the inclusion of P D (representing the proportion of dead space in the modeled tissue) had the functional effect of varying transmission with infectious cell density. This resulted in the following system of ordinary differential equations:\n\nWe defined 'induced immunity' as complete, modeling all cells as susceptible to viral invasion at disease-free equilibrium, with defenses induced subsequent to viral exposure through the term r. By contrast, we allowed the extent of constitutive immunity to vary across the parameter range of \" > 0, defining a 'constitutive' system as one containing any antiviral cells at disease-free equilibrium. In fitting this model to tissue culture data, we independently estimated both r and \"; as well as the cell-to-cell transmission rate, b, for each cell-virus combination. Since the extent to which constitutively-expressed IFN-a is constitutively translated into functional protein is not yet known for bat hosts (Zhou et al., 2016) , this approach permitted our tissue culture data to drive modeling inference: even in PaKiT01 cell lines known to constitutively express IFN-a, the true constitutive extent of the system (i.e. the quantity of antiviral cells present at disease-free equilibrium) was allowed to vary through estimation of \": For the purposes of model-fitting, we fixed the value of c, the return rate of antiviral cells to susceptible status, at 0. The small spatial scale and short time course (max 200 hours) of our experiments likely prohibited any return of antiviral cells to susceptible status in our empirical system; nonetheless, we retained the term c in analytical evaluations of our model because regression from antiviral to susceptible status is possible over long time periods in vitro and at the scale of a complete organism (Radke et al., 1974; Rasmussen and Farley, 1975; Samuel and Knutson, 1982) . Before fitting to empirical time series, we undertook bifurcation analysis of our theoretical model and generated testable hypotheses on the basis of model outcomes. From our within-host model system (Equation 1-5), we derived the following expression for R 0 , the pathogen basic reproduction number (Supplementary file 2):\n\nPathogens can invade a host tissue culture when R 0 >1. Rapid rates of constitutive antiviral acquisition (\") will drive R 0 <1: tissue cultures with highly constitutive antiviral immunity will be therefore resistant to virus invasion from the outset. Since, by definition, induced immunity is stimulated following initial virus invasion, the rate of induced antiviral acquisition (r) is not incorporated into the equation for R 0 ; while induced immune processes can control virus after initial invasion, they cannot prevent it from occurring to begin with. In cases of fully induced or absent immunity (\" ¼ 0), the R 0 equation thus reduces to a form typical of the classic SEIR model:\n\nAt equilibrium, the theoretical, mean field model demonstrates one of three infection states: endemic equilibrium, stable limit cycles, or no infection ( Figure 2) . Respectively, these states approximate the persistent infection, virus-induced epidemic extinction, and immune-mediated epidemic extinction phenotypes previously witnessed in tissue culture experiments ( Figure 1 ). Theoretically, endemic equilibrium is maintained when new infections are generated at the same rate at which infections are lost, while limit cycles represent parameter space under which infectious and susceptible populations are locked in predictable oscillations. Endemic equilibria resulting from cellular regeneration (i.e. births) have been described in vivo for HIV (Coffin, 1995) and in vitro for herpesvirus plaque assays (Howat et al., 2006) , but, because they so closely approach zero, true limit cycles likely only occur theoretically, instead yielding stochastic extinctions in empirical time series. Bifurcation analysis of our mean field model revealed that regions of no infection (pathogen extinction) were bounded at lower threshold (Branch point) values for b, below which the pathogen was unable to invade. We found no upper threshold to invasion for b under any circumstances (i.e. b high enough to drive pathogen-induced extinction), but high b values resulted in Hopf bifurcations, which delineate regions of parameter space characterized by limit cycles. Since limit cycles so closely approach zero, high bs recovered in this range would likely produce virus-induced epidemic extinctions under experimental conditions. Under more robust representations of immunity, with higher values for either or both induced (r) and constitutive (\") rates of antiviral acquisition, Hopf bifurcations occurred at increasingly higher values for b, meaning that persistent infections could establish at higher viral transmission rates ( Figure 2 ).\n\nQuestion: Why was the field of virus dynamics developed?", "role": "user" }, { "content": "to describe the mechanistic underpinnings of long-term patterns of steady-state viral load exhibited by patients in chronic phase infections with HIV, who appeared to produce and clear virus at equivalent rates", "role": "assistant" } ]

[ { "content": "You will be shown biomedical passages and your task is to answer the provided question. Provide a concise and accurate response and do not include any additional text in the response other than the answer.\n\nQuestion: Where does gemtuzumab ozogamicin bind?\n\nContext: Gemtuzumab ozogamicin is a CD33-targeted antibody-drug conjugate joined to calicheamicin.", "role": "user" }, { "content": "CD33", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\", \"Disease\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Naloxone\", ...], \"Disease\": [\"Hypotensive\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nChoreoathetoid movements associated with rapid adjustment to methadone. Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.", "role": "user" }, { "content": "{\"Chemical\": [\"heroine\", \"cocaine\", \"methadone\"], \"Disease\": [\"Choreoathetoid movements\", \"Choreatiform hyperkinesias\", \"movement abnormalities\", \"choreoathetoid movements\", \"Choreatiform\", \"hyperkinesias\"]}", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a JSON array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the JSON array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: [Colonization of cental venous catheter in the Intensive Care Units at the Institute of Cardiovascular Disease \"Dedinje\"--one year study]. The application of Central Venous Catheters (CVC) is associated with increased risk of microbial colonization and infection. The aim of present study was to assess the frequency of pathogens colonizing CVC and to determine their susceptibility pattern to various antimicrobial agents. ### Materials And Methods A total of 253 samples of CVC from intensive care units (ICU) patients were received for culture during 2003. All microorganisms were identified by standard microbiological methods and the susceptibility to antimicrobial agents was determined according to NCCLS recommendations. ### results A total of 184 (72.7%) cultures were positive and 223 pathogens were isolated. Coagulase negative staphylococci (CNS) were the dominant isolates (24.7%), followed by Enterobacter spp. (12.1%), Pseudomonas spp. (11.7%), Enterococcus spp. (9.9%), Klebsiella spp. (8.6%), Candida spp. (7.6%), Acinetobacter spp. (7.6%), other Gram negative nonfermentative bacilli (5.8%), Serratia spp. (4.5%), Staphylococcus aureus (2.6%), Proteus mirabilis (2.2%), E. coli (1.8%) and Citrobacter spp. (0.9%). Meropenem ( 84.5 % ) and vancomycin ( 100 % ) remain the most effective antimicrobial agents against Gram negative and Gram positive bacteria , respectively . ### conclusion Gram negative bacilli and CNS are the commonest microorganisms colonizing CVC from ICU patients. The increasing resistance of the bacteria to antimicrobial agents is the major problem in spite of restricted policy of using antimicrobial agents in ICU.\n\nsentence: Meropenem ( 84.5 % ) and vancomycin ( 100 % ) remain the most effective antimicrobial agents against Gram negative and Gram positive bacteria , respectively .", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Are there any clinical trials of the effect of evening primrose oil on postmenopausal symptoms ?\n\nContext: To analyze whether the time (morning/evening) of administration of a compound containing 60 mg of dry soy seed extract (glycine max) with 40% of total isoflavones, primrose oil and α-tocopherol modifies the effect on the climacteric syndrome.\nThe object of this study was to evaluate the effect of different doses of a compound containing isoflavones 60 mg, primrose oil 440 mg and vitamin E 10 mg. (IOVE) on menopausal complaints. This was an open, multicentre, randomised, group comparative, efficacy and safety trial.\nEmphasis was placed on randomized, double-blind, placebo-controlled clinical trials, as these provide the best efficacy and safety data\nNonprescription therapies reviewed include black cohosh, dong quai, evening primrose oil, physical activity, phytoestrogens, and red clover\nThe effect of oral evening primrose oil on menopausal hot flashes: a randomized clinical trial.\nThe aim of this study was to compare the efficacy of evening primrose with placebo in improvement of menopausal hot flashes.\nThe application of oral evening primrose oil compared with placebo for controlling hot flashes may decrease more the intensity of attacks\nOur search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose,\nSingle clinical trials have found no benefit for dong quai, evening primrose oil,\nSingle clinical trials have found that dong quai, evening primrose oil,\nTo evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause. DESIGN: Randomised, double blind, placebo controlled study.", "role": "user" }, { "content": "yes", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"AnatomicalEntity\"].\n\nPlease return the output as a JSON object of the format: {\"AnatomicalEntity\": [\"tumor cells\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be an empty JSON array \"[]\".\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nAntibiotic-induced persistence of cytotoxic Staphylococcus aureus in non-phagocytic cells.\nOBJECTIVES:\nAfter infection of non-phagocytic cells, some Staphylococcus aureus strains are able to survive and kill their host cells. The purpose of this study was to determine the action of various antibiotics on the survival of host cells and/or intracellular S. aureus.\nMETHODS:\nMurine keratinocyte (PAM212) and fibroblast (mKSA) cell lines were infected with cytotoxic S. aureus and cultured in the presence of various antibiotics at graded concentrations. The viability of host cells was measured 24 h after infection. To determine the bacterial viability within host cells, cellular lysates were prepared and colony forming units were quantified using a spiral plater. Host cells infected with fluorescein isothiocyanate (FITC)-labelled S. aureus were analysed by flow cytometry and microscopy to determine the subcellular localization S. aureus.\nRESULTS:\nOxacillin, vancomycin, gentamicin, ciprofloxacin and trimethoprim/sulfamethoxazole did not rescue host cells from cell death induced by intracellular S. aureus. In contrast, linezolid, rifampicin, azithromycin, clindamycin, erythromycin and quinupristin/dalfopristin suppressed the cytotoxic action of S. aureus. After withdrawal of antibiotics, intracellular S. aureus regained cytotoxic activity and killed their host cells. Only rifampicin was able to eliminate intracellular S. aureus completely within 72 h. In contrast, clindamycin, azithromycin and linezolid induced a state of intracellular persistence of viable S. aureus.\nCONCLUSIONS:\nAntibiotics commonly used for the management of S. aureus infections appear to create a niche for invasive intracellular S. aureus, which may play an important role for persistence and recurrence of infection. Because of its unique ability to eliminate intracellular S. aureus, rifampicin appears to be valuable for the treatment of invasive S. aureus infections.", "role": "user" }, { "content": "{\"AnatomicalEntity\": [\"cellular lysates\", \"cells\", \"cell\", \"non-phagocytic cells\", \"colony\", \"intracellular\", \"strains\", \"PAM212\", \"subcellular\", \"fibroblast (mKSA) cell lines\", \"keratinocyte\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Finding\", \"Bacterium\", \"ProfessionalOrOccupationalGroup\", \"InjuryOrPoisoning\", \"Eukaryote\", \"BodySystem\", \"Virus\", \"ResearchActivity\", \"BodySubstance\", \"PopulationGroup\", \"Chemical\", \"AnatomicalStructure\", \"SpatialConcept\", \"HealthCareActivity\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Food\", \"ClinicalAttribute\", \"MedicalDevice\", \"BiologicFunction\", \"IntellectualProduct\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nMolecular profile of 5-fluorouracil pathway genes in colorectal carcinoma This study addresses involvement of major 5-fluorouracil (5-FU) pathway genes in the prognosis of colorectal carcinoma patients. Testing set and two validation sets comprising paired tumor and adjacent mucosa tissue samples from 151 patients were used for transcript profiling of 15 5-FU pathway genes by quantitative real-time PCR and DNA methylation profiling by high resolution melting analysis. Intratumoral molecular profiles were correlated with clinical data of patients. Protein levels of two most relevant candidate markers were assessed by immunoblotting. Downregulation of DPYD and upregulation of PPAT, UMPS, RRM2, and SLC29A1 transcripts were found in tumors compared to adjacent mucosa in testing and validation sets of patients. Low RRM2 transcript level significantly associated with poor response to the first-line palliative 5-FU -based chemotherapy in the testing set and with poor disease-free interval of patients in the validation set irrespective of 5-FU treatment. UPP2 was strongly methylated while its transcript absent in both tumors and adjacent mucosa. DPYS methylation level was significantly higher in tumor tissues compared to adjacent mucosa samples. Low intratumoral level of UPB1 methylation was prognostic for poor disease-free interval of the patients (P = 0.0002). The rest of the studied 5-FU genes were not methylated in tumors or adjacent mucosa. The observed overexpression of several 5-FU activating genes and DPYD downregulation deduce that chemotherapy naïve colorectal tumors share favorable gene expression profile for 5-FU therapy. Low RRM2 transcript and UPB1 methylation levels present separate poor prognosis factors for colorectal carcinoma patients and should be further investigated.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"mucosa\", \"activating genes\", \"UMPS\", \"tumor tissues\", \"DPYS\", \"PPAT\", \"SLC29A1\", \"genes\", \"UPP2\", \"RRM2\", \"DPYD\", \"UPB1\", \"mucosa tissue\"], \"Bacterium\": [], \"BiologicFunction\": [\"pathway\", \"na\\u00efve colorectal tumors\", \"downregulation\", \"overexpression\", \"Downregulation\", \"colorectal carcinoma\", \"tumors\", \"tumor\", \"methylation\", \"upregulation\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"transcript\", \"transcripts\", \"5-FU\", \"5-fluorouracil\"], \"ClinicalAttribute\": [\"prognosis factors\", \"markers\"], \"Eukaryote\": [], \"Finding\": [\"Protein levels\"], \"Food\": [], \"HealthCareActivity\": [\"immunoblotting\", \"therapy\", \"prognosis\", \"treatment\", \"chemotherapy\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"testing set\", \"validation sets\", \"prognostic\", \"validation set\", \"Testing set\", \"clinical data\", \"testing\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"study\", \"quantitative real-time PCR\", \"profiling\", \"DNA methylation profiling\"], \"SpatialConcept\": [\"Intratumoral\", \"adjacent\", \"intratumoral\"], \"Virus\": []}", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your response other than the answer.\n\nParagraph: ZS: conceived the study and drafted the manuscript. ZLL: The member of the emergency management and infection control team (EMICT)\nand was involved in the formulation of the measures. WXC: The member of the EMICT and was involved in the formulation of the\nmeasures. LHZ: The member of the EMICT and was involved in the formulation of the\nmeasures. LPD: The member of the EMICT and was involved in the formulation of the\nmeasures. BS: Leader of the EMICT, conceived the study and reviewed the manuscript. All authors read and approved the final manuscript. The authors declare no conflict of interest. The authors declare that they had full access to all of the data in this study and the\nauthors take complete responsibility for the integrity of the data and the accuracy of\nthe data analysis\n1\nThe Battle Against Novel Coronavirus Pneumonia (COVID-19): Emergency\nManagement and Infection Control in a Radiology Department\nAbstract\nObjective: To describe the strategy and the emergency management and infection control\nprocedure of our radiology department during the COVID-19 outbreak. Methods: We set up emergency management and sensing control teams. The team formulated\nvarious measures: reconfiguration of the radiology department, personal protection and training\nof staff, examination procedures for patients suspected of or confirmed with COVID-19 as well\nas patients without an exposure history or symptoms. Those with suspected or confirmed\nCOVID-19 infection were scanned in the designated fever-CT unit. Results: From January 21, 2020 to March 9, 2020, 3,083 people suspected of or confirmed with\nCOVID-19 underwent fever-CT examinations. Including initial examinations and\nreexaminations, the total number of fever-CT examinations numbered 3,340. As a result of our\nprecautions, none of the staff of the radiology department were infected with COVID-19. Conclusion: Strategic planning and adequate protections can help protect patients and staff\nagainst a highly infectious disease while maintaining function at a high volume capacity. Keywords: Coronavirus, COVID-19, novel coronavirus pneumonia, infection control\n\n2\nIntroduction\nThe whole world has been closely focusing on an outbreak of respiratory disease caused by a\nnovel coronavirus that was first reported in Wuhan, China, on December 31, 2019, and that\ncontinues to spread. On February 11, 2020, the World Health Organization (WHO) named the\ndisease “coronavirus disease 2019” (COVID-19). As of 24:00 on March 11, 2020, the National Health Commission (NHC) had received reports\nof 80,793 confirmed cases and 3,169 deaths on the Chinese mainland. There remain 14,831\nconfirmed cases (including 4,257 in serious condition) and 253 suspected cases still\nhospitalized. To date, 677,243 people have been identified as having had close contact with\ninfected patients of whom13,701 are under medical observation [1]. Outside China, 44,067\nlaboratory-confirmed cases and 1,440 deaths have occurred in 117 countries /territories/areas\naccording to the WHO [2]. COVID-19 poses significant threats to international health. Like the\nflu, COVID-19 is thought to spread mainly from person-to-person between people who are in\nclose contact with one another through respiratory droplets produced when an infected person\ncoughs or sneezes. In light of the infectious nature of this disease, healthcare workers are at\nhigh risk of infection of COVID-19. In China, healthcare workers account for 1,716 confirmed\ncases of COVID-19, including six deaths [3]. Computed tomography (CT) can play a role in both diagnosing and categorizing\nCOVID-19 on the basis of case definitions issued by the WHO and the treatment guidelines\nfrom the NHC [4]. Suspected patients having the virus may undergo chest CT. Isolation and\nbarrier procedures are necessary to protect both the department staff and other patients in the\nhospital. Note should be made that due to overlap of imaging findings with other respiratory\n3\ndiseases, CT is not helpful as a screening tool. But it can help identify the degree of pulmonary\ninvolvement and disease course. Our hospital is a national regional medical center with 4,300 beds and a tertiary referral\ncenter in Sichuan province. The initial response started on January 21, 2020, after transmission\nof COVID-19 was confirmed to be human-to-human on January 20, 2020. The first suspected\ncase of COVID-19 in Sichuan province was reported on January 21, 2020. The Sichuan\nprovincial government immediately launched the first-level response to major public health\nemergencies. On the same day, our hospital was designated to care for Sichuan province\npatients with COVID-19. This article describes the emergency management procedure of our radiology department\nfor situations involving severe infectious diseases, such as COVID-19, and the\ninfection-protection experience of the department staff. Methods\nThe hospital provided personal protective equipment (medical protective clothing,\nsurgical cap, N95 mask, gloves, face shields, and goggles) to all its healthcare staff, erected\nthree medical tents (fever tents) for screening of fever cases in the parking lot of the emergency\ndepartment, planned an examination route and examination area for patients suspected of\nharboring the virus, and placed confirmed patients in an isolation ward. “Fever” was the\ncolloquial term used to designate suspected COVID-19 based on symptoms such as a fever or\nwith an epidemiological history of a potential exposure as well as those with confirmed\nCOVID-19 referred for treatment. Further, during outbreak, emergency and outpatient patients\n4\nwithout fever were asked for information such as epidemiological history and sent to fever tents\nas long as they met suspected criteria. The radiology department has 65 diagnostic radiologists and 161 other staff members\n(trained technologists, nurses, engineers, and support staff). The equipment of the radiology\ndepartment includes 12 magnetic resonance (MR) scanners, 14 CT scanners, 15 digital\nsubtraction angiography (DSA) systems, 32 sets of digital radiography (DR) systems\n(including nine mobile bedside DR sets), and 130 imaging diagnostic workstations for picture\narchiving and communication systems (PACS). Most of the equipment is distributed among\nfour buildings at the hospital main campus. 4 CT scanners, 4 MR scanners, 1 DR are located on\nthe first floor of the first inpatient building, and 9 DR and 8 DSA are located on the second\nfloor. 1 CT and 1 MR scanner are located in the third inpatient building. 1 CT and 1 MR scanner\nare located in the sixth inpatient building. 2 CT scanners, 2 MR scanners and 7 DSA are located\nin the technical building. The rest of the equipment is located in the seventh inpatient building\nin the branch campus. The first inpatient building, located next to the emergency department, was reconfigured to\nhandle cases of COVID-19. Fever tents were set up by the emergency department in the\nemergency department parking lot to separate normal emergency patients from patients with\nsymptoms or exposure history suspicious of COVID-19. We established separate means of\naccess between fever tents and between the fever examination area of the radiology department\nto avoid cross-contamination. The emergency management and infection control measures, as described below and\nimplemented in the radiology department during the outbreak, have been approved by the\n5\ninfection control committee of hospital. These measures are in accordance with relevant laws\nand regulations, in order to protect patients as well as the staff. Radiology Emergency Management and Infection Control Team (EMICT)\nThe radiology department director chaired the EMICT. Its members include the deputy\ndirector, chief technologist, head nurse, equipment engineer supervisor, and infection control\nnurse of the radiology department. Team responsibilities included (1) coordination between the\nhospital’s management and planning of infection control and radiology departments; (2)\ncollection of the most up-to-date protection-related information to educate and train staff in the\ndepartment; (3) reallocation of staff according to the actual situation; (4) establishment of the\nCT procedures for patients with COVID-19; and (5) establishment of an emergency\nmanagement plan for the radiology department to ensure that the department would run\nnormally. Suspected patients\nThe suspected patients were identified according to the Diagnosis and Treatment Program of\nthe Novel Coronavirus Pneumonia of the NHC [5], mainly based on epidemiological history. Reconfiguration of the radiology department\nThe radiology department was divided into four areas [6]: contaminated, semicontaminated,\nbuffer, and clean areas (Figure 1). The contaminated area is connected to the fever clinic and\nincludes the fever accessway, the CT examination room, and the DR examination room for\n6\nconfirmed and suspected cases. One CT scanner and one DR system closest to the emergency\ndepartment are designated the fever-CT and fever-DR to examine patients with suspected and\nconfirmed COVID-19. There is a separate dedicated access between the contaminated area and\nthe fever screening tents. The semicontaminated area includes the fever-CT control room,\nfever-DR control room, and other patient examination access areas. The buffer zone includes\naccess areas for medical personnel and a dressing area for technologists. The clean area\nincludes the administrative office and the diagnostic room. The contaminated area was isolated from other areas using physical barricades. Directional signs were newly installed to guide patients and staff. Personal protection and training of staff\nFor providing care for patients with confirmed and suspected COVID-19, all hospital staff\nare required to wear complete personal protective equipment [7]: medical protective clothing,\nsurgical cap, N95 mask, gloves, face shields, and goggles. Wearing and removing of the\nequipment must be performed in accordance with the procedures and under the supervision of\nthe infection control nurse. Because staff members working in the contaminated area are under much situational\npressure, periodically taking time off could lower their physical and mental stress levels. The\ntechnologists on fever-CT duty shifts are provided a break once a week for four hours. In\naddition, the health of staff in the contaminated area must be monitored closely for the\nsymptoms of COVID-19. Pregnant staff must be assigned to the clean area. 7\nThe EMICT formulates and continually updates guidelines and educates all staff for West\nChina Hospital of Sichuan University. The EMICT training for staff is mainly involves\ndocuments regarding infection control and CT findings of COVID-19 and maintains an EMICT\nWeChat group for West China Hospital of Sichuan University. WeChat is the most widely used\nsocial media app in China. The EMICT releases the latest national and hospital-based\ninformation regarding COVID-19, guidance documents, and other notices from the hospital\nand radiology department in the WeChat group on a daily basis. Staff can also report to the\nEMICT in the WeChat group any time. Protocols for each modality and infection control\ninstructions are posted on the walls in all examination rooms. The EMICT periodically reminds\nstaff to undertake personal measures to reduce infection, such as wearing masks at all instances\nin the radiology department and N95 masks if working in the contaminated area; not touching\nthe mask and the eyes; practicing hand hygiene; facing away from colleagues when eating,\ndrinking, and talking; and not using personal cell phones while on duty. In addition, the chief thoracic radiologist provided lectures on all radiologists and\ntechnologists on typical CT findings of COVID-19 infection using materials developed in\nWuhan, the epicenter of the outbreak in China. CT examination procedures\nThere are two sets of procedures for CT examination: the fever-CT procedure and routine CT\nprocedure for those not suspected of COVID-19. The fever-CT procedure for suspected or confirmed COVID-19 (Figure 2)\n8\nBefore the fever-CT technologist operates the equipment, he or she should wear personal\nprotective equipment according to three-level protection standard [8]. Before the CT\nexamination of patients with suspected and confirmed COVID-19 begins, the fever tent or\nisolation ward notifies the radiologist in advance. The fever-CT technologist checks the\nequipment and prepares to disinfect the imaging equipment immediately after the examination. The patient enters the fever-CT waiting area through the fever access area. If the patient\ncan get onto and off the examination table by themselves, the patient is allowed to do so. If the\npatient cannot get onto or off the examination table independently, the person accompanying\nthe patient assists the patient, rather than the technologist. The technologist checks the patient\ninformation and, using an intercom system in the examination room, asks the patient to remove\nany metal ornaments on the neck and chest. Also, by intercom, the technologist trains the\npatient to hold his or her breath during the examination. The technologist uses a low-dose chest CT protocol to scan the patient. After scanning, the\noriginal images are reconstructed as 1 mm-thick layers. The technologist browses the images to\nensure that their quality meets the diagnostic requirements and then guides the patient to leave\nthrough the fever access area. The disposable sheets for patient examination are changed after\neach patient. The equipment is disinfected according to the procedure below. To protect themselves, the technologists assigned to the fever-CT wear N95 mask and\nother personal protection as established by the EMICT. The CT procedure for regular patients (figure.3)\n9\nSome patients with COVID-19 have no symptoms, and they may call at the general clinic for\nother reasons. The following CT procedure is applicable under these circumstances:\nWhen the patient makes an appointment for examination, the staff asks the patient about\ntheir epidemiological history, symptoms, and signs. If suspected criteria are met, the patient\nwill be sent to the fever tent for further screening. When a patient presents to the radiology\ndepartment entrance, his/her temperature is measured. If the temperature is higher than 37.2 , ℃\nthe patient is sent to the fever tent for further investigation. Those with no exposure history, suspicious symptoms or fever are screened in one of the\nnon-contaminated CT scanners. The technologists assigned to these scanners wear surgical\nmasks. All patients and the person accompanying them are required to wear surgical masks. After the CT examination, the technologist browses the images quickly. If the CT appearance is\ntypical of lung infection, the technologist immediately reports it to the chest radiologist on duty\nand asks the patient to wait in the CT examination room. If the chest radiologist does not\nsuspect COVID-19 infection, the patient can leave the CT examination room. If the chest\nradiologist does suspect COVID-19 infection, the technologist immediately reports it to the\nEMICT and sends the patient to the fever tent. The floor and equipment in the CT examination\nroom are disinfected according to regulations, and air disinfection is conducted for 30 min\nbefore examining other patients. These CT scanners are considered noncontaminated (not\nfever-CTs) after these sterilization procedures.\n\nQuestion: What can lower the physical and mental stress levels of staff members?", "role": "user" }, { "content": "periodically taking time off", "role": "assistant" } ]

[ { "content": "You will be shown a claim related to the COVID-19 pandemic, and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\".\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract.\n\nFor instance, if the model were given the claim \"the COVID vaccine is safe for healthy adults\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that the risks of severe COVID vaccine side effects are low for healthy adults.\"]\n}\n\nClaim: Hydroxychloroquine-mediated inhibition of pas-cov-2 entry is attenuated by tmprss2\n\nAbstract:\nHydroxychloroquine, used to treat malaria and some autoimmune disorders, potently inhibits viral infection of SARS coronavirus (SARS-CoV-1) and SARS-CoV-2 in cell-culture studies.\nHowever, human clinical trials of hydroxychloroquine failed to establish its usefulness as treatment for COVID-19.\nThis compound is known to interfere with endosomal acidification necessary to the proteolytic activity of cathepsins.\nFollowing receptor binding and endocytosis, cathepsin L can cleave the SARS-CoV-1 and SARS-CoV-2 spike (S) proteins, thereby activating membrane fusion for cell entry.\nThe plasma membrane-associated protease TMPRSS2 can similarly cleave these S proteins and activate viral entry at the cell surface.\nHere we show that the SARS-CoV-2 entry process is more dependent than that of SARS-CoV-1 on TMPRSS2 expression.\nThis difference can be reversed when the furin-cleavage site of the SARS-CoV-2 S protein is ablated.\nWe also show that hydroxychloroquine efficiently blocks viral entry mediated by cathepsin L, but not by TMPRSS2, and that a combination of hydroxychloroquine and a clinically-tested TMPRSS2 inhibitor prevents SARS-CoV-2 infection more potently than either drug alone.\nThese studies identify functional differences between SARS-CoV-1 and-2 entry processes, and provide a mechanistic explanation for the limited in vivo utility of hydroxychloroquine as a treatment for COVID-19.\nAuthor SummaryThe novel pathogenic coronavirus SARS-CoV-2 causes COVID-19 and remains a threat to global public health.\nChloroquine and hydroxychloroquine have been shown to prevent viral infection in cell-culture systems, but human clinical trials did not observe a significant improvement in COVID-19 patients treated with these compounds.\nHere we show that hydroxychloroquine interferes with only one of two somewhat redundant pathways by which the SARS-CoV-2 spike (S) protein is activated to mediate infection.\nThe first pathway is dependent on the endosomal protease cathepsin L and sensitive to hydroxychloroquine, whereas the second pathway is dependent on TMPRSS2, which is unaffected by this compound.\nWe further show that SARS-CoV-2 is more reliant than SARS coronavirus (SARS-CoV-1) on the TMPRSS2 pathway, and that this difference is due to a furin cleavage site present in the SARS-CoV-2 S protein.\nFinally, we show that combinations of hydroxychloroquine and a clinically tested TMPRSS2 inhibitor work together to effectively inhibit SARS-CoV-2 entry.\nThus TMPRSS2 expression on physiologically relevant SARS-CoV-2 target cells may bypass the antiviral activities of hydroxychloroquine, and explain its lack of in vivo efficacy.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Thus TMPRSS2 expression on physiologically relevant SARS-CoV-2 target cells may bypass the antiviral activities of hydroxychloroquine, and explain its lack of in vivo efficacy.\"]}", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Does radiotherapy for prostate cancer increase bladder cancer risk?\n\nContext: External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis.\nOn multivariable competing risk regression analyses, treatment with EBRT was independently associated with the risk of developing a second primary BCa (hazard ratio: 1.35, CI: 1.18-1.55; p<0.001), but not RCa (p=0.4).\nCONCLUSIONS: Patients treated with EBRT are at increased risk of developing a second primary BCa compared with those treated with RP. However, no differences were found considering RCa incidence in patients treated with RP or EBRT within the first 5 yr after primary therapy.\nWe found that those treated with external beam radiotherapy are at an increased risk of developing a second primary bladder cancer tumor.\nAll radiation modalities were found to have an increased RR of developing BlCa after 10 years, with brachytherapy having a significantly higher RR than external beam radiation (EBRT) or combined EBRT and brachytherapy in Caucasian men and a significantly higher RR than EBRT in men of other/unknown ethnicity.\nCONCLUSIONS: The increased risk of BlCa after prostate radiation occurs predominantly after 10 years, regardless of ethnicity. The RR of developing BlCa after 10 years is significantly higher following brachytherapy than after EBRT or EBRT and brachytherapy.\nBased on the data in the literature, there is a consistently increased risk of bladder cancer (HR: 1.67, 95% CI 1.55-1.80), rectal cancer (HR: 1.79, 95% CI 1.34-2.38), and colorectal cancer (HR: 1.79, 95% CI 1.34-23.8) following percutaneous radiation therapy. Following brachytherapy only an increased for the development of bladder cancer (HR: 2.14, 95% CI 1.03-3.94) has been observed.\nWhen comparing with a matched general French population, the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46-1.93).\nLDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer.\nCompared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy.\nOBJECTIVE: Although it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown.\nRESULTS: During the median follow-up period of 4.3 and 3.1 years, secondary bladder cancer occurred in 11 (3.4%) and 5 (1.1%) of patients with prostate cancer treated with external beam radiotherapy and radical prostatectomy, respectively.\nCONCLUSIONS Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population.\nRadiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study.\nRESULTS The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively.\nCompared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively.\nOBJECTIVE Although it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown.\nOBJECTIVE Although it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown.\nCONCLUSIONS Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population.\nPURPOSE Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer.\nRESULTS The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively.\nCONCLUSIONS: Taken together, these findings suggest that smoking history might be one of criteria to choose radical prostatectomy than external beam radiotherapy for prostate cancer, and that age would not be a criterion for therapeutic selection in terms of secondary bladder cancer.\nPURPOSE: Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer.\nRESULTS: The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively.\nCompared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively.\nPre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer.\nMen who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population.\nThe relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively.\nRadiotherapy for prostate cancer is associated with an increased incidence of secondary bladder cancer (BC).\nRadiation therapy for prostate cancer is associated with an increased risk of bladder cancer.\nRadiotherapy for prostate cancer was associated with higher risks of developing second malignancies of the bladder, colon, and rectum compared with patients unexposed to radiotherapy, but the reported absolute rates were low.", "role": "user" }, { "content": "yes", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nintroduction\n\nContext before the citation:\nFinite state transducers, which can be learned from bilingual corpora, have been proposed for automatic translation (Amengual et al., 2000), as have been bilingual stochastic grammars (Wu, 1996). This approach, known as translation memory, example-based or case-based translation, can work on the word level as well as on structured examples as they are generated during analysis and generation in more grammar-based translation paradigms (Kitano, 1993; Brown, 1996). In the simplest form, translations are stored and reused for the translation of new input.\n\nCitation Sentence:\nFinite state transducers , which can be learned from bilingual corpora , have been proposed for automatic translation ( Amengual et al. , 2000 ) , as have been bilingual stochastic grammars ( Wu , 1996 ) .\n\nContext after the citation:\nStatistical approaches (Wang and Waibel, 1997; Och et al., 1999) also fall into the category of corpus based approaches. In this paper, a translation method is proposed which is based on the very same principles as the aforementioned approaches. One difference is, that not a fully automatic training of the translation model is performed. Rather, a number of special purpose transducers are hand-crafted and used then at two points.", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "Below are the Abstract, Introduction, and Conclusion sections of a computer science research paper. Please summarize the main contribution of the work in a single sentence. Your response should include the summary sentence and no additional text.\n\nPaper text:\n\nA well-trained model should classify objects with unanimous score for every category.\nThis requires the high-level semantic features should be alike among samples, despite a wide span in resolution, texture, deformation, etc.\nPrevious works focus on re-designing the loss function or proposing new regularization constraints on the loss.\nIn this paper, we address this problem via a new perspective.\nFor each category, it is assumed that there are two sets in the feature space: one with more reliable information and the other with less reliable source.\nWe argue that the reliable set could guide the feature learning of the less reliable set during training - in spirit of student mimicking teacher’s behavior and thus pushing towards a more compact class centroid in the high-dimensional space.\nSuch a scheme also benefits the reliable set since samples become more closer within the same category - implying that it is easilier for the classifier to identify.\nWe refer to this mutual learning process as feature intertwiner and embed the spirit into object detection.\nIt is well-known that objects of low resolution are more difficult to detect due to the loss of detailed information during network forward pass.\nWe thus regard objects of high resolution as the reliable set and objects of low resolution as the less reliable set.\nSpecifically, an intertwiner is achieved by minimizing the distribution divergence between two sets.\nWe design a historical buffer to represent all previous samples in the reliable set and utilize them to guide the feature learning of the less reliable set.\nThe design of obtaining an effective feature representation for the reliable set is further investigated, where we introduce the optimal transport (OT) algorithm into the framework.\nSamples in the less reliable set are better aligned with the reliable set with aid of OT metric.\nIncorporated with such a plug-and-play intertwiner, we achieve an evident improvement over previous state-of-the-arts on the COCO object detection benchmark.\nClassifying complex data in the high-dimensional feature space is the core of most machine learning problems, especially with the emergence of deep learning for better feature embedding (Krizhevsky et al., 2012; BID3 BID10 .\nPrevious methods address the feature representation problem by the conventional cross-entropy loss, l 1 / l 2 loss, or a regularization constraint on the loss term to ensure small intra-class variation and large inter-class distance (Janocha & Czarneck, 2017; BID16 BID29 BID15 .\nThe goal of these works is to learn more compact representation for each class in the feature space.\nIn this paper, we also aim for such a goal and propose a new perspective to address the problem.Our observation is that samples can be grouped into two sets in the feature space.\nOne set is more reliable, while the other is less reliable.\nFor example, visual samples may be less reliable due to low resolution, occlusion, adverse lighting, noise, blur, etc.\nThe learned features for samples from the reliable set are easier to classify than those from the less reliable one.\nOur hypothesis is that the reliable set can guide the feature learning of the less reliable set, in the spirit of a teacher supervising the student.\nWe refer to this mutual learning process as a feature intertwiner.In this paper, a plug-and-play module, namely, feature intertwiner, is applied for object detection, which is the task of classifying and localizing objects in the wild.\nAn object of lower resolution will inevitably lose detailed information during the forward pass in the network.\nTherefore, it is well-known that the detection accuracy drops significantly as resolutions of objects decrease.\nWe can treat samples with high resolution (often corresponds to large objects or region proposals) as the reliable set and samples with low resolution (small instances) as the less reliable set 1 .\nEquipped with these two 'prototypical' sets, we can apply the feature intertwiner where the reliable set is leveraged to help the feature learning of the less reliable set.\nWithout intertwiner in\n(a), samples are more scattered and separated from each other.\nNote there are several samples that are far from its own class and close to the samples in other categories (e.g., class person in blue), indicating a potential mistake in classification.\nWith the aid of feature intertwiner in\n(b), there is barely outlier sample outside each cluster.\nthe features in the lower resolution set approach closer to the features in the higher resolution set -achieving the goal of compact centroids in the feature space.\nEmpirically, these two settings correspond to the baseline and intertwiner experiments (marked in gray) in TAB3 .\nThe overall mAP metric increases from 32.8% to 35.2%, with an evident improvement of 2.6% for small instances and a satisfying increase of 0.8% for large counterparts.\nThis suggests the proposed feature intertwiner could benefit both sets.Two important modifications are incorporated based on the preliminary intertwiner framework.\nThe first is the use of class-dependent historical representative stored in a buffer.\nSince there might be no large sample for the same category in one mini-batch during training, the record of all previous features of a given category for large instances is recorded by a representative, of which value gets updated dynamically as training evolves.\nThe second is an inclusion of the optimal transport (OT) divergence as a deluxe regularization in the feature intertwiner.\nOT metric maps the comparison of two distributions on high-dimensional feature space onto a lower dimension space so that it is more sensible to measure the similarity between two distributions.\nFor the feature intertwiner, OT is capable of enforcing the less reliable set to be better aligned with the reliable set.We name the detection system equipped with the feature intertwiner as InterNet.\nFull code suite is available at https://github.com/hli2020/feature intertwiner.\nFor brevity, we put the descriptions of dividing two sets in the detection task, related work (partial), background knowledge on OT theory and additional experiments in the appendix.\nIn this paper, we propose a feature intertwiner module to leverage the features from a more reliable set to help guide the feature learning of another less reliable set.\nThis is a better solution for generating a more compact centroid representation in the high-dimensional space.\nIt is assumed that the high-level semantic features within the same category should resemble as much as possible among samples with different visual variations.\nThe mutual learning process helps two sets to have closer distance within the cluster in each class.\nThe intertwiner is applied on the object detection task, where a historical buffer is proposed to address the sample missing problem during one mini-batch and the optimal transport (OT) theory is introduced to enforce the similarity among the two sets.\nSince the features in the reliable set serve as teacher in the feature learning, careful preparation of such features is required so that they would match the information in the small-object set.\nThis is why we design different options for the large set and finally choose OT as a solution.\nWith aid of the feature intertwiner, we improve the detection performance by a large margin compared to previous state-of-the-arts, especially for small instances.Feature intertwiner is positioned as a general alternative to feature learning.\nAs long as there exists proper division of one reliable set and the other less reliable set, one can apply the idea of utilizing the reliable set guide the feature learning of another, based on the hypothesis that these two sets share similar distribution in some feature space.\nOne direction in the future work would be applying feature intertwiner into other domains, e.g., data classification, if proper set division are available.", "role": "user" }, { "content": "(Camera-ready version) A feature intertwiner module to leverage features from one accurate set to help the learning of another less reliable set.", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a JSON array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the JSON array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: Efficacy of varenicline to prompt quit attempts in smokers not currently trying to quit: a randomized placebo-controlled trial. nicotine replacement therapy to aid smoking reduction increases the probability of a future quit attempt among smokers not currently planning to quit smoking. We tested whether varenicline , a partial nicotine agonist , would also increase future quit attempts . ### methods This randomized, placebo-controlled trial recruited 218 smokers who were interested in quitting but had no plans to quit in the next month. Participants used varenicline (2 mg/day) or placebo for 2-8 weeks plus received brief counseling on methods to reduce cigarettes/day. The primary measure was the incidence of a quit attempt within 6 months of study entry. Secondary measures were point prevalence abstinence, motivation to stop smoking, and reduction in cigarettes/day. ### results varenicline increased the incidence of a quit attempt more than placebo at the Nebraska site (73% vs. 41%; p < .001) but not at the Vermont site (45% vs. 51%; p = .45). varenicline increased most other measures of quit attempts, motivation and abstinence, independent of site. The beneficial effects of varenicline in quit attempts appeared to be mediated by greater reductions in cigarettes/day, dependence, craving, and cigarette satisfaction. varenicline had a greater effect on quit attempts in less-dependent smokers, in minority smokers, and in those who had less prior cessation or reduction activity. Adverse events were minimal. ### conclusions varenicline increased quit attempts in smokers who are not currently trying to quit at one of the two study sites and improved most all secondary outcomes independent of site. This appeared to be due to decreasing cigarettes/day and level of dependence.\n\nsentence: We tested whether varenicline , a partial nicotine agonist , would also increase future quit attempts .", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should only include the abstract and no additional text.\n\nPaper text:\nmost of the screening in epidemiological studies is conducted by research workers from the mental health profession .\nthere are not many epidemiological studies wherein the general physicians in a general hospital or community have collected the data .\nhowever , studies have assessed the skills of physicians in general hospitals in identifying mental illnesses .\nsingh et al . evaluated the psychiatric knowledge of 52 nonpsychiatrists , and only one doctor could give satisfactory diagnoses to the cases .\nthe deficits in the way nonpsychiatrists interview patients also hinder the identification and treatment of psychiatric disorders .\nmayou and hawton opined that many cases are overlooked because the treating doctor lacks substantial skills and research techniques in gathering more evidence about the nature of the disorder .\nimproving the psychiatric knowledge and skills of the undergraduate students can go a long way in increasing and improving the psychiatric care across the nation.[46]training undergraduates to identify psychiatric disorders will also prevent them from misdiagnosing organic conditions with psychiatric manifestations as functional in the community or in the emergency setup .\nscreening of psychiatric cases in the community helps in assessing the extent of the problem and also paves way for organizing community - based mental health programs .\nscreening tools like general health questionnaire ( ghq ) , and composite international diagnostic interview ( cidi ) have been used .\nsurtees and tansella recommended the use of interval ghq in situations where there are time constraints . while key informant method is used as a screening instrument , arrol et al . used a brief and easy approach for screening depression which involved asking only two questions .\npatients with neurosis sometimes presenting only with somatic complaints may be missed when questions based only on psychological symptoms are posed .\nhence , for screening , one should be trained to interview patients based on somatic complaints , using tools like bradford somatic inventory .\nclinical interview schedule - revised has also been used in epidemiological studies . in this study\nmentally disabled by the internees while conducting a comprehensive community survey of assessing disability in the rural and urban populations of selected areas in mysore using mini plus .\nthe department of community medicine , jss medical college , jss university , conducted a comprehensive community survey of all individuals in their field action area in 2007 - 2008 .\nthe areas included were jss urban health centre ( 5,945 ) in mysore district and the rural areas of suttur ( 2,821 ) , hadinaru ( 2,968 ) , sargur ( 1,216 ) , and nagarle ( 2,633 ) of the nanjangud taluk , with a total population of 15,583 .\nthe survey was carried out by the internees under the supervision of the faculty of the department of community medicine .\nthe head of each household was contacted to elicit information regarding chronic illnesses and disabilities including mental disability in each individual in the respective household .\nno screening tool was used for the survey . of the urban population of 5,945 , there were 3,048 men and 2,897 women and of the rural population of 9,638 , there were 4,834 men and 4,804 women .\nof 15,583 , 29 individuals were identified in the community by the internees as mentally disabled, that is , 9 men and 20 women .\nthe 29 cases identified by the internees were evaluated by two qualified psychiatrists and one clinical psychologist through home visits .\nvisits were paid to these houses over a period of 10 days and an effort was made to trace the individuals with the help of the community health worker .\nthe urban health centre was visited on 6 days because the houses or individuals could not be traced easily .\ninformed consent was taken from the patients or their legal guardians before conducting the interview .\nthe cases were screened for their psychiatric status using mini plus , and the diagnoses confirmed . in cases of children and adults with whom interview was not possible , history was collected from the significant family member / head of the family of each house hold .\nthe department of community medicine , jss medical college , jss university , conducted a comprehensive community survey of all individuals in their field action area in 2007 - 2008 .\nthe areas included were jss urban health centre ( 5,945 ) in mysore district and the rural areas of suttur ( 2,821 ) , hadinaru ( 2,968 ) , sargur ( 1,216 ) , and nagarle ( 2,633 ) of the nanjangud taluk , with a total population of 15,583 .\nthe survey was carried out by the internees under the supervision of the faculty of the department of community medicine .\nthe head of each household was contacted to elicit information regarding chronic illnesses and disabilities including mental disability in each individual in the respective household .\nno screening tool was used for the survey . of the urban population of 5,945 , there were 3,048 men and 2,897 women and of the rural population of 9,638 , there were 4,834 men and 4,804 women .\nof 15,583 , 29 individuals were identified in the community by the internees as mentally disabled, that is , 9 men and 20 women .\nthe 29 cases identified by the internees were evaluated by two qualified psychiatrists and one clinical psychologist through home visits .\nvisits were paid to these houses over a period of 10 days and an effort was made to trace the individuals with the help of the community health worker .\nthe urban health centre was visited on 6 days because the houses or individuals could not be traced easily .\ninformed consent was taken from the patients or their legal guardians before conducting the interview .\nthe cases were screened for their psychiatric status using mini plus , and the diagnoses confirmed . in cases of children and adults with whom interview was not possible ,\nhistory was collected from the significant family member / head of the family of each house hold .\ninformed consent was taken from the patients or their legal guardians before conducting the interview .\nthe cases were screened for their psychiatric status using mini plus , and the diagnoses confirmed . in cases of children and adults with whom interview was not possible , history was collected from the significant family member / head of the family of each house hold .\nof the 29 cases identified as having mental disability in the phase i , only 24 could be traced , of which only 19 could be given a diagnosis and 5 were not found to have any mental disability at all .\nof these 19 cases , only 16 were found to have a psychiatric disorder , that is , four were cases of schizophrenia , one bipolar affective disorder , two depression , nine mental retardation , and the remaining three consisted of two cases of epilepsy and one with speech and hearing problem without any signs of mental disability [ table 1 ] .\nalso , the cases with only epilepsy , which is a neurological disorder , have been wrongly identified as having mental disability.\nhowever , the prevalence rate as confirmed through mini plus was only 1.02 per 1000 .\ndiagnoses of the identified cases twenty cases other than those identified by the internees could be identified during the visit to the community .\nthe information was given by the community dwellers about individuals afflicted with mental disorders while enquiring about the target cases , though this was not the objective of the study .\nthese included 11 mental retardation , two schizophrenia , four bipolar affective disorder ( bpad ) , one depression , one conversion disorder , and one epilepsy cases .\nas per the results of the phase i , the prevalence was found to be 1.9 per 1 000 .\nthe fact that more cases could be identified during the visit to the community , though it was not the objective of the study , shows that the prevalence rate could be higher as substantiated by studies on psychiatric epidemiology in india that found a prevalence ranging between 9.5 and 370 per 1,000.other community studies in india have shown a prevalence of 5.8% and as estimated by the world health organization , 10% of the world 's population suffers from mental disability . in a study conducted in rural karnataka , kumar et al\nthacore et al . in india showed a high prevalence of neurosis , alcohol dependence , mental retardation , and nocturnal enuresis in a community in north india and this data was obtained by doing a house to house survey for 1 year .\nthe present finding of a low prevalence could have happened due to a host of reasons like interviewing only one informant without actually interviewing the patient as opined by suresh bada math et al .\n, lack of substantial interview skills , absence of a tool to screen the population , and a lack of awareness among the individuals in the community regarding mental health and mental disorders .\nanother factor could be that the internees were unsure as to what comprises mental disability. a search for the literature on disability yields information mostly on \nmental retardation and indian disability evaluation and assessment scale ( ideas ) ; the scale to measure mental disability includes schizophrenia , bipolar disorder , dementia , and obsessive - compulsive disorder without any mention of mental retardation .\nsethi and trivedi have highlighted the need for revamping the psychiatric training of the undergraduate medical students.though there is an increasing need for mental health care , there seems to exist an apathy among the medical fraternity toward learning and teaching psychiatry . as a result of this\n, there is a dearth of professionals with psychiatric skills to identify and treat mental disorders .\nstudents do not get enough clinical exposure in psychiatry and hence lack the skills to elicit a psychiatric history or make a psychiatric diagnosis .\nthey are not trained to use structured scales which aid in making a psychiatric diagnosis .\nthere definitely is a need for adequate mental health training at the undergraduate level , but it is not reflected in the medical curricula . the percentage of the lecture time dedicated for psychiatry is only 15 days and jacob suggested that a teaching period of at least 1 month is required .\nit has also been suggested that this training is mostly required for nonpsychiatrists . despite all this evidence of epidemiological studies and the usefulness of scales\nreported that the epidemiological studies in india have been inadequate in identifying panic disorders , social phobia , ocd , sexual dysfunction and substance use in the community .\none of the limitations of the phase 1 of the study is that the internees were not provided with a screening tool .\nhowever , there are epidemiological studies that have been conducted with only two questions to screen depression in the community . in addition , in the phase ii , the cases were interviewed by one investigator only and hence , inter - rater reliability in making a diagnosis could not be determined . moreover ,\nthough there is evidence for a high prevalence of mental disorders in the community , the internees had found the prevalence to be very low .\nthis may be a reflection of the skills of the internees in identifying the mentally disabled and also a lack of awareness regarding mental health in the community .\ntherefore , there is a need to hone the skills of the undergraduate students by improving undergraduate psychiatric training and teaching them to use screening tools to identify mental disorders and also improve awareness in the community .", "role": "user" }, { "content": "background : studies have been conducted on the skills of physicians in general hospitals in identifying mental disorders , but there are no studies assessing the proficiency of internees in identifying mental disorders.aim:to confirm the diagnosis of the cases identified by 40 internees in the community as mentally disabled.materials and methods : of 15,583 people,29 were identified in the community by the internees as \n mentally disabled. this was followed by home visits to the houses of these 29 individuals conducted by two qualified psychiatrists and one clinical psychologist , and these cases were screened for their psychiatric status using mini plus.results:most of the cases identified by internees as having \n mental disability were cases of mental retardation and the others were mood and psychotic disorders and epilepsy . \n cases of mental retardation and mental disorders other than those identified by the internees could also be identified while visiting the respective geographical areas.conclusions:there is a need to hone the skills of the medical students during the course of their training in identifying cases of mental retardation , severe as well as minor psychiatric disorders , as a part of their training . \n there is also a need for the use of structured scales for the same .", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nHighly Responsive Ultrathin GaS Nanosheet Photodetectors on Rigid and Flexible Substrates. The first GaS nanosheet-based photodetectors are demonstrated on both mechanically rigid and flexible substrates. Highly crystalline, exfoliated GaS nanosheets are promising for optoelectronics due to strong absorption in the UV-visible wavelength region. Photocurrent measurements of GaS nanosheet photodetectors made on SiO2/Si substrates and flexible polyethylene terephthalate (PET) substrates exhibit a photoresponsivity at 254 nm up to 4.2 AW(-1) and 19.2 AW(-1), respectively, which exceeds that of graphene, MoS2, or other 2D material-based devices. Additionally, the linear dynamic range of the devices on SiO2/Si and PET substrates are 97.7 dB and 78.73 dB, respectively. Both surpass that of currently exploited InGaAs photodetectors (66 dB). Theoretical modeling of the electronic structures indicates that the reduction of the effective mass at the valence band maximum (VBM) with decreasing sheet thickness enhances the carrier mobility of the GaS nanosheets, contributing to the high photocurrents. Double-peak VBMs are theoretically predicted for ultrathin GaS nanosheets (thickness less than five monolayers), which is found to promote photon absorption. These theoretical and experimental results show that GaS nanosheets are promising materials for high-performance photodetectors on both conventional silicon and flexible substrates.", "role": "user" }, { "content": "{\"Chemical\": [\"silicon\", \"Si\", \"polyethylene terephthalate\", \"MoS2\", \"GaS\", \"PET\", \"graphene\", \"SiO2\"]}", "role": "assistant" } ]

[ { "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: Negative sampling methods in knowledge graph embeddings\n\nKeyphrases: link prediction\n\nDataset description:\nHACS: HACS is a dataset for human action recognition. It uses a taxonomy of 200 action classes, which is identical to that of the ActivityNet-v1.3 dataset.\nFrameNet: FrameNet is a linguistic knowledge graph containing information about lexical and predicate argument semantics of the English language. FrameNet contains two distinct entity classes: frames and lexical units, where a frame is a meaning and a lexical unit is a single meaning for a word.\nCookie: The dataset is constructed from an Amazon review corpus by integrating both user-agent dialogue and custom knowledge graphs for recommendation.\nWN18: The WN18 dataset has 18 relations scraped from WordNet for roughly 41,000 synsets, resulting in 141,442 triplets. It was found out that a large number of the test triplets can be found in the training set with another relation or the inverse relation.\nConceptNet: ConceptNet is a knowledge graph that connects words and phrases of natural language with labeled edges. Its knowledge is collected from many sources that include expert-created resources, crowd-sourcing, and games with a purpose.\nMutualFriends: In MutualFriends, two agents, A and B, each have a private knowledge base, which contains a list of friends with multiple attributes (e.g., name, school, major, etc.). The agents must chat with each other to find their unique mutual friend.\nFB15k: The FB15k dataset contains knowledge base relation triples and textual mentions of Freebase entity pairs. It has a total of 592,213 triplets with 14,951 entities and 1,345 relationships.\n\nOptions:- A: HACS B: FrameNet C: Cookie D: WN18 E: ConceptNet F: MutualFriends G: FB15k", "role": "user" }, { "content": "[\"WN18\", \"FB15k\"]", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nThe role of plastic wound drapes in the prevention of wound infection following abdominal surgery.\nAbstract 1:\nA randomized controlled trial has been performed to assess the value of plastic wound drapes in the prevention of surgical wound infection. One hundred and forty-four patients undergoing abdominal surgery were allocated to one of three groups; a control group (A) in which standard cloth towels were applied to the abdominal wound, group B in which an adhesive plastic drape was added and group C in which a plastic ring protector was inserted into the wound. There were 26 cases (18 per cent) of wound infection. The wound infection rate in the plastic drape groups did not differ significantly from that in the control group. Bacteriological culture from a wound swab taken at operation was positive in 32 per cent of the cases. The presence of a plastic wound drape did not influence the positive culture rate. In 68 per cent of wounds which became infected the operative swab was positive as compared with 24 per cent in those not developing a wound infection. Thirteen of the 33 patients (39 per cent) with a positive wound swab subsequently developed a wound infection. In 10 of these 13 cases of infection the operative swab permitted an accurate prediction of the organism responsible for the subsequent infection.\n\n\nTitle 2:\nThe effect of incisional plastic drapes and redisinfection of operation site on wound infection following caesarean section.\nAbstract 2:\nIn a randomized prospective multicentre study of post-caesarean wound infection among 1,340 women in eight hospitals, the effect of redisinfection of the skin around the incision before skin closure and the effect of adhesive skin drapes were investigated. The overall rate of wound infection with pus was 5.0% (range 3.5-8.9%). The study showed a reduction in postoperative wound infection associated with redisinfection (P = 5.5%), while no benefit from adhesive plastic drapes could be demonstrated.\n\n\nTitle 3:\nThe value of a plastic adhesive drape in the prevention of wound infection. A controlled trial.\nAbstract 3:\nnan\n\n\nTitle 4:\nPreoperative skin preparation of cardiac patients.\nAbstract 4:\nNurses at a large southwestern hospital undertook an initiative to optimize the preoperative skin preparation of patients undergoing open heart surgery. After an extensive review of the literature, a proposal was submitted to and accepted by the surgeons and internal review board of the hospital. High-risk patients were identified before surgery and randomized into groups to receive one of four different skin preps. The incidence of infection was lower in the two groups of patients who were prepped with insoluble iodine, indicating that the type of surgical skin prep could affect whether patients develop surgical site infections. The clinical practice of skin preparation in this hospital changed based on the results.\n\n\nTitle 5:\nPlastic adhesive drapes and wound infection after hip fracture surgery.\nAbstract 5:\nOne hundred and twenty patients with acute hip fractures treated operatively were randomized into two groups. In the 'drape' group (n = 65) the operation site was covered with plastic adhesive drape after preparation. In the 'no drape' group (n = 55) the operation site was left uncovered. The two groups were otherwise matched. Swabs for culture were taken from skin adjacent to the wound before closure. The drape group had four positive wound swabs. There was only one positive wound swab for the no-drape group. There was no difference in the post-operative wound infection rates.\n\n\nTitle 6:\nThe use of an iodophor-impregnated plastic incise drape in abdominal surgery--a controlled clinical trial.\nAbstract 6:\nA prospective randomized clinical trial comparing the use of a new iodophor-impregnated incise drape with a standard skin preparation technique in 1102 patients undergoing abdominal surgical procedures is reported. The effect of the incise drape on wound bacterial contamination and subsequent wound infections is compared. The iodophor-impregnated plastic incise drape reduced the contamination of the wound. In particular, isolates of normal skin organisms were less frequent when the drape was used in clean and clean contaminated procedures. However, no difference was found between the wound infection rates for the patients on whom the iodophor drape was used and those patients on whom the drape was not used.\n\n\nTitle 7:\nDo plastic adhesive drapes prevent post caesarean wound infection?\nAbstract 7:\nWe conducted a prospective randomized controlled double-blind trial at a regional referral centre for the Eastern Cape area, (Livingstone Hospital) to determine whether the use of plastic adhesive drapes intraoperatively would prevent Post Caesarean Section Wound Infection. A total of 620 patients undergoing Caesarean section (CS) were enrolled for randomization in the trial. Fifteen patients were excluded, while 305 received drapes (test group) and 300 did not (control group). Two patients in the control group were subsequently excluded. The primary outcome measure was the presence of Post Caesarean Wound Infection. A secondary outcome measure was the number of days in hospital post operation. The study and control groups were comparable at entry. Results show that 34 patients in the test group (N= 305) developed wound sepsis (11.1%) compared with 30 in the control group (N= 298) (10.1%) (difference not significant; Fisher's exact test 0.6933). Average days spent in hospital postoperatively were similar for both test (infected cases: mean 10.56 SD 3.84; non-infected cases: mean 5.21 SD 1.3) and control groups (infected cases: mean 10.18 SD 3.81; non-infected cases: mean 5.2 SD 0.93) (NS). We concluded that the use of plastic adhesive skin drapes did not avert PCWS or decrease the length of post operative stay in hospital for septic cases.\n Copyright 2001 The Hospital Infection Society.", "role": "user" }, { "content": "There was no evidence from the seven trials that plastic adhesive drapes reduce surgical site infection rates, and some evidence that they increase infection rates. Further trials may be justified, using blinded outcome assessment to examine the effect of adhesive drapes on surgical site infection, based on different wound classifications.", "role": "assistant" } ]

[ { "content": "You will be shown biomedical passages and your task is to answer the provided question. Provide a concise and accurate response and do not include any additional text in the response other than the answer.\n\nQuestion: Which glands are subject to attack by lymphocytes in Sjogren's syndrome?\n\nContext: In Sjögren's syndrome the autoimmune response is directed against the exocrine glands, which, as histopathological hallmark of the disease, display persistent and progressive focal mononuclear cell infiltrates.\nSjögren's syndrome (SS) is an autoimmune disease characterized by clonal B cell attack of the exocrine glands and dysregulated expression of B cell-activating factor (BAFF).\nSjögren's syndrome (SjS) is a human autoimmune disease characterized by exocrine dysfunction resulting from chronic autoimmune attack primarily against the lacrimal and/or salivary glands.\nSjögren's syndrome is an autoimmune disease in which immune cells chronically attack the lachrymal and salivary glands.\nSjögren's syndrome (SjS) is a systemic autoimmune disease in which an immunological attack against the salivary and lacrimal glands results, respectively, in severe dry mouth and dry eye diseases.\nSjögren's syndrome (SS) is a chronic autoimmune disease affecting epithelial tissues. Exocrine glands are the primary target and their functional impairment comes as a result of immune attack of epithelial cells of the affected organs (autoimmune epithelitis).\nSjögren's syndrome (SjS) is a human autoimmune disease characterized by the loss of exocrine function as a result of a chronic immune attack directed primarily against the salivary and lacrimal glands leading to xerostomia (dry mouth) and xerophthalmia (dry eyes).\nThe purpose of this qualitative research was to explore the lived experiences of women with Sjogren's Syndrome (SS), a chronic autoimmune syndrome in which invading lymphocytes attack moisture-producing glands of the body. This syndrome, affecting 4 million Americans, involves extreme dryness of the eyes and mouth and other systemic complications such as fatigue and muscle and joint pain.\nNOD mice manifest many features of autoimmune exocrinopathy (Sjögren's syndrome), a disease generally characterized by a chronic, progressive immunological attack against the exocrine tissues of the salivary and lacrimal glands.", "role": "user" }, { "content": "The lacrimal and/or salivary glands", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Can we detect DNA strand asymmetries using dinucleotide relative abundance \"genomic signatures\"?\n\nContext: comparing the heterogeneities of bacterial genomes with respect to strand-independent first- and second-order features, (i) G + C content and (ii) dinucleotide relative abundance,\nthe concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes.\ndinucleotide relative abundance values (the genomic signature)\nThe dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome.\nThe profile is computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling).\nThe genome signatures (dinucleotide relative abundance values)\nEarly biochemical experiments measuring nearest neighbor frequencies established that the set of dinucleotide relative abundance values (dinucleotide biases) is a remarkably stable property of the DNA of an organism.\nthe set of dinucleotide biases constitutes a 'genomic signature' that can discriminate sequences from different organisms.\nthe set of dinucleotide odds ratio (relative abundance) values constitute a signature of each DNA genome\nDinucleotide relative abundance extremes: a genomic signature.\nThe dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome.\nPreviously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes.\nComparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement).\nDinucleotide relative abundances (i.e., dinucleotide representations normalized by the component nucleotide frequencies) are consonant with respect to the leading and lagging strands", "role": "user" }, { "content": "no", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Finding\", \"Bacterium\", \"ProfessionalOrOccupationalGroup\", \"InjuryOrPoisoning\", \"Eukaryote\", \"BodySystem\", \"Virus\", \"ResearchActivity\", \"BodySubstance\", \"PopulationGroup\", \"Chemical\", \"AnatomicalStructure\", \"SpatialConcept\", \"HealthCareActivity\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Food\", \"ClinicalAttribute\", \"MedicalDevice\", \"BiologicFunction\", \"IntellectualProduct\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nNationwide hospital -based survey of idiopathic normal pressure hydrocephalus in Japan: Epidemiological and clinical characteristics There have been no nationwide epidemiological studies of idiopathic normal pressure hydrocephalus (iNPH) in Japan. Therefore, a nationwide epidemiologic survey of iNPH was performed to determine the number of cases and clinical characteristics by sex and diagnostic level. The first survey examined the numbers of cases that met the diagnostic criteria of iNPH and those who underwent shunt operations in 2012. The second survey gathered patients ' details to clarify their clinical background characteristics. The estimated number of cases meeting the diagnostic criteria in 2012 was 12,900, with 6,700 undergoing shunt operations. The estimated crude prevalence was 10.2/100,000 persons. The age of onset was in the 70s in more than 50% of both men and women. Significantly higher (p < .05) frequencies of gait impairment in men and cognitive decline in women were observed as initial symptoms. At the time of definitive diagnosis, gait impairment was observed most frequently in patients with definite iNPH (77.7%). Hypertension was the most frequent comorbidity (40.0%), followed by diabetes mellitus (17.8%) and Alzheimer's disease (14.8%). Hypertension was observed more frequently in men, but diabetes was observed more frequently in women (p < .05). An LP shunt was the first-choice (55.1%) treatment of iNPH, followed by a VP shunt (43.2%). This study showed that iNPH occurs most frequently in the 70s, gait impairment and cognitive decline are the most frequent initial symptoms in men and women, respectively, and hypertension and diabetes are the most frequent comorbidities in men and women, respectively.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"diabetes mellitus\", \"Hypertension\", \"diabetes\", \"Alzheimer\\u0027s disease\", \"idiopathic normal pressure hydrocephalus\", \"iNPH\", \"hypertension\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"symptoms\", \"diagnosis\", \"cognitive decline\", \"gait impairment\"], \"Food\": [], \"HealthCareActivity\": [\"shunt operations\", \"LP shunt\", \"VP shunt\", \"treatment\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"epidemiologic survey\", \"diagnostic criteria\", \"survey\"], \"MedicalDevice\": [], \"Organization\": [\"hospital\"], \"PopulationGroup\": [\"persons\", \"men\", \"women\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"epidemiological studies\"], \"SpatialConcept\": [\"Japan\"], \"Virus\": []}", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nthe andreev reflection hole current at ballistic normal - superconducting point contacts can be reduced by many mechanisms : normal reflection , finite cooper pair life time , and spin polarization produce characteristic anomalies and represent the material and device properties that we are usually interested in @xcite .\nothers are associated with locally exceeding the superconducting critical temperature , field , or the condensation energy @xcite .\nthey result in sharp structures or side peaks of the spectra which can be easily reckognized .\nhowever , they are difficult to handle because of their strong dependence on the geometric shape of the contact .\nanother mechanism causes broad side peaks at finite bias voltage that have neither well - defined beginning nor end .\nthey add considerable uncertainty in the analysis of the spectra .\nwe suggest here that those broad maxima origin from the interaction of the andreev reflection hole current with the wind of non - equilibrium phonons generated at large bias voltages . in a previous study on point contacts between ultra - high purity superconducting tantalum ( ta ) and normal conducting silver ( ag ) , hahn _ et al . _\n@xcite have found anomalies in the spectra that they interpreted in terms of a huge normal bubble - or hot spot - inside the superconductor .\nthey assumed that high - energy electrons are resonantly trapped between the normal - superconductor interface of the hot spot itself and the contact .\nsuch a normal bubble would extend up to several times the superconducting coherence length of ta .\nthis length scale was supported by observing interference phenomena in a magnetic field @xcite . while hahn _\net al . _\n@xcite were mainly interested in the resonances that appeared in the @xmath0 spectra to explain their observation , we have used a different approach based on the ar hole current derived from the difference of the measured normal and superconducting current - voltage @xmath1 characteristics of superconducting niobium ( nb ) in contact with a normal metal .\nour point contacts were fabricated using the shear method where the two sample wires ( typically @xmath2 mm diameter ) were brought into contact in the form of a cross .\nthe differential resistance @xmath0 and the @xmath1 characteristics were recorded in standard four - wire mode with low - frequency current modulation .\nthe thermal coupling between the contact , through the sample wires and their anchorage , to the cooling stage at temperature @xmath3 was measured by injecting a large power into the contact and using the critical temperature @xmath4k of nb as marker for the contact turning normal .\nthis heating of the contact is described by @xmath5 with the lorenz number @xmath6 and an equivalent thermal resistance @xmath7m@xmath8 .\nan other upper bound for the local temperature distribution in the point contact is given by kohlrausch s formula @xcite @xmath9 .\nthis is valid in the thermal limit , while in the diffusive and the ballistic regime the temperature differences are much smaller . to measure the andreev reflection excess current directly , we recorded the contact characteristics both at low temperature ( 1k ) in the superconducting and at high temperature ( 10k ) in the normal state of nb .\nthis required thermal cycling until the contact stabilized and which worked well for normal - state contact resistances up to @xmath10 or contact diameters down to around @xmath11 nm . @xmath0 versus @xmath12 spectra of a ) a nb - ag and c ) a nb - cu contact at @xmath13k and at @xmath14k .\nthe corresponding excess current is shown in b ) and d ) . ]\n@xmath0 versus @xmath12 spectra of a ) a nb - al and c ) a nb - brass contact at @xmath13k and at @xmath14k .\nthe corresponding excess current @xmath15 is shown in b ) and d ) . at @xmath13k al\nis superconducting ( @xmath16 ) and the contact of josephson type .\nhowever , the contribution of al to the excess current is negligible compared to that of nb . ]\nfigures [ spectra-1 ] and [ spectra-2 ] show typical @xmath0 spectra of nb in contact with ag , copper ( cu ) , aluminum ( al ) , and brass at @xmath13k and at @xmath14k as reference .\nthey look qualitatively similar to those observed by hahn _\net al . _\n@xcite for ta - ag contacts .\nthe spectra have the typical andreev - reflection double - minimum anomaly ( except the contacts with al ) and also broad side peaks with a superposed fine structure . at large voltages the spectra in the superconducting and the normal state coincide . the magnitude of the excess current @xmath17 drops continuously with increasing bias voltage which can roughly be described by @xmath18 .\nsome of the contacts had a small residual excess current at large voltages , possibly due to a reversible change of the contact upon thermal cycling .\nwe have observed similar behaviour for all nb - normal metal contacts .\nfigure [ v0 ] summarizes the decay constant @xmath19 of the excess current as function of normal - state contact resistance .\nit increases only slightly with @xmath20 and it apparently does not depend on the normal metal .\nat large bias voltage heating might become a problem . from the measured thermal coupling of the samples we estimate maximum temperatures that are still far below @xmath21 of nb .\nthe weak dependence of @xmath19 on the contact size also excludes heating effects , because heating at a @xmath22 contact would be 100 times stronger than at a @xmath23 contact , assuming the same bias voltage .\nthis would contradict the experimental data in figure [ v0 ] .\ndecay constant @xmath19 of nb in contact with the indicated metals as function of normal - state resistance @xmath20 .\nthe solid line is @xmath24{r_n}$ ] as a guide - to - the - eye . ] to avoid the _ ad hoc _ assumptions of specific boundary conditions used by hahn _\net al . _\n@xcite , we want to find a more conventional interpretation of the experiments .\na rather straightforward mechanism to reduce the excess current without heating is electron scattering at the non - equilibrium phonons generated by the bias voltage @xcite .\nfigure [ epi ] shows the calculated electron - phonon scattering length @xmath25 at low temperatures using @xmath26 derived from the measured electron - phonon interaction function @xcite and a fermi velocity @xcite @xmath27 m/s of nb . at large voltages @xmath28\nis comparable to the superconducting coherence length @xmath29 nm of nb .\nwe estimate the density @xmath30 of excess phonons as follows : phonons are generated at the point - like contact at a rate of @xmath31 , that is one phonon per injected electron .\nthe phonon density is constant inside a half - sphere of radius @xmath28 around the contact .\nthey escape from this volume with sound velocity @xmath32 m/s of niobium at a rate @xmath33 .\nthus in the stationary state @xmath34 .\nthese excess phonons scatter the low - energy holes with a mean - free path @xmath35 comparable to that of the high - energy electrons @xmath28 and destroy the coherence of andreev reflection .\nsuch a scattering event deflects the hole from the path of the incident electron and thereby reduces its chances to fly back through the contact , thereby reducing the andreev - reflection excess current .\nsince ballistic electrons have a preferred forward direction , a cone would be more appropriate than a half - sphere .\nthis would lead to a larger phonon density by reducing the volume and decreasing the area from which phonons can escape .\nin addition , each electron could create more than just a single phonon .\nalso the target area for the holes becomes smaller with increasing contact resistance which could explain the very weak @xmath36 dependence .\nelectron - phonon scattering length @xmath28 as function of bias voltage @xmath12 for nb as derived from the point - contact electron - phonon interaction function and the excess phonon density @xmath30 discussed in the text for contacts with the indicated normal - state resistance @xmath20 .\ninset : schematic of the normal ( n ) - superconducting ( s ) contact .\nthe excess phonon density is confined to a half - sphere of radius @xmath28 around the contact . ]\nour model also explains why some of the contacts have pronounced maxima and side peaks while others have very small anomalies .\nlarge maxima of the type discussed here require the presence of an excess current which can be suppressed , that is such a contact has little normal reflection and a small polarization as well as a long cooper pair lifetime . to extract those parameters from the measured spectra one should use the part around zero bias with a reasonable estimate of the normal contact resistance , and ignore - as much as possible - the side peaks .\nthe suggested scenario offers no way to overcome the side - peak problem because generating non - equilibrium phonons is an intrinsic property of the material and the contacts , and inherent to measuring the spectra .\nthis makes a precise measurement of the energy gap of superconductors with large @xmath21 and large @xmath37 difficult .\nside peaks can be avoided only when the superconductor has a small gap and the voltage range can be kept sufficiently small .\nwe thank the jenny and antti wihuri foundation and the magnus ehrnroot foundation for financial support .", "role": "user" }, { "content": "we have investigated how the andreev - reflection hole current at ballistic point contacts responds to a large bias voltage . \n its strong suppression could be explained by the drag excerted by the non - equilibrium phonon wind generated by high - energy electrons flowing through the contact . \n the hole - phonon interaction leads to scattering lengths of the low - energetic holes down to 100 nm , thereby destroying the coherent retracing of the electron path by the andreev - reflected holes .", "role": "assistant" } ]

[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: Reliable SPIN in Wireless Sensor Network: A Review \nChapter Title: III. Improvement Over Spin \n1. Abstract of Cited Paper (BIB001): Protocols for sensor networks have traditionally been designed using the best effort delivery model. However, there are many specific applications that need a reliable data dissemination protocol. We present a protocol for efficient and reliable data delivery to all sensor nodes in an energy-constrained, event-driven sensor network in which nodes are mobile or static. The new protocol, SPROID (scalable protocol for robust information dissemination), identifies data generated by a unique tag, uses content tables for faster dissemination of information and guarantees reliable dissemination to all nodes in the network within a finite time. SPROID can be made to work with any kind of physical layer requirements, but we focus on the case of a single-channel broadcast medium. Simulations results show that SPROID achieves complete data dissemination in shorter time and with more energy efficiency than SPIN (sensor network protocols using information negotiation). \n2. Abstract of Cited Paper (BIB002): This paper presents a survey on transport and routing protocols for wireless sensor networks(WSN). Research challenges regarding the problem of end-to-end reliability are addressed in particular. \n3. Abstract of Cited Paper (BIB003): techniques in Wireless Sensor Network has always been important area of exploration due to change in demands of various applications such as Area monitoring, Environmental/Earth monitoring, passive localization and tracking, Industrial monitoring etc. Energy efficiency is crucial issue in WSN because sensor nodes in WSN are with limited battery power/Resources .This results in rapid change in design of routing algorithms. Day by day various routing techniques are being proposed. It is because of energy efficiency, Scalability, Network lifetime and other important factors of routing techniques. Each routing mechanism has its advantages and disadvantages related to energy efficiency also. There is no single, best routing protocol that is suitable for all applications. Routing mechanism might differ depending on the application, network architecture and topologies. This paper gives review of recent research of the network structure and topology based different routing strategies and gives brief idea about energy efficiency of routing protocols in WSN. This paper also represents classification of various routing techniques with their advantages and disadvantages.\n\nLiterature Review:", "role": "user" }, { "content": "The comparison in data centric protocols in respect of parameters like average energy consumption, lifetime of nodes, average time taken to travel from source node to sink node, average number of nodes participated in the network are shown in . The protocols which are compared are Flooding Mechanism, SPIN (Sensor Protocol for Information via Negotiation), MFCA (Minimum Cost Forwarding Algorithm). Out of these three, Flooding Mechanism achieves best performance because a node sends out the received data or the management packets to its neighbors by broadcasting, unless a maximum number of hops for that packet are reached or the destination of the packets is arrived but it has some problems like implosion, overlap and resource blindness. SPIN removes the problem of flooding but do not provide good performance. MFCA send data in to the direction of the sink where algorithm estimate the cost of data reached to sink. The concept of end to end acknowledgment at transport layer is suggested in BIB003 . When data is to be transmitted between source node to the destination, there should be an acknowledgement of data in between the middle of nodes. Thus, data will reach to the sink in reliable format without any loss. This mechanism performs with the help of MAC automatic repeat request. When a middle node transfers data to other intermediate node, they acknowledged the data by ACK/NACK. So, in this way, the loss of data will reduce and quality of data increased. In , authors proposed idea of PEQ (periodic, event driven and query based) algorithm in direct diffusion data centric protocol and simulated on network simulator (NS-2). PEQ is a routing algorithm, which works in three steps. First step is constructing the hop tree, and then involves utilization of sensors and last step is responsible for data transmission. • Source floods the notification message and all possible path information to the sink. Sink select one path from this information and send reply from that path for receiving the data. If any node becomes dead then sink send reply to another path and source will send whole data again. In BIB001 , authors proposed a Modified SPIN for Wireless Sensor Networks. This paper shows that whenever data is to be transferred, it should be deliver to those nodes which are nearer to the sink and whose hop count is few which is calculated from distance discovery to save energy of nodes. The three phases of modified spin are: This protocol is faster than the basic SPIN protocol as it avoids unnecessary flooding of data to those nodes which have higher hop count. Corroborative Aggregation Protocol (CAP) is proposed in BIB002 , in which, each sensor that detects a report from its neighbour that contradicts its own findings generates its own report to dispute the faulty report. The numbers of correct reports in the event are used to overcome adverse effects that may arise due to the wrong reports. CAP helps to improve the credibility of the fused content in the presence of faulty sensors. CAP works on the principle of having multiple sensors corroborate each other. In this paper, author has proposed a new protocol SPROID (Scalable Protocol for Robust Information Dissemination) BIB004 [16] for efficient and reliable data delivery over the SPIN (Sensor Protocol for Information via Negotiation). SPROID achieve reliability by building a correct neighbour list in finite time. This protocol work as: suppose node A has its neighbour and node B. Node B have its neighbour and node A. When node A have data and broadcast the advertise packet about data. Node B request for data and got that data. Now node B advertises the message about data which received by the node A and match that information to its own stored data. If match successful then it will be acknowledgement otherwise node A sends data again to node B.", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nThe course of established ankylosing spondylitis and the effects of sulphasalazine over 3 years.\nAbstract 1:\nA 3-year placebo-controlled trial of sulphasalazine (SASP) in 89 patients with established AS (including radiological sacroiliitis) showed a reduced frequency of peripheral arthritis in the treated group but did not show any definite benefit in the maintenance of spinal mobility. Adverse effects causing treatment withdrawal occurred in five placebo-treated patients and eight SASP-treated patients, but 22 patients preferred to stop taking daily medication of unproven benefit for the full 3 years. The natural history of established AS suggested two groups of patients: the majority with principally spinal symptoms and infrequent peripheral arthritis or iritis, and a minority who tend to have recurrent extra-spinal problems.\n\n\nTitle 2:\nSulphasalazine in ankylosing spondylitis.\nAbstract 2:\nIn recent years sulphasalazine has gained acceptance as an effective agent for the treatment of rheumatoid arthritis. Ankylosing spondylitis is a disease where remission inducing drugs so far have been lacking. In this double blind trial sulphasalazine was compared with placebo in 37 patients with ankylosing spondylitis. Evaluation after three months' treatment showed reduction of inflammatory activity and improvement of clinical variables. The side effects were mild. The results suggest that sulphasalazine is a potentially effective and safe drug in the treatment of ankylosing spondylitis.\n\n\nTitle 3:\n[Sulfasalazine in ankylosing spondylitis: a prospective, randomized, double-blind placebo-controlled study and comparison with other controlled studies].\nAbstract 3:\nTo assess the efficacy and tolerability of sulfasalazine in ankylosing spondylitis including a meta-analysis of comparable trials.\n In a prospective, randomized, double-blind, placebo-controlled trial 70 patients with established diagnosis of ankylosing spondylitis and a mean disease duration of 16.7 years were investigated in two centers for 26 weeks comparing 3 g/d sulfasalazine to placebo.\n The main outcome parameters, pain score, fingers-to-floor test, and CRP, did not improve significantly in the sulfasalazine group compared to the placebo group. Altogether sulfasalazine was significantly superior to placebo only concerning the IgA levels. The dropout rate was 47% for the sulfasalazine group and 19% for the placebo group. Due to side effects, 38% and 11%, respectively, stopped treatment. Ten other prospective, double-blind, controlled studies were analyzed. Altogether 959 patients with a mean disease duration of 13.9 years were evaluated. Most parameters did not improve significantly in the sulfasalazine groups compared to the placebo groups. Spinal motility remained nearly unchanged (0.3-3.5% improvement). Pain, morning stiffness, functional index, and global assessment were slightly influenced (1.9-11.7%). Reduction of ESR, CRP, IgA, IgG, and IgM was more distinct (12.6-20.3%). In 4 studies SSZ had greater efficacy in patients with peripheral joint involvement.\n Sulfasalazine has no clinically relevant benefit in patients with ankylosing spondylitis. The dropout-rate due to adverse effects is high with a daily dose of 3 g. Sulfasalazine may be beneficial in peripheral joint involvement. Only few data exist about patients with a disease duration of less than 10 years.\n\n\nTitle 4:\nComparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veterans Affairs Cooperative Study.\nAbstract 4:\nTo determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy.\n Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments.\n While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints.\n SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients.\n\n\nTitle 5:\nA controlled trial of sulphasalazine treatment of chronic ankylosing spondylitis: failure to demonstrate a clinical effect.\nAbstract 5:\nSixty-two patients with long established but symptomatic ankylosing spondylitis were treated with sulphasalazine or matching placebo in a randomized double-blind controlled trial for 48 weeks. There were no consistent significant differences between the treatment groups in clinical parameters despite multiple assessments. Equivalent numbers in each group were able to decrease or stop non-steroidal anti-inflammatory drug ingestion during the study period (four active, eight placebo). Side effects were reported more commonly in the sulphasalazine group (27 versus 17, NS), but only 21 patients stopped treatment because of side effects (12 versus 9, NS). Analysis of the subgroup with an initial ESR greater than 20 mm/h failed to show any persisting differences of response between sulphasalazine and placebo. We conclude that sulphasalazine therapy does not have a role in the treatment of chronic ankylosing spondylitis.\n\n\nTitle 6:\nSulphasalazine in ankylosing spondylitis. A radiological, clinical and laboratory assessment.\nAbstract 6:\nIn a 12-month double-blind placebo-controlled trial, the effect of sulphasalazine was studied in 40 patients with ankylosing spondylitis. The treatment group showed significant improvement in pain, stiffness, sleep disturbance (p less than 0.05), finger/floor distance, erythrocyte sedimentation rate, C-reactive protein, orosomucoid and IgA levels (p less than 0.01). There was improvement in sleep disturbance (p less than 0.05), finger/floor distance and erythrocyte sedimentation rate (p less than 0.01) in the placebo group. Sulphasalazine did not retard radiological progression as measured either by plain X-ray or computerised tomographic scans. Multiple analysis of variance did not show a significant difference in disease activity indicators between the 2 groups.\n\n\nTitle 7:\n[Sulfasalazine in the treatment of ankylosing spondylitis].\nAbstract 7:\nNinety-five patients with ankylosing spondylitis received either sulphasalazine (less than or equal to 3 g/day) or placebo for 24 weeks. The patients who received sulphasalazine showed significantly improved clinical parameters [duration of morning stiffness (p less than 0.05), the number of painful and swollen joints (less than 0.05)] and laboratory parameters [erythrocyte sedimentation rate (p less than 0.001), haptoglobin (p less than 0.05), IgG (p less than 0.05), IgA (p less than 0.001), IgM (p less than 0.05)]. No statistically significant differences were seen in the patients receiving placebo. The results suggest that sulphasalazine is effective for the treatment of patients with ankylosing spondylitis. In these patients, there was also a diminution of the daily dosage of nonsteroidal antiinflammatory drugs. In the majority of patients, clinical and laboratory improvements were expressed more pronouncedly in the peripheral form of ankylosing spondylitis than in the axial form, but statistically no significant differences were found between the two groups.\n\n\nTitle 8:\nWhich is the active moiety of sulfasalazine in ankylosing spondylitis? A randomized, controlled study.\nAbstract 8:\nTo compare the efficacy of sulfasalazine (SSZ) with its two moieties, 5-aminosalicylic acid (ASA) and sulfapyridine (SP), in patients with active ankylosing spondylitis (AS).\n A 26-week randomized, observer-blinded, 2-center, controlled study of treatment with either SSZ, ASA, or SP was conducted in 90 patients with active AS. Patients were evaluated at baseline and at monthly intervals, using several clinical and laboratory measures of disease activity. A global assessment of treatment efficacy was made by both patients and observers at the end of the study period.\n There were no significant changes in any of the parameters of disease activity in the ASA treatment group. Levels of serum IgG, IgA, and IgM fell significantly during treatment with SP, but none of the other changes reached statistical significance. Plasma viscosity and IgG and IgA levels fell significantly during treatment with SSZ, as did nocturnal spinal pain and overall spinal pain. Patients and observers reported a favorable outcome after treatment with SSZ or SP significantly more often than with ASA treatment.\n SP appears to be the active moiety in AS, although there was a trend suggesting a better outcome in the SSZ group compared with the SP group, perhaps suggesting the importance of a common sulfonamide structure for efficacy.\n\n\nTitle 9:\nSulfasalazine in the treatment of ankylosing spondylitis. A twenty-six-week, placebo-controlled clinical trial.\nAbstract 9:\nEighty-five patients with active ankylosing spondylitis (AS) were randomized to receive either sulfasalazine (less than or equal to 3 gm/day, mean 2.5) or placebo for 26 weeks. There was a statistically significant improvement, compared with baseline, in most of the clinical variables in patients receiving the active drug. Laboratory parameters (erythrocyte sedimentation rate, C-reactive protein, IgG, IgM, and IgA) also improved during the active treatment, suggesting a beneficial effect of sulfasalazine on AS. At the end of the treatment, significant differences between the sulfasalazine and placebo groups were observed in morning stiffness, chest expansion, erythrocyte sedimentation rate, and in all immunoglobulin classes. Two patients in each treatment group discontinued the trial because of side effects. Enteric-coated sulfasalazine seemed to be effective and well tolerated in patients with active AS.\n\n\nTitle 10:\nSulphasalazine in ankylosing spondylitis: a double blind controlled study in 60 patients.\nAbstract 10:\nSulphasalazine has been reported to be effective in ankylosing spondylitis with peripheral arthritis, but its efficacy in spondylitis is unknown. Thus 60 patients with active ankylosing spondylitis without peripheral arthritis or gastrointestinal symptoms were randomly allocated to one of two therapeutic groups. One group received 2 g sulphasalazine daily for six months and the other a placebo. Thirteen patients (six given placebo and seven given sulphasalazine) dropped out of the trial and were considered to be treatment failures. After six months' follow up efficacy was rated as good or very good by 15 of the 30 patients given sulphasalazine and by only six of the 30 given placebo (p less than 0.02). Furthermore, in the patients given sulphasalazine the daily consumption of non-steroidal anti-inflammatory drugs, functional index, and plasma IgG concentrations had fallen significantly. These data suggest that sulphasalazine may be a safe and effective treatment for spondylitis in ankylosing spondylitis.\n\n\nTitle 11:\nSulphasalazine therapy in ankylosing spondylitis: its effect on disease activity, immunoglobulin A and the complex immunoglobulin A-alpha-1-antitrypsin.\nAbstract 11:\nSerum levels of immunoglobulin A (IgA) and the complex immunoglobulin A-alpha 1 antitrypsin (IgA-alpha 1AT) were measured at the commencement and after 3 months of a double-blind, placebo-controlled trial of sulphasalazine (SAS) in patients with active ankylosing spondylitis (AS). Twenty-eight patients were evaluated, 15 on sulphasalazine, 13 on placebo. Significant falls were seen in both IgA (p less than 0.01) and IgA-alpha 1AT (p less than 0.001) in the actively treated patients. In addition, significant improvement in clinical and laboratory measures of disease were observed. It is concluded that SAS is effective in AS and modulates the immune response.", "role": "user" }, { "content": "Across all AS patients, SSZ demonstrated some benefit in reducing ESR and easing morning stiffness, but no evidence of benefit in physical function, pain, spinal mobility, enthesitis, patient and physician global assessment. Patients at early disease stage, with higher level of ESR (or active disease) and peripheral arthritis might benefit from SSZ.", "role": "assistant" } ]

[ { "content": "You will be shown an excerpt from a computer science research paper, followed by a question about the paper. Please answer the question given the context. Do not include any text in your response other than the answer.\n\nContext: We used data augmentation methods to achieve the goals in the training data. However, color enhancement, such as brightness, contrast, and saturation, as well as position enhancement, by way of scaling, cropping, flipping, and revolution, was used. The technique of data enhancement also included random rotations from -15 to 15 degrees, rotations of 90 degrees by accident, accidental distortion, bending, vertical reversal, horizontal reversal, skate, and luminous intensity conversion. In this approach, 10 enhanced images were created from each original image. The selection of a subset of transformations helps to enhance a heterogeneous image.\n\nQuestion: How many extra image is generated for each class?", "role": "user" }, { "content": "10 enhanced images were created from each original image. But it doesn't directly answer how many for each class. We can refer that 10 times extra images is generated for each class.", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nthe first of the ten @xmath0,@xmath1-digit challenges @xcite , proposed to calculate the integral @xmath2 to ten digits .\nthis was a real challenge since the integrand oscillates infinitely often inside the interval of integration . in this note\n, a general result is proved that will allow us to determine exactly the value of some highly oscillating integrals .\nto give you the flavour of what we will prove , here is one of our results : @xmath3 where the graph of the integrand is depicted in the following figure [ fig1 ] . on @xmath4.,scaledwidth=50.0% ] in section [ sec2 ] we will prove our main results and in section [ sec4 ] we will give some detailed examples and applications .\nfirst , let us set the framework of our investigation . our starting point will be a @xmath5-periodic locally integrable function @xmath6 . for a nonzero real number @xmath7\n, we are interested in the evaluation of the integrals : @xmath8 where @xmath9 and @xmath10 are , respectively , the even and the odd components of @xmath11 . they are defined on @xmath12 by the formul : @xmath13 on the other hand , the cauchy principal value @xmath14 of the integral @xmath15 , plays an important role in this study . recall that @xmath14 is defined as follows : @xmath16 in the next proposition , we prove the convergence of the integrals defined by and , and we describe their relationship to the principal value defined by . [ pr41 ] consider @xmath6 , and a nonzero real @xmath7 .\n[ pr411 ] the integral @xmath17 is absolutely convergent .\n[ pr412 ] if @xmath18 , then the integral @xmath19 is convergent .\n[ pr413 ] the principal value @xmath14 is well defined and @xmath20 where @xmath21 and @xmath22 are defined by and , respectively . indeed ,\nthe first point is easy since , for @xmath23 , we have @xmath24 so @xmath25 and follows.to prove we consider the function @xmath26 defined by @xmath27 . since @xmath11 belongs to @xmath28 and @xmath29\nwe conclude immediately that @xmath26 is continuous and @xmath5-periodic . in particular ,\n@xmath26 is bounded on @xmath12 .\nan integration by parts shows that , for @xmath30 , we have @xmath31 indeed , this version of `` integration by parts '' is a dirct application of fubini s theorem , see for instance ( * ? ? ? * theorem 5.2.3 ) .\nnow , the following inequality @xmath32 proves the absolute convergence of the integral @xmath33 .\nthis implies the convergence of @xmath34 and shows that @xmath35 on the other hand , for @xmath36 , we have @xmath37 because @xmath38 is odd , and @xmath39 is even . finally , noting that @xmath40 since @xmath10 is odd , and using and , we obtain by letting @xmath41 tend to @xmath42 , and the proposition follows . using the notation of the preceding proposition , and the parity of @xmath43 and @xmath44\n, we obtain the following corollary that reduces the determination of @xmath21 and @xmath22 to that of @xmath14 .\n[ co41 ] using the notation of proposition [ pr41 ] , we have @xmath45 thus , the question is reduced to determining @xmath46 .\nthe next proposition expresses differently this quantity .\n[ pr42 ] for @xmath6 , and a nonzero real @xmath7 , we have @xmath47 where @xmath14 is defined by .\nrecall that,(see @xcite , ) @xmath48 with normal convergence on every compact set @xmath49 contained in @xmath50 . applying this to the compact segment @xmath51\\right\\}$ ] , and recalling that @xmath6 ,\nwe conclude that @xmath52 which is the desired conclusion .\nthe following lemma , will be of interest in formulating our main theorem .\n[ pr43 ] for @xmath6 , and a nonzero real @xmath7 , we have @xmath53 where @xmath54 is the sign of @xmath55 if @xmath56 and @xmath57 , and @xmath58 are the exponential fourier coefficients of @xmath11 . for a nonzero real @xmath7 ,\nconsider the continuous , @xmath5-periodic , function @xmath59 defined by @xmath60 the exponential fourier coefficients @xmath61 of @xmath59 are given by @xmath62 indeed , let us consider two cases : * for @xmath63 , we have @xmath64 * and , for @xmath65 , we have @xmath66 combining these two points proves .now , since @xmath67 for every @xmath68 , we see that @xmath69 thus , the continuous , @xmath5-periodic , function @xmath70 is equal to its fourier series expansion . in particular , @xmath71 that is , by , @xmath72 finally , using proposition [ pr42 ] , we obtain .\nnow , combining corollary [ co41 ] , proposition [ pr41 ] and proposition [ pr43 ] , we come to our main theorem .\n[ th41 ] consider @xmath6 and a positive real @xmath7 , then the following two integrals are convergent @xmath73 where @xmath9 and @xmath10 are , respectively , the even and odd components of @xmath11 defined by .\nmoreover , @xmath74 [ cor2 ] consider @xmath6 and a positive real @xmath7 .\nif @xmath11 is , and its fourier series expansion is @xmath75(x)=\\frac{a_0}{2}+\\sum_{n\\geq1}a_n\\cos nx$ ] , then @xmath76 if @xmath11 is , and its fourier series expansion is @xmath75(x)= \\sum_{n\\geq1}b_n\\sin nx$ ] , then @xmath77 there is a case where theorem [ th41 ] takes a more practical form .\nso , let us change our point of view .\nlet @xmath78 be an analytic function on a domain @xmath79 , that _ contains _ the closed unit disk @xmath80 .\nfor a positive real number @xmath7 , we are interested in determining the value of the integrals : @xmath81 where the real variable functions @xmath82 and @xmath83 are , respectively , the `` cos '' and the `` sin '' components of the function @xmath84 , defined on @xmath12 by the formul : @xmath85 the next theorem gives the answer to this question : [ th1 ] let @xmath86 be an anlytic function on a domain @xmath79 that contains the closed unit disk , then , for every positive real @xmath7 , one has @xmath87 where @xmath82 and @xmath83 are defined by .\nindeed , by assumption , there is a power series @xmath88 with radius of convergence @xmath89 such that @xmath90 so , we can define a continuous , @xmath5-periodic function @xmath11 by @xmath91 . comparing and we see that @xmath92 and @xmath93 . on the other hand , from we conclude that the fourier coefficients of @xmath11 are given by @xmath94 if @xmath95 and @xmath96 if @xmath97 .\nthus , theorem [ th1 ] proves @xmath98 which is the desired conclusion .\nlet @xmath55 be a positive number , and consider the analytic function @xmath86 defined on the domaine @xmath99 , by @xmath100 here , it is straightforward to check that @xmath101 so @xmath102 using theorem [ th1 ] we see that , for @xmath65 , we have @xmath103 thus , from , and after making the change of variables @xmath104 and @xmath105 , we get : @xmath106 or , equivalently @xmath107 this can be expressed as follows : for positive @xmath7 and @xmath108 , we have @xmath109 in particular , choosing @xmath110 we find the integral that we used to introduce our discussion . on the other hand , using @xmath83 from , and the second part of theorem [ th1 ] , we find that , for @xmath65 , we have in our second example we consider the even function @xmath6 defined by @xmath114 it is well - known , ( see for instance ( * ? ? ? * chapter 3 , $ 14 ) , ) that @xmath11 has the following fourier series expansion @xmath115(t)=\\ln2+\\sum_{n=1}^\\infty\\frac{\\cos nt}{n}\\ ] ] thus , applying corollary [ cor2 ] we obtain that for every @xmath65 we have @xmath116 the change of variables @xmath117 and @xmath105 yields the following result : @xmath118 let @xmath119 and @xmath41 be positive real numbers , such that @xmath120 consider the meromorphic function @xmath86 defined by @xmath121 clearly , @xmath86 is analytic in the domain @xmath122 that contains the closed unit disk .\nfor a given real @xmath123 , let @xmath124 to simplify the notation , we will simply write @xmath125 and @xmath126 to denote @xmath127 and @xmath128 respectively .\nit is clear that @xmath129 thus , @xmath130 on the other hand , since @xmath131 , we see immediately that @xmath132 therefore , using theorem [ th1 ] , with @xmath133 , we obtain @xmath134 , that is @xmath135 the evaluation of the integral , when @xmath136 and @xmath137 for some @xmath138 , is an unsolved problem proposed by narayana aiyar in the begining of the twentieth century @xcite , while the generalization , corresponding to @xmath36 and @xmath137 for some @xmath139 , is a problem proposed by m. d. hirchhorn @xcite . note that theorem [ th1 ] yields the following more precise results , valid for @xmath65 : @xmath140 where @xmath141 are real numbers from the interval @xmath142 and the @xmath125 s and @xmath126 s are defined by .\nin this example we consider the sequence @xmath143 of _ bernoulli polynomials_. they can be defined via the generating function @xmath144 or recursively by @xmath145 and @xmath146 in particular , @xmath147 now , denote by @xmath148 the @xmath5-periodic function defined by @xmath149 for @xmath150 , the fourier series expansion of @xmath151 , is well - known and easy to find ( using the recursive definition , see , for example ( * ? ? ?\n* chapter 23 ) . )\nwe have @xmath152(x)&=\\frac{(-1)^m2(2m-1)!}{(2\\pi)^{2m-1}}\\sum_{n=1}^\\infty\\frac{\\sin(nx)}{n^{2m-1}}\\\\ s[\\widetilde{b}_{2m}](x)&=\\frac{(-1)^m2(2m)!}{(2\\pi)^{2m}}\\sum_{n=1}^\\infty\\frac{\\cos(nx)}{n^{2m}}\\end{aligned}\\ ] ] applying corollary [ cor2 ] we conclude that , for @xmath153 and @xmath65 , we have @xmath154 the change of variables @xmath155 and @xmath156 yields the following result , for @xmath153 and @xmath65 : @xmath157 where the function @xmath158 is the polylogarithm of order @xmath159 . the function @xmath158 is defined on open unit disk by the series @xmath160 .\n( for an extensive account of the polylogarithms see @xcite . ) in particular , since @xmath161 , we see that @xmath65 , we have @xmath162 also , from the expressions of @xmath163 and @xmath164 we conclude that , for @xmath65 , we have @xmath165 adding one forth of to we see that , for @xmath65 , we have @xmath166 * for positive real numbers @xmath108 and @xmath7 , we have @xmath167 * for positive real numbers @xmath108 and @xmath7 , we have @xmath168 * for real numbers @xmath108 and @xmath7 such that @xmath169 and @xmath65 , we have @xmath170 * for real numbers @xmath108 and @xmath7 such that @xmath169 and @xmath65 , we have @xmath171 * for @xmath172 and a positive @xmath7 , we have @xmath173 where @xmath174 is the well - known bessel function of the first kind of order @xmath175 . * for positive @xmath7 , we have @xmath176", "role": "user" }, { "content": "in this note a general result is proved that can be used to evaluate exactly a class of highly oscillatory integrals .", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nmore than half of all stars in the local universe are found in massive spheroidal components ( e.g. @xcite ) . to understand the history of assembling of the bulk of stellar mass in the universe is thus fundamental to derive how and when the present day massive early type galaxies built up .\nhowever , the formation and evolution of early type galaxies is still a matter of debate . according to the standard @xmath0 cold dark matter scenario ( @xmath0 cdm ) for structure formation\n, galaxies built up their present day mass through a continuous assembly driven by the hierarchical merging of dark matter halos ( e.g.@xcite ) . in this scenario ,\nmassive early - type galaxies appear rather late in the history of the universe as the culmination of a hierarchical merging process . on the other hand , in the traditional monolithic collapse scenario ( e.g. @xcite ; @xcite ) the spheroidal component forms by the gravitational collapse of a gas cloud at relatively high redshifts . as a result of the rapidity of this collapse\n, the bulk of stars in ellipticals should be relatively old .\nthe study of absorption line indices in local early type galaxies has proven to be one of the most powerful diagnostics to constrain star formation history and to trace star evolution over time .\nbesides `` direct '' age estimates , indirect evidences of the duration of the star formation process can be analyzed through the study of the chemical enrichment pattern , and more specifically of the @xmath1/fe enhancement .\nhere we present a study of the stellar populations in a sample 65 nearby early - type galaxies , predominantly located in low density environments .\nwe look in particular for correlations of the stellar population parameters with galaxy mass and environment , in order to understand the role played by them on the evolution of massive early - type systems . this work has been presented in three separate papers ( @xcite , paper i ; @xcite , papers ii and iii ) to which we refer for details .\nthe total sample of 65 galaxies includes both gas and dust free galaxies taken from the samples of @xcite and @xcite , and objects taken from a compilation of galaxies showing ism traces in at least one of the following bands : iras 100 @xmath2 m , x - ray , radio , hi and co ( @xcite ) .\nall galaxies belong to the _ revised shapley ames catalog of bright galaxies ( rsa ) _ ( @xcite ) , and have a redshift of less than 5500 km s@xmath3 . the sample should then be biased towards objects that are expected to have ongoing and recent star formation , at least in small amounts , because of the presence of emission lines .\non the other hand , studies of randomly selected samples of early - type galaxies suggest that the incidence of ionized - gas emission in early - type galaxies is quite high ( @xmath4 75% , @xcite )\n. thus , our sample should not be too dissimilar from randomly selected samples of early - type galaxies .\nfigure [ fig1 ] summarizes the basic characteristics of the sample .\nthe right panel provides evidence that a large fraction of galaxies is in low density environments .\ngalaxies were observed during three separate runs ( march 1998 , september 1998 and may 1999 ) at the 1.5 m eso telescope ( la silla ) . our long \nslit spectra cover the 3700 - 7250 wavelength range with a spectral resolution of @xmath57.6 at 5550 . for each galaxy\nwe have extracted 7 luminosity weighted apertures ( with radii : 1.5 , 2.5 , 10 , r@xmath6/10 , r@xmath6/8 , r@xmath6/4 and r@xmath6/2 ) and 4 gradients ( 0 @xmath7 r @xmath7r@xmath6/16 , r@xmath8/16 @xmath7 r @xmath7r@xmath6/8 , r@xmath8/8 @xmath7 r @xmath7r@xmath6/4 and r@xmath8/4 @xmath7 r @xmath7r@xmath6/2 ) .\nfor each aperture and gradient we measured 25 line strength indices : 21 belonging to the original set defined by the lick - ids `` standard '' system ( @xcite ) and 4 subsequently introduced by @xcite to include the higher - order balmer lines .\nstrength indices have been corrected for several effects ( contamination by possible emission , velocity dispersion ) and conformed to the lick ids system .\nfigure [ fig2 ] shows selected lick indices measured in the central aperture ( @xmath9 ) for our sample as a function of central velocity dispersion .\nit is clear that metallic indices show a well established positive trend with @xmath10 ( with a significantly shallower variation for the fe indices ) . on the contrary\n, balmer indices decrease with velocity dispersion .\nthe observed behavior suggests that metallicities or ages increase with galaxy mass , but for the quantitative results we refer to the comparison with ssp models performed in section 5 .\nto derive ages and chemical compositions from observed narrow band indices of galaxies , appropriate models are needed .\nthus we have derived new simple stellar population ( ssp ) models for a wide range of ages ( @xmath11 gyr ) , metallicitites ( z@xmath12 ) and [ @xmath1/fe ] ratios ( 00.8 ) .\nthe ssps are based on the padova stellar evolution tracks and isochrones ( see @xcite ) .\nthe standard \ncomposition narrow band indices are computed on the basis of the fitting functions of @xcite and @xcite . the new @xmath1enhanced ssps have been computed starting from the standard ssps , and accounting for the effect of element abundance variations on the stellar atmospheres .\nin particular , the index correction due to non solar abundance partitions has been derived following the main guidelines provided by previous works in literature ( @xcite , @xcite ) , although we have revised the index dependence on element abundance .\nwe refer to paper iii for details .\nthe models are available to the public at http://www.inaoep.mx/@xmath4abressan or www.stsci.edu/@xmath4annibali/.\nto derive stellar population parameters from the observed line strength indices of our sample , we have implemented the new @xmath1-enhanced ssps within an algorithm based on the probability density function .\nthe derived average ages for the whole sample , e and s0 are 8 , 8.7 , and 6.3 gyr , respectively .\nthe average metallicities ( [ z / h ] ) for the whole sample , e and s0 , are 0.21 , 0.22 , and 0.19 , respectively .\nthe average [ @xmath1/fe ] ratios for the whole sample , e and s0 , are 0.21 , 0.23 , and 0.17 , respectively .\n= -10 cm we looked for possible correlation of the stellar population parameters with both central velocity dispersion and local galaxy density . in the left panel of figure [ fig3 ]\nwe plot ages , metallicities , and [ @xmath1/fe ] ratios , derived within a @xmath13 aperture , as function of @xmath10 .\nwe do not find the clear signature of a global trend of age with velocity dispersion ; on the other hand , significant positive trends are derived for metallicity and @xmath1/fe enhancement . in the right panel of fig .\n[ fig3 ] , we plot the same stellar population parameters as a function of the richness parameter @xmath14 , measured as galaxies @xmath15 mpc@xmath16 .\nit is interesting to note that the fit suggests a positive trend of age with local galaxy density . in particular , in spite of containing more than 40% of the sample with determined @xmath14 , the region above log(@xmath14 ) @xmath17 - 0.4 does not contain galaxies younger than 4 gyr . if we consider only galaxies with ages older than 4 gyr , the resulting fit is flat , indicating that the age \nenvironment relation is actually due to the presence of very young objects in the poorer environments .\nthis suggests that the relations with velocity dispersion may be `` disturbed '' by the presence of such objects populating very low density environments .\nif we exclude the galaxies in very low density environments , we find that the relations with velocity dispersion have a smaller scatter .\nthe good quality of our data allowed us also to analyze the stellar population gradients within the single galaxies .\nthe distributions of age , metallicity , and @xmath1-enhancement gradients are showed in fig .\n[ fig4 ] . while there is not clear presence of age and [ @xmath1/fe ] gradients , we definitely derive negative metallicity gradients ( metallicity decreases from the central regions outwards ) of the order of @xmath18 .\nwe have analyzed the stellar populations of a sample of 65 early type galaxies , mainly located in the field , and biased toward the presence of emission lines . summarizing our results : * we derive a large age spread , from a few gyr to 15 gyr .\nthe average ssp - equivalent ages for the whole sample , e and s0 are 8 , 8.7 , and 6.3 gyr , respectively ; the metallicity distribution shows a broad peak at @xmath19<0.3 $ ] ; finally , the [ @xmath1/fe ] ratio definitely presents a peak at @xmath40.22 .\n* we do not find a clear global trend of age with velocity dispersion ; on the other hand , significant positive trends are derived for metallicity and @xmath1/fe enhancement .\nthese results testify that the chemical enrichment is more efficient in more massive galaxies , and that the overall duration of the star formation process is shorter within deeper potential wells .\nthese two relations do not depend on galaxy morphological type , indicating that the galaxy gravitational potential is the main driver of the chemical enrichment process of the galaxy .\n* very young objects ( from 1 gyr to 4 gyr ) are found in very low density environments ( @xmath20 ) .\nnone of the galaxies in high density regions is younger than 4 - 5 gyr .\nthe lack of environmental effect on the ( @xmath1-enhancement)@xmath10 relation indicates that in very low environments rejuvenation episodes , rather than more prolonged star formation , are frequent .\n* by comparing the number of `` young '' objects with the total number of galaxies , and by means of simple two - ssp component models , we estimate that in these rejuvenation episodes ( like major mergers ) , not more than 25% of the galaxy mass could be formed , that is , about 75% of the galaxy mass is formed during the initial epoch of formation . *\nwe derive negative metallicity gradients within single galaxies , while on average the @xmath1-enhancement remains quite flat within r@xmath6/2 .\nthis indicates that the star formation proceeded on typical lifetimes not significantly different across r@xmath6/2 , but evidently with a larger efficiency in the center .", "role": "user" }, { "content": "we have acquired intermediate resolution spectra in the 3700 - 7000 wavelength range for a sample of 65 early - type galaxies predominantly located in low density environments , a large fraction of which show emission lines . \n the spectral coverage and the high quality of the spectra allowed us to derive lick line - strength indices and to study their behavior at different galacto - centric distances . ages , metallicities and element abundance ratios have been derived for the galaxy sample by comparison of the line - strength index data set with our new developed simple stellar population ( ssp ) models . \n we have analyzed the behavior of the derived stellar population parameters with the central galaxy velocity dispersion and the local galaxy density in order to understand the role played by mass and environment on the evolution of early - type galaxies . \n we find that the chemical path is mainly driven by the halo mass , more massive galaxies exhibiting the more efficient chemical enrichment and shorter star formation timescales . \n galaxies in denser environments are on average older than galaxies in less dense environments . \n the last ones show a large age spread which is likely to be due to rejuvenation episodes .", "role": "assistant" } ]

[ { "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: We propose a data-driven method to generate synthetic training data for supervised learning of object detection.\n\nKeyphrases: vehicle detection remote sensing imagery\n\nDataset description:\nSPIRS: A first-of-its-kind large dataset of sarcastic/non-sarcastic tweets with high-quality labels and extra features: (1) sarcasm perspective labels (2) new contextual features. The dataset is expected to advance sarcasm detection research.\nTHEODORE: Recent work about synthetic indoor datasets from perspective views has shown significant improvements of object detection results with Convolutional Neural Networks(CNNs). In this paper, we introduce THEODORE: a novel, large-scale indoor dataset containing 100,000 high- resolution diversified fisheye images with 14 classes.\nBIKED: BIKED is a dataset comprised of 4500 individually designed bicycle models sourced from hundreds of designers. BIKED enables a variety of data-driven design applications for bicycles and generally supports the development of data-driven design methods.\nCelebA: CelebFaces Attributes dataset contains 202,599 face images of the size 178×218 from 10,177 celebrities, each annotated with 40 binary labels indicating facial attributes like hair color, gender and age.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\nVirtual KITTI: Virtual KITTI is a photo-realistic synthetic video dataset designed to learn and evaluate computer vision models for several video understanding tasks: object detection and multi-object tracking, scene-level and instance-level semantic segmentation, optical flow, and depth estimation. Virtual KITTI contains 50 high-resolution monocular videos (21,260 frames) generated from five different virtual worlds in urban settings under different imaging and weather conditions.\nYCBInEOAT Dataset: A new dataset with significant occlusions related to object manipulation.\n\nOptions:- A: SPIRS B: THEODORE C: BIKED D: CelebA E: COCO F: Virtual KITTI G: YCBInEOAT Dataset", "role": "user" }, { "content": "[\"CelebA\", \"COCO\"]", "role": "assistant" } ]

[ { "content": "Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.\n\nThe relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].\n\nPlease format your output as a JSON array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<RELATION_A_B>\", \"<Entity_B>\"]. If no relations can be found, please output an empty JSON array [].\n\nAbstract:\n\nDifferential interactions of heparin and heparan sulfate glycosaminoglycans with the selectins. Implications for the use of unfractionated and low molecular weight heparins as therapeutic agents. The selectins are calcium-dependent C-type lectins that bind certain sialylated, fucosylated, sulfated glycoprotein ligands. L-selectin also recognizes endothelial proteoglycans in a calcium-dependent manner, via heparan sulfate (HS) glycosaminoglycan chains enriched in unsubstituted glucosamine units. We now show that these HS chains can also bind P-selectin, but not E-selectin. However, while L-selectin binding requires micromolar levels of free calcium, P-selectin recognition is largely divalent cation-independent. Despite this, HS chains bound to P-selectin are eluted by ethylenediamine tetraacetic acid (EDTA), but only at high concentrations. Porcine intestinal mucosal (mast cell-derived) heparin (PIM-heparin) shows similar properties, with no binding to E-selectin, calcium-dependent binding of a subfraction to L-selectin and to P-selectin, and calcium-independent binding of a larger fraction to P-selectin, the latter being disrupted by high EDTA concentrations. Analysis of defined heparin fragment pools shows a size dependence for interaction, with tetradecasaccharides showing easily detectable binding to L- and P-selectin affinity columns. L-selectin binding fragments include more heavily sulfated and epimerized regions and, as with the endothelial HS chains, they are enriched in free amino groups. The P-selectin binding component includes this fraction as well as some less highly modified regions. Thus, endothelium-derived HS chains and mast cell-derived heparins could play a role in modulating the biology of selectins in vivo. Notably, P- and L-selectin binding to sialyl-Lewisx and to HL-60 cells (which are known to carry the native ligand PSGL-1) is inhibited by unfractionated pharmaceutical heparin preparations at concentrations 12-50-fold lower than those recommended for effective anticoagulation in vivo. In contrast, two low molecular weight heparins currently considered as clinical replacements for unfractionated heparin are much poorer inhibitors. Thus, patients undergoing heparin therapy for other reasons may be experiencing clinically significant inhibition of L- and P-selectin function, and the current switchover to low-molecular weight heparins may come at some loss of this effect. Low-dose unfractionated heparin should be investigated as a treatment option for acute and chronic diseases in which P- and L-selectin play pathological roles.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nchemical elements are mostly created by stellar nucleosynthesis , and eventually ejected and diluted in the interstellar medium when stars die .\nthey are then incorporated into the successive generations of stars .\nthis cycle of formation and death of stars and the subsequent ejection of elements may occur many times , if the star formation rate ( sfr ) is high , with elemental abundances increasing rapidly in the interstellar medium ( ism ) ; if the sfr is low , the abundances will increase slowly , maintaining low during a long time . this way , elemental abundances give clues about when , how and with which rate stars form , existing a direct link between the evolutionary histories of galaxies or galaxy regions and the abundances measured within them .\nchemical evolution models try to understand the metal enrichment process , predicting the elemental abundances expected in each region as depending on different inputs and hypotheses , as the initial mass function ( imf ) , the star formation law , the existence or not of inflows or outflows of gas , or the stellar nucleosynthesis yields .\nonce computed a model for a galaxy , it is possible to compare with the observational data and deduce if our assumptions are valid or it is necessary to modify them .\nmany numerical chemical evolution models have been presented in the literature from decades ago @xcite , @xcite,@xcite , @xcite , @xcite .\nall of them are usually computed to reproduce the milky way galaxy ( mwg ) and other nearby spiral galaxies data as radial distributions of star formation , gas density , surface density stellar profile and the radial gradient of most common elements ( c , n , o , fe ... ) , which define the present state of our galaxy .\nthe existence of a radial gradient of abundances in the spiral disks is well known @xcite .\nthis gradient was first observed in the mwg @xcite and later in other external galaxies @xcite , and it is now well characterized in our local universe as shown by @xcite . however , even fitting the present day data , differences among models appear for other evolutionary times . in particular ,\nthe time evolution of the radial gradient of abundances is not the same for all models .\nthus , in @xcite or @xcite a flat radial gradient appears in the early times of evolution of a galaxy , steepening with time ; on the contrary , in @xcite , and @xcite , the gradient is steep , and then it flattens with time . in the first case ,\na disk is already formed in time zero with an infall of primordial gas which dilutes the enrichment of the disk due to the stars death . in the second type of models , the disk forms out from the gas infalling onto the equatorial plane .\ntherefore , the evolution of the metallicity gradient seems to be directly related on the formation process of the disk , stressing the importance of this point . in @xcite\nwe analyzed the existing data for mwg about this question : planetary nebulae ( pn ) abundances , globular and open clusters metallicities and stellar abundances .\neach data set has his own problems to determine the time evolution of the radial gradient .\nthe pn are useful to estimate the radial gradient of oxygen , an element not modified by the nucleosynthesis in the progenitors stars of pn .\nthe early data analyzing this question @xcite showed a radial gradient steeper than the one for the present time , although , due to error bars , the observational points mixed with the hii regions data in the plot of o / h _ vs _ galactocentric radius @xmath0 .\nthe open clusters problems are derived of the necessary classification in thin or thick disk or even halo populations before their use in a radial distribution of metallicity .\nfurthermore , the ages determination , coming from a fit of their spectra to stellar models , which depend on metallicity and on age simultaneously , added to differences depending on the use of lte or nlte models , may be uncertain .\nthe estimate of age and metallicity of globular clusters ( gc ) seems less problematic since there was assumed that they form as a single stellar population , with a single burst of star formation and , consequently , to obtain only an age and a metallicity for all the stars of a gc is more precise .\nbased on these gcs data , we concluded that the radial gradient of abundances in mwg was steeper in the past , and it has been flattening with time until arriving to the present value .\nhowever , these old objects may also be part of the thick disk or the halo populations .\nas for the open clusters , the kinematic information is essential to determine their group and , therefore , to know if the corresponding data may be included in the study of the time evolution of the radial distribution of * disk * abundances . in @xcite(hereinafter md05 ) , we show 440 chemical evolution models , for 44 different galaxy masses and 10 possible star formation efficiencies in each one . from a mwg - like model\n, we obtained the evolution of the radial gradient of oxygen abundances , finding a gradient of @xmath1 dexkpc@xmath2 for @xmath3 which flattens with time until reaching the present time value @xmath4 dexkpc@xmath2 .\nthis behavior was in agreement with the cosmological simulations from @xcite and also with the @xcite value found at @xmath5 .\nhowever , it is necessary to take into account that this gradient was calculated with the o abundances of all radial regions computed in our model ( which arrived until 25kpc ) .\nin fact , the optical radius of mwg is @xmath6kpc , and , therefore , to include the regions out of a given radius might be considered as inadequate , since there thick or halo populations may being mixed with the thin disk . taking into account that these outer regions of the galaxy are not evolved , this implies a steepening of the radial gradient , more strongly for the highest redshift since the parts not evolved of the disk will be more inner . if we only consider the regions within the optical radius to compute the radial gradient , the evolution of this last one along the redshift is smoother , with a value @xmath7 dexkpc@xmath2 for all redshifts .\nwe have now revised our chemical evolution models to include more realistic and updated inputs in our code . in this work\nwe analyze the corresponding results for our new mwg model , used to calibrating the model grid .\nwe study in particular the evolution of the radial gradient of oxygen , searching for the possible differences with the old model from md05 and checking if the new prescriptions related on stellar yields , star formation or infall rate have modified the behavior of this gradient .\nwe also compare the results with the most recent data in the literature .\nin the recent years , new sets of data have been published , as consequence of better instruments , techniques and telescopes . @xcite give a summary of the observations ( see their fig.5 ) , referring to pn , open clusters , and stars from mwg in order to analyze the evolution of the radial gradient of metallicity along the time .\nthe problem is that each type of objects shows a different evolution .\nthus , pns which gave a steep radial gradient for a time @xmath88gyr compared with the one corresponding to the present time given by hii regions , give now , following the most recent findings , a flat evolution along the time ; that is , the radial gradient for o is basically the same from 5 - 6gyr ago until now @xcite , or even has steepen slightly on time @xcite . a radial gradient\nconstant along the time is also obtained by @xcite for m33 , m31 , m81 and ngc300 , comparing their radial distributions of oxygen abundances given by hii regions and pn , finding no evidences of evolution of the radial gradient with time .\nthe pn give precise measurements of abundances since they are very bright , allowing to observe them even being far away .\nhowever , to estimate their masses ( an in consequence their ages ) and their distances is not an easy task , as explained in @xcite , which makes the magrini et al .\n( 2016 ) constraint not totally sure .\nfrom open clusters data , practically all of works , as @xcite , arrive to a similar conclusion : the radial gradient of metallicity was steeper in the past than now .\nthe number of points of the complete sample in these works is usually small and , therefore , each defined bin of age is wide with a handful of points .\nfinally , stellar abundances , as given @xcite , show a flattening of the radial gradient .\nhowever , the oldest age bin ( around 12 - 13gyr old ) has a radial gradient zero .\nit means that the radial gradient started flat , then it did steeper , and after it flattened again .\n@xcite do not agree with these results , obtaining a radial gradient steepening continuously with time .\nlooking at these data in detail , we find some problems for the precise determination of the radial gradient for the old ages bin .\n@xcite give the metallicity radial distribution as the iron abundance dividing their sample in different stellar ages , with a radial range for the whole sample of @xmath9kpc ( actually not very wide ) , but the oldest stars are located in a reduced region around the solar vicinity , with a radial range of @xmath10kpc .\nit is impossible to estimate a gradient with such a short radial range .\nthis problem for the oldest age bin also occurs in @xcite , where the radial range reduces from the 3 - 4kpc for the youngest bin to 1 - 1.5kpc for the oldest one . for the corogee sample from @xcite the total sample\nhas a good radial range from 4kpc to 14kpc , but the oldest bin has a range much shorter , from 8 to 12kpc .\nthis produces a cloud of points around @xmath11kpc of galactocentric distance , which does not allow the computation of a precise radial gradient .\nour basic model is well described in @xcite .\nwe start with a spherical protogalaxy with a dynamical mass distribution given by the rotation curve .\nthis initial gas falls onto the equatorial plane forming out the disk . in the halo\nthe star formation follows a schmidt - kennicutt law , while in the disk molecular clouds form first , and then stars are created from cloud - cloud collisions and from the interaction of massive stars with the surrounding clouds .\nincluding the star mean lifetime and the stellar yields , we compute abundances for 15 elements until fe , being this element mostly created by the supernova type ia yields from @xcite . in this standard model ( std ) ,\nthe star and molecular cloud formation are calculated with two efficiencies for each galaxy model , which we vary simultaneously with values among 0 and 1 .\nwe have now an updated grid of models ( moll et al , in preparation ) , where we use the stellar yields from @xcite and imf from @xcite , selected as the best combination of stellar yields and imf from 144 models in @xcite .\nwe have also revised the infall rates of gas , calculated to create disks as observed following @xcite .\ndetails are given in @xcite .\nmoreover , we now follow the prescription by ascasibar et al .\n( in preparation ) to form molecular clouds from the diffuse gas .\nthis model ( asc ) is compared with our standard model ( std ) .\nthe details are given in @xcite .\nfor a mwg - like model , we use a dynamical mass of 10@xmath12m@xmath13 , able to create a disk of @xmath14m@xmath13 . in fig .\n[ fig1 ] we represent the evolution of the region located a @xmath15kpc as function of time in panels a ) and c ) , and as function of the metallicity [ fe / h ] in panels b ) and d ) , compared with the solar region data . in fig .\n[ fig2 ] we draw the surface densities of hi , h@xmath16 , stars and sfr for the disk component , compared with the mwg data .\nwe compare both std and asc models , finding that basically both fit the data within errors , with differences only in the outer regions with a more extended disk for std .\nin fig . [ fig3 ] we show the radial distribution for o / h as given by std ( top panels ) and asc ( bottom panels ) prescriptions , for different redshifts as labelled in the top right panel .\nthis way , we may check the effect of the star formation law on the evolution of the radial gradient .\nthe distributions shows a sharp cut of the disk in asc while this is smoother in std , with a more extended disk , as said before .\nthis is due to the effect of threshold of asc , since the necessary density or metallicity must be reached to create molecular clouds . in left panels we show these distributions as a function of the galactocentric distance @xmath0 ( in kpc ) . in right panels\nwe show the same distributions as a function of the normalized radius @xmath17 .\nit is clear that the slope of the distribution within the optical disk , defined as @xmath18 ( @xmath19kpc for the std model at @xmath20 ) , is almost the same for all redshifts , as shown in right panels .\nwe must remember that @xmath21 changes with redshift : the stellar disk increases their size when stars form in an inside - out scenario ; at the early times stars form only in the inner disk . in the std model ,\n@xmath21 is around 5kpc for the present time , but it is @xmath22kpc at @xmath23 .\nhowever , @xmath21 increases very slowly in asc model , being @xmath24kpc at @xmath23 .\nthus , at this redshift , the optical radius would be around @xmath25 kpc in std model , but it only arrives to @xmath26kpc in asc .\ntherefore , it seems quite evident that the slope of the radial gradient is basically the same for all redshifts when is measured within the optical radius , where we must define a radial gradient of the disk oxygen abundance . if a radial gradient different than the one of the present time is obtained at other time / redshift , it implies that it is being measured with regions out of the optical disk , with stellar populations of the thick disk , or of the halo , not unexpected if we are observing the phases of the disk formation at @xmath27 .\nwe summarize our results in fig .\n[ fig4 ] , with the evolution along redshift of the o / h radial gradient , measured as dexkpc@xmath2 in the top panels and as dexr@xmath28 in the bottom ones . in left panels\nthe gradient is calculated using the whole radial range that we run our mwg model , while in the right ones we use only regions within the optical radius .\ntop panel results are compared with our old model md05 , cosmological simulations by @xcite and recent data as labelled , including @xcite and @xcite for high redshift galaxies .\nthe main conclusions can be summarised as : 1 . the radial range where the least - squares straight line fit is done is crucial to determine the value of the abundance radial gradient .\n2 . our mwg models produce a smooth evolution of the o abundances radial gradient with a value of -0.15dexkpc@xmath2 at @xmath29 arriving to -0.05 dexkpc@xmath2 at @xmath20 when the whole radial range is used .\n3 . the radial gradient has a value around @xmath30dexkpc@xmath2 for @xmath31 when it is measured within the optical radius ( variable with @xmath32 ) .\n4 . the radial gradient computed by our new models is flatter than the obtained in md05 as consequence of the new infall rates , smoother than the old ones . 5 .\nif the radial gradient is measured as a function of a normalized radius ( @xmath17 ) , differences arise between std and asc proceeding from the different grow of size of the stellar disk in both models ( even with the same infall rates ) , if all radial regions are used .\nif the radial gradient is computed within the optical radius , as a function of a normalized radius ( @xmath17 ) , it has a constant value of @xmath33 dexr@xmath28 for @xmath31 , which agrees with @xcite result for the califa local galaxies .", "role": "user" }, { "content": "we review the state of our chemical evolution models for spiral and low mass galaxies . \n we analyze the consequences of using different stellar yields , infall rate laws and star formation prescriptions in the time / redshift evolution of the radial distributions of abundances , and other quantities as star formation rate or gas densities , in the milky way galaxy ; in particular we will study the evolution of the oxygen abundance radial gradient analyzing its relation with the ratio sfr / infall . \n we also compare the results with our old chemical evolution models , cosmological simulations and with the existing data , mainly with the planetary nebulae abundances .", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Gene\"].\n\nPlease return the output as a JSON object of the format: {\"Gene\": [\"IGF\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nPI3K/mTOR inhibitor PF-04691502 antitumor activity is enhanced with induction of wild-type TP53 in human xenograft and murine knockout models of head and neck cancer. PURPOSE: Phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway activation is often associated with altered expression or mutations of PIK3CA, TP53/p73, PTEN, and TGF-beta receptors (TGFBR) in head and neck squamous cell carcinomas (HNSCC). However, little is known about how these alterations affect response to PI3K/mTOR-targeted agents. EXPERIMENTAL DESIGN: In this preclinical study, PI3K/Akt/mTOR signaling was characterized in nine HNSCC (UM-SCC) cell lines and human oral keratinocytes. We investigated the molecular and anticancer effects of dual PI3K/mTOR inhibitor PF-04691502(PF-502) in UM-SCC expressing PIK3CA with decreased wild-type TP53, mutant TP53-/+ mutantTGFBR2, and in HNSCC of a conditional Pten/Tgfbr1 double knockout mouse model displaying PI3K/Akt/mTOR activation. RESULTS: UM-SCC showed increased PIK3CA expression and Akt/mTOR activation, and PF-502 inhibited PI3K/mTORC1/2 targets. In human HNSCC expressing PIK3CA and decreased wtTP53 and p73, PF-502 reciprocally enhanced TP53/p73 expression and growth inhibition, which was partially reversible by p53 inhibitor pifithrin-alpha. Most UM-SCC with wtTP53 exhibited a lower IC50 than those with mtTP53 status. PF-502 blocked growth in G0-G1 and increased apoptotic sub-G0 DNA. PF-502 suppressed tumorigenesis and showed combinatorial activity with radiation in a wild-type TP53 UM-SCC xenograft model. PF-502 also significantly delayed HNSCC tumorigenesis and prolonged survival of Pten/Tgfbr1-deficient mice. Significant inhibition of p-Akt, p-4EBP1, p-S6, and Ki67, as well as increased p53 and TUNEL were observed in tumor specimens. CONCLUSIONS: PI3K-mTOR inhibition can enhance TP53/p73 expression and significantly inhibit tumor growth alone or when combined with radiation in HNSCC with wild-type TP53. PIK3CA, TP53/p73, PTEN, and TGF-beta alterations are potential modifiers of response and merit investigation in future clinical trials with PI3K-mTOR inhibitors.", "role": "user" }, { "content": "{\"Gene\": [\"Akt\", \"4EBP1\", \"mTORC1/2\", \"Tgfbr1\", \"TGFBR2\", \"TP53\", \"TGF-beta\", \"Phosphoinositide 3-kinase\", \"Ki67\", \"PI3K\", \"S6\", \"Pten\", \"PIK3CA\", \"TGFBR\", \"mTOR\", \"PTEN\", \"TGF-beta receptors\", \"p73\", \"mammalian target of rapamycin\", \"p53\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nThe 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK\nAbstract 1:\nSummary Background Women born around 1940 in countries such as the UK and USA were the first generation in which many smoked substantial numbers of cigarettes throughout adult life . Hence , only in the 21st century can we observe directly the full effects of prolonged smoking , and of prolonged cessation , on mortality among women in the UK . Methods For this prospect i ve study , 1·3 million UK women were recruited in 1996–2001 and resurveyed postally about 3 and 8 years later . All were followed to Jan 1 , 2011 , through national mortality records ( mean 12 woman-years , SD 2 ) . Participants were asked at entry whether they were current or ex-smokers , and how many cigarettes they currently smoked . Those who were ex-smokers at both entry and the 3-year resurvey and had stopped before the age of 55 years were categorised by the age they had stopped smoking . We used Cox regression models to obtain adjusted relative risks that compared categories of smokers or ex-smokers with otherwise similar never-smokers . Findings After excluding 0·1 million women with previous disease , 1·2 million women remained , with median birth year 1943 ( IQR 1938–46 ) and age 55 years ( IQR 52–60 ) . Overall , 6 % ( 66 489/1 180 652 ) died , at mean age 65 years ( SD 6 ) . At baseline , 20 % ( 232 461 ) were current smokers , 28 % ( 328 417 ) were ex-smokers , and 52 % ( 619 774 ) were never-smokers . For 12-year mortality , those smoking at baseline had a mortality rate ratio of 2·76 ( 95 % CI 2·71–2·81 ) compared with never-smokers , even though 44 % ( 37 240/85 256 ) of the baseline smokers who responded to the 8-year resurvey had by then stopped smoking . Mortality was tripled , largely irrespective of age , in those still smoking at the 3-year resurvey ( rate ratio 2·97 , 2·88–3·07 ) . Even for women smoking fewer than ten cigarettes per day at baseline , 12-year mortality was doubled ( rate ratio 1·98 , 1·91–2·04 ) . Of the 30 most common causes of death , 23 were increased significantly in smokers ; for lung cancer , the rate ratio was 21·4 ( 19·7–23·2 ) . The excess mortality among smokers ( in comparison with never-smokers ) was mainly from diseases that , like lung cancer , can be caused by smoking . Among ex-smokers who had stopped permanently at ages 25–34 years or at ages 35–44 years , the respective relative risks were 1·05 ( 95 % CI 1·00–1·11 ) and 1·20 ( 1·14–1·26 ) for all-cause mortality and 1·84 ( 1·45–2·34 ) and 3·34 ( 2·76–4·03 ) for lung cancer mortality . Thus , although some excess mortality remains among these long-term ex-smokers , it is only 3 % and 10 % of the excess mortality among continuing smokers . If combined with 2010 UK national death rates , tripled mortality rates among smokers indicate 53 % of smokers and 22 % of never-smokers dying before age 80 years , and an 11-year lifespan difference . Interpretation Among UK women , two-thirds of all deaths of smokers in their 50s , 60s , and 70s are caused by smoking ; smokers lose at least 10 years of lifespan . Although the hazards of smoking until age 40 years and then stopping are substantial , the hazards of continuing are ten times greater . Stopping before age 40 years ( and preferably well before age 40 years ) avoids more than 90 % of the excess mortality caused by continuing smoking ; stopping before age 30 years avoids more than 97 % of it . Funding Cancer Research UK , Medical Research Council\n\n\nTitle 2:\nChanges in craving for a cigarette and arterial nicotine plasma concentrations in abstinent smokers\nAbstract 2:\nAlthough the relationship between nicotine and changes in heart rate and blood pressure has been demonstrated , the relationship between nicotine and subjective effects such as decreased craving , relaxation , sickness , and decreased nervousness , is less well delineated . In this study , arterial nicotine levels were drawn in 21 smokers who smoked two average nicotine ( AN ) cigarettes and one low nicotine ( LN ) cigarette . Craving for a cigarette , relaxation , sickness , and decreased nervousness were rated on a visual analog scale ( VAS ) before and after smoking each cigarette . None of these subjective measures except craving for a cigarette was changed significantly by smoking . The change in craving was significantly correlated with the area under the plasma nicotine concentration versus time curve ( r = -0.57 , p = 0.01 ) calculated from the arterial nicotine sample s drawn up to 20 min after the initiation of smoking the first AN cigarette . Although well-documented behavioral manipulations , such as smoking denicotinized cigarettes , reduce craving , increases in plasma arterial nicotine concentrations after smoking the first cigarette of the day also reduce craving . Both the psychology and pharmacology of nicotine/tobacco smoking are involved in craving reduction\n\n\nTitle 3:\nSmoking and major depression. A causal analysis.\nAbstract 3:\nAmong 1566 personally evaluated female twins from a population -based register , average lifetime daily cigarette consumption was strongly related to lifetime prevalence and to prospect ively assessed 1-year prevalence of major depression ( MD ) . Using the cotwin control method , we evaluated whether the association between smoking and lifetime MD was causal or noncausal . While the relative risk ( 95 % confidence interval ) for ever smoking given a lifetime history of MD was 1.48 ( 1.30 to 1.65 ) in the entire sample , it was 1.18 ( 0.88 to 1.47 ) and 0.98 ( 0.71 to 1.26 ) , respectively , in dizygotic and monozygotic twin pairs discordant for a history of MD . The relative risk for a history of MD given ever smoking was 1.60 ( 1.39 to 1.83 ) in the entire sample , while in dizygotic and monozygotic twins discordant for smoking , it was 1.29 ( 0.87 to 1.74 ) and 0.96 ( 0.59 to 1.42 ) , respectively . Controlling for personal smoking history , family history of smoking predicted risk for MD ; controlling for the personal history of MD , family history of MD predicted smoking . The best-fitting bivariate twin model suggested that the relationship between lifetime smoking and lifetime MD result ed solely from genes that predispose to both conditions . These results suggest that the association between smoking and MD in women is not a causal one but arises largely from familial factors , which are probably genetic , that predispose to both smoking and MD\n\n\nTitle 4:\nEfficacy of initiating tobacco dependence treatment in inpatient psychiatry: a randomized controlled trial.\nAbstract 4:\nOBJECTIVES We evaluated the efficacy of a motivational tobacco cessation treatment combined with nicotine replacement relative to usual care initiated in inpatient psychiatry . METHODS We r and omized participants ( n = 224 ; 79 % recruitment rate ) recruited from a locked acute psychiatry unit with a 100 % smoking ban to intervention or usual care . Prior to hospitalization , participants averaged 19 ( SD = 12 ) cigarettes per day ; only 16 % intended to quit smoking in the next 30 days . Results . Verified smoking 7-day point prevalence abstinence was significantly higher for intervention than usual care at month 3 ( 13.9 % vs 3.2 % ) , 6 ( 14.4 % vs 6.5 % ) , 12 ( 19.4 % vs 10.9 % ) , and 18 ( 20.0 % vs 7.7 % ; odds ratio [ OR ] = 3.15 ; 95 % confidence interval [ CI ] = 1.22 , 8.14 ; P = .018 ; retention > 80 % ) . Psychiatric measures did not predict abstinence ; measures of motivation and tobacco dependence did . The usual care group had a significantly greater likelihood than the intervention group of psychiatric rehospitalization ( adjusted OR = 1.92 ; 95 % CI = 1.06 , 3.49 ) . CONCLUSIONS The findings support initiation of motivationally tailored tobacco cessation treatment during acute psychiatric hospitalization . Psychiatric severity did not moderate treatment efficacy , and cessation treatment appeared to decrease rehospitalization risk , perhaps by providing broader therapeutic benefit", "role": "user" }, { "content": "Smoking cessation is associated with reduced depression , anxiety , and stress and improved positive mood and quality of life compared with continuing to smoke .\nThe effect size seems as large for those with psychiatric disorders as those without .\nThe effect sizes are equal or larger than those of antidepressant treatment for mood and anxiety disorders", "role": "assistant" } ]

[ { "content": "You will be shown biomedical passages and your task is to answer the provided question. Provide a concise and accurate response and do not include any additional text in the response other than the answer.\n\nQuestion: Where does CTCF colocalize with cohesin?\n\nContext: In human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF).\nTo investigate cohesin-non-CTCF (CNC) binding events in vivo we mapped cohesin and CTCF, as well as a collection of tissue-specific and ubiquitous transcriptional regulators using ChIP-seq in primary mouse liver.\nIn contrast to regions of the genome where cohesin and CTCF colocalize, CNC sites coincide with the binding of master regulators and enhancer-markers and are significantly associated with liver-specific expressed genes.\nFinally, we observe that the presence of mirrored CTCF binding events at promoters and their nearby cohesin-bound enhancers is associated with elevated expression levels.\nRecently, cohesins have been implicated in transcriptional regulation and insulation through genome-wide colocalization with the insulator protein CTCF, including involvement at the imprinted H19/Igf2 locus.\nHere we report that cohesins colocalize with CTCF at two additional imprinted loci, the Dlk1-Dio3 and the Kcnq1/Kcnq1ot1 loci.\nTo determine the functional importance of the binding of CTCF and cohesins at the three imprinted loci, CTCF and cohesins were depleted in mouse embryonic fibroblast cells.\nResults of these experiments demonstrate an unappreciated role for CTCF and cohesins in the repression of imprinted genes in somatic cells.\nHere, we show in different cell types that cohesin functionally behaves as a tissue-specific transcriptional regulator, independent of CTCF binding.\nBy performing matched genome-wide binding assays (ChIP-seq) in human breast cancer cells (MCF-7), we discovered thousands of genomic sites that share cohesin and estrogen receptor alpha (ER) yet lack CTCF binding\nBy use of human hepatocellular carcinoma cells (HepG2), we found that liver-specific transcription factors colocalize with cohesin independently of CTCF at liver-specific targets that are distinct from those found in breast cancer cells\nTogether, our data show that cohesin cobinds across the genome with transcription factors independently of CTCF, plays a functional role in estrogen-regulated transcription, and may help to mediate tissue-specific transcriptional responses via long-range chromosomal interactions.\nBecause cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci. The differential binding of cohesin to CTCF sites may promote multiple loop formation and thus effective V(D)J recombination\nThese numerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement.\nWe conclude that cohesins interact with CTCF in mid-S phase and repress CTCF-regulated genes in a cell cycle-dependent manner.\nWe propose that the CTCF-cohesin complex plays a critical role in regulating the cell cycle control of viral gene expression during latency and that failure to maintain cell cycle control of latent transcripts inhibits host cell proliferation and survival\nWe conclude that cohesin subunits associate with viral and cellular CTCF sites involved in complex gene regulation and chromatin organization.\nBecause cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci.\nIn human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF).\nHere, we show that ATRX, MeCP2, and cohesin, chromatin regulators implicated in ATR-X, RTT, and CdLS syndromes, respectively, interact in the brain and colocalize at the H19 imprinting control region (ICR) with preferential binding on the maternal allele.\nSubcellular distribution of CTCF and colocalization with cohesins also varied across the cell cycle.\nChIP sequencing was performed on pro-B cells, revealing colocalization of CTCF and Rad21 binding at ~60 sites throughout the V(H) region and 2 other sites within the Igh locus.\nRecently, cohesins have been implicated in transcriptional regulation and insulation through genome-wide colocalization with the insulator protein CTCF, including involvement at the imprinted H19/Igf2 locus.\nCTCF colocalizes with cohesin but not RNA Polymerase II.\nBecause cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci.\nBecause cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci. The differential binding of cohesin to CTCF sites may promote multiple loop formation and thus effective V(D)J recombination.\nHere we report that cohesins colocalize with CTCF at two additional imprinted loci,", "role": "user" }, { "content": "In imprinted and repressed, highly compacted loci that are prone to recombination events.", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nexperiments\n\nContext before the citation:\nA similar problem is discussed in the psycholinguistics of interpretation (Sedivy et al. 1999): Interpretation is widely assumed to proceed incrementally, but vague descriptions resist strict incrementality, since an adjective in a vague description can only be fully interpreted when its comparison set is known. This means that the linguistic realization cannot start until CD is concluded, contradicting eye-tracking experiments suggesting that speakers start speaking while still scanning distractors (Pechmann 1989). This question is especially pertinent in the case of vague expressions, since gradable properties are selected last, but realized first (Section 6).\n\nCitation Sentence:\nA similar problem is discussed in the psycholinguistics of interpretation ( Sedivy et al. 1999 ) : Interpretation is widely assumed to proceed incrementally , but vague descriptions resist strict incrementality , since an adjective in a vague description can only be fully interpreted when its comparison set is known .\n\nContext after the citation:\nSedivy and colleagues resolve this quandary by allowing a kind of revision, whereby later words allow hearers to refine their interpretation of gradable adjectives. Summarizing the situation in generation and interpretation, it is clear that the last word on incrementality has not been said. \u0000\u0000\u0000\u0000", "role": "user" }, { "content": "CompareOrContrast", "role": "assistant" } ]

[ { "content": "You will be presented with a citation sentence from a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nWe compare the proposed classification algorithm (denoted as “CoLiBRi” for “Concept Lattice-Based Rule-learner”) with Scikit-learn [12] implementations of CART [2], Random Forest [1] and kNN on several datasets from the UCI machine learning repository.1\n 1 http://repository.seasr.org/Datasets/UCI/csv/\n We used Gini impurity as a criterion for rule selection and MDL [3] for continuous feature discretization.", "role": "user" }, { "content": "Method", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Is CHEK2 involved in cell cycle control?\n\nContext: Moreover, cell-cycle progression genes [i.e. E2F transcription factor (E2F) family and histone deacetylase ( HDAC )] and DNA-repair genes [i.e. growth arrest and DNA-damage-inducible, gamma ( GADD45G ) family and serine/threonine-protein kinase Chk2 ( CHEK2)] were also increased.\nAs CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated with increased risk of malignant melanoma.\nIn the current study, we evaluated the possible associations of seven common variants of the DNA repair and cell cycle control genes BRCA2 and CHEK2 with malignant melanoma (MM).\nPromotor methylation analysis of key regulatory genes involved in cell cycle control (p14, p15, p16, CHK2), DNA repair (hMLH1), apoptosis (p73, survivin, DAPK), and differentiation (RARb, WT1) was performed by methylation-specific polymerase chain reaction.\nCHEK2 is a key cell cycle control gene encoding a pluripotent kinase that can cause arrest or apoptosis in response to unrepaired DNA damage.\nHigh-fidelity maintenance of genomic integrity in eukaryotes is ensured by cell cycle checkpoints and DNA repair. The checkpoint kinase, Chk2, has been implicated in both of these responses. In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation. The fully activated Chk2 then phosphorylates downstream substrates of cell cycle control.\nCheckpoint kinase 2 (hCHK2/hCds1) is a tumor suppressor gene involved in cell-cycle control.", "role": "user" }, { "content": "yes", "role": "assistant" } ]

[ { "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nA Unified Route to the Welwitindolinone Alkaloids: Total Synthesis of (\\xe2\\x88\\x92)-N-Methylwelwitindolinone C Isothiocyanate, (\\xe2\\x88\\x92)N-Methylwelwitindolinone C Isonitrile, and (\\xe2\\x88\\x92)-3-Hydroxy-N-Methylwelwitindolinone C Isothiocyanate\n\nPaper sections:\n\n<p>In the continuing search for effective new therapies to combat human disease, the field of medicine has often benefited from the discovery of novel compounds isolated from natural sources. As part of this pursuit, Moore and co-workers investigated a series of marine and terrestrial cyanobacteria and found their lipophilic extracts to display an array of cytotoxic properties.1 This biological activity was traced to a new family of polycyclic oxindole-containing alkaloids—the welwitindolinones (e.g., 1–4) (Figure 1). Nearly all members of this family possess a common bicyclo[4.3.1]decane ring system set within a densely functionalized tetracyclic scaffold. Given their interesting biological activities and unique molecular architectures, the welwitindolinones have been the focus of numerous synthesis groups for nearly fifteen years.2,3 Early this year, we reported the first synthesis of a bridged bicyclic member of the family, that of N-methylwelwitindolinone D isonitrile (4),4 and this was followed by the synthesis of dihydro N-methylwelwitindolinone B isothiocyanate.5 Most recently, Garg and co-workers completed a remarkable synthesis of (−)-N-methylwelwitindolinone C isothiocyanate (2a).6 As part of an ongoing program aimed at the development of a comprehensive approach toward this intriguing family of alkaloids, we now report the total syntheses of (−)-N-methylwelwitindolinone C isothiocyanate (2a), (−)-N-methylwelwitindolinone C isonitrile (2b), and (−)-3-hydroxy-N-methylwelwitindolinone C isothiocyanate (3a).</p><p>From the outset, our objective was to design a unified strategy, one that would enable rapid assembly of a tetracyclic core unit, adorned in such a way as to provide avenues to all members of the bridged welwitindolinones. Toward this goal, we designed a concise sequence to forge the central bicyclo[4.3.1]decane ring system (6) through successive Lewis acid-mediated alkylative coupling and palladium-catalyzed enolate arylation transformations, starting from readily available cyclohexanone- (7) and indole-containing precursors (Scheme 1).2g,4 Having successfully employed tetracycle 6 in the synthesis of welwitindolinone D (4), we sought to use this intermediate as a key branching point from which to direct our efforts toward the subclass that possesses a vinylic chloride at C13, in particular N-methylwelwitindolinone C isothiocyanate (2a). Unique among this family of alkaloids, welwitindolinone 2a possesses the ability to antagonize the efflux activity of P-glycoprotein, the overexpression of which leads to the development of multiple drug resistance in several types of human cancers.7 However, the studies that identified this activity were carried out prior to the isolation of welwitindolinones 3a, 3b, and 4, and as such these more highly oxidized congeners have yet to undergo biological assay. Total synthesis therefore holds the potential to provide new access to the oxidized members, and their analogues, for further screening.</p><p>Our approach toward N-methylwelwitindolinone C isothiocyanate (2a) hinged on late-stage introduction of the vinylic chloride through electrophilic chlorination of hydrazone 5, which would be available from ketone 6. We envisioned the use of this compound, whose synthesis was established en route to N-methylwelwitindolinone D isonitrile (4), as a strategic branching point from which to target several members of the family. In order to realize an asymmetric synthesis of (−)-2a, this intermediate was ultimately prepared from enantioenriched acetate (−)-8 (>99.5% ee), which was obtained through pig liver esterase-catalyzed resolution of racemic 4-acetoxy-3-methylcyclohexenone.8</p><p>A key challenge for the synthesis of N-methylwelwitindolinone C isothiocyanate is installation of the vinyl chloride at C13.9 Our plan was to introduce the chloride through electrophilic chlorination of the C13 hydrazone.10,11 Of the three different carbonyl groups in the starting tetracycle (6), the least likely to condense with hydrazine was the bridging ketone at C10, due to its congested steric environment. So as to avoid formation of the hydrazone with the remaining carbonyl, the aldehyde, the plan was to protect this functionality as the corresponding dioxolane (9). Remarkably, when subjected to standard acetalization conditions, compound 6 gave none of the expected acetal and instead transformed cleanly into pentacycle 10. In fact, the same product was formed upon simply heating 6 in toluene at 85 °C, absent any additional reagents.12,13 A rationale for the structural reorganization is presented in Scheme 2 and involves an initial dearomatizing Cope rearrangement between the indole and the neighboring vinyl moiety to generate macrocycle 11, followed by rearomatization to provide vinylogous acid 12.14 Isomerization of the initially formed E-olefin to the required Z-olefin (14), possible through the intermediacy of dienol 13, enables an intramolecular aldol reaction leading to the product. The ease with which the Cope rearrangement takes place is ascribed to the rigidity of the bridged skeleton as well as the presence of the two electron-withdrawing groups on the benzylic carbon, which may serve to weaken the central σ bond (C11–C12).</p><p>The path toward the target was expected to be facilitated by reduction of the aldehyde, which would serve the dual purpose of obviating its protection and circumventing the undesired skeletal rearrangement. In the event, treatment of tricarbonyl 6 with NaBH(OMe)3 chemoselectively reduced the aldehyde, and, as expected, the resulting alcohol (15) was found to be thermally stable, even at 100 °C (Scheme 3). We then returned our attention to introduction of the vinyl chloride. Condensation of diketone 15 with hydrazine required elevated temperatures and the presence of acetic acid, but gave the desired hydrazone (16) selectively.15 We were pleased to find that exposure of the crude hydrazone to N-chlorosuccinimide in pyridine afforded vinyl chloride 17 in 61% yield. The next task was the oxidation of the indole. While this oxidation was achieved using m-CPBA, the transformation proceeded more cleanly using the milder oxidant, magnesium monoperoxyphthalate (MMPP). Additionally, in order to obtain oxindole 18 in optimum yield, we found it necessary to perform the oxidation in a mixture of trifluoroacetic acid and acetic acid (2:3). In less acidic solvents (e.g., MeOH or AcOH), products of over-oxidation, such as the corresponding 3-hydroxyoxindole, were observed. Having served its role, the primary alcohol was returned to the aldehyde state in nearly quantitative yield using the Dess–Martin periodinane. We were surprised to find that condensation of aldehyde 19 with hydroxylamine provided a variable mixture of separable oximes ((3S)-20 and (3R)-20, 1.6:1 to 4.4:1),16 epimeric at C3. The ready formation of the 3S diastereomer is noteworthy, as this stereochemistry is found in at least one member of the welwitindolinone family.17 Interestingly, the mixture of oxime diastereomers ultimately proved inconsequential, as both diastereomers when subjected to our modified protocol for Kim's oxime rearrangement4,18 converted smoothly to (−)-N-methylwelwitindolinone C isothiocyanate (2a), spectroscopically identical to the natural product.</p><p>With an efficient route to N-methylwelwitindolinone C isothiocyanate (2a) at hand, our next goal was to uncover pathways by which this product could be directly converted to its siblings, N-methylwelwitindolinone C isonitrile (2b) and 3-hydroxy-N-methylwelwitindolinone C isothiocyanate (3a) (Scheme 4). Desulfurization of isothiocyanate 2a with Mukaiyama's oxazaphospholidine (21) gave rise to the first of these targets, isonitrile 2b, in 65% yield.4,19 Conversion of 2a to hydroxyoxindole 3a posed a greater challenge, given the susceptibility of sulfur to oxidants and the need for diastereoselective oxidation. Based on prior work,1b,4 the conformation of the natural product was expected to provide some measure of diastereocontrol during oxidation. Indeed, we found that treatment of 2a with KHMDS followed by Davis' oxaziridine (22) afforded a single compound in 67% yield possessing the exact mass of the expected 3-hydroxyoxindole derivative.20 We were puzzled to find, however, that the 1H and 13C NMR data for this compound did not correspond to those reported in the literature for the natural product,1b suggesting that the oxidation had taken place from the opposite face or perhaps some other transformation had occurred. To definitively establish the identity of the oxidation product, a single crystal X-ray analysis was carried out, and the results showed our synthetic material to possess the very same chemical structure reported by Moore and co-workers for 3-hydroxy-N-methylwelwitindolinone C isothiocyanate (3a). The discrepancy between our spectral data and that reported for the natural product implied that either the structure was misassigned or the data was incorrectly reported. In order to resolve this issue, we requested new NMR data for the authentic sample corresponding to 3a and found that, indeed, the newly recorded 1H and 13C NMR spectra were different from those in the original published work and fully matched those of our synthetic material.21–23</p><p>In summary, we have completed concise syntheses of three members of the welwitindolinone C group of alkaloids. The synthesis of N-methylwelwitindolinone C isothiocyanate (2a) was achieved in 12% overall yield through a longest linear sequence of 16 steps from commercially available starting materials. This compound was then transformed directly into two additional members of the welwitindolinone C group, isonitrile 2b and 3-hydroxyoxindole 3a, thereby enabling correction of the reported spectral data for 3a. With the completion of this work, we have successfully employed our unified synthetic strategy toward members of each of the three structural subclasses comprising the bridged welwitindolinone alkaloids.</p>", "role": "user" }, { "content": "As part of a comprehensive strategy to the welwitindolinone alkaloids possessing a bicyclo[4.3.1]decane core, we report herein concise asymmetric total syntheses of (\\xe2\\x88\\x92)-N-methylwelwitindolinone C isothiocyanate (2a), (\\xe2\\x88\\x92)-N-methylwelwitindolinone C isonitrile (2b), and (\\xe2\\x88\\x92)-3-hydroxy-N-methylwelwitindolinone C isothiocyanate (3a) from a common tetracyclic intermediate. The crucial vinyl chloride moiety was installed through electrophilic chlorination of a hydrazone, but only after adjustment of reactivity to circumvent a facile skeletal rearrangement. Selective desulfurization and oxidation of 2a provided access to 2b and 3a, respectively. Notably, this work provides corrected 1H and 13C NMR spectral data for 3a.", "role": "assistant" } ]

[ { "content": "You are provided with the abstract of a scientific paper and the abstracts of the papers it references. Your task is to write a Related Work section for the main paper. This section should concisely summarize and integrate the key points from the cited abstracts, reflecting how they relate to the main paper's contributions and context. In your summary, use numerical citation markers like [1], [2], etc., to refer to the corresponding papers.\n\nMain Abstract:\nIntel and AMD support the carry-less multiplication (CLMUL) instruction set in their x64 processors. We use CLMUL to implement an almost universal 64-bit hash family (CLHASH). We compare this new family with what might be the fastest almost universal family on x64 processors (VHASH). We find that CLHASH is at least 60 faster. We also compare CLHASH with a popular hash function designed for speed (Google’s CityHash). We find that CLHASH is 40 faster than CityHash on inputs larger than 64 bytes and just as fast otherwise.\n\nCited Abstract(s):\n[1]: In this work, we provide a software benchmark for a large range of 256-bit blockcipher-based hash functions. We instantiate the underlying blockcipher with AES, which allows us to exploit the recent AES instruction set (AESNI). Since AES itself only outputs 128 bits, we consider double-blocklength constructions, as well as (single-block-length) constructions based on RIJNDAEL- 256. Although we primarily target architectures supporting AES-NI, our framework has much broader applications by estimating the performance of these hash functions on any (micro-)architecture given AES-benchmark results. As far as we are aware, this is the first comprehensive performance comparison of multiblocklength hash functions in software.\n\n[2]: PCLMULQDQ, a new instruction that supports GF(2)[x] multiplication, was introduced by Intel in 2010. This instruction brings dramatic change to software implementation of multiplication in GF(2^m) fields. In this paper, we present improved Karatsuba formulae for multiplying two small binary polynomials, compare different strategies for PCLMULQDQ-based multiplication in the five GF(2^m) fields recommended by NIST and conclude the best design approaches to software implementation of GF(2)[x] multiplication.\n\n[3]: This paper describes a new method for efficient implementation of the Galois Counter Mode on general purpose processors. Our approach is based on three concepts: a) having a 64-bit carry-less multiplication instruction in the processor; b) a method for using this instruction to efficiently multiply binary polynomials of degree 127; c) a method for efficient reduction of a binary polynomial of degree 254, modulo the polynomial x^1^2^8+x^7+x^2+x+1 (which defines the finite field of the Galois Counter Mode). The two latter concepts can be used for writing an efficient and lookup-table free software implementation of the Galois Counter Mode, for processors that have a carry-less multiplication instruction. Our approach uses only a generic carry-less multiplication instruction, without any field-specific reduction logic, making the instruction applicable to multiple use cases, and therefore an appealing addition to the instruction set of a general purpose processor. This research played a significant role in the process that eventually led to adding a carry-less multiplication instruction (called PCLMULQDQ) to the Intel Architecture. PCLMULQDQ and six AES instructions are introduced in the new 2010 Intel Core processor family, based on the 32 nm Intel microarchitecture codename ''Westmere''. On the new Westmere processors, the software that implements the methods described here, computes AES-GCM more than six times faster than the current, lookup table-based, state-of-the-art implementation. This new capability adds motivation to using AES-GCM for high performance secure networking.\n\n[4]: In this paper we introduce new methods for computing constant-time variable-base point multiplications over the Galbraith-Lin-Scott (GLS) and the Koblitz families of elliptic curves. Using a left-to-right double-and-add and a right-to-left halve-and-add Montgomery ladder over a GLS curve, we present some of the fastest timings yet reported in the literature for point multiplication. In addition, we combine these two procedures to compute a multi-core protected scalar multiplication. Furthermore, we designed a novel regular ( )-adic scalar expansion for Koblitz curves. As a result, using the regular recoding approach, we set the speed record for a single-core constant-time point multiplication on standardized binary elliptic curves at the (128 )-bit security level.\n\n[5]: This paper presents an efficient and side-channel-protected software implementation of scalar multiplication for the standard National Institute of Standards and Technology (NIST) and Standards for Efficient Cryptography Group binary elliptic curves. The enhanced performance is achieved by leveraging Intel’s AVX architecture and utilizing the pclmulqdq processor instruction. The fast carry-less multiplication is further used to speed up the reduction on the Haswell platform. For the five NIST curves over (GF(2^m) ) with (m ) ( ) ( 163,233,283,409,571 ), the resulting scalar multiplication implementation is about 5–12 times faster than that of OpenSSL-1.0.1e, enhancing the ECDHE and ECDSA algorithms significantly.\n\n[6]: The availability of a new carry-less multiplication instruction in the latest Intel desktop processors significantly accelerates multiplication in binary fields and hence presents the opportunity for reevaluating algorithms for binary field arithmetic and scalar multiplication over elliptic curves. We describe how to best employ this instruction in field multiplication and the effect on performance of doubling and halving operations. Alternate strategies for implementing inversion and half-trace are examined to restore most of their competitiveness relative to the new multiplier. These improvements in field arithmetic are complemented by a study on serial and parallel approaches for Koblitz and random curves, where parallelization strategies are implemented and compared. The contributions are illustrated with experimental results improving the state-of-the-art performance of halving and doubling-based scalar multiplication on NIST curves at the 112- and 192-bit security levels and a new speed record for side-channel-resistant scalar multiplication in a random curve at the 128-bit security level. The algorithms presented in this work were implemented on Westmere and Sandy Bridge processors, the latest generation Intel microarchitectures.\n\n[7]: In this work, we present new arithmetic formulas for a projective version of the affine point representation ((x,x+y x), ) for (x 0, ) which leads to an efficient computation of the scalar multiplication operation over binary elliptic curves. A software implementation of our formulas applied to a binary Galbraith–Lin–Scott elliptic curve defined over the field ( F _ 2^ 254 ) allows us to achieve speed records for protected unprotected single multi-core random-point elliptic curve scalar multiplication at the 127-bit security level. When executed on a Sandy Bridge 3.4 GHz Intel Xeon processor, our software is able to compute a single multi-core unprotected scalar multiplication in 69,500 and 47,900 clock cycles, respectively, and a protected single-core scalar multiplication in 114,800 cycles. These numbers are improved by around 2 and 46 on the newer Ivy Bridge and Haswell platforms, respectively, achieving in the latter a protected random-point scalar multiplication in 60,000 clock cycles.", "role": "user" }, { "content": "The work that lead to the design of the pclmulqdq instruction by Gueron and Kounavis [3] introduced efficient algorithms using this instruction, e.g., an algorithm for 128-bit modular reduction in Galois Counter Mode. Since then, the pclmulqdq instruction has been used to speed up cryptographic applications. Su and Fan find that the Karatsuba formula becomes especially efficient for software implementations of multiplication in binary finite fields due to the pclmulqdq instruction [2] . [1] used the CLMUL instruction set for 256-bit hash functions on the Westmere microarchitecture. Elliptic curve cryptography benefits from the pclmulqdq instruction [4] [7] [6] . Bluhm and Gueron pointed out that the benefits are increased on the Haswell microarchitecture due to the higher throughput and lower latency of the instruction [5] .", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Gene\"].\n\nPlease return the output as a JSON object of the format: {\"Gene\": [\"IGF\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nSmall RNA in situ hybridization in Caenorhabditis elegans, combined with RNA-seq, identifies germline-enriched microRNAs. Over four hundred different microRNAs (miRNAs) have been identified in the genome of the model organism the nematode Caenorhabditis elegans. As the germline is dedicated to the preservation of each species, and almost half of all the cells in an adult nematode are germline, it is likely that regulatory miRNAs are important for germline development and maintenance. In C. elegans the miR35 family has strong maternal effects, contributing to normal embryogenesis and to adult fecundity. To determine whether any particular miRNAs are greatly enriched in the C. elegans germline we used RNA-seq to compare the miRNA populations in several germline-defective strains of adult C. elegans worms, including glp-4(germline proliferation-4), glh-1(germline helicase-1) and dcr-1(dicer-1). Statistical analyses of RNA-seq comparisons identified 13 miRNAs that are germline-enriched, including seven members of the well-studied miR35 family that were reduced as much as 1000-fold in TaqMan qRT PCR miRNA assays. Along with the miR35s, six others: miR-56 (a member of the miR51 family),-70, -244, -260 , -788 and -4813, none of which previously considered as such, were also identified by RNA-seq as germline-enriched candidates. We went on to develop a successful miRNA in situ hybridization protocol for C. elegans, revealing miR35s specifically concentrate during oogenesis in the pachytene region of the gonad, and persist throughout early embryogenesis, while in adult animals neither let-7 nor miR-228 has a germline-bias.", "role": "user" }, { "content": "{\"Gene\": [\"microRNAs\", \"glp-4\", \"miR-228\", \"dicer-1\", \"-4813\", \"let-7\", \"miR-56 (a member of the miR51 family),-70, -244, -260 , -788 and -4813\", \"dcr-1\", \"miR35\", \"miRNAs\", \"germline helicase-1\", \"-244\", \"glh-1\", \"-260\", \"-788\", \"-70\", \"germline proliferation-4\", \"miRNA\"]}", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your response other than the answer.\n\nParagraph: The pathogenesis of rhinoviral infection, along with other ARIs, in exacerbations of airway disease, has been investigated extensively. Impaired host responses to virus infection, a better understanding of the mechanisms of abnormal immune responses and the potential to develop novel therapeutic targets for virus-induced exacerbations have all used the HVC model [12, [31] [32] [33] [34] . Despite previous research work on multiple small molecule antivirals, such as pleconaril which have been tested using both the experimental challenge model and field studies [35] [36] [37] , there is currently no licensed treatment for HRV infections Other compounds have been tested against HRV, such as Vapendavir (BTA798) which prevented the release of viral RNA into the target cell and demonstrated a reduction in peak viral load in the HVC model [38] . A subsequent study in asthmatics was completed and although not published the compound did have a limited effect [39] . Pirodavir an intranasal capsid-binding molecule reached phase 3 clinical trials for HRV prevention and treatment in the 1990s. Although the compound decreased viral replication and shedding, it failed to show a significant reduction in the duration or severity of symptoms [40, 41] . A Protease inhibitor, rupintrivir thats prevents cleavage of viral proteins required for replication was tested in an HRV challenge trial. Rupintrivir was well tolerated and reduced viral loads and respiratory symptoms [36] . However, in studies of natural infection, it did not significantly affect viral loads or symptom severity [42] . Treatments such as zinc-containing products are now widely discredited as demonstrated by the withdrawal of a Cochrane report and JAMA editorial [43] [44] [45] . Current treatment of HRV infections primarily consists of over-the-counter (OTC) medicines to manage symptoms. There is also no licensed vaccine, and while there has been some progress on developing multivalent vaccines [46] , development in this area is hampered by the sheer number of serotypes that need to be covered (at present over 160). Despite HRV being associated with up to 50% of adult asthma exacerbations and up to 80% of childhood exacerbations, there are no HRV-specific asthma therapies [34] . As we better understand the interaction between the virus and the host, new therapies such as the monoclonal antibodies (anti-IgE [omalizumab] and anti-IL-5 [mepolizumab]) along with small molecules carefully targeting specific immune signalling pathways, HRV-specific prophylactic treatment may become practical [47] [48] [49] [50] . In order to prevent exacerbations, the design of new therapeutics could potentially improve efficacy by both directly acting to inhibit viral replication and alleviate the symptoms of asthma and COPD [51] . Influenza virus is a well-known human pathogen and can cause severe morbidity and mortality, particularly in older patients, those with co-morbidities and in the immunocompromised. In 2009, the first pandemic virus of the 21 st century hospitalised 195,000 to 403,000 in the US alone resulting in 8,870 to 18,300 deaths by mid-2010 [52] . A World Health Organization (WHO) global pooled analysis of 70,000 laboratory-confirmed hospitalised H1N1 pandemic patients from 19 countries revealed that of the 9,700 patients admitted to intensive care units, 2,500 died, and that morbid obesity might be a risk factor for hospitalisation and/or death [52] . Obesity was confirmed as a factor associated with a higher likelihood of admission to hospital in influenzainfected patients [53] . The 2009 pandemic was considered mild. However, the classic W shaped age distribution curve of infection for a pandemic virus was observed. That is high mortality in the very young and the old, but an additional spike in death amongst the \"young and healthy\". The pandemic, as did previous outbreaks, occurred in successive waves, but despite national policies favouring the use of antiviral drugs, few patients received these before admission to hospital, and many were given antibiotics [54] . The lack of real, or perceived, \"real world\" efficacy of currently available antivirals leads to the overuse of antibiotics and the subsequent problems that may arise [55] [56] [57] . The yearly seasonal morbidity and mortality of influenza results in hospitalisation and death mainly among the high-risk groups. Each year epidemics of seasonal influenza are estimated to result in about 3 to 5 million cases of severe illness, and about 290,000 to 650,000 deaths worldwide [58] . In first world / industrialised countries, most deaths associated with influenza occur among people age 65 or older [59] . Clinics and hospitals, in many countries, can be overwhelmed during peak illness periods, and there can be substantial economic cost [60] . The virus itself has been well characterised, and the two surface proteins, the haemagglutinin (HA) and the neuraminidase (NA) are important in both vaccine and antiviral development [61] . The effects of seasonal influenza epidemics in developing countries are not fully known, but research estimates that 99% of deaths in children under five years of age with influenza-related lower respiratory tract infections are found in developing countries [59, 62] . Currently, vaccines and antivirals exist for the prevention and treatment of influenza, but both have limitations in efficacy due to the rapid evolution of the virus as it mutates on a yearly basis and the sudden unexpected emergence of pandemic influenza strains. The effectiveness of recent annual influenza vaccines (to date mostly based on the HA, and rarely the NA surface glycoproteins) has languished between 37% and 70% over successive influenza seasons. In particular, the failure of the vaccine across the winter season of 2014-2015, where the overall adjusted effectiveness was 23% [95% confidence interval 14, 31] [63] is memorable. In a mismatched year, the mortality rate is increased in the most at-risk populations [64, 65] . The problem of ensuring that the seasonal vaccine is correctly matched to the upcoming circulating strain highlights the need for rapid development of inter-seasonal/universal vaccines and also the need for a way of testing their efficiency rapidly and accurately before the lengthy and expensive mass production is engaged which takes many months [66, 67] . Antiviral drugs exist of which currently the NA inhibitor oseltamivir is most commonly used. This is active against all known NA subtypes of influenza, and one would, therefore, assume against all influenza strains. They may have decreasing effect with the emergence of resistant influenza strains in which NA protein changes preventing efficient oseltamivir binding and thus its ability to inhibit the essential activity of the viral NA. For example, one genetic mutation known as 'H275Y'a substitution of histidine for tyrosine at NA position 275 -confers an evolutionary advantage to the virus including the 2009 H1N1 influenza [68] . During the 2013-2014 influenza season, 59 (1.2%) of 1,811 influenza A(H1N1) pdm09 virus isolates in 20 of 50 US states had the H275Y oseltamivir resistance substitution. No isolates were resistant to zanamivir [69] . Although animal studies have demonstrated limited transmission of mutant viruses [70, 71] , it is thought that the rise of oseltamivir resistance may be due to community transmission [72, 73] rather than the H275Y mutation becoming fixed in the viral genome. Asystematic systematic review and meta-analysis of published data from 2000 onwards concluded that most RSV-associated child deaths occur particularly in preterm infants and in infants up to 1-year of age [62, 74] . An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group [75] . The RSV-specific monoclonal antibody palivizumab is approved for prevention of serious LRI caused by RSV in susceptible infants. Economic benefit in a UK health setting has not been shown due to the high cost and lack of benefit on serious outcomes [76] . A single-centre cohort study of 22 infants showed no difference in treatment outcomes for patients receiving palivizumab when compared to patients only receiving \"standard of care\" treatment [77] . Despite the lack of evidence for clinical benefit, post-licensure data supports the use of palivizumab for reducing RSV-associated hospitalisations in premature infants under 33 weeks and in children with chronic lung and heart diseases [78] . Importantly, palivizumab resistant mutant virus has rarely been isolated in clinical specimens [79] . The RSV treatment ribavirin is limited due to difficulty with aerosol delivery, cost and potential harm to healthcare workers, despite off-label treatment of immunocompromised patients being reasonably successful. In the immunocompromised, therapy with a concomitant immunoglobulin or palivizumab has had mixed results, probably due to the difficulty of knowing when to initiate treatment [80] . Despite the call for the accelerated development of prevention and treatment strategies for an effective RSV vaccine for children [81] , research has stalled for decades since the death in the 1960s of two subjects in a clinical study. These subjects were infected with a communityacquired RSV infection after receiving the US National Institutes for Health (NIH's) formalin-inactivated, alumprecipitated RSV candidate vaccine. In contrast to influenza for which vaccines to date have shown themselves to be moderately effective but in need of improvement, RSV vaccines require substantially more research. There is currently no licensed vaccine for RSV; the most advanced candidate vaccine recently failed to show efficacy in a field study [82] . Effective treatments are urgently required. RSV is, even amongst healthcare professionals, considered a childhood disease and other confounders have obscured the understanding of the consequences of RSV in adults. RSV is poorly understood as a disease in the elderly [83] , and while the morbidity and mortality in children are of importance, it has been clearly shown that RSV has a comparable health burden to influenza in the elderly [84] . As an example, a recent study was conducted on adult (≥18 years) patients admitted to an emergency department with suspected ARI during 2013-2015 (N = 3743). Multiplex PCR was used to diagnose the cause of the respiratory infection. Eighty-seven patients were identified with RSV. A comparator group with influenza (n=312) was utilised. Based on a 20-day all-cause mortality endpoint, adult patients were less likely to be diagnosed with RSV than with flu (2.3 vs 8.3%, respectively), also they were older, often diagnosed with pneumonia, COPD, hypoxemia, and bacterial co-infection. RSV infection in the elderly was significantly associated with a greater risk of death than seasonal influenza, adjusted for potential confounders and comorbidities. [85] \n\nThe clinical significance of viral/bacterial co-infections has long been a controversial topic. While severe bacterial pneumonia following influenza infection has been well described, associations are less clear among infections caused by viruses common in young children; secondary infections due to other viruses are less well understood and has been reviewed by others [86] . Although assessing the overall contribution of bacteria to disease severity is complicated by the presence of many confounding factors in clinical studies, understanding the role of viral/bacterial co-infections in defining the outcome of paediatric ARI may potentially reveal novel treatment and prevention strategies, improving patient outcomes [33, [86] [87] [88] [89] [90] [91] [92] [93] [94] [95] . A recent (2017) publication considered the role of bacterial colonisation with Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis during symptomatic and asymptomatic viral upper respiratory infection in the nasopharynx of 4 to 7-year-old children during URI and when well. Using a multiplex PCR, virus was detected in about 80% of upper respiratory tract infections (URIs) in children and is also detectable in the nasopharynx of 30% of asymptomatic children. All three bacteria \"levels\" were higher during acute URI visits compared to asymptomatic surveillance visits by the children. Of note, however, is that even during asymptomatic follow-up visits, if the virus was present, all bacteria were detected at higher levels [96] . It is worth noting that the presence of confounding infections, can mask the importance of the primary aetiology. Taylor et al. [8] report the incidence of HBoV following its identification in 2005 from the respiratory tract samples of children, as an important respiratory pathogen in children. However, the role of this virus on its own as a pathogen of significance was initially unclear, co-infection with other viruses or bacteria was common and confounding. Moesker et al. [97] studied whether HBoV alone could cause acute respiratory infections in children. Using Next Generation Sequencing (NGS), they were able to exclude co-infections amongst those admitted to intensive care unit and studied HBoV viral loads. Of the 990 children who tested positive for a respiratory virus by RT-PCR, HBoV and RSV were detected in 178 and 366 of the children respectively. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the intensive care. Seven HBoV-infected cases with severe ARI had no other co-infection (7/49, 14%). Importantly, these children did not have another detectable virus as determined by highly sensitive NGS. Also, they had much higher HBoV loads than other patients positive for HBoV, i.e., those with a co-infection. Although small, this study provides strong support that HBoV can cause serious ARI in children with no viral and bacterial co-infections. The history of the human viral challenge model Since Sir Edward Jenner performed the first documented HVC study with smallpox on the 14 th of May 1796 the usefulness of such studies has been apparent [98] . More than a century later, Sir Christopher Andrews returned from the US in 1931 he had observed the use of chimpanzees in the study of influenza. The funding for similar work in the UK was insufficient, and therefore Sir Christopher enrolled students from St Bartholomew's Hospital in London. He explained the next best thing would be a \"Bart's\" student as \"they were cheaper than chimpanzees\".\n\nQuestion: What is the mechanism of action for rupintrivir?", "role": "user" }, { "content": "prevents cleavage of viral proteins required for replication", "role": "assistant" } ]

[ { "content": "You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.\n\nQuestion: What is the result of the interaction between TSC1 and PLK1?\n\nContext: Phosphorylated hamartin interacts with Plk1 independent of tuberin with all three proteins present in a complex.\nHamartin negatively regulates the protein levels of Plk1.\nFinally, Tsc1(-/-) mouse embryonic fibroblasts (MEFs) have increased number of centrosomes and increased DNA content, compared to Tsc1(+/+) cells.\nBoth phenotypes are rescued after pre-treatment with the mTOR inhibitor rapamycin. RNAi inhibition of Plk1 in Tsc1(-/-) MEFs failed to rescue the increased centrosome number phenotype. These data reveal a novel subcellular localization for hamartin and a novel interaction partner for the hamartin/tuberin complex and implicate hamartin and mTOR in the regulation of centrosome duplication.", "role": "user" }, { "content": "Phosphorylated TSC1 (hamartin) interacts with Plk1 independent of TSC2 (tuberin), with all three proteins present in a complex, and negatively regulates the protein levels of Plk1, to control centrosome duplication.", "role": "assistant" } ]

[ { "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSelective Regulation of Aromatase Expression for Drug Discovery\n\nPaper sections:\n1. Introduction\n<p>Estrogens are biosynthesized from androgens by the cytochrome P450 enzyme complex called aromatase [1;2]. The highest levels of enzyme are present in the ovaries of premenopausal women, in the placenta of pregnant women, and in the peripheral adipose tissues of postmenopausal women and of men. Aromatase activity has also been demonstrated in breast tissue in vitro [3–5], and expression of aromatase is highest in or near breast tumor sites [4;6]. Regulation of aromatase in various tissues is complex, and several tissue-specific promoter regions have been identified upstream from the CYP19 gene [2;7;8]. Promoter I.1 is the major promoter used in placental tissues and is the farthest upstream. The PII promoter is utilized in the ovary and in breast cancer tissues and contains a cAMP response element. Promoters I.3, I.4, I.6, and I.7 are the promoters used in extraglandular sites. Promoter PI.4 is the primary promoter used in normal adipose tissue and is responsive to glucocorticoids and cytokines such as IL-1β, IL-6 and TNFα.</p><p>In breast cancer tissues, an increased expression of aromatase cytochrome P450 is observed due to utilization of multiple promoter regions for gene expression. In the normal breast cells, aromatase expression is primarily derived by the tissue-specific promoter I.4 for transcription, whereas expression from breast cancer patients is primarily derived from the utilization of promoter I.3 and promoter II [9]. As a result of the use of the alternate promoters, the regulation of estrogen biosynthesis switches from one controlled primarily by glucocorticoids and cytokines to a promoter regulated through cAMP-mediated pathways, and the prostaglandin PGE2 increases intracellular cAMP levels and stimulates estrogen biosynthesis [9].</p><p>Research in our laboratories focuses on the development of novel therapeutic interventions targeting tissue-specific expression of aromatase. Our small molecule approach utilizes drug discovery technologies to develop novel sulfonanilides as selective agents regulating aromatase expression [10–14]. A second pharmacological approach involves the development of siRNA molecules that interfere with aromatase expression [10]. This manuscript reviews our recent publications in this area and presents preliminary results.</p>\n\n2. Novel Sulfonanilide Analogs for Suppression of Aromatase Expression and Activity\n<p>Previously, we demonstrated that COX-2 inhibitors nimesulide, N-(2-phenoxy-4-nitrophenyl)-methanesulfonamide, and NS-398, N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide, suppress aromatase activity in breast cancer cells by suppressing aromatase transcription [15]. Interestingly, these two agents share very similar chemical structures (Figure 1). In addition, introduction of a methyl group at the N atom of the sulfonamide group to the COX-2 inhibitor nimesulide resulted in no COX-2 inhibitory activity [16]. This structural modification was utilized in our drug design of novel sulfonanilide derivatives of nimesulide and NS-398. The nitro group at the 4 position of the sulfonanilides was retained and modifications of the sulfonamide and of the 2 position group were made to generate the targeted libraries of new compounds (Figure 1) [11].</p><p>Evaluations of the synthetic compounds were performed in both SK-BR-3 breast cancer cells, which produce aromatase expression from promoter II and I.3 mediated by cAMP [12]. SK-BR-3 cells grown in defined media containing DMEM/F12 media, 1.0 mg/mL human albumin, 5.0 mg/L human transferin and 5.0 mg/L bovine insulin were treated with the synthetic compounds for 24 hours. Cells were then incubated for three hours with fresh media, and aromatase activity measured by the tritiated water release assay [12]. Many compounds significantly decreased aromatase activity in SK-BR-3 cells at 2.5µM (Figure 2), and those compounds with enhanced activities were further evaluated for selective regulation of aromatase expression.</p><p>Dose-response studies of the effects on aromatase activity were performed in SK-BR-3 cells on six compounds. All six compounds exhibited dose-response curves for suppression of aromatase activity (Figure 3), and the corresponding IC50 values range from 0.33 to 2.68 µM. Furthermore, real time PCR experiments demonstrated that these compounds significantly decreased CYP19 gene expression at 5µM in SK-BR-3 cells [12]. The results of the cellular aromatase assay demonstrated that a one carbon extension at the 2-position of nimesulide results in significant increase in suppression of aromatase in breast cancer cells compared with nimesulide.</p><p>A combinatorial chemistry approach was used to generate diversely substituted nimesulide derivatives (Figure 4) by parallel synthesis [13;14]. This innovative technology of producing libraries of structurally related compounds is particularly beneficial in the step of lead optimization, facilitating structural modifications of a lead scaffold to enhance pharmacological activity, improve pharmacokinetic properties, and/or reduce unwanted side effects. Their pharmacological evaluation as agents for suppression of aromatase activity in breast cancer cells was further explored in the SK-BR-3 breast cancer cell lines and in MCF-7 cells transfected with the aromatase gene. A ligand-based pharmacophore model identified four chemical features critical for biological activity, namely, the central aromatic ring, one hydrophobic function (Figure 4, position A) and two hydrogen bond acceptors (Figure 4, positions C and D).</p>\n\n3. RNA Interference of Aromatase Expression\n<p>Newly developed RNA interference (RNAi) technology was utilized to further probe the interactions between aromatase and cyclooxygenases in breast cancer [10]. RNAi technology permits transient suppression of the levels of endogenous proteins in mammalian cells by enhancing the degradation of target mRNA. One RNAi approach involves transfection of 21–23 nucleotide double-stranded, short interfering RNAs (siRNA) into mammalian cells. These siRNAs are then incorporated into the RNA-inducing silencing complex (RISC), and RISC unwinds the siRNA duplex using ATP. The unwound, single-stranded antisense strand guides RISC to mRNA that has a complementary sequence, and the complex results in the endonucleolytic cleavage of the target mRNA.</p><p>Short interfering RNAs (siRNA) were designed to target either human CYP19 mRNA or human COX-2 mRNA. The effects of siAROM and siCOX2 on aromatase enzyme activity in SK-BR-3 cells were examined (Figure 5). The transfection of siAROM resulted in suppression of basal levels of aromatase activity by greater than 90% compared with cells transfected with a nonspecific control siRNA or untreated cells. Also shown in this figure, the siCOX2 also resulted in suppression of aromatase activity by approximately 67%. Furthermore, the administration of PGE2 to cells treated with the siRNAs results in antagonism of only the siCOX2 and restores aromatase activity to untreated levels (Figure 5) [10].</p><p>The effect of the siAROM on aromatase enzyme activity in several cancer cells were also examined (Figure 6). The siAROM silenced aromatase enzyme activity by greater than 90% in the SK-BR-3 human breast cancer cell line, in MCF-7 human breast cancer cells transfected with the aromatase gene, and in the JAr human choriocarcinoma cell line. The suppression of aromatase enzyme activity was greater than 80% in the JEG-3 human choriocarcinoma cell line.</p>\n\n4. Discussion\n<p>Two pharmacological approaches of novel therapeutic interventions targeting tissue-specific expression of aromatase have been recently developed in our laboratories. Our small molecule approach utilizes drug discovery technologies to develop novel sulfonanilides as selective agents regulating aromatase expression. Targeted synthetic libraries of novel sulfonanilide analogs, derived from COX-2 inhibitiors nimesulide and NS-398, decreased CYP19 mRNA expression and suppressed aromatase enzyme activity in SK-BR-3 breast cancer cells in a dose dependent manner. Furthermore, N-methyl sulfonanilide analogs without COX-2 inhibitory activity showed similar effects of decreased CYP19 mRNA expression and suppression of aromatase activity. Thus, these results suggest that the novel sulfonanilides targeting aromatase expression may be valuable tools for selective regulation of aromatase in breast cancer.</p><p>Investigations using RNA interference (RNAi) technology confirmed the interactions between aromatase and cyclooxygenases in breast cancer. Short interfering RNAs (siRNA) were designed against either human CYP19 mRNA or human COX-2 mRNA. Treatment of breast cancer cells with siAROM suppressed CYP19 mRNA and aromatase enzyme activity. Treatment with siCOX2 downregulated the expression of COX-2 mRNA and also resulted in suppression of aromatase mRNA. The administration of PGE2 to cells treated with the siRNAs results in antagonism of only the siCOX2 and restores aromatase activity to untreated levels. Finally, the siAROM was also very effective in silencing aromatase enzyme activity in human breast cancer cells in culture and in human choriocarcinoma cells in culture.</p><p>The regulation of aromatase in breast cancer involves complex autocrine and paracrine interactions, resulting in significant consequences on the pathogenesis of hormone-dependent breast cancer. The breast cancer tissue microenvironment can influence the extent of estrogen biosynthesis and metabolism, resulting in altered levels of hormonally active estrogens and therefore influencing breast tumor development and growth. Furthermore, novel sulfonanilides and various RNAi technologies targeting aromatase expression may be valuable tools for selective regulation of aromatase in breast cancer and could be developed into the first generation of Selective Aromatase Modulators for the treatment of hormone-dependent breast cancer.</p>\n\n\n<p>Presented at the IX International Aromatase Conference, Shanghai, China, October 14–17, 2008.</p>", "role": "user" }, { "content": "Aromatase is a particularly attractive drug target in the treatment of hormone-responsive breast cancer, and aromatase activity in breast cancer patients is greater in or near the tumor tissue compared with the normal breast tissue. Complex regulation of aromatase expression in human tissues involves alternative promoter sites that provide tissue-specific control. Previous studies in our laboratories suggested a strong association between aromatase (CYP19) gene expression and the expression of cyclooxygenase (COX) genes. Additionally, COX selective inhibitors can suppress CYP19 gene expression and decrease aromatase activity. Our current hypothesis is that pharmacological regulation of aromatase can act locally to decrease the biosynthesis of estrogen and may provide additional therapy options for patients with hormone-dependent breast cancer. Two pharmacological approaches are being developed, one approach utilizing small molecule drug design and the second approach involving mRNA silencing technology. The small molecule drug design approach focuses on the synthesis and biological evaluation of a novel series of sulfonanilide analogs derived from COX-2 selective inhibitors. Combinatorial chemistry approaches were used to generate diversely substituted novel sulfonanilides. The compounds suppress aromatase enzyme activity in SK-BR-3 breast cancer cells in a dose and time dependent manner, and structure activity analysis does not find a correlation between aromatase suppression and COX inhibition. Real-time PCR analysis demonstrates that the sulfonanilide analogs decrease aromatase gene transcription in breast cells. Furthermore, the sulfonanilide compounds selectively decrease aromatase gene expression in several breast cancer cells, without exhibiting cytotoxic or apoptotic effects at low micromole concentrations. A ligand based pharmacophore model for selective aromatase modulation (SAM) by the novel sulfonanilides identified an aromatic ring, two hydrogen bond acceptors, and a hydrophobic function as four key chemical features. In the second approach, short interfering RNAs (siRNA) were designed targeting human aromatase mRNA. Treatment of breast cancer cells with siRNAs targeting aromatase (siAROMs) completely masked the aromatase enzyme activity and resulted in suppression of CYP19 mRNA. Thus, these results suggest that the novel sulfonanilides and the siRNAs targeting aromatase expression may be valuable tools for selective regulation of aromatase in breast cancer.", "role": "assistant" } ]

[ { "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: This is the first attempt to introduce SMG block into CNN architecture.\n\nKeyphrases: classification images text\n\nDataset description:\nLEAF-QA: LEAF-QA, a comprehensive dataset of 250,000 densely annotated figures/charts, constructed from real-world open data sources, along with ~2 million question-answer (QA) pairs querying the structure and semantics of these charts. LEAF-QA highlights the problem of multimodal QA, which is notably different from conventional visual QA (VQA), and has recently gained interest in the community.\nTHEODORE: Recent work about synthetic indoor datasets from perspective views has shown significant improvements of object detection results with Convolutional Neural Networks(CNNs). In this paper, we introduce THEODORE: a novel, large-scale indoor dataset containing 100,000 high- resolution diversified fisheye images with 14 classes.\nImageNet: The ImageNet dataset contains 14,197,122 annotated images according to the WordNet hierarchy. Since 2010 the dataset is used in the ImageNet Large Scale Visual Recognition Challenge (ILSVRC), a benchmark in image classification and object detection.\nNAS-Bench-101: NAS-Bench-101 is the first public architecture dataset for NAS research. To build NASBench-101, the authors carefully constructed a compact, yet expressive, search space, exploiting graph isomorphisms to identify 423k unique convolutional architectures.\nCIFAR-10: The CIFAR-10 dataset (Canadian Institute for Advanced Research, 10 classes) is a subset of the Tiny Images dataset and consists of 60000 32x32 color images. The images are labelled with one of 10 mutually exclusive classes: airplane, automobile (but not truck or pickup truck), bird, cat, deer, dog, frog, horse, ship, and truck (but not pickup truck).\n\nOptions:- A: LEAF-QA B: THEODORE C: ImageNet D: NAS-Bench-101 E: CIFAR-10", "role": "user" }, { "content": "[\"ImageNet\", \"CIFAR-10\"]", "role": "assistant" } ]

[ { "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nDynamics of methyl radical formation by 266 nm photolysis of xylenes and mesitylene\n\nPaper sections:\n\n<p>observation be attributed to the formation of the methyl radical from alternate channels.</p><p>The total kinetic energy distribution profiles were rationalized based on the dissociation of {sp 2 }C-C{sp 3 } bond in the cationic state, wherein the {sp 2 }C-C{sp 3 } bond dissociation energy is lowered relative to the ground state.</p><p>The dissocaiton in the cationic state follows a resonant three-photon absorption process, resulting in maximum total kinetic energy of about 1.6 -1.8 eV for the photofragments. A results in. Fitting of the TKER distribution profiles to empirical function reveals that the dynamics of {sp 2 }C-C{sp 3 } bond dissociation is insensitive to the position of substitution but marginally dependent on the number of methyl groups.</p>\n\nINTRODUCTION\n<p>Benzene and its derivatives are prototypical molecules used frequently for studying photodissociation dynamics, [1][2][3][4][5][6] as they serve as building blocks of complex (bio)molecules and various factors such as the presence of the aromatic chromophore, type and position of the substitution influences the photophysical properties of these molecules. Alkylbenzenes such as toluene and xylenes have very important applications in combustion chemistry as anti-knock agents. 7,8 Even though the electronic structure of alkylbenzenes is similar to that of benzene owing to the π electron structure, the substitution of the methyl group changes the symmetry of the states and selection rules, thereby altering the photophysics and photochemistry, in comparison to benzene. 9,10 In case of benzene, a single photon absorption in the range of 190 to 270 nm leads to several radiative and non-radiative decay processes such as photodissociation and isomerization. 2 Photodissociation in case of toluene and xylene results primarily in the α-H atom elimination, which leads to the formation of benzyl radical either by direct dissociation from the excited state or indirect dissociation after internal conversion to the vibrationally hot ground state 3,[11][12][13] The presence of the aromatic chromophore increases the probability of multiphoton absorption which enables the molecules to access the ground and excited states of the cation. [14][15][16] Earlier experiments on the dynamics of methylbenzene cations have been investigated mostly using photoelectron spectroscopy. In the case of 1,3,5-cycloheptatriene and toluene, only the H-atom loss channel opens up during dissociative photoionization, leading to the formation of tropylium and benzyl cations. 17 On the other hand, the loss of methyl fragment is a prominent product channel in the case of xylenes. [18][19][20] However, reports on direct detection of methyl fragment following the photodissociation of methyl substituted benzene are sparse and especially, the 266 nm photolysis of alkylbenzenes in the gas-phase is conspicuously missing in the literature. In xylenes and mesitylene the {sp 2 }C-C{sp 3 } bond dissociation (around 4.50 eV) 21 and the S0 ⟶S1 excitation (around 4.60 eV) 22,23 energies are marginally lower than the 266 nm (4.66 eV) excitation energy. This leads to an interesting scenario of competing pathways in the molecules and provides motivation to investigate 266 nm photodissociation of methyl benzenes using velocity map imaging technique. Along with this, effect of the position of methyl substitution on the aromatic ring and the effect of the number of methyl substitutions on photodissociation dynamics has also been explored in this work.</p>\n\nMETHODOLOGY\n<p>The setup for carrying out velocity map imaging experiments is described elsewhere. 24 Briefly, a skimmed molecular beam of helium (3 atm) doped with the desired reagent (oxylene, m-xylene, p-xylene, or mesitylene; Sigma Aldrich) was intersected by counterpropagating pump (266 nm) and probe (333.45 nm) lasers. The ensuing cations were imaged using a four-electrode velocity map imaging (VMI) spectrometer fitted with a 50 mm diameter two-stage microchannel plate (MCP) and a P47 phosphor screen (MCP-50DLP47VF; Tectra). In the time-of-flight (TOF) mode, the front-plate of the MCP is grounded, the back-plate and the phosphor screen are held around +1500 V and an RC circuit was used to extract the signal which is processed with a 350 MHz preamplifier (SR445A;</p><p>Stanford Research Systems). In the imaging mode, the front-plate of the MCP detector is gated with a 75 ns pulse of -1000 V (HTS 40-06-OT-75; Behlke), while the back-plate and the phosphor are held at +800 and +3000 V, respectively. The gate time of the front plate is adjusted to match the arrival time of the desired ion. The image on the phosphor screen was recorded with a high-performance, easy-to-use USB, GigE CMOS camera (IDS Imaging Development Systems) and the raw images were acquired using NuAcq software 25 with 50,000 shots. The aquired images were further processed (symmetrized) using ImageJ software 26 and Abel inversion was carried out by the Basis Set Expansion method (BASEX) to extract the kinetic energy spectrum. 27 In the present set of experiments the pump laser (266 nm) is the fourth harmonic of an Nd: YAG laser (Brilliant-B; Quantel) and the probe laser (333.45 nm) is the frequency-doubled output of a tunable dye laser (LiopStar-HQ; LIOP-TEK) pumped with the second harmonic of an Nd: YAG laser (Brilliant-B; Quantel). The plane of polarization of both the lasers is kept parallel to the plane of the detector. The delay between the pump and probe lasers is approximately 10 ns. The timings for the opening of the pulsed nozzle, the firing of the two lasers (both flashlamp and Q-switch triggers), gating the frontplate of the MCP detector, and the opening of the camera shutter were electronically controlled with an 8-channel digital delay pulse generator (DDG-9520; Quantum Composers). The energy of the pump and the probe lasers were kept around 1 mJ/pulse and 500 μJ/pulse, respectively. The laser flux was optimized such that signal intensity was negligible for the methyl fragment in the absence of probe laser.</p>\n\nRESULTS and DISCUSSION\n<p>The mass spectra presented in Figure 1, following 266 nm photolysis of three xylene isomers and mesitylene, show intense peaks corresponding to the molecular ion peak at 106</p><p>[C6H4(CH3)2] + and 120 [C6H4(CH3)3] + amu, respectively. Further, extensive fragmentation leading to the appearance of CnHm (n=2-6) can be seen in almost all the cases, except for mxylene, wherein the fragmentation appears to be less efficient. However, in all the other cases the loss of one methyl group is the dominant fragmentation pathway. This loss of the methyl fragment was probed using the well-known 2+1 REMPI method with 333.45 nm excitation of its ground (ν=0) state, 28 and the resulting pump-probe mass spectra (shown as greentraces in Figure 1) show the appearance of the methyl fragment at 15 amu. Comparison of the pump-only mass spectra (red-traces in Figure 1) with the pump-probe mass spectra (green-traces in Figure 1), in general, suggests that the probe laser enhances the intensity of the CnHm (n=1-4) fragments, while lowering the intensity corresponding to n=5, 6 fragments, 29 shows significant intensity close to the center indicating that these cations have near-zero kinetic energy. In comparison, the velocity map images of methyl fragment are more diffused and exhibit a central blob-like feature indicating a broader kinetic energy distribution. 24 The isotropic nature of the images can be attributed to{sp 2 }C-C{sp 3 } bond cleavage via predissociation pathway, which has a longer time scale than rotational reorientation time, 30 unlike the case of methyl iodide or dimethyl sulfide. 31,32 The KER (Kinetic Energy Release) 1). These results suggest that the dynamics of co-fragment formation are different for the two sets (o-xylene and p-xylene versus m-xylene and mesitylene). Therefore, in the case of m-xylene and mesitylene the differences in the TKER profiles of the methyl group and the co-fragment are attributed to probe induced dissociation following pump excitation of the parent molecule and/or probe induced sequential dissociation (loss methyl group from hot neutral co-fragment). 29 The mismatch in the TKER plots (see Figure 2B) is more pronounced in the case of m-xylene, and the peak is shifted to lower energy in comparison with other co-fragments (see Figure 2F) as a result of probe induced fragmentation due to 'accidental resonance'. Further, experiments on xylyl radicals have shown a difference for the m-xylyl radicals compared to the other isomers. The largest change in geometry occurs in meta substitution, which facilitates the faster deactivation owing access to several conical intersections. 33 Further, the absorption of the probe laser photon by the parent molecular cation could lead to direct dissociation, which can contribute to lowering of the kinetic energy distribution, as seen in the case of mxylene.</p><p>The generalized energy level scheme for the formation of CH3 radicals in all four compounds is shown in Figure 3. The values corresponding to bond dissociation energies in the neutral and cationic ground states were calculated using the G3B3 34 method with Gaussian-16, 35 experimentally measured ionization energies 22,36 and S0⟶S1 transition energies 22,23 are listed in Table 2. In xylenes and mesitylene the {sp 2 }C-C{sp 3 } bond dissociation energy in the neutral ground state [BDE(S0), see Table 2] is about 0.2 eV lower than the 266 nm (4.66 eV) photon energy. Thus, {sp 2 }C-C{sp 3 } dissociation in the S0 state would result in TKER of about 0.2 eV, which is much lower than the experimentally observed value (see Figure 2). In all the four compounds, the S0⟶S1 transition energy is marginally less than 4.66 (266 nm), therefore absorption of the first 266 nm photon results in vibrionic excitation just above the band-origin (0 0 0 ) of the S1 state, which serves as a resonant intermediate level for the subsequent absorption of the second 266 nm photon leading to ionization, which however, will not result in the {sp 2 }C-C{sp 3 } dissociation. Absorption of the third photon excites the parent molecule above the {sp 2 }C-C{sp 3 } bond dissociation energy in the cationic ground state [BDE(D0), see Table 2], resulting in excess energy, which is termed as 𝐸 𝑇 𝑚𝑎𝑥 , and in the present scenario based on the energy level scheme shown in Figure 3, the value of 𝐸 𝑇 𝑚𝑎𝑥 can be calculated using equation (1).</p><p>The calculated 𝐸 𝑇 𝑚𝑎𝑥 values are also listed in Table 2 and range from 1.62 to 1.77 eV. Further, the TKER distribution profiles of the methyl fragments were fitted to an empirical function given by equation (2). [37][38][39] 𝑃(𝐸 𝑇 ) = 𝐶 • (𝐸 𝑇 ) 𝑎 • (𝐸 𝑇 𝑚𝑎𝑥 − 𝐸 𝑇 ) 𝑏</p><p>where [𝑃(𝐸 𝑇 )] is the translational energy distribution function, 'a', 'b' are adjustable parameters, while 'C' is a normalization constant and 𝐸 𝑇 𝑚𝑎𝑥 is the maximum translational energy available for the fragments in the center-of-mass frame after dissociation. However, it must be pointed out that 𝐸 𝑇 𝑚𝑎𝑥 also includes the electron kinetic energy after ionization, therefore 𝐸 𝑇 𝑚𝑎𝑥 is the sum of kinetic energies of the electron and the mass fragments. Fits to the TKER distribution profiles of the methyl fragment with equation 2 by fixing the 𝐸 𝑇 𝑚𝑎𝑥 value (calculated by equation 1, see Table 2) resulted in a value of 'a' in the range of 0.9 -1.1.</p><p>Therefore, global analysis was performed by fixing the value of 'a' as 1in equation (2). Figure 4 shows the fitting of the empirical function (equation 2) to the TKER distribution profiles for all four cases, the agreement between the experimental data and the fits are excellent. It is known that a=1 in equation ( 2) indicates non-statistical TKER distribution. 39 Moreover, deviations on the higher kinetic energy side, originating due to multiphoton detection of the methyl radical, which appear to be only marginal in the present case, have been neglected. 39 Interestingly, the value of 'b' (from equation 2) are very similar for all the three isomers of xylene (4.87, 4.61 and 4.32 for ortho, meta and para isomers, respectively) and moderately different from mesitylene (5.20), which suggests that overall dynamics of methyl radical formation is insensitive to the position of substitution in xylenes but marginally dependent on the number of methyl groups.</p>", "role": "user" }, { "content": "The 266 nm photodissociation of three xylene isomers and mesitylene leading to the formation of methyl radical was examined. The kinetic energy release profiles for the methyl radical were almost identical for all the three isomers of xylene and mesitylene, while substantial differences were observed for the corresponding profiles of the co-fragment produced by loss of one methyl group. This", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nA controlled trial of bladder drill and drug therapy in the management of detrusor instability.\nAbstract 1:\nnan\n\n\nTitle 2:\nControlled trial of bladder drill for detrusor instability.\nAbstract 2:\nnan\n\n\nTitle 3:\nA randomized trial of behavioral management for continence with older rural women.\nAbstract 3:\nUrinary incontinence (UI) is a commonly underreported and underdiagnosed condition. The purpose of this trial was to implement and evaluate behavioral management for continence (BMC), an intervention to manage symptoms of UI with older rural women in their homes. Participants were randomized into BMC or a control group, and 178 were followed for between 6 and 24 months. The intervention involved self-monitoring, bladder training, and pelvic muscle exercise with biofeedback. The primary outcome variable-severity of urine loss-was evaluated by pad test. Secondary variables were episodes of urine loss, micturition frequency, voiding interval, quality of life, and subjective report of severity. Urine loss severity at baseline evaluation was not significantly different in the two groups. But using the generalized linear mixed model analysis, at the four follow-ups, severity of urine loss, episodes of urine loss, quality of life, and subjective report of severity were significantly different. At 2 years the BMC group UI severity decreased by 61%; the control group severity increased by 184%. Self-monitoring and bladder training accounted for most of the improvement. The results support the use of simple strategies based on bladder diaries before implementing more complex treatments.\n Copyright 2002 John Wiley & Sons,\n\n\nTitle 4:\nThe effects of treatment of urinary incontinence in general practice.\nAbstract 4:\nA total of 110 women who had reported urinary incontinence to their general practitioners were randomly assigned to a treatment or control group. Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence. The results were measured after 3 and 12 months by a research assistant on the basis of a constructed severity scale, an incontinence diary, and a comparison by the patients themselves of their previous and current conditions. After 3 months the control group were given the same treatment. After a further 3 and 12 months, they were assessed in exactly the same way as the treatment group. After 3 months about 60% of the patients were either dry or only mildly incontinent; the mean number of wet episodes had gone down from 20 to 7, and 74% of the women felt improved or cured. These results were later corroborated by the control group. After 12 months this successful outcome was improved slightly further. It may be concluded that the majority of women with incontinence can be successfully treated by the general practitioner. The effect of this treatment continues after one year.\n\n\nTitle 5:\nSimplified bladder training augments the effectiveness of tolterodine in patients with an overactive bladder.\nAbstract 5:\nTo compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder.\n In a multicentre, single-blind study at 51 Scandinavian centres, 505 patients aged >or= 18 years with symptoms of urinary frequency (>or= 8 micturitions/24 h) and urgency, with or without urge incontinence, were randomized to oral treatment with either tolterodine 2 mg twice daily plus simplified BT or tolterodine alone. Changes in voiding diary variables were evaluated after 2, 12 and 24 weeks of treatment. The patients' perceptions of their bladder symptoms and tolerability (adverse events) were also determined.\n In all, 501 patients (75% women) were evaluable on an intention-to-treat basis (244 on tolterodine + BT and 257 on tolterodine alone). Tolterodine significantly reduced the voiding frequency and increased the volume voided per void at all sample times; these effects were significantly increased by adding BT. At the end of the study the median percentage reduction in voiding frequency was greater with tolterodine + BT than with tolterodine alone (33% vs 25%, P < 0.001), while the median percentage increase in volume voided per void was 31% with tolterodine + BT and 20% with tolterodine alone (P < 0.001). There was a median of 81% fewer incontinence episodes than at baseline with tolterodine alone, which was not significantly different from that with tolterodine + BT (- 87%). The two groups had comparable median percentage reductions in urgency episodes. Some 76% of patients on tolterodine + BT reported an improvement in their bladder symptoms relative to baseline, compared with 71% on tolterodine alone. Tolterodine was well tolerated; the most common adverse event was mild dry mouth.\n Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen.\n\n\nTitle 6:\nA comparison of effectiveness of bladder training and pelvic muscle exercise on female urinary incontinence.\nAbstract 6:\nThis study compared the effectiveness of bladder training versus pelvic muscle exercises in the treatment of urinary incontinence in women. It was revealed that the two intervention groups showed improvement compared with the control group, but differed in their effects on outcome measures. The pelvic muscle exercise group was more effective in increasing the peak and the average pressures of pelvic muscle contraction. The bladder-training group was more effective in reducing urinary frequency and in increasing voided volume. Further research is needed to explore the relationship among the various outcome measures of urinary incontinence.\n Copyright 2002 Elsevier Science Ltd.\n\n\nTitle 7:\nComparative efficacy of behavioral interventions in the management of female urinary incontinence. Continence Program for Women Research Group.\nAbstract 7:\nWe compared the efficacy of bladder training, pelvic muscle exercise with biofeedback-assisted instruction, and combination therapy, on urinary incontinence in women. The primary hypothesis was that combination therapy would be the most effective in reducing incontinent episodes.\n A randomized clinical trial with three treatment groups was conducted in gynecologic practices at two university medical centers. Two hundred and four women diagnosed with genuine stress incontinence (n = 145) and/or detrusor instability (n = 59) received a 12-week intervention program (6 weekly office visits and 6 weeks of mail/telephone contact) with immediate and 3-month follow-up. Outcome variables included number of incontinent episodes, quality of life, perceived improvement, and satisfaction. Data analyses consisted of analysis of covariance using baseline values as covariates and chi2 tests.\n The combination therapy group had significantly fewer incontinent episodes, better quality of life, and greater treatment satisfaction immediately after treatment. No differences among groups were observed 3 months later. Women with genuine stress incontinence had greater improvement in life impact, and those with detrusor instability had less symptom distress at the immediate follow-up; otherwise, no differences were noted by diagnosis, incontinence severity, or treatment site.\n Combination therapy had the greatest immediate efficacy in the management of female urinary incontinence regardless of urodynamic diagnosis. However, each of the 3 interventions had similar effects 3 months after treatment. Results suggest that the specific treatment may not be as important as having a structured intervention program with education, counseling, and frequent patient contact.\n\n\nTitle 8:\nEfficacy of bladder training in older women with urinary incontinence.\nAbstract 8:\nThe efficacy of bladder training was evaluated in a randomized clinical trial involving 123 noninstitutionalized women 55 years and older with urinary incontinence. Subjects were urodynamically categorized as those with urethral sphincteric incompetence (N = 88) and those with detrusor instability with or without concomitant sphincteric incompetence (N = 35). Bladder training reduced the number of incontinent episodes by 57%; the effect was similar for both urodynamic diagnostic groups. The quantity of fluid loss was reduced by 54%. This was greater for patients with detrusor instability than for those without it. Diurnal and nocturnal voluntary micturitions were also reduced. The effect on nocturnal micturition, however, was not observed in subjects with unstable detrusor function. It is recommended that bladder training be considered as an initial step in treatment of women with urinary incontinence. Provided prior comprehensive clinical evaluation is done, it can be prescribed without the need for urodynamic characterization.", "role": "user" }, { "content": "The limited evidence available suggests that bladder training may be helpful for the treatment of urinary incontinence, but this conclusion can only be tentative as the trials were of variable quality and of small size with wide confidence intervals around the point estimates of effect. There was also not enough evidence to determine whether bladder training was useful as a supplement to another therapy. Definitive research has yet to be conducted.", "role": "assistant" } ]

[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: Search-Theoretic Models of the Labor Market: a Survey \nChapter Title: Random Matching and Bargaining \n1. Abstract of Cited Paper (BIB001): An equilibrium theory of unemployment assumes that firms and workers maximize their payoffs under rational expectations and that wages are determined to exploit the private gains from trade. This book focuses on the modeling of the transitions in and out of unemployment, given the stochastic processes that break up jobs and lead to the formation of new jobs, and on the implications of this approach for macroeconomic equilibrium and for the efficiency of the labor market.This approach to labor market equilibrium and unemployment has been successful in explaining the determinants of the \"natural\" rate of unemployment and new data on job and worker flows, in modeling the labor market in equilibrium business cycle and growth models, and in analyzing welfare policy. The second edition contains two new chapters, one on endogenous job destruction and one on search on the job and job-to-job quitting. The rest of the book has been extensively rewritten and, in several cases, simplified.\n\nLiterature Review:", "role": "user" }, { "content": "This section introduces a popular line of research, emanating from BIB001 BIB002 , used to study the determinants of arrival rates, match formation, match dissolution, and wages. We present a sequence of models that emphasize different margins, including entry, the decision to consummate matches, and the decision to terminate matches. Before we begin, there are two issues that need to be addressed: how do workers and firms meet, and how are wages determined. These models assume meetings are determined through a matching function and wages through bargaining.", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\none of the main observables of pulsar emission is its flux density @xmath3 , measured at a given central frequency @xmath4 of the receiver bandwidth .\nflux measurements are crucial for deriving , the so called , pulsar luminosity function and therefore the birth rate of the galactic population of neutron stars .\nthe first spectrum of a pulsar taken at 5 frequencies was published by robinson et al .\n( @xcite ) .\nthe flux density variations and spectra for frequencies between 0.15 and 1.6 ghz were later reported for a number of pulsars by mclean ( @xcite ) .\nspectra of 27 pulsars were published by sieber ( @xcite ) who used pulse energy values obtained with the 100-m and 25-m telescopes of the max - planck - institute for radioastronomy ( mpifr ) as well as other values published in the literature .\nhe was the first to show a turn - over behaviour at low frequencies around 100 mhz and a break in spectrum at high frequencies ( about 1 ghz ) .\nsieber et al .\n( @xcite ) published pulse shapes and their energies for 35 pulsars at 2.7 and 4.9 ghz , and for 7 pulsars at 10.7 ghz .\nizvekova et al .\n( @xcite ) and slee et al . (\n@xcite ) presented an analysis of flux measurements for pulsars at meter wavelengths ( @xmath2 80 mhz ) .\na compilation of spectra of 45 pulsars over a wide frequency range was published for the first time by malofeev et al .\n( @xcite ) .\nseiradakis et al .\n( @xcite ) published a collection of high frequency data on pulsar profiles and flux densities for 183 pulsars at 1.4 ghz , 46 pulsars at 4.85 ghz and 24 pulsars at 10.5 ghz .\nthe catalogue of pulsar flux density measurements for 281 pulsars at frequencies ranging from 0.4 ghz to 1.6 ghz was published by lorimer et al .\n( @xcite ) .\nthe first spectra for four millisecond pulsars were published by foster et al .\n( @xcite ) .\nkramer et al .\n( @xcite ) presented the results of flux density measurements for 23 millisecond pulsars at frequencies 1.4 and 1.7 ghz and an analysis of their spectra .\nvan ommen et al .\n( @xcite ) presented polarimetric data together with flux density measurements for a large number of southern pulsars at frequencies of 800 mhz and 950 mhz .\nmost recently , toscano et al .\n( @xcite ) have presented flux density measurements for southern millisecond and slow pulsars at frequencies between 0.4 ghz and 1.6 ghz , and kramer et al .\n( @xcite ) studied the emission properties of millisecond pulsars up 4.85 ghz .\na first large sample of flux densities of weak pulsars at 4.85 ghz was published by kijak et al .\n( @xcite ) .\nit has been long believed that flux density spectra for most of the pulsars have been well described by a simple power law @xmath5 with spectral index of @xmath6 ( sieber @xcite and lorimer et al .\n@xcite ) . however , a considerable fraction of pulsars demonstrated spectra that required modelling by two power laws ( sieber @xcite and malofeev et al .\nthese were commonly called the broken - type spectra . in this paper\nwe show that the two power law spectra are rare exception and that majority of pulsars can be modelled by a single power law .\nour analysis shows that only 10% of pulsars requires two power law spectra .\nrecently , pulsar flux density measurements have been extended to the mm - wavelengths region , which provided information about this newly explored spectral region .\nthese measurements suggested that spectrum flattens out or even turns up at very high frequencies ( kramer et al .\n@xcite ) . in this paper\nwe present a new and most complete compilation of spectra for 281 pulsars in the frequency range from 39 mhz to 43 ghz .\nthe flux density measurements for frequencies from 300 mhz to 1.4 ghz were done at jodrell bank ( lorimer et al .\n@xcite ) . for frequencies equal or above 1.4 ghz\nwe have utilized flux measurements made by different authors at the effelsberg radiotelescope of the max - planck institute for radioastronomy ( sieber et al .\n@xcite , bartel et al .\n@xcite , sieber & wielebinski @xcite , wielebinski et al .\n@xcite , seiradakis et al .\n@xcite , kramer et al .\n@xcite , hoensbroech et al .\n@xcite , kramer et al .\n@xcite , kijak et al .\nwe have also reduced a significant amount of the unpublished data available at the archives of the mpifr .\nmost of these data is available throughout the european pulsar network database ( lorimer et al .\nwe have also included the data published by izvekova et al .\n( @xcite ) and malofeev et al .\n( @xcite ) containing observations made at low radio frequencies from 39 mhz to 102.5 mhz . our own observations at 4.85 ghz made in effelsberg in 1998\nare also included .\nas a basis for our database we have taken the flux density measurements published by lorimer et al .\n( @xcite ) .\nthese observations were made between july 1988 and october 1992 using the 76-m lovell radio telescope at jodrell bank , at frequencies 408 , 606 , 925 , 1408 and 1606 mhz .\nlorimer et al .\n( @xcite ) excluded from their sample those pulsars which were too weak to obtain reliable flux density measurements as well as the millisecond pulsars .\nwe have extended this database by observations made at higher frequencies by different authors mentioned earlier or those unpublished but made available at mpifr archives in bonn .\nall observations at frequency range from 1.4 ghz to 43 ghz were made with the 100-m radio telescope of the mpifr at effelsberg and are available in european pulsar network database ( lorimer et al .\nsome values at 1.4 and 1.6 ghz were also published by lorimer et al .\n( @xcite ) .\nwe performed additional observations at 4.85 ghz of 43 very weak pulsars in august 1998 .\nwe managed to detect 30 objects and those undetected are listed in table 1 .\nthe detection limit of @xmath7 for the survey published by kijak et al .\n( @xcite ) is clearly visible from this table .\nthe observations published by izvekova et al .\n( @xcite ) and malofeev et al .\n( @xcite ) were performed at the pushchino radio astronomical observatory of the lebedev physical institute .\nwe thank christoph lange for his help with our observations in august 1998 .\nom thanks the director of the mpifr prof .\nr. wielebinski for invitation and support\nand jk gratefully acknowledge several discussions with j. gil in the course of this work .\nthe authors also thank v.m .\nmalofeev for unpublished data at 102 mhz and his helpful comments .\nthis work was supported in part by the polish state committee for scientific research grant 2 p03d 008 19 bartel n. , sieber w. , wielebinski r. , 1978 , a&a 68,361 foster r.s .\n, fairhead l. , backer d.c . , 1991 , apj 378 , 687 gil j.a . , jessner a. , kijak j. et al .\n, 1994 , a&a 282 , 45 hoensbroech a. von , xilouris k.m .\n, 1997 , a&as 126 , 121 hoensbroech a. von , kijak j. , krawczyk a. , 1998 , a&a 334 , 571 izvekova v.a .\n, kuzmin a.d . ,\nmalofeev v.m .\n, shitov yu.p , 1981 , ass 78 , 45 kijak j. , kramer m. , wielebinski r. , jessner a. , 1998 , a&as 127 , 153 kramer m. , 1995 , phd , high frequency observations of pulsars , university of bonn kramer m. , xilouris k.m . , jessner a. et al . , 1996 , a&a 306 , 867 kramer m. , jessner a. , doroshenko o. , wielebinski r. , 1997 , apj 488 , 364 kramer m. , xilouris k.m .\n, lorimer d.r .\net al . , 1998 ,\napj 501 , 270 kramer , m. , lange c. , lorimer d.r .\net al . , 1999 ,\napj 526 , 957 kuzmin , a.d , losovsky , b.ya . , 2000 ,\nasp conference series , vol . 202 , m. kramer , n. wex and r. wielebinski , eds lorimer d.r . , yates j.a . ,\nlyne a.g . , gould d.m .\n, 1995 , mnras 273 , 411 lorimer d.r .\n, jessner a. , seiradakis j.h .\net al . , 1998 , a&as 128 , 541 malofeev v.m . ,\ngil j.a . , jessner a. et al .\n, 1994 , a&a 285 , 201 malofeev v.m .\n, shishov v.i . , sieber w. et al . , 1996 ,\na&a 308 , 180 malofeev v.m . , 1996 ,\nasp conference series , vol .\n105 , s. johnson , m.a . walker and m. bailes , eds malofeev v.m .\n, malov o. , shchegoleva n. , 2000 , astronomy reports 44 , 436 mclean a.i.o . , 1973 , mnras , 165 , 133 moffet d.a .\n, hankins t.h . , 1999 , astro - ph/9904421 morris d. , kramer m. , thum c. et al . , 1997 , a&a 322l , 17 nelder j.a . , mead r. , 1965 , computer journal , vol . 7 , 308 ommen van t.d . , dalessandro f.d . , hamilton p.a .\n, mcculloch p.m. , 1997 , mnras 287 , 307 press w.h . , teukolsky s.a .\n, vetterling w.t .\n, flannery b.p . , 1996 ,\nnumerical recipes in c , cambridge university press robinson b.j .\n, cooper b.f.c .\n, gardner f.f .\n, wielebinski r. , landecker t.l . , 1968 , nat 218 , 1143 seiradakis j.h . , gil j.a\n, graham d.a .\net al . , 1995 , a&as 111 , 205 sieber w. , 1973 , a&a 28 , 237 sieber w. , reinecke r. , wielebinski r. , 1975 , a&a 38 , 169 sieber w. & wielebinski r. , 1987 , a&a 177 , 342 slee o.b .\n, alurkar s.k . ,\nbobra a.d . , 1986 ,\n39 , 103 stinebring d.r .\n, condon j.j . , 1990 , apj , 352 , 207 thorsett s.e . , 1991 , apj , 377 , 263 toscano m. , bailes m. , manchester r.n .\n, sandhu j.s . , 1998 , apj 506 , 863 wielebinski r. , jessner a. , kramer m. , j. gil j.a.,1993 , a&a 272 , l13 xilouris k.m . , kramer m , jessner a. , wielebinski r. , timofeev m. , 1996 , a&a , 309 , 481", "role": "user" }, { "content": "we have collected pulsar flux density observations and compiled spectra of 281 objects . \n the database of lorimer et al . \n ( @xcite ) has been extended to frequencies higher than 1.4 ghz and lower than 300 mhz . \n our results show that above 100 mhz the spectra of the majority of pulsars can be described by a simple power law with average value of spectral index @xmath0 . a rigorous analysis of spectral fitting revealed only about 5% of spectra which can be modelled by the two power law . \n thus , it seems that single power law is a rule and the two power law spectrum is a rather rare exception , of an unknown origin , to this rule . \n we have recognized a small number of pulsars with almost flat spectrum ( @xmath1 ) in the wide frequency range ( from 300 mhz to 20 ghz ) as well as few pulsars with a turn - over at unusually high frequency ( @xmath2 1 ghz ) .", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nSubtle alterations in swimming speed distributions of rainbow trout exposed to titanium dioxide nanoparticles are associated with gill rather than brain injury. The effects of engineered nanomaterials on fish behaviours are poorly understood. The present study aimed to determine the locomotor behaviours of trout during waterborne exposure to titanium dioxide nanoparticles (TiO(2) NPs) as well as inform on the underlying physiological mechanisms involved. Trout were exposed to either control (without TiO(2)), 1 mg l(-1) TiO(2) NPs or 1 mg l(-1) bulk TiO(2) for 14 days. Titanium dioxide exposure resulted in 31 (bulk) and 22 fold (nano) increases in the Ti concentrations of gill tissue compared to controls, but there were no measurable increases of Ti in the internal organs including the brain. Gill pathologies were observed in both TiO(2) treatments. Locomotor behaviours were quantified using video tracking software and the proportion of time spent swimming at high speed (>20 cms(-1)) was significantly decreased in fish exposed to TiO(2) NPs, compared to controls, but not fish exposed to bulk TiO(2). The shift in swimming speed distribution in the TiO(2) NP-exposed fish was associated with decreased area of red pulp in the spleen, increases in haematocrit and whole blood haemoglobin, all consistent with a compensation for respiratory hypoxia without the accumulation of plasma lactate. Fish exposed to TiO(2) NPs also retained competitive abilities when paired with controls in aggressive social encounters. The duration of competitive contests, the level of aggression and contest outcome were not affected by NP exposure. Neurological injury did not explain the changes in locomotor behaviour, although there was some apparent enlargement of the blood vessels on the brain. Whole brain homogenates showed a statistically significant increase in oxidative stress defences such as the total glutathione pool, but without loss of Na(+)K(+)-ATPase or acetylcholinesterase activities.", "role": "user" }, { "content": "{\"Chemical\": [\"TiO(2)\", \"Titanium dioxide\", \"glutathione\", \"Ti\", \"Na(+)K(+)\", \"titanium dioxide\", \"lactate\"]}", "role": "assistant" } ]

[ { "content": "You will be shown a claim about public health and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: T cells may help COVID-19 patients - and people never exposed to the virus\n\nAbstract:\nThe WHO has declared SARS-CoV-2 outbreak a public health emergency of international concern.\nHowever, to date, there was hardly any study in characterizing the immune responses, especially adaptive immune responses to SARS-CoV-2 infection.\nIn this study, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and analyzed their SARS-CoV-2-specific antibody and T cell responses.\nWe observed SARS-CoV-2-specific humoral and cellular immunity in the patients.\nBoth were detected in newly discharged patients, suggesting both participate in immune-mediated protection to viral infection.\nHowever, follow-up patients (2 weeks post discharge) exhibited high titers of IgG antibodies, but with low levels of virus-specific T cells, suggesting that they may enter a quiescent state.\nOur work has thus provided a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases.\nIt has also implications in designing an effective vaccine to protect and treat SARS-CoV-2 infection.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.\n\nThe relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].\n\nPlease format your output as a JSON array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<RELATION_A_B>\", \"<Entity_B>\"]. If no relations can be found, please output an empty JSON array [].\n\nAbstract:\n\nalpha-Linolenic acid, Delta6-desaturase gene polymorphism, and the risk of nonfatal myocardial infarction. BACKGROUND: Delta (6) -Desaturase (FADS2) is the rate-limiting step in the polyunsaturated fatty acid (PUFA) biosynthetic pathway. OBJECTIVE: The aim was to test whether the common deletion [ T/- ] in the promoter of FADS2 affects the PUFA biosynthetic pathway and consequently modifies the effect of alpha-linolenic acid (ALA) on myocardial infarction (MI). DESIGN: Case subjects (n = 1694) with a first nonfatal acute MI were matched by age, sex, and area of residence to 1694 population-based control subjects in Costa Rica. PUFAs were quantified by gas-liquid chromatography from plasma and adipose tissue samples. Least-squares means from generalized linear models and odds ratios (ORs) and 95% CIs from multiple conditional logistic regression models were estimated. RESULTS: The prevalence of the variant T/- allele was 48%. Eicosapentaenoic acid, gamma-linolenic acid, and arachidonic acid decreased in adipose tissue and plasma with increasing number of copies of the variant allele with a monotonic trend (P < 0.05 for all). Fasting plasma triacylglycerols by genotype were 2.08 mmol/L for TT, 2.16 mmol/L for T-, and 2.26 mmol/L for-- [ ie, homozygous for the variant (deletion) allele ] (P = 0.03). The FADS2 deletion was not associated with MI and did not significantly modify the association between adipose tissue ALA and the risk of MI. CONCLUSIONS: The FADS2 deletion may prevent the conversion of ALA into very-long-chain PUFAs. However, this metabolic effect is not translated into an attenuated risk between ALA and MI among carriers of the variant. It is possible that, at current intakes of ALA, any potential defect in the transcription of the gene is masked by the availability of substrate. Further research in populations deficient in ALA intake is warranted.", "role": "user" }, { "content": "[[\"ALA\", \"SUBSTRATE\", \"FADS2\"], [\"alpha-linolenic acid\", \"SUBSTRATE\", \"FADS2\"], [\"PUFA\", \"PRODUCT-OF\", \"FADS2\"]]", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Are Crocus sativus compounds being considered against Alzheimer's disease?\n\nContext: Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer's disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD.\nCollectively, findings from this study support the positive effect of Crocus sativus against AD by reducing Aβ pathological manifestations.", "role": "user" }, { "content": "yes", "role": "assistant" } ]

[ { "content": "You will be presented with a citation sentence from a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nIt may be interesting to study the security in context of multi-level proxy signatures [16].", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nintroduction\n\nContext before the citation:\nThe list, a synthesis of a number of relation lists cited in the literature, has been designed to be general, domainindependent (Barker et al., 1997a). We have a list of 47 relations that manifest themselves in compound clauses, inside a simple clause or in noun phrases. If such a graph is found, then the system maps previously assigned semantic relations onto the current syntactic graph.\n\nCitation Sentence:\nThe list , a synthesis of a number of relation lists cited in the literature , has been designed to be general , domainindependent ( Barker et al. , 1997a ) .\n\nContext after the citation:\nSection 2 overviews research in semantic relation analysis. Section 3 describes the text we used in ex- \u0000\u0000\u0000\u0000\u0000\u0000 Workshop on TextGraphs, at HLT-NAACL 2006, pages 81–88, New York City, June 2006. c �2006 Association for Computational Linguistics periments, and the semantic relation list.", "role": "user" }, { "content": "Motivation", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nInterleukin-18 and IL18 −607A/C and −137G/C Gene Polymorphisms in Patients with Penicillin Allergy\nAbstract 1:\nThis study investigated the association between polymorphisms ( −607A/C and −137G/C ) in the promoter region of the IL18 gene ( which encodes interleukin [IL]-18 ) and serum levels of IL-18 , using st and ard genotyping techniques ( sequence specific primer — polymerase chain reaction ) and an enzyme-linked immunosorbent assay , respectively , in patients allergic to penicillin . A higher frequency of A alleles and the AA genotype was found at position −607A/C in patients allergic to penicillin than in control subjects . For the −137G/C position , the C allele was more frequent in patients allergic to penicillin than in control subjects . Haplotype analysis showed that the −607A/−137C haplotype was more frequent in patients allergic to penicillin than in control subjects . The patients had a significantly higher serum IL-18 level than the control subjects . In conclusion , IL18 −607A/C and −137G/C promoter polymorphisms are associated with susceptibility to penicillin allergy . In particular , the −137G/C position appears to play an important role in IL18 expression\n\n\nTitle 2:\nFamilial aggregation of aspirin‐induced urticaria and leukotriene C4 synthase allelic variant\nAbstract 2:\nBackground We have reported that in patients with chronic idiopathic urticaria ( CIU ) who reacted adversely to aspirin , the frequency of the −444C allele of the leukotriene C4 synthase gene ( LTC4S ) was higher than in patients who tolerated aspirin well\n\n\nTitle 3:\nCharacteristics of subjects experiencing hypersensitivity to non‐steroidal anti‐inflammatory drugs: patterns of response\nAbstract 3:\nBackground Non‐steroidal anti‐inflammatory drugs ( NSAIDs ) are one of the most frequently involved groups of medicines in hypersensitivity drug reactions . Two mechanisms can induce the reaction : immunological ( sensitization ) due to a specific IgE or T cell response and pharmacological ( cyclooxygenase inhibition ) . The contribution of each of these mechanisms to the reactions is not well known", "role": "user" }, { "content": "Genes involved in NAR to aspirin belonged to arachidonic acid pathway , membrane-spanning 4A gene family , histamine production pathway , and pro-inflammatory cytokines , while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway .\nALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs .", "role": "assistant" } ]

[ { "content": "You will be given an abstract from a computer science research paper. Given the abstract, your task is to extract all unique relationships between entities of the following, and ONLY the following, types:\n\n- \"USED-FOR\": For instance, \"Our method models user proficiency\" -> [\"method\", \"user proficiency\", \"USED-FOR\"].\n- \"EVALUATE-FOR\": For instance, \"We evaluate our method using F1-measure\" -> [\"F1-measure\", \"method\", \"EVALUATE-FOR\"].\n- \"FEATURE-OF\": For instance, \"prior knowledge of the model\" -> [\"prior knowledge\", \"model\", \"FEATURE-OF\"].\n- \"HYPONYM-OF\": For instance, \"TUIT is a software library\" -> [\"TUIT\", \"software library\", \"HYPONYM-OF\"].\n- \"PART-OF\": For instance, \"We incorporate NLU module into the system\" -> [\"NLU module\", \"system\", \"PART-OF\"].\n- \"COMPARE\": For instance, \"Unlike the quantitative prior, the qualitative prior is often ignored\" -> [\"quantitative prior\", \"qualitative prior\", \"COMPARE\"].\n- \"CONJUNCTION\": For instance, \"obtained from human expert or knowledge base\" -> [\"human expert\", \"knowledge base\", \"CONJUNCTION\"].\n\nFormat your output as a JSON array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<Entity_B>\", \"<RELATION_A_B>\"]. An example output might look like:\n\n[[\"neural networks\", \"classification\", \"USED-FOR\"], [\"neuron\", \"neural network\", \"PART-OF\"]].\n\nIf no relations are found, please return an empty JSON array \"[]\".\n\nAbstract:\n\nIn this paper, we investigate the problem of automatically predicting segment boundaries in spoken multiparty dialogue. We extend prior work in two ways. We first apply approaches that have been proposed for predicting top-level topic shifts to the problem of identifying subtopic boundaries. We then explore the impact on performance of using ASR output as opposed to human transcription. Examination of the effect of features shows that predicting top-level and predicting subtopic boundaries are two distinct tasks: (1) for predicting subtopic boundaries, the lexical cohesion-based approach alone can achieve competitive results, (2) for predicting top-level boundaries, the machine learning approach that combines lexical-cohesion and conversational features performs best, and (3) conversational cues, such as cue phrases and overlapping speech, are better indicators for the top-level prediction task. We also find that the transcription errors inevitable in ASR output have a negative impact on models that combine lexical-cohesion and conversational features, but do not change the general preference of approach for the two tasks.", "role": "user" }, { "content": "[[\"lexical cohesion-based approach\", \"identifying subtopic boundaries\", \"USED-FOR\"], [\"identifying subtopic boundaries\", \"predicting top-level and predicting subtopic boundaries\", \"PART-OF\"], [\"ASR output\", \"human transcription\", \"COMPARE\"], [\"machine learning approach\", \"predicting top-level boundaries\", \"USED-FOR\"], [\"overlapping speech\", \"cue phrases\", \"CONJUNCTION\"], [\"transcription errors\", \"ASR output\", \"FEATURE-OF\"], [\"conversational cues\", \"predicting top-level boundaries\", \"USED-FOR\"], [\"overlapping speech\", \"conversational cues\", \"HYPONYM-OF\"], [\"cue phrases\", \"conversational cues\", \"HYPONYM-OF\"], [\"spoken multiparty dialogue\", \"predicting segment boundaries\", \"USED-FOR\"], [\"predicting top-level topic shifts\", \"identifying subtopic boundaries\", \"FEATURE-OF\"], [\"approaches\", \"predicting top-level topic shifts\", \"USED-FOR\"], [\"machine learning approach\", \"lexical-cohesion and conversational features\", \"CONJUNCTION\"], [\"approaches\", \"identifying subtopic boundaries\", \"USED-FOR\"], [\"lexical-cohesion and conversational features\", \"machine learning approach\", \"CONJUNCTION\"], [\"predicting top-level boundaries\", \"predicting top-level and predicting subtopic boundaries\", \"PART-OF\"]]", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nexperiments\n\nContext before the citation:\nWhen objects are compared in terms of several dimensions, these dimensions can be weighed in different ways (e.g., Rasmusen 1989). 9.3.1 Combinations of Adjectives.\n\nCitation Sentence:\nWhen objects are compared in terms of several dimensions , these dimensions can be weighed in different ways ( e.g. , Rasmusen 1989 ) .\n\nContext after the citation:\nLet us focus on references to an individual referent r, starting with a description that contains more than one gradable adjective. The NP the tall fat giraffe, for example, can safely refer to an element b in a situation like the one below, where b is the only element that exceeds all distractors with respect to some dimension (a different one for a than for c, as it happens) while not being exceeded by any distractors in any dimension: Cases like this would be covered if the decision-theoretic property of Pareto optimality (e.g., Feldman 1980) was used as the sole criterion: Formally, an object r E C has a Pareto-optimal combination of Values V iff there is no other x E C such that 1. ]", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\", \"Protein\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\" : [\"Dexamethasone\", ...], \"Protein\" : [\"BRCA-1\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nDevelopment of a cell-based high-throughput peroxisome proliferator-activated receptors (PPARs) screening model and its application for evaluation of the extracts from Rhizoma Coptis.\nTo date, peroxisome proliferator-activated receptors (PPARs) are becoming the new therapeutic targets for the treatment of metabolic diseases, such as Type 2 diabetes, obesity, and cardiovascular disease. In this study, a cell-based high-throughput PPARs (PPARα/β/γ) model was developed for the screening of PPARs agonists. The screening conditions were evaluated through analyzing the expression value of luciferase. Finally, 24 h of drug acting time, 5 times of the dilution factor of luciferase zymolyte, and about 2 × 10(4) cells/ well on HeLa cells in 96-well plates were used, respectively. Furthermore, the quality of high-throughput screening (HTS) in stability and reliability was evaluated by the Z'-factor. Additionally, different extracts of Rhizoma Coptis and berberine were tested by the developed method. The results suggested that both the EtOAc extract and berberine were able to activate PPARα/β/γ, and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. In conclusion, the developed HTS assay is a simple, rapid, stable, and specific method for the screening of PPARs natural agonists.", "role": "user" }, { "content": "{\"Chemical\": [\"EtOAc\", \"berberine\"], \"Protein\": [\"PPARs\", \"peroxisome proliferator-activated receptors\", \"PPAR\\u03b1/\\u03b2/\\u03b3\"]}", "role": "assistant" } ]

[ { "content": "You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.\n\nQuestion: How does phospholamban affect the biological activity of the calcium ATPase SERCA?\n\nContext: Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum.\nSR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition.\nRegulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. In spite of numerous mutagenesis and kinetic studies, we still do not have a clear mechanistic picture of how PLB influences the calcium transport cycle of SERCA.\nPhospholamban (PLN) regulates cardiac contractility via its modulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity. Impairment of this regulatory process causes heart failure.\nBased on structural and dynamics data, we propose a model in which PLN undergoes allosteric activation upon encountering SERCA.\nThe membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. β-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism.\nWe found that the allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain interconverts between three different states: a ground T state (helical and membrane associated), an excited R state (unfolded and membrane detached), and a B state (extended and enzyme-bound), which is noninhibitory. Phosphorylation at Ser-16 of PLN shifts the populations toward the B state, increasing SERCA activity.\nPhospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle.", "role": "user" }, { "content": "SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum. Based on structural and dynamics data, a model in which PLN undergoes allosteric activation upon encountering SERCA has been proposed. The allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain interconverts between three different states: a ground T state (helical and membrane associated), an excited R state (unfolded and membrane detached), and a B state (extended and enzyme-bound), which is noninhibitory. Phosphorylation of PLN shifts the populations toward the B state, increasing SERCA activity. Phospholamban (PLN) regulates cardiac contractility via its modulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity. Impairment of this regulatory process causes heart failure.", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Gene\"].\n\nPlease return the output as a JSON object of the format: {\"Gene\": [\"SSX\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nLocalization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. A set of 11 clones encoding putative GTP binding proteins highly homologous to the yeast YPT1/SEC4 gene products have been isolated from an MDCK cell cDNA library. We localized three of the corresponding proteins in mammalian cells by using affinity-purified antibodies in immunofluorescence and immunoelectron microscopy studies. One, the MDCK homolog of rab2, is associated with a structure having the characteristics of an intermediate compartment between the endoplasmic reticulum and the Golgi apparatus. The second, rab5, is located at the cytoplasmic surface of the plasma membrane and on early endosomes, while the third, rab7, is found on late endosomes. These findings provide evidence that members of the YPT1/SEC4 subfamily of GTP binding proteins are localized to specific exocytic and endocytic subcompartments in mammalian cells.", "role": "user" }, { "content": "{\"Gene\": [\"GTP binding proteins\", \"rab2\", \"YPT1\", \"SEC4\", \"rab7\", \"Golgi\", \"rab5\"]}", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2018 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from the options provided. A short description of the datasets is also provided to help you.\n\nQuery: A novel salient object detection method based on Conditional GAN.\n\nKeyphrases: salient object detection images\n\nDataset description:\nVT5000: Includes 5000 spatially aligned RGBT image pairs with ground truth annotations. VT5000 has 11 challenges collected in different scenes and environments for exploring the robustness of algorithms.\nECSSD: The Extended Complex Scene Saliency Dataset (ECSSD) is comprised of complex scenes, presenting textures and structures common to real-world images. ECSSD contains 1,000 intricate images and respective ground-truth saliency maps, created as an average of the labeling of five human participants.\nSIP: The Salient Person dataset (SIP) contains 929 salient person samples with different poses and illumination conditions.\nHS-SOD: HS-SOD is a hyperspectral salient object detection dataset with a collection of 60 hyperspectral images with their respective ground-truth binary images and representative rendered colour images (sRGB).\n\nOptions: A: VT5000 B: ECSSD C: SIP D: HS-SOD", "role": "user" }, { "content": "ECSSD", "role": "assistant" } ]

[ { "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: PGRP-LD mediates A. stephensi vector competency by regulating homeostasis of microbiota-induced peritrophic matrix synthesis\nArticle:\nAbstract:\nPeptidoglycan recognition proteins( PGRPs) and commensal microbes mediate pathogen infection outcomes in insect disease vectors. Although PGRP-LD is retained in multiple vectors, its role in host defense remains elusive. Here we report that Anopheles stephensi PGRP-LD protects the vector from malaria parasite infection by regulating gut homeostasis. Specifically, knock down of PGRP-LD( dsLD) increased susceptibility to Plasmodium berghei infection, decreased the abundance of gut microbiota and changed their spatial distribution. This outcome resulted from a change in the structural integrity of the peritrophic matrix( PM), which is a chitinous and proteinaceous barrier that lines the midgut lumen. Reduction of microbiota in dsLD mosquitoes due to the upregulation of immune effectors led to dysregulation of PM genes and PM fragmentation. Elimination of gut microbiota in antibiotic treated mosquitoes( Abx) led to PM loss and increased vectorial competence. Recolonization of Abx mosquitoes with indigenous Enterobacter sp. restored PM integrity and decreased mosquito vectorial capacity. Silencing PGRP-LD in mosquitoes without PM didn’t influence their vector competence. Our results indicate that PGPR-LD protects the gut microbiota by preventing hyper-immunity, which in turn promotes PM structurally integrity. The intact PM plays a key role in limiting P. berghei infection.\nIntroduction:\nMalaria is caused by parasites from the genus Plasmodium. The disease kills over 500, 000 people annually, most of which are children under the age of 5[1]. In order to transmit between humans, Plasmodium must overcome several obstacles to complete its development in Anopheles mosquitoes[2–4]. The peritrophic matrix( PM), and immuno-competent midgut epithelial cells, are two barriers that interfere with parasite transmission through their mosquito vector. The PM is non-cellular and composed of chitin fibrils and chitin-binding proteins. The structure lines the midgut lumen and wraps the food bolus within the endoperitrophic space, thus protecting the epithelium from abrasive food particles and enteric pathogens[5]. The tight junctions between midgut epithelial cells form another contiguous barrier against parasite invasion[6]. Midgut epithelial cells invaded by Plasmodium undergo apoptosis and are replaced by new cells. This rapid turnover not only maintains the integrity of the epithelium, but also clears invading parasites[7]. In addition to overcoming physical barriers present in the mosquito midgut, epithelial cells in this environment also present robust cellular and humoral immunity[3]. This activity includes the synthesis of antimicrobial peptides( AMPs), reactive oxygen species( ROS) and nitric oxide( NO), all of which contribute to parasite clearance[4]. Anopheles mosquitoes have 3 types of hemocytes: granulocytes, oenocytoids and prohemocytes[3]. These cells eliminate pathogens via phagocytosis and encapsulation. Hemocytes are also important in Plasmodium-mediated immune memory, which enhances the mosquito’s ability to clear parasites upon reinfection[8]. In addition, complement like protein TEP1 by forming TEP1/LRIM1/APL1C complex, is another key systemic antiplasmodial immune mechanism that recognizes and eliminates Plasmodium ookinetes in the midgut[3]. Three major immune signaling pathways, Toll, IMD( Immune Deficiency) and JAK/STAT, are critical mediators of malaria infection dynamics in Anopheles mosquitoes[3]. Peptidoglycan recognition proteins( PGRP) are pattern recognition molecules that function as receptors and regulators of the Toll and IMD signaling pathways[9]. Anopheles has 7 PGRP genes, 4 in the Long subfamily( including PGRP-LA,-LB,-LC and-LD) and 3 in the short subfamily( PGRP-S1,-S2 and –S3)[10]. Anopheles PGRP-LC is a receptor of the Immune Deficiency( Imd) pathway that is responsible for triggering synthesis of downstream effector molecules[11]. Knock down of PGRP-LC results in increasing susceptibility to Plasmodium infection. PGRP-LA, another receptor of the Imd pathway, protects A. coluzzii from Plasmodium infection in a manner similar to that of PGRP-LC[12]. PGRP-LB, a negative regulator of the Imd pathway, has a dual role in Anopheles mosquitoes, facilitating parasite infection and protecting natural gut bacteria[12, 13]. However, mechanisms of other PGRPs in response to parasite infection are still inadequate. The gut microbiota is another important factor that strongly influences vector competence[14]. Interactions between enteric bacteria and the mosquito immune system help to maintain gut homeostasis and protect mosquitoes from pathogens infection[13, 15–17]. In the absence of gut microbes, Anopheles become highly susceptible to Plasmodium infection. Co-feeding parasites with bacteria restores resistance to parasite infection in mosquitoes previously treated with antibiotics to remove their indigenous microbiota. Gut microbes also induce expression of several immune molecules, including antimicrobial peptides and pattern recognition receptors[13], and enhance vector refractoriness by promoting hemocyte differentiation[8]. Some residential bacteria, including Enterobacter and Chromobacterium isolated from field mosquitoes, directly inhibit parasite infection by secreting secondary metabolites such as reactive oxygen species[15, 18]. In this study, we examined the function of PGRP-LD in A. stephensi and found that this receptor protects the mosquito against Plasmodium infection. PGRP-LD helped maintain homeostasis of the mosquito gut microbiota by negatively regulating innate immune responses. The healthy microbiota in turn contributed to the integrity of PM, and the intact PM enhanced Anopheles resistance to malaria parasites. Our results suggest that a finely tuned balance between the immune system, gut microbes and the PM is key to determining the capacity of mosquitoes to transmit malaria.\nDiscussion:\nIn both invertebrates and vertebrates PGRPs play important roles in regulating interactions with pathogens and commensal bacteria[9]. In this study, we show that PGRP-LD protects A. stephensi from parasite infection by regulating homeostasis of the mosquito’s gut microbiota( Fig 7). Reduced pgrp-ld activates the host immune system, which depletes the abundance of gut microbes in this niche. This impairs PM structure and increases susceptibility to parasite infection. PGRP family members were first identified because they share a conserved PGRP domain that is able to detect peptidoglycan( PGN) present on the cell wall of both Gram+ and Gram- bacteria[9, 33]. Recent studies using disease vectors show that PGRPs also play important roles in parasite defense[9, 12, 34–36]. The function of PGRP-LC is well characterized in Anopheles mosquitoes and the tsetse fly, where the protein is responsible for initiating synthesis of downstream effectors in response to both native microbes and invading pathogens[9, 11, 37]. PGRP-LA participates in defense against parasite infection by functioning similarly to PGRP-LC[12]. PGRP-LB acts as a negative regulator of Imd signaling pathway through its amidase activity[12, 38–40]. In tsetse, PGRP-LB has evolved to exhibit bactericidal and anti-parasitic activity[41]. Unlike the above-mentioned PGRPs, little is known about the mechanistic role of PGRP-LD in pathogen defense in either Drosophila or other insects, except that it protects Armigeres mosquitoes from E. coli infection by modulating expression of downstream antimicrobial peptides[42]. We show here that A. stephesi PGRP-LD promotes host defense against P. berghei. Experimental knock down of pgrp-ld expression induces the expression of downstream effectors both in the presence or absence of parasite challenge. Based on its structure, A. stephensi PGRP-LD lacks conserved residues essential for either PGN binding or amidase activity, which has been identified in Drosophila PGRPs[43–45]. This is in contrast with most of PGRPs, which function as negative regulators that prevent over activation of immune signaling pathways by catabolizing immunostimulatory peptidoglycan[46, 47]. One explanation is that PGRP-LD may use less well conserved residues to bind peptidoglycan. Alternatively, PGRP-LD may interfere the signal transduction of immune pathways, as does Drosophila PGRP-LF that dampens Imd signaling strength by interfering with PGRP-LC-peptidoglycan binding activity[48]. Further investigations are required to determine how PGRP-LD regulates immune system function. The gut microbiota enhances host intestinal barrier function and pathogen tolerance in both vertebrates and invertebrates[47, 49]. In A. stephensi, pgrp-ld knockdown elevates immune activity that eliminates the majority of gut microbes but fails to eliminate P. berghei. In these mosquitoes, the spatial structure of remaining bacteria was altered. Gut microbes that are usually restrained within the endoperitrophic space localize in close contact with midgut epithelium. Our results indicate that PM structure is compromised in dsLD treated mosquitoes. We then observe PM structure is impaired and expression of PM genes varies significantly. These results suggest that the defect of PM structure results from the dysregulation of PM genes. In addition, we also find that the PM of A. stephensi is absent 48 hr post blood meal in antibiotic treated mosquitoes in which most enteric microbes are cleared. This defect is also associated with decreasing peritrophin and increasing chitinase expression. Thus PM structural integrity is associated with the homeostasis of gut bacteria in A. stephensi, similarly as in many disease vectors[27–29]. When mosquitoes treated with antibiotics are re-colonized by Enterobacter sp, both PM structural integrity and vector competence are restored. In agreement with the finding in An. coluzzii that PM is induced by gut microbiota[29], our results further confirm that gut microbiota of Anopheles mosquitoes is essential for PM integrity. However, we are currently unable to say at what abundance and how gut microbiota are able to maintain intact PM structure. The PM serves as a physical barrier to parasite infection establishment in multiple disease transmitting vectors, including tsetse flies, sand flies and ticks[27, 32, 50–56]. Our study shows that in antibiotic treated mosquitoes that present a compromised PM, knockdown of pgrp-ld expression does not change infection prevalence compared to controls. This result reinforces that increasing susceptibility of dsLD mosquitoes to P. berghei infection is due to the comprised PM as opposed to reduced levels as of PGRP-LD directly. In agreement with most vectors, our results show that PM is a major physical barrier that prevents P. berghei infection establishment in A. stephensi. In summary, our data demonstrate that a complex interplay exists between the host immune system, gut microbes and the PM, and this interplay determines parasite infection outcomes in A. stephensi. PGRP-LD, functioning as a key mediator, helps to maintain this balance. Detailed studies on the regulation of PGRP-LD on immune signaling pathways, and the influence of gut microbiota on PM formation, are currently under way and may provide new insights into interactions between immune system, gut microbiota and parasites.", "role": "user" }, { "content": "Malaria parasites must overcome several obstacles to complete their development in mosquito . Understanding the interactions between parasites and mosquitoes will provide potential targets to control malaria transmission . PGRP-LD is a peptidoglycan recognition protein , of which limit information is available in insects . Here we show that A . stephensi PGRP-LD mediates malaria parasite infection outcomes by influencing homeostasis of the gut microbiota . Reduction of the gut microbiota density , resulting from upregulation of immune activities in PGRP-LD knock down mosquitoes , changes expression of PM genes and causes PM fragmentation . The compromised PM leads to increasing susceptibility to parasite infection . We also discovered that the PM is lost in mosquitoes in which the gut microbiota is removed by antibiotic treatment . Knock down of PGRP-LD in these mosquitoes doesn’t increase their vector competence . Altogether , these results indicate that capacity of Anopheles mosquito to transmit parasites is determined by a finely tuned balance between host immunity , gut microbiota and peritrophic matrix . PGRP-LD is a key mediator in regulating this balance . Our results expand knowledge on interactions between immune system , gut microbiota and Plasmodium , and will shed light on equivalent processes in other disease transmitting vectors .", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nIn vivo and in vitro characterization of naltrindole-derived ligands at the κ-opioid receptor. Accumulating evidence supports a role for κ-opioid receptor antagonists in the treatment of mood disorders. Standard κ-antagonists have an unusual pharmacodynamic action, with a single injection blocking receptor signaling for several weeks. Here, we have characterized the κ-selective properties of two ligands, 5'-(2-aminomethyl) naltrindole (5'-AMN) and N-((Naltrindol-5-yl) methyl) pentanimidamide (5'-MABN), to identify whether modifications of the naltrindole side chain produces short-acting κ-antagonists. Opioid receptor binding affinity and activity were assessed using [(3)H]-diprenorphine binding, guanosine-5'-O-(3-[35S]-thio) triphosphate ([(35)S]-GTPγS) binding and isolated guinea-pig ileum. Pharmacodynamic profiles of 5'-AMN and 5'-MABN (1-10 mg/kg) were investigated using the tail-withdrawal assay and diuresis. Efficacy was also determined in depression- and anxiety-related behavioral paradigms in CD-1 mice. Both 5'-AMN and 5'-MABN had high affinity for κ-receptors (K (i) 1.36 ± 0.98 and 0.27 ± 0.08, respectively) and were revealed as potent κ-antagonists (pA(2) 7.43 and 8.18, respectively) and μ-receptor antagonists (pA(2) 7.62 and 7.85, respectively) in the ileum. Contrary to our hypothesis, in vivo, 5'-AMN and 5'-MABN displayed long-lasting antagonist effects in mice, reducing the antinociceptive actions of U50,488 (10 mg/kg) at 28 and 21 days post-injection, respectively. Interestingly, while 5'-AMN and 5'-MABN were not κ-selective, both compounds did show significant antidepressant- and anxiolytic-like effects at 7-14 days post-injection in mice.", "role": "user" }, { "content": "{\"Chemical\": [\"N-((Naltrindol-5-yl) methyl) pentanimidamide\", \"U50,488\", \"5\\u0027-AMN\", \"5\\u0027-(2-aminomethyl) naltrindole\", \"[(3)H]-diprenorphine\", \"[(35)S]-GTP\\u03b3S\", \"naltrindole\", \"5\\u0027-MABN\", \"guanosine-5\\u0027-O-(3-[35S]-thio) triphosphate\"]}", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nperhaps due to the exceptional appearance of two superconducting(sc ) transitions with two associated critical field curves , upt@xmath0 is one of the most well studied heavy fermion superconductors .\nthe history of this subject was described in ref.@xcite .\nthe t linear dependence of the low temperature thermal conductivity both parallel to the c axis and the a axis was in favor of the e@xmath2 rather than e@xmath3- type sc order parameter@xcite .\nfurther pt- nmr experiments confirmed the triplet nature of the superconductivity and the details of the triplet gap function * d * ( * k ) n a , b , and c- phases were determined@xcite .\nthis assignment of the spin configuration is consistent with the weak spin - orbit coupling limit@xcite also assumed here .\nh@xmath4 along the c axis requires a strong pauli limiting effect@xcite .\nthis favors strong spin orbit coupling but then h@xmath4 results are inconsistent with the nmr data .\nwe assume that * d * ( * k)=@xmath5 to be weakly pinned along c. then the e@xmath2 gap functions of for the low temperature b and c phases of upt@xmath0 are given by * * @xmath6 here @xmath7 are the polar and azimuthal angles of * k * .\nthe angular dependence of @xmath8 is shown in fig .\n[ gapfun ] . in the b- phase\nthe poles are second order node points and the equator is a node line . in the c- phase\ntwo additional vertical nodal lines appear at 45 degrees away from the vertical plane containing * h * .\nthe thermal conductivity in the vortex phase for field along the symmetry axis also decided in favor of the e@xmath2 state and against the e@xmath3- state@xcite , this is reviewed in @xcite .\nthe angular dependent thermal conductivity has been measured in @xcite and analyzed in @xcite .\nunfortunately the experiment was done for t@xmath90.3 k which is not sufficiently low to determine node structures .\nrecently we have been studying the thermal conductivity in nodal superconductors@xcite .\nin particular we shall restrict to the low temperature limit t@xmath10 and the superclean limit @xmath11 , where @xmath12 , @xmath13 is the scattering rate and @xmath14 are the anisotropic fermi velocities .\nthe condition @xmath15 can be satisfied in the b- phase while @xmath16 in the c- phase since the latter appears only for h@xmath17 0.6 t and h@xmath17 1.2 t for field along a and c respectively .\nour results in the c- phase may therefore only have qualitative significance .\nrestriction to the superclean limit does not influence the main conclusions on the connection between node topology and magnetothermal conductivity .\nwe first examine the quasiparticle dos and the thermodynamic properties of the b and c phase of upt@xmath0 in the presence of a magnetic field with arbitrary orientation at low temperatures .\nthen we study the thermal conductivity in the b and c phase in the low temperature regime which provides clear evidence for the nodal positions in @xmath18 . in this regime the influence of the af order in upt@xmath0 may be neglected contrary to the a- phase regime .\nthe quasiparticle dos in the vortex state of upt@xmath0 is given by @xmath19 where the brackets denote both fermi surface and vortex lattice average . with the form factor f@xmath20(z)=@xmath21 and f@xmath22(z , z)=(2z@xmath23 - 1)f@xmath20(z ) ( z=@xmath24 , z=@xmath25 ) for b and c- phase respectively the average may be computed and one obtains @xmath26{\\rangle}\\bigr)\\nonumber\\\\ g_c(0)&=&\\frac{1}{\\sqrt{3 } } \\bigl(\\frac{\\pi}{2}{\\langle}x\\ln\\bigl(\\frac{2}{x}\\bigr){\\rangle}+ \\frac{2}{\\pi}c_0{\\langle}\\ln^2(\\frac{2}{x}){\\rangle}\\bigr)\\end{aligned}\\ ] ] where x=@xmath27 is the normalized doppler shift of quasiparticle energies , c@xmath28 and @xmath29 is the renormalized quasiparticle energy in the presence of impurity scattering@xcite .\nfurthermore * v * is the quasiparticle velocity and 2*q * is the pair momentum around the vortex . following volovik@xcite we obtain @xmath30 here e(@xmath31 ) is the complete elliptic integral of the second kind .\nfurthermore we used the definition @xmath32 where @xmath33 is the anisotropy of fermi velocities and @xmath34 is the polar angle of * h * with respect to c axis .\nthe averages in eq .\n[ xav ] are evaluated by replacing the * k * space integration by a summation over nodal positions and then integrating out the superfluid velocity field@xcite .\nwe assume a square vortex lattice for simplicity , a hexagonal lattice would lead to an additional numerical factor 0.93 . substituting eq .\n[ xav ] into eq .\n[ densex ] we obtain @xmath35 in addition we have c@xmath36=@xmath37^{-1}$ ] .\nthe low temperature specific heat , the spin susceptibility etc .\nare given by @xmath38 where @xmath39 is the superfluid density .\nthe @xmath34- dependence of g(0 ) for b- and c- phases is shown in figs .\n[ btheta ] and [ ctheta ] respectively .\nthe thermal conductivity tensor in the vortex phase depends on the angles ( @xmath40 ) of * h * due to the angle dependence of the doppler shift energy @xmath41x . here\n@xmath42 is the azimuthal angle between * h * and the direction of the heat current * j@xmath43 in the ab- plane .\nfollowing@xcite we obtain for the b- phase * @xmath44 \\nonumber\\end{aligned}\\ ] ] the thermal hall coefficient in the b- phase is obtained as @xmath45\\nonumber\\end{aligned}\\ ] ] the @xmath34- and @xmath42- angle dependences of @xmath46 ( ij = xx , zz , xy ) in the b- phase are shown in fig .\n[ btheta ] and fig .\n[ bphi ] . for heat current along c ( @xmath47 )\nno @xmath42- dependence appears . in the limit @xmath48 , i@xmath49=@xmath50 and then @xmath51 the maximum in @xmath52 at @xmath42= @xmath5390 occurs for heat current @xmath54 * h when the doppler shift gives rise to the largest quasiparticle dos parallel to the heat current and we have @xmath55=2 . *\nnow we consider the c- phase . again\n@xmath47 does not exhibit a @xmath42- dependence .\nthe c - phase according to eq .\n[ gapfun ] has two additional perpendicular node lines .\nrotating the field at a given @xmath34 around c ( i.e. changing @xmath42 ) will lead to a co- rotation of these node lines such that the vertical plane containing * h * always stays at half angle between the two perpendicular planes of the node lines parallel to c@xcite(see inset of fig .\n[ cphi ] ) .\nconsequently @xmath56 will again be independent of @xmath42 while @xmath57 depends on both field angles .\nwe find for heat current along c : @xmath58^\\frac{1}{2}\\end{aligned}\\ ] ] on the other hand we obtain for heat current along a : @xmath59 as is readily seen @xmath47 depends only on @xmath34 , while @xmath60 depends both on @xmath34 and @xmath42 .\nboth angular dependences are shown in fig .\n[ ctheta ] and fig .\n[ cphi ] respectively . in both b and c phase @xmath46 ( ij= xx , zz ) and also the specific heat which is determined by i@xmath61 exhibit clear cusps at the poles @xmath34=0 ( and @xmath62 ) caused by the contributions from the respective second order node points which are present in both b and c phase .\nthis is very similar to what has been recently observed and analyzed in yni@xmath63b@xmath63c@xcite .\nthere the second order node points lie along the equator and hence the cusps appear as function of @xmath42 .\nthe most significant difference in the b- and c- phase results can be seen in the behaviour of @xmath47 for small polar angle @xmath34 . while in the b- phase it approaches zero\nit remains finite in the c- phase .\nfurthermore the @xmath64 anisotropy for @xmath48 is considerably smaller in the c- phase as compared to the b - phase . in both b- and c- phase the xx- component exhibts nonmonotonic behaviour as function of @xmath34 .\nthe thermal hall coefficient in the c- phase reads @xmath65 where f@xmath66 holds because the contributions from perpendicular node lines with * h * lying at half angle in between cancel and so as in the b- phase one is left with polar and equatorial contributions to the thermal hall constant . for numerical calculations we used the anisotropy ratio @xmath67 = 1.643 .\nit can be directly obtained from experimental anisotropies of thermal and electrical conductivities@xcite @xmath68= @xmath68=2.7 which are equal to @xmath69 .\nwe have found that in upt@xmath0 at low temperatures ( i.e. t@xmath70 ) and in the superclean limit ( @xmath11 ) , the thermal conductivity exhibits clear angular dependence which will help to identify the nodal directions in @xmath18and to verify the predictions of the commonly discussed e@xmath2 model for the gap function in b and c phases .\nmost significantly we predict that i ) cusps appear in the thermal conductivity and specific heat for @xmath34=0 ( and @xmath62 ) due to the polar point nodes of upt@xmath0 in both b- and c- phase .\nii ) in the c- phase for heat current along the nodal direction ( @xmath71 ) a finite @xmath72 occurs even for @xmath730 which is caused by the contribution from the additional perpendicular node regions . for the b- phase this contribution vanishes .\niii ) the @xmath64 anistropy for * h * in the ab- plane ( @xmath74 ) is considerably larger in the b- phase as compared to c- phase .\nthis is again caused by the perpendicular node lines which contribute and enhance @xmath60 only for the c- phase .\nwe hope that these different features in the field- angle dependent thermal conductivity tensor above and below the critical field of the b - c transition will resolve a part of the remaining controversy surrounding @xmath18 in upt@xmath0 .\nwe recall that thermal conductivity experiments have been very useful to identify @xmath18 in unconventional superconductors .\nfor example izawa et al have succeded to identify @xmath18 in sr@xmath63ruo@xmath75@xcite , cecoin@xmath76@xcite , organic salts@xcite and more recently yni@xmath63b@xmath63c@xcite .\nindeed the thermal conductivity appears to provide a unique window to access the nodal structure in unconventional superconductors .", "role": "user" }, { "content": "although the superconductivity in upt@xmath0 is one of the most well studied , there are still lingering questions about the nodal directions in the b and c phase in the presence of a magnetic field . limiting ourselves to the low temperature regime ( t@xmath1 ) \n , we study the magnetothermal conductivity with in semiclassical approximation using volovik s approach . the angular dependence of the magnetothermal conductivity for an arbitrary field direction is calculated for both phases . \n we show that cusps in the polar angle dependence appear in b and c phases which are due to the polar point nodes .", "role": "assistant" } ]

[ { "content": "You will be shown a claim about public health and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: smokers are at greater risk of complications from COVID-19 than non-smokers. \n\nAbstract:\nObjectives: To investigate whether there is a causal effect of cardiometabolic traits on risk of sepsis and severe covid-19.\nDesign: Mendelian randomisation analysis.\nSetting: UK Biobank and HUNT study population-based cohorts for risk of sepsis, and genome-wide association study summary data for risk of severe covid-19 with respiratory failure.\nParticipants: 12,455 sepsis cases (519,885 controls) and 1,610 severe covid-19 with respiratory failure cases (2,205 controls).\nExposure: Genetic variants that proxy body mass index (BMI), lipid traits, systolic blood pressure, lifetime smoking score, and type 2 diabetes liability - derived from studies considering between 188,577 to 898,130 participants.\nMain outcome measures: Risk of sepsis and severe covid-19 with respiratory failure.\nResults: Higher genetically proxied BMI and lifetime smoking score were associated with increased risk of sepsis in both UK Biobank (BMI: odds ratio 1.38 per standard deviation increase, 95% confidence interval [CI] 1.27 to 1.51; smoking: odds ratio 2.81 per standard deviation increase, 95% CI 2.09-3.79) and HUNT (BMI: 1.41, 95% CI 1.18 to 1.69; smoking: 1.93, 95% CI 1.02-3.64).\nHigher genetically proxied BMI and lifetime smoking score were also associated with increased risk of severe covid-19, although with wider confidence intervals (BMI: 1.75, 95% CI 1.20 to 2.57; smoking: 3.94, 95% CI 1.13 to 13.75).\nThere was limited evidence to support associations of genetically proxied lipid traits, systolic blood pressure or type 2 diabetes liability with risk of sepsis or severe covid-19.\nSimilar findings were generally obtained when using Mendelian randomization methods that are more robust to the inclusion of pleiotropic variants, although the precision of estimates was reduced.\nConclusions: Our findings support a causal effect of elevated BMI and smoking on risk of sepsis and severe covid-19.\nClinical and public health interventions targeting obesity and smoking are likely to reduce sepsis and covid-19 related morbidity, along with the plethora of other health-related outcomes that these traits adversely affect.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Results: Higher genetically proxied BMI and lifetime smoking score were associated with increased risk of sepsis in both UK Biobank (BMI: odds ratio 1.38 per standard deviation increase, 95% confidence interval [CI] 1.27 to 1.51; smoking: odds ratio 2.81 per standard deviation increase, 95% CI 2.09-3.79) and HUNT (BMI: 1.41, 95% CI 1.18 to 1.69; smoking: 1.93, 95% CI 1.02-3.64).\", \"Conclusions: Our findings support a causal effect of elevated BMI and smoking on risk of sepsis and severe covid-19.\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Disease\"].\n\nPlease return the output as a JSON object of the format: {\"Disease\": [\"COVID-19\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nThe effects of dystrophin gene mutations on the ERG in mice and humans. PURPOSE. The authors earlier findings of a negative electroretinogram (ERG) in a boy with Duchenne muscular dystrophy (DMD) led them to investigate dystrophin gene deletions and ERGs in five boys with DMD. The authors wanted to determined whether there were similar ERG findings in an animal model for DMD, the mdx mouse. METHODS. Ganzfeld ERGs were recorded in five boys with DMD after a complete ophthalmic examination. The dystrophin gene was analyzed by Southern blot hybridization. ERGs were recorded in anesthetized mdx and control mice with a modified Grass photostimulator (Grass Instrument Company, Quincy, MA). RESULTS. Ophthalmic examinations in all five boys had normal findings, yet an abnormal negative ERG was recorded for each subject. The subjects gene deletions were variable, ranging from large deletions to no detectable deletions. The ERGs of the mdx mice were normal and did not differ significantly from those of the control mice. CONCLUSIONS. The authors believe the unique ERG recorded for the human subjects is a manifestation of DMD associated with defects at the dystrophin gene locus and represents a new clinical entity. The ERG of the mdx mouse may be spared for several reasons, including milder effects of the mouse gene defect, differences in muscle and retinal gene product, or species differences in the biochemical role of dystrophin. The ERG shows promise of becoming a noninvasive diagnostic tool for DMD and its milder allelic forms..", "role": "user" }, { "content": "{\"Disease\": [\"Duchenne muscular dystrophy\", \"DMD\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nA Comparison of Two-Way Text Versus Conventional Paging Systems in an Academic Ophthalmology Department\nAbstract 1:\nAlphanumeric paging systems are unidirectional without prioritization capabilities . Newer electronic communication devices such as two-way text paging systems are capable of bidirectional paging and prioritization . While previous studies have evaluated alphanumeric paging systems in academic hospital setting s , bidirectional two-way text paging systems have not been investigated . The goal of this study was to evaluate efficiency and impact on patient care delivery of a two-way text paging system compared to conventional one-way alphanumeric pagers . This unmasked , crossover prospect i ve study was divided into three phases . In phase one , surveys were distributed to all ophthalmology attending physicians , residents , clinical technicians , and secretaries to assess the conventional alphanumeric paging system . In phase two , these participants used two-way text pagers without instruction ( unstructured format ) that they subsequently compared to the alphanumeric system with devised surveys assessing ( on a scale of 0 to 100 ) time saved , increased daily efficiency , facilitation in patient care , and overall impression (helpfulness).In phase three , participants used a specific communication prioritization protocol ( structured format ) with the two-way text pagers with subsequent comparison and assessment with the same surveys . Compared to traditional alphanumeric pagers , new digital two-way text pagers were found to be statistically ( p < 0.0001 ) more helpful by participants in all categories : as a time saver ( 80.33 vs. 56.95 ) p < 0.0001 , increased daily efficiency ( 78.15 vs. 57.13 ) p < 0.0001 , facilitation in patient care ( 78.79 vs. 56.95 ) p < 0.0001 , and overall impression ( helpfulness ) ( 61.82 vs. 84.33 ) p < 0.0001 . When compared to the alphanumeric pager , the two-way text pager was found to decrease subjectively call backs ( 73.6 % to 45.6 % , p < 0.0001 ) , reduce interruptions of learning activities ( 43.63 % to 26.6 % , p < 0.0001 ) and enabled better patient care ( 59.8 % to 42.2 % , p < 0.0001 ) . No significant statistical difference was found between the structured and unstructured system . Two-way text paging ( structured versus unstructured guidance ) was preferred over the conventional one-way alphanumeric paging system in every participant category . Two-way text paging is an effective alternative to alphanumeric paging , demonstrating saved time , increased daily efficiency , reduced call backs and interruptions of educational activities , and facilitation in patient care\n\n\nTitle 2:\nThe Canadian Adverse Events Study: the incidence of adverse events among hospital patients in Canada\nAbstract 2:\nBackground : Research into adverse events ( AEs ) has highlighted the need to improve patient safety . AEs are unintended injuries or complications result ing in death , disability or prolonged hospital stay that arise from health care management . We estimated the incidence of AEs among patients in Canadian acute care hospitals . Methods : We r and omly selected 1 teaching , 1 large community and 2 small community hospitals in each of 5 provinces ( British Columbia , Alberta , Ontario , Quebec and Nova Scotia ) and review ed a r and om sample of charts for nonpsychiatric , nonobstetric adult patients in each hospital for the fiscal year 2000 . Trained review ers screened all eligible charts , and physicians review ed the positively screened charts to identify AEs and determine their preventability . Results : At least 1 screening criterion was identified in 1527 ( 40.8 % ) of 3745 charts . The physician review ers identified AEs in 255 of the charts . After adjustment for the sampling strategy , the AE rate was 7.5 per 100 hospital admissions ( 95 % confidence interval [ CI ] 5.7– 9.3 ) . Among the patients with AEs , events judged to be preventable occurred in 36.9 % ( 95 % CI 32.0%–41.8 % ) and death in 20.8 % ( 95 % CI 7.8%–33.8 % ) . Physician review ers estimated that 1521 additional hospital days were associated with AEs . Although men and women experienced equal rates of AEs , patients who had AEs were significantly older than those who did not ( mean age [ and st and ard deviation ] 64.9 [ 16.7 ] v. 62.0 [ 18.4 ] years ; p = 0.016 ) . Interpretation : The overall incidence rate of AEs of 7.5 % in our study suggests that , of the almost 2.5 million annual hospital admissions in Canada similar to the type studied , about 185 000 are associated with an AE and close to 70 000 of these are potentially preventable\n\n\nTitle 3:\nPatterns of nurse–physician communication and agreement on the plan of care\nAbstract 3:\nBackground Interdisciplinary communication is critically important to provide safe and effective care , yet it has been inadequately studied for hospitalised medical patients . Our objective was to characterise nurse – physician communication and their agreement on patients ' plan of care . Methods During a one-month period , r and omly selected hospitalised patients , their nurses and their physicians were interviewed . Nurses and physicians were asked to identify one another , whether communication had occurred , and about six aspects of the plan of care . Two internists rated nurse – physician agreement on aspects of the plan of care as none , partial or complete agreement . Measures included the percentage of nurses and physicians able to identify one another and reporting communication and the percentage of nurse – physician pairs in agreement on aspects of the plan of care . Results 310 ( 91 % ) and 301 ( 88 % ) of 342 eligible nurses and physicians completed interviews . Nurses correctly identified patients ' physicians 71 % of the time and reported communicating with them 50 % of the time . Physicians correctly identified the patients ' nurses 36 % of the time and reported communicating with them 62 % of the time . Physicians and nurses showed no agreement on aspects of the plan of care ranging from 11 % for planned procedures to 42 % for medication changes . Conclusions Nurses and physicians did not reliably communicate with one another and were often not in agreement on the plan of care for hospitalised medical patients\n\n\nTitle 4:\nDirect cellular vs. indirect pager communication during orthopaedic surgical procedures: a prospective study.\nAbstract 4:\nBACKGROUND Cellular phone use within the hospital setting has increased as physicians , nurses , and ancillary staff incorporate wireless technologies in improving efficiencies , cost , and maintaining patient safety and high quality healthcare [ 11 ] . Through the use of wireless , cellular communication , an overall improvement in communication accuracy and efficiency between intraoperative orthopaedic surgeons and floor nurses may be achieved . METHODS Both communication types occurred while the surgeon was scrubbed in the operating room ( OR ) . Indirect communication occurred when the pager call was answered by the OR circulating nurse with communication between the surgeon , circulating nurse , and floor nurse . Direct communication consisted of cell phone and Jabra Bluetooth BT200 wireless ear piece used by the surgeon . The surgeon answered the floor nurse 's cellular call by phone ring-activated automatic answering . The study was conducted during scheduled orthopaedic procedures . An independent observer measured time variables with a stop-watch while orthopaedic nurses r and omly called via pager or cell phone . The nurses asked for patient caregiver confirmation and answers to 30 different patient-care questions . RESULTS Sixty trials were performed with 30 cell and 30 page communications . Direct cellular communication showed a better response rate than indirect page ( Cell 100 % , Page 73 % ) . Indirect page communication allowed a 27 % and 33 % error rate with patient problem and surgeon solution communications , respectively . There were no reported communication errors while using direct wireless , cellular communication . When compared to page communications , cellular communications showed statistically significant improvements in mean time intervals in response time ( Cell = 11s , Page = 211s ) , correct patient identification ( Cell = 5s , Page = 172s ) , patient problem and solution time ( Cell = 13s , Page = 189s ) , and total communication time ( Cell = 32s , Page = 250s ) ( s = seconds , all P < 0.001 ) . Floor nurse satisfaction ratings ( dependent on communication times and /or difficulties ) were improved with direct cellular communication ( Cell = 29 excellent , Page = 11 excellent ) . Intraoperative case interruptions ( defined as delaying surgical progress ) were more frequent with indirect page communication ( 10 page v. 0 cell ) . CONCLUSION AND SIGNIFICANCE Our study demonstrates that direct wireless communication may be used to improve intraoperative communication and enhance patient safety . Direct wireless , cellular intraoperative communication improves communication times , communication accuracy , communication satisfaction , and minimizes intraoperative case interruption . As a result of this study , we hope to maintain our transition to direct wireless , cellular intraoperative orthopaedic communication to reduce medical errors , improve patient care , and enhance both orthopaedic surgeon and nursing efficiencies\n\n\nTitle 5:\nInterrupted care. The effects of paging on pediatric resident activities.\nAbstract 5:\nOBJECTIVE To determine the content and urgency of pages and their effect on the activities of pediatric residents . DESIGN Prospect i ve survey . SETTING University-affiliated teaching hospital . PARTICIPANTS Seventeen pediatric residents on regular pediatric services . INTERVENTIONS None . MEASUREMENTS /MAIN RESULTS On daily logs , interns recorded the activity interrupted by a page and rated the urgency and importance of the page . Almost half of all pages interrupted patient care activities , and 24 % interrupted scheduled work rounds or teaching conferences . Interns reported that 34 % of pages result ed in a change in patient treatment , but they rated 25 % of all pages as unimportant . CONCLUSIONS \" Beepers \" frequently interrupt pediatric residents involved in patient care activities and scheduled educational conferences . Studies of interventions aim ed at decreasing unnecessary interruptions by pages are needed", "role": "user" }, { "content": "Qualitative studies described improvements in efficiency of communication but also issues of loss of control and reliability .\nCONCLUSIONS Despite the rapid advancement in information and communications technology over the last decade , there is limited evidence suggesting improvements in the ability of health professionals to communicate effectively .", "role": "assistant" } ]

[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: Multi-Agent Systems and Blockchain: Results from a Systematic Literature Review \nChapter Title: Principles of Blockchain \n1. Abstract of Cited Paper (BIB001): Keyless Signatures Infrastructure KSI is a globally distributed system for providing time-stamping and server-supported digital signature services. Global per-second hash trees are created and their root hash values published. We discuss some service quality issues that arise in practical implementation of the service and present solutions for avoiding single points of failure and guaranteeing a service with reasonable and stable delay. Guardtime AS has been operating a KSI Infrastructure for 5 years. We summarize how the KSI Infrastructure is built, and the lessons learned during the operational period of the service. \n2. Abstract of Cited Paper (BIB002): Bitcoin is a digital cryptocurrency that has generated considerable public interest, including both booms in value and busts of exchanges dealing in Bitcoins. One of the fundamental concepts of Bitcoin is that work, called mining, must be done in checking all monetary transactions, which in turn creates Bitcoins as a reward. In this paper we look at the energy consumption of Bitcoin mining. We consider if and when Bitcoin mining has been profitable compared to the energy cost of performing the mining, and conclude that specialist hardware is usually required to make Bitcoin mining profitable. We also show that the power currently used for Bitcoin mining is comparable to Ireland's electricity consumption. \n3. Abstract of Cited Paper (BIB003): Bitcoin cryptocurrency demonstrated the utility of global consensus across thousands of nodes, changing the world of digital transactions forever. In the early days of Bitcoin, the performance of its probabilistic proof-of-work (PoW) based consensus fabric, also known as blockchain, was not a major issue. Bitcoin became a success story, despite its consensus latencies on the order of an hour and the theoretical peak throughput of only up to 7 transactions per second. \n4. Abstract of Cited Paper (BIB004): Consensus, or state machine replication is a foundational building block of distributed systems and modern cryptography. Consensus in the classical, \"permissioned\" setting has been extensively studied in the 30 years of distributed systems literature. Recent developments in Bitcoin and other decentralized cryptocurrencies popularized a new form of consensus in a \"permissionless\" setting, where anyone can join and leave dynamically, and there is no a-priori knowledge of the number of consensus nodes. So far, however, all known permissionless consensus protocols assume network synchrony, i.e., the protocol must know an upper bound of the network's delay, and transactions confirm slower than this a-priori upper bound. ::: ::: We initiate the study of the feasibilities and infeasibilities of achieving responsiveness in permissionless consensus. In a responsive protocol, the transaction confirmation time depends only on the actual network delay, but not on any a-priori known upper bound such as a synchronous round. Classical protocols in the partial synchronous and asynchronous models naturally achieve responsiveness, since the protocol does not even know any delay upper bound. Unfortunately, we show that in the permissionless setting, consensus is impossible in the asynchronous or partially synchronous models. ::: ::: On the positive side, we construct a protocol called Hybrid Consensus by combining classical-style and blockchain-style consensus. Hybrid Consensus shows that responsiveness is nonetheless possible to achieve in permissionless consensus (assuming proof-of-work) when 1) the protocol knows an upper bound on the network delay; 2) we allow a non-responsive warmup period after which transaction confirmation can become responsive; 3) honesty has some stickiness, i.e., it takes a short while for an adversary to corrupt a node or put it to sleep; and 4) less than 1/3 of the nodes are corrupt. We show that all these conditions are in fact necessary - if only one of them is violated, responsiveness would have been impossible. Our work makes a step forward in our understanding of the permissionless model and its differences and relations to classical consensus. \n5. Abstract of Cited Paper (BIB005): Proof of Work (PoW) powered blockchains currently account for more than 90% of the total market capitalization of existing digital cryptocurrencies. Although the security provisions of Bitcoin have been thoroughly analysed, the security guarantees of variant (forked) PoW blockchains (which were instantiated with different parameters) have not received much attention in the literature. This opens the question whether existing security analysis of Bitcoin's PoW applies to other implementations which have been instantiated with different consensus and/or network parameters. In this paper, we introduce a novel quantitative framework to analyse the security and performance implications of various consensus and network parameters of PoW blockchains. Based on our framework, we devise optimal adversarial strategies for double-spending and selfish mining while taking into account real world constraints such as network propagation, different block sizes, block generation intervals, information propagation mechanism, and the impact of eclipse attacks. Our framework therefore allows us to capture existing PoW-based deployments as well as PoW blockchain variants that are instantiated with different parameters, and to objectively compare the tradeoffs between their performance and security provisions.\n\nLiterature Review:", "role": "user" }, { "content": "Blockchain is a peer-to-peer distributed ledger technology that provides a shared, immutable, and transparent append-only register of all the actions that have happened to all the participants of the network. It is secured using cryptographic primitives such as hash function, digital signature, and encryption . The data in the form of transactions, digitally signed and broadcasted by the participants, are grouped into the blocks in the chronological order and timestamped. A hash function is applied to the content of the block and forms a unique block identifier, which is stored in the subsequent block. Due to the properties of the hash function, (result is deterministic and can not be reversed) it could be easily verified if the content of the block was modified by hashing the block content again and comparing it with the identifier from the subsequent block. The blockchain is replicated and maintained by every participant. With this decentralized approach there is no need for setting up a trusted centralized entity for managing the registry. A malicious attempt to tamper the information stored in the registry will be noticed by the participants, thus guaranteeing immutability of the ledger. Many blockchains can execute arbitrary tasks, typically called smart contracts BIB001 , written in a domain-specific or a general-purpose programming language BIB005 . To add a new block to the ledger a consensus protocol is employed . Based on how the identity of a participant and its right to participate in the consensus are defined within a network, one could distinguish between public and private, permissioned and permissionless blockchain systems. In a permissionless blockchain, such as Bitcoin or Ethereum , anyone can can join the network, anyone can \"write\" to the shared state through invoking transactions (provided transaction fees are paid for), and anyone can participate in the consensus process for determining the \"valid\" state. Permissionless (or \"public\") blockchains are coupled to a cryptocurrency and their consensus protocols, such as proof-of-work (PoW). PoW consensus protocol was presented in in the framework of the first application of blockchain technology for Bitcoin cryptocurrency management. PoW is based on so-called \"mining\": a process of looking for a nonce -a random number that is stored in every block -so that the resulting hash of a new valid block satisfies certain requirements. These requirements set the difficulty threshold for the process of finding the nonce and determines the average number of hashes needed to mine one block. This impacts the amount of energy to be spent to find such nonce. In 2013 the amount of energy used by Bitcoin mining was already comparable to the Irish national energy consumption BIB003 . Existing PoW blockchains can achieve throughput of not more than 60 transactions per second without significantly affecting the blockchain's security BIB006 . These findings show that PoW can negatively impact the system scalability and overall throughput BIB004 . Trying to address these issues researchers have challenged various aspects of the Bitcoin system and proposed modifications in its core operation, e.g., modification of the block generation rate or alternative proof of work implementations. A security analysis of PoW based consensus protocols can be found in . A permissioned blockchain in contrast has means to identify the nodes that can control and update the shared state, and often also have ways to control who can issue transactions. Consensus protocols for reaching an agreement by exchanging messages even if some nodes fail, collude, or send the corrupted messages could be employed in permissioned blockchain systems. In the authors present an overview of consensus protocols used in the context of permissioned blockchains. The authors also review the underlying principles, and compare the resilience and trustworthiness of some protocols as well as the permissioned blockchain systems (e.g., Hyperledger Fabric, Tendermint, R3 Corda, and MultiChain). Another approach to constructing a blockchain relies on properties of Keyless Signatures Infrastructure (KSI) BIB002 . KSI is a globally distributed system for providing time-stamping and server-supported digital signature services. KSI blockchain (Guardtime) employs chain-resistance property of hash functions to verify the integrity of the data using hash-chain. KSI Blockchain deployed, for instance, in Estonian government networks to insure the integrity of the data stored in government repositories and protect them against insider threats. The number of participants in the KSI consensus protocol is limited, which allows to eliminate the need for PoW and ensuring that settlement can occur within one second. However, major drawbacks of such approach is limited decentralization and required trust in the participants of KSI consensus.", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nconclusion\n\nContext before the citation:\nFor projective parsing, it is significantly faster than exact dynamic programming, at the cost of small amounts of search error, We are interested in extending these ideas to phrase-structure and lattice parsing, and in trying other higher-order features, such as those used in parse reranking (Charniak and Johnson, 2005; Huang, 2008) and history-based parsing (Nivre and McDonald, 2008). Belief propagation improves non-projective dependency parsing with features that would make exact inference intractable.\n\nCitation Sentence:\nFor projective parsing , it is significantly faster than exact dynamic programming , at the cost of small amounts of search error , We are interested in extending these ideas to phrase-structure and lattice parsing , and in trying other higher-order features , such as those used in parse reranking ( Charniak and Johnson , 2005 ; Huang , 2008 ) and history-based parsing ( Nivre and McDonald , 2008 ) .\n\nContext after the citation:\nWe could also introduce new variables, e.g., nonterminal refinements (Matsuzaki et al., 2005), or secondary links Mid (not constrained by TREE/PTREE) that augment the parse with representations of control, binding, etc. (Sleator and Temperley, 1993; Buch-Kromann, 2006). Other parsing-like problems that could be attacked with BP appear in syntax-based machine translation. Decoding is very expensive with a synchronous grammar composed with an n-gram language model (Chiang, 2007)—but our footnote 10 suggests that BP might incorporate a language model rapidly. String alignment with synchronous grammars is quite expensive even for simple synchronous formalisms like ITG (Wu, 1997)—but Duchi et al. (2007) show how to incorporate bipartite matching into max-product BP.", "role": "user" }, { "content": "FutureWork", "role": "assistant" } ]

[ { "content": "You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.\n\nQuestion: When is the protein NFL a biomarker?\n\nContext: Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.\nCSF neurofilament light chain reflects corticospinal tract degeneration in ALS.\nRaised neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal damage in a range of neurological disorders.\nSerum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome.\nDetection of neurofilament-H in serum as a diagnostic tool to predict injury severity in patients who have suffered mild traumatic brain injury.\nCerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders, including frontotemporal degeneration (FTD).\nWe examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method.\nFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.\nAnalysis of MBP, NFL and GFAp provides direct means to measure tissue damage and is a useful addition to our methods for evaluation of MS.\nThe association of prolonged CSF NFL increase in boxers with impairment of processing speed is an interesting observation, which needs to be verified in larger studies.\nneurofilament light chain (NfL) levels in CSF of relapsing remitting (RR) patients with MS were normalized by natalizumab treatment\nOur results suggest that NfL is superior over NfH(SMI) (35) as therapeutic biomarker and is a promising candidate to measure neuroaxonal damage in MS treatment trials.\nIncreased neurofilament light chain blood levels in neurodegenerative neurological diseases.\nOur data supports further longitudinal studies of serum NfL in neurodegenerative diseases as a potential biomarker of on-going disease progression, and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.\nWe confirmed and expanded upon previous findings regarding neurofilaments as quantitative markers of neurodegeneration\nCSF T-tau, GFAP, and NFL are differently altered across different neurologic diseases in children\nCerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia.\nhe marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies.\nHigh levels of NFL also correlated with the presence of an AD biomarker pattern defined by Aβ42/P-tau and T-tau.\nIncreased CSF levels of T-tau, NFL, GFAP, and S-100B in>80% of the boxers demonstrate that both the acute and the cumulative effect of head trauma in Olympic boxing may induce CSF biomarker changes that suggest minor central nervous injuries.\neurofilament light protein (NFL), may both be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS). We investigated GFAP and NFL levels in CSF as possible biomarkers for progression in multiple sclerosis (MS).\nA CSF profile with higher levels of NFL, Abeta42, and CSF/serum albumin ratio may indicate neuropathological and vascular events in depression etiology.\nAt present we cannot recommend CSF NfH and NfL levels for use as a screening test in the diagnosis of dementia because of the rather small effect size. However, both neurofilament proteins may be of value for targeted investigation of some patients with FTLD, SVD and AD.\nDifferences in CSF biomarker profiles might reflect differential involvement of neurofilaments and tau in FTD and EAD. The subgroup of FTD patients with high CSF neurofilament levels may have a different neuropathological substrate and future studies addressing this specific issue are needed.\nIncreased levels of neurofilament light chain and tau and decreased levels of 3-methoxy-4-hydroxyphenylethyleneglycol were associated with high accuracy levels in differentiating the cerebellar subtype of multiple-system atrophy from idiopathic late-onset cerebellar ataxia (LOCA).\nIncreased level of NFL is a general feature of MS, indicating continuous axonal damage during the entire course of the disease with the most profound damage during acute relapses.\nNeurofilament light protein and glial fibrillary acidic protein as biological markers in MS.", "role": "user" }, { "content": "Neurofilament light protein (NFL), may be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS).\nNeurofilament light chain is a prognostic biomarker in neurological disorders such as amyotrophic lateral sclerosis, frontotemporal degeneration, axonal injury, late-onset cerebellar ataxia, multiple sclerosis and head trauma.", "role": "assistant" } ]

[ { "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: We propose a new fully convolutional architecture for lip reading. We train the proposed model with CTC loss and\n\nKeyphrases: lip reading video paragraph-level\n\nDataset description:\nLRS2: The Oxford-BBC Lip Reading Sentences 2 (LRS2) dataset is one of the largest publicly available datasets for lip reading sentences in-the-wild. The database consists of mainly news and talk shows from BBC programs.\nLRW: The Lip Reading in the Wild (LRW) dataset a large-scale audio-visual database that contains 500 different words from over 1,000 speakers. Each utterance has 29 frames, whose boundary is centered around the target word.\nLocalized Narratives: We propose Localized Narratives, a new form of multimodal image annotations connecting vision and language. We ask annotators to describe an image with their voice while simultaneously hovering their mouse over the region they are describing.\nUASOL: The UASOL an RGB-D stereo dataset, that contains 160902 frames, filmed at 33 different scenes, each with between 2 k and 10 k frames. The frames show different paths from the perspective of a pedestrian, including sidewalks, trails, roads, etc.\nCOCO-Text: The COCO-Text dataset is a dataset for text detection and recognition. It is based on the MS COCO dataset, which contains images of complex everyday scenes.\nNAS-Bench-101: NAS-Bench-101 is the first public architecture dataset for NAS research. To build NASBench-101, the authors carefully constructed a compact, yet expressive, search space, exploiting graph isomorphisms to identify 423k unique convolutional architectures.\n\nOptions:- A: LRS2 B: LRW C: Localized Narratives D: UASOL E: COCO-Text F: NAS-Bench-101", "role": "user" }, { "content": "[\"LRS2\", \"LRW\"]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"RNA\", \"CellType\", \"CellLine\", \"Protein\", \"DNA\"].\n\nPlease return the output as a JSON object of the format: {\"DNA\" : [\"TAL1\", ...], \"RNA\": [\"mRNAs\", ...], \"CellLine\": [\"T cells\", ...], \"CellType\": [\"monocytes\", ...], \"Protein\": [\"IL-2\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nOxidants, transcription factors, and intestinal inflammation. It is now well appreciated that chronic gut inflammation is characterized by enhanced production of reactive metabolites of oxygen and nitrogen. Some of these oxidants are known to modulate the expression of a variety of genes that are involved in the immune and inflammatory responses. For example, certain oxidants are known to activate the nuclear transcription factor kappa B, which regulates the expression of a variety of different adhesion molecules, cytokines, and enzymes. Oxidants are also known to activate another transcription factor, activator protein-1. This transcription factor is composed of products from the fos and jun proto-oncogene family and is believed to be important in regulating cell growth and proliferation. Finally, oxidants are believed to promote intestinal epithelial cell apoptosis, and the B-cell lymphoma / leukemia-2 gene product is believed to inhibit this phenomenon in an antioxidant-dependent manner. Taken together, these observations suggest that nontoxic concentrations of reactive metabolites of oxygen and nitrogen play an important role in regulating the expression of genes involved in the inflammatory response and in modulating apoptosis.", "role": "user" }, { "content": "{\"CellLine\": [], \"CellType\": [\"intestinal epithelial cell\"], \"DNA\": [], \"Protein\": [\"cytokines\", \"transcription factor\", \"activator protein - 1\", \"B - cell lymphoma / leukemia - 2 gene product\", \"transcription factors\", \"fos and jun proto - oncogene family\", \"adhesion molecules\", \"nuclear transcription factor kappa B\", \"enzymes\"], \"RNA\": []}", "role": "assistant" } ]

[ { "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nThe missing slope: paradoxical shortening of activated partial thromboplastin time in a patient on unfractionated heparin therapy\n\nPaper sections:\nIntroduction\n<p>Activated partial thromboplastin time (aPTT) is a widely used coagulation test intended for screening of clotting factor deficiencies within intrinsic and common coagulation pathways, for detecting presence of circulating inhibitors such as lupus anticoagulant, and for therapeutic monitoring of unfractionated heparin (UFH). The principle of the test is based on measuring platelet-poor plasma clotting time after addition of contact activators, phospholipids and calcium. The test is nowadays usually performed on fully automated or semiautomated coagulometers with photo-optical or mechanical detection. Clot formation is identified by a change in optical density (OD) of the reaction mixture and aPTT is defined as elapsed time in seconds when the reaction mixture OD has exceeded a predefined threshold (1). Interfering substances that change the sample OD inevitably influence optical coagulometer readings (2). Besides the well-documented effects of hemolysis, icterus and lipemia on aPTT determination, it has been reported that in some critically ill conditions deviations from the normal sigmoidal OD curve pattern can occur, leading to erroneous optical readings (2, 3). The most common example is the biphasic waveform which can be encountered in patients with hemostatic dysfunction caused by disseminated intravascular coagulation (DIC) and sepsis (1, 4).</p><p>Hereby, we present an unusual case of a falsely shortened aPTT result due to erroneous optical reading of the clotting point in the presence of both UFH and a biphasic waveform.</p>\n\nCase report\n<p>Activated partial thromboplastin time was requested as part of routine laboratory monitoring of UFH therapy. A blood sample drawn into a 4.5 mL 0.105 M (3.2%) trisodium citrate vacutainer (Becton Dickinson, Plymouth, United Kingdom) was promptly delivered to the Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Croatia. Upon receipt, the sample was processed without delay according to standard laboratory operation procedure, i.e. visual inspection for clots followed by centrifugation of the sample tube at 2000xg for 15 minutes at room temperature within one hour from blood collection. The obtained plasma was clear, without visible turbidity or haemolysis.</p><p>Activated partial thromboplastin time determination was performed by coagulometric method using Dade Actin FS and Calcium Chloride (Siemens Healthcare, Marburg, Germany) with photo-optical clot-detection system on the Sysmex CS-5100 automated coagulation analyser (Siemens Healthcare, Marburg, Germany) according to manufacturer's recommendations. A normal aPTT measurement curve is shown in Figure 1.</p>\n\n\n<p>A normal, sigmoidal activated partial thromboplastin time (aPTT) clotting curve with an initial plateu, followed by decrease in light transmittance due to clot formation and a final plateau once the clot formation is completed. The clotting point is set at 50% of the descending clotting curve.</p>\n\nCase report\n<p>An ambiguous aPTT result was obtained and therefore numerical result was omitted and replaced by asterisks (******). The analyser software generated a flag indicating that further review by laboratory staff was required. The clotting point read by the analyser was at 65 seconds (reference interval: 24-33 seconds). Detailed visual inspection revealed an atypical clotting curve as shown in Figure 2A, accompanied by a flag indicating Early reaction error: Slow reaction, which raised a suspicion about a non-specific initial decrease in light transmittance and interference in optical reading.</p>\n\n\n<p>aPTT clotting curves with clotting points obtained on the coagulometer with photo-optical detection and accompanying analyser flags at (A) initial blood draw, after (B) 3 hours, (C) 7 hours and (D) 11 hours; The biphasic waveforms are in (A) and (B), and to a less extent in (C), masked by a prolonged aPTT due to unfractionated heparin, and caused erroneous optical reading of the clotting point; Reported aPTT values were in cases (A) and (B) obtained using the mechanical clot detection method, while for (C) by manual reading of the clotting point at 50% of the secondary decreasing slope of the clotting curve obtained photo-optically; (D) represents a typical biphasic aPTT waveform with proper photo-optical reading of the clotting point which corresponds to the reported aPTT. aPTT - activated partial thromboplastin time.</p>\n\nCase report\n<p>Therefore, we additionally performed aPTT measurement by a mechanical clot detection method utilizing the semiautomated dual-channel BEHRING Fibrintimer (Sysmed Lab, Europe Inc., Poland) analyser and using the same reagents as for the optical method. No clot formation was detected and an unmeasurable aPTT was obtained (> 150 seconds).</p><p>Since the most common cause of aPTT prolongation is heparin presence, we performed another heparin-sensitive coagulation assay - thrombin time (TT). The measurement was done utilizing Test Thrombin reagent (Siemens Healthcare, Marburg, Germany) on the Sysmex CS-5100 analyser. An unmeasurably prolonged result was observed (> 150 seconds, reference interval: 16-18 seconds).</p><p>Further investigation of the case, done through communication with clinicians, revealed that the patient was treated with extracorporeal membrane oxygenation (ECMO) after a cardiorespiratory arrest and therefore inevitably required continuous UFH infusion. The patient's condition was additionally complicated by sepsis, as confirmed by blood culture, and by a markedly elevated C-reactive protein (CRP) of 289 mg/L (reference interval: < 5 mg/L). Procalcitonin was not requested since it was not needed for case clarification.</p><p>Furthermore, aPTT for the same patient was requested three more times during the same day, i.e. 3, 7 and 11 hours after the initial blood draw, with clotting curves as shown in Figures 2B-2D, respectively. These subsequent analyses revealed gradual aPTT shortening and unveiled a peculiar biphasic waveform pattern which was not visible in the initial aPTT determination due to unmeasurably prolonged aPTT. Figure 2D represents a typical biphasic aPTT waveform.</p>\n\nWhat happened?\n<p>Unmeasurably prolonged aPTT due to UFH therapy was masked by a biphasic aPTT curve pattern, making only the first slope of the biphasic waveform visible within the measuring range. Early decrease in plasma light transmittance mimicked optical changes related to clot formation, thus causing erroneous optical reading and yielding a falsely shortened aPTT.</p>\n\nDiscussion\n<p>Automated coagulation analysers with photo-optical detection measure a change in light transmittance in the reaction mixture during the entire clotting process and yield an appropriate curve. Regular clotting curves have an initial, horizontal plateau with no change in light transmittance, followed by an abrupt decrease once the coagulation process begins due to fibrin polymerisation, ending with a final, steady-state plateau when clot formation is completed, eventually forming a sigmoid-shaped curve (1, 4). Abnormal biphasic clotting curves due to non-clot formation-related changes of light transmittance, as those described herein, trigger a particular analyzer flag and inevitably require visual inspection by the operator. Typical biphasic aPTT waveforms are characterized by absence of the initial plateau coupled with immediate, steady decline in light transmittance in the early precoagulation phase, followed by a secondary, sigmoidal decreasing slope when clot formation actually occurs (5). This is thought to be attributable to the rapid formation of Ca2+-dependent macroscopic complex consisting of CRP and very low density lipoprotein (VLDL) that is triggered by recalcification of citrate plasma through addition of aPTT reagents. This immediately causes changes in the reaction mixture OD, reflected as an early drop in light transmittance (5). Although the underlying mechanism has not been completely elucidated, it was suggested that both a substantially elevated CRP and adequate levels of VLDL that exhibit a high surface activity for prothrombin activation are necessary for the complex formation (1, 5). The reaction itself requires calcium ions, but does not depend on the composition of the aPTT reagent. Such pattern can be seen in critically ill patients with conditions that often lead to DIC, the most common being sepsis, but also in cases of trauma, severe burns or malignancies (4). Earlier studies have shown that the presence of a biphasic waveform is associated with increased mortality rates and can be an early indicator of adverse outcomes (4, 6-8). Given the diagnosis of sepsis and a concomitant high CRP level in the studied case, it can be highly suspected that the observed biphasic waveform resulted from the formation of CRP-VLDL complexes once the plasma recalcification had occurred. Unlike other described cases, this one was additionally complicated by UFH therapy that caused aPTT prolongation, masked the biphasic shape of the clotting curve and paradoxically yielded false shortening of aPTT when measured photo-optically.</p><p>The nowadays less frequently used semiautomated mechanical clot detection method was a valuable alternative in our case since it simply measures the clotting endpoint by detecting changes in the movement of a steel ball or rod in the reaction cuvette, and is therefore not susceptible to optical interferences (3). This method revealed an unmeasurable aPTT, a result which was consistent with UFH therapy that the patient was receiving during ECMO support. The presence of UFH in the sample was further supported by unmeasurably prolonged TT. Heparin binds to antithrombin and in that way exhibits its inhibitory effect on thrombin, prolonging both aPTT and TT (9). Neither D-dimers nor fibrinogen were concomitantly determined to evaluate the possible development of DIC, which could have elucidated the underlying pathophysiological cause of the interference.</p>\n\n\n<p>A biphasic aPTT clotting curve should be considered when an early and progressive decrease in light transmittance is present.</p><p>Such pattern should serve as an alert for a possible underlying interference in optical reading that might require manual reading of the clotting point or even adoption of a mechanical clot detection method.</p><p>Special attention should be given to the combination of a critically ill condition, most commonly sepsis or DIC, and UFH therapy which can result in an ambiguous biphasic aPTT waveform where the slope related to clot formation is not present due to the anticoagulant effect of UFH.</p><p>Biological interference should not be overlooked as a potential source of preanalytical errors in coagulation testing.</p><p>Potential conflict of interest</p><p>None declared.</p>", "role": "user" }, { "content": "This case report describes false shortening of activated partial thromboplastin time (aPTT) due to erroneous optical reading of the clotting point in the presence of unfractionated heparin (UFH), and a biphasic waveform. Activated partial thromboplastin time performed on a coagulometer with photo-optical detection yielded an ambiguous clotting curve characterized by an early and steady decrease in light transmittance throughout the whole measuring range, with the clotting point read at 65 seconds. Further investigations included measurement of aPTT by means of a mechanical clot detection method as well as determination of another heparin-sensitive coagulation assay, that is thrombin time (TT), both being unmeasurably prolonged (> 150 seconds). Communication with clinicians revealed that the patient was on continuous UFH therapy and had an underlying sepsis, with highly elevated C-reactive protein (289 mg/L). The aPTT measurements requested at three timepoints later during the same day revealed gradual aPTT shortening and unveiled a peculiar biphasic waveform pattern. In this case, unmeasurably prolonged aPTT due to UFH therapy was masked by a biphasic aPTT curve pattern making only the first slope of the biphasic waveform visible within the measuring range. The early decrease in plasma light transmittance mimicked optical changes related to clot formation, thus causing erroneous optical reading and yielding a falsely shortened aPTT. This case emphasizes that such a pattern should be carefully inspected, especially when a combination of a critically ill condition and UFH therapy is present, in order to prevent erroneous reporting of aPTT and potential adverse effects on patient care.", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a materials science research paper. Your task is to extract all synthesis operations described in the abstract into a structured JSON format. Your output should be a JSON array. Each entry in the array should be a JSON object describing a single synthesis operation. Your output JSON object should have the following two fields:\n\n- \"trigger\": A verbal predicate indicating a synthesis operation. This should be a string extracted directly from the abstract.\n- \"arguments\": An array of arguments specifying aspects of the synthesis operation. Each entry in the array should be a length-2 array formatted as [<argument_text>, <argument_type>]. The `argument_text` should be a string extracted directly from the abstract. The `argument_type` should be one of the following types: [\"Recipe_Precursor\", \"Solvent_Material\", \"Atmospheric_Material\", \"Participant_Material\", \"Recipe_Target\"].\n\nFor instance, suppose an excerpt from the abstract reads:\n\nTetraethoxysilane (TEOS, 98%) and cetyltrimethylammonium bromide (CTAB, 98%) were purchased from Fluka. The MTTZ-siloxy derivative (triethoxysilyl-propyl-5-mercapto-1-methyl-tetrazole) was synthesized as previously described [38].\n\nThis excerpt includes two operations, which could be annotated as follows:\n\n[{\"arguments\": [[\"Tetraethoxysilane\", \"Recipe_Precursor\"], [\"cetyltrimethylammonium bromide\", \"Recipe_Precursor\"]], \"trigger\": \"purchased\"}, {\"arguments\": [[\"MTTZ-siloxy derivative\", \"Recipe_Target\"]], \"trigger\": \"synthesized\"}]\n\nIn your response, please include the JSON and no other text.\n\nAbstract:\n10.1016/j.snb.2015.03.104\nAn electrochemical sensor for H2O2 based on a new Co-metal-organic framework modified electrode\n\nA mixture of Co(AC)2*4H2O (0.25 mM, 62 mg), H2pbda (H2pbda = 3-(pyridine-3-yloxy)benzene-1,2-dicarboxylic acid) (0.25 mM, 78 mg), 4,4-bpy(0.25 mM, 48 mg) and KOH (0.05 mM, 28 mg) was added in 10 ml distilled water and stirred at room temperature for 30 min, then the resulting mixture was sealed in a 25 ml Teflon-lined stainless steel vessel and heated at 160 degC for 3 days. After the reactant was cooled slowly to room temperature with a cooling rate of 5 degC/h, purple block-shaped crystals were obtained in 60% yield (based on Co). Elemental anal. (%): Calcd. For [Co(pbda)(4,4-bpy)*2H2O]n: C 51.44, H 3.12, N 6.67. Found: C 50.13, H 3.32, N 6.78. Crystallographic parameters for (Co(pbda)(4,4-bpy)*2H2O)n: a = 21.9803(8) Å, b = 17.2195(7) Å, c = 9.2491(3) Å, α = 90.00deg, β = 105.929(2)deg, γ = 90.00deg, Mr = 841.48, monoclinic, space group C2/c, V = 3366.3(2) Å3, Z = 4, goodness-of-fit = 1.029, R1 = 0.0559 ([I > 2σ(I)]) and wR2 = 0.0965 (all data). Crystallographic data (CIF file) of [Co(pbda)(4,4-bpy)*2H2O]n have been deposited at the Cambridge Crystallographic Data Centre and CCDC deposition number is 1034563. These data can be obtained free of charge via email deposit@ccdc.cam.ac.uk.", "role": "user" }, { "content": "[{\"arguments\": [[\"KOH\", \"Participant_Material\"], [\"H2pbda\", \"Recipe_Precursor\"], [\"Co(AC)2*4H2O\", \"Recipe_Precursor\"], [\"4,4-bpy\", \"Recipe_Precursor\"], [\"water\", \"Solvent_Material\"]], \"trigger\": \"added\"}, {\"arguments\": [[\"mixture\", \"Participant_Material\"]], \"trigger\": \"sealed\"}, {\"arguments\": [[\"reactant\", \"Participant_Material\"]], \"trigger\": \"cooled\"}, {\"arguments\": [[\"crystals\", \"Participant_Material\"]], \"trigger\": \"obtained\"}]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nAspirin and aspirin resistance in coronary artery disease. Aspirin is still the mainstay of antiplatelet therapy in the secondary prevention of coronary artery disease. However certain patients do not benefit from the antithrombotic effects of aspirin. The phenomenon of so-called aspirin resistance can be considered from the clinical and laboratory perspective. A variety of methods have emerged for the laboratory diagnosis of aspirin resistance. None of them is considered ideal as they provide conflicting information with significant inter-individual variability and weak correlation between them. With the mechanisms of aspirin resistance not fully understood and the phenomenon commonly observed in individuals with poor compliance, the existence of aspirin resistance has been challenged. The aim of this review is to present recent data on the impact of aspirin resistance in primary and secondary prevention of coronary artery disease.", "role": "user" }, { "content": "{\"Chemical\": [\"aspirin\", \"Aspirin\"]}", "role": "assistant" } ]

[ { "content": "You will be shown sections from a scientific research paper, together with a question about the paper. This is an extractive question-answering task, where you must find and extract relevant text spans directly from the paper to answer the question. Your response should strictly be a `json` object with two fields:\n\n\"answer\": An array of strings extracted directly from the paper which, collectively, answer the question.\n\"evidence\": An array of strings. Each should be an excerpt from the paper, in which one or more of the extracted answers can be found.\n\nFor example, for the question \"What baselines did the authors compare against?\", a sample response might be:\n{\n \"answer\": [\"BERT\", \"RoBERTa\"],\n \"evidence\": [\"In our experiments, we compare the performance of our model against BERT and RoBERTa.\"]\n}\n\nDo not include any text in your response other than the json.\n\nIf the question is unanswerable given the provided excerpts, respond with the single word \"null\".\n\nPaper: Recognizing Musical Entities in User-generated Content\n\nRecognizing Musical Entities is important for Music Information Retrieval (MIR) since it can improve the performance of several tasks such as music recommendation, genre classification or artist similarity. However, most entity recognition systems in the music domain have concentrated on formal texts (e.g. artists' biographies, encyclopedic articles, etc.), ignoring rich and noisy user-generated content. In this work, we present a novel method to recognize musical entities in Twitter content generated by users following a classical music radio channel. Our approach takes advantage of both formal radio schedule and users' tweets to improve entity recognition. We instantiate several machine learning algorithms to perform entity recognition combining task-specific and corpus-based features. We also show how to improve recognition results by jointly considering formal and user-generated content\n\nIntroduction\nThe increasing use of social media and microblogging services has broken new ground in the field of Information Extraction (IE) from user-generated content (UGC). Understanding the information contained in users' content has become one of the main goal for many applications, due to the uniqueness and the variety of this data BIBREF0 . However, the highly informal and noisy status of these sources makes it difficult to apply techniques proposed by the NLP community for dealing with formal and structured content BIBREF1 .\nIn this work, we analyze a set of tweets related to a specific classical music radio channel, BBC Radio 3, interested in detecting two types of musical named entities, Contributor and Musical Work.\nThe method proposed makes use of the information extracted from the radio schedule for creating links between users' tweets and tracks broadcasted. Thanks to this linking, we aim to detect when users refer to entities included into the schedule. Apart from that, we consider a series of linguistic features, partly taken from the NLP literature and partly specifically designed for this task, for building statistical models able to recognize the musical entities. To that aim, we perform several experiments with a supervised learning model, Support Vector Machine (SVM), and a recurrent neural network architecture, a bidirectional LSTM with a CRF layer (biLSTM-CRF).\nThe contributions in this work are summarized as follows:\nThe paper is structured as follows. In Section 2, we present a review of the previous works related to Named Entity Recognition, focusing on its application on UGC and MIR. Afterwards, in Section 3 it is presented the methodology of this work, describing the dataset and the method proposed. In Section 4, the results obtained are shown. Finally, in Section 5 conclusions are discussed.\n\nRelated Work\nNamed Entity Recognition (NER), or alternatively Named Entity Recognition and Classification (NERC), is the task of detecting entities in an input text and to assign them to a specific class. It starts to be defined in the early '80, and over the years several approaches have been proposed BIBREF2 . Early systems were based on handcrafted rule-based algorithms, while recently several contributions by Machine Learning scientists have helped in integrating probabilistic models into NER systems.\nIn particular, new developments in neural architectures have become an important resource for this task. Their main advantages are that they do not need language-specific knowledge resources BIBREF3 , and they are robust to the noisy and short nature of social media messages BIBREF4 . Indeed, according to a performance analysis of several Named Entity Recognition and Linking systems presented in BIBREF5 , it has been found that poor capitalization is one of the main issues when dealing with microblog content. Apart from that, typographic errors and the ubiquitous occurrence of out-of-vocabulary (OOV) words also cause drops in NER recall and precision, together with shortenings and slang, particularly pronounced in tweets.\nMusic Information Retrieval (MIR) is an interdisciplinary field which borrows tools of several disciplines, such as signal processing, musicology, machine learning, psychology and many others, for extracting knowledge from musical objects (be them audio, texts, etc.) BIBREF6 . In the last decade, several MIR tasks have benefited from NLP, such as sound and music recommendation BIBREF7 , automatic summary of song review BIBREF8 , artist similarity BIBREF9 and genre classification BIBREF10 .\nIn the field of IE, a first approach for detecting musical named entities from raw text, based on Hidden Markov Models, has been proposed in BIBREF11 . In BIBREF12 , the authors combine state-of-the-art Entity Linking (EL) systems to tackle the problem of detecting musical entities from raw texts. The method proposed relies on the argumentum ad populum intuition, so if two or more different EL systems perform the same prediction in linking a named entity mention, the more likely this prediction is to be correct. In detail, the off-the-shelf systems used are: DBpedia Spotlight BIBREF13 , TagMe BIBREF14 , Babelfy BIBREF15 . Moreover, a first Musical Entity Linking, MEL has been presented in BIBREF16 which combines different state-of-the-art NLP libraries and SimpleBrainz, an RDF knowledge base created from MusicBrainz after a simplification process.\nFurthermore, Twitter has also been at the center of many studies done by the MIR community. As example, for building a music recommender system BIBREF17 analyzes tweets containing keywords like nowplaying or listeningto. In BIBREF9 , a similar dataset it is used for discovering cultural listening patterns. Publicly available Twitter corpora built for MIR investigations have been created, among others the Million Musical Tweets dataset BIBREF18 and the #nowplaying dataset BIBREF19 .\n\nMethodology\nWe propose a hybrid method which recognizes musical entities in UGC using both contextual and linguistic information. We focus on detecting two types of entities: Contributor: person who is related to a musical work (composer, performer, conductor, etc). Musical Work: musical composition or recording (symphony, concerto, overture, etc).\nAs case study, we have chosen to analyze tweets extracted from the channel of a classical music radio, BBC Radio 3. The choice to focus on classical music has been mostly motivated by the particular discrepancy between the informal language used in the social platform and the formal nomenclature of contributors and musical works. Indeed, users when referring to a musician or to a classical piece in a tweet, rarely use the full name of the person or of the work, as shown in Table 2.\nWe extract information from the radio schedule for recreating the musical context to analyze user-generated tweets, detecting when they are referring to a specific work or contributor recently played. We manage to associate to every track broadcasted a list of entities, thanks to the tweets automatically posted by the BBC Radio3 Music Bot, where it is described the track actually on air in the radio. In Table 3, examples of bot-generated tweets are shown.\nAfterwards, we detect the entities on the user-generated content by means of two methods: on one side, we use the entities extracted from the radio schedule for generating candidates entities in the user-generated tweets, thanks to a matching algorithm based on time proximity and string similarity. On the other side, we create a statistical model capable of detecting entities directly from the UGC, aimed to model the informal language of the raw texts. In Figure 1, an overview of the system proposed is presented.\n\nNER system\nAccording to the literature reviewed, state-of-the-art NER systems proposed by the NLP community are not tailored to detect musical entities in user-generated content. Consequently, our first objective has been to understand how to adapt existing systems for achieving significant results in this task.\nIn the following sections, we describe separately the features, the word embeddings and the models considered. All the resources used are publicy available.\nWe define a set of features for characterizing the text at the token level. We mix standard linguistic features, such as Part-Of-Speech (POS) and chunk tag, together with several gazetteers specifically built for classical music, and a series of features representing tokens' left and right context. For extracting the POS and the chunk tag we use the Python library twitter_nlp, presented in BIBREF1 .\nIn total, we define 26 features for describing each token: 1)POS tag; 2)Chunk tag; 3)Position of the token within the text, normalized between 0 and 1; 4)If the token starts with a capital letter; 5)If the token is a digit. Gazetteers: 6)Contributor first names; 7)Contributor last names; 8)Contributor types (\"soprano\", \"violinist\", etc.); 9)Classical work types (\"symphony\", \"overture\", etc.); 10)Musical instruments; 11)Opus forms (\"op\", \"opus\"); 12)Work number forms (\"no\", \"number\"); 13)Work keys (\"C\", \"D\", \"E\", \"F\" , \"G\" , \"A\", \"B\", \"flat\", \"sharp\"); 14)Work Modes (\"major\", \"minor\", \"m\"). Finally, we complete the tokens' description including as token's features the surface form, the POS and the chunk tag of the previous and the following two tokens (12 features).\nWe consider two sets of GloVe word embeddings BIBREF20 for training the neural architecture, one pre-trained with 2B of tweets, publicy downloadable, one trained with a corpora of 300K tweets collected during the 2014-2017 BBC Proms Festivals and disjoint from the data used in our experiments.\nThe first model considered for this task has been the John Platt's sequential minimal optimization algorithm for training a support vector classifier BIBREF21 , implemented in WEKA BIBREF22 . Indeed, in BIBREF23 results shown that SVM outperforms other machine learning models, such as Decision Trees and Naive Bayes, obtaining the best accuracy when detecting named entities from the user-generated tweets.\nHowever, recent advances in Deep Learning techniques have shown that the NER task can benefit from the use of neural architectures, such as biLSTM-networks BIBREF3 , BIBREF4 . We use the implementation proposed in BIBREF24 for conducting three different experiments. In the first, we train the model using only the word embeddings as feature. In the second, together with the word embeddings we use the POS and chunk tag. In the third, all the features previously defined are included, in addition to the word embeddings. For every experiment, we use both the pre-trained embeddings and the ones that we created with our Twitter corpora. In section 4, results obtained from the several experiments are reported.\n\nSchedule matching\nThe bot-generated tweets present a predefined structure and a formal language, which facilitates the entities detection. In this dataset, our goal is to assign to each track played on the radio, represented by a tweet, a list of entities extracted from the tweet raw text. For achieving that, we experiment with the algorithms and features presented previously, obtaining an high level of accuracy, as presented in section 4. The hypothesis considered is that when a radio listener posts a tweet, it is possible that she is referring to a track which has been played a relatively short time before. In this cases, we want to show that knowing the radio schedule can help improving the results when detecting entities.\nOnce assigned a list of entities to each track, we perform two types of matching. Firstly, within the tracks we identify the ones which have been played in a fixed range of time (t) before and after the generation of the user's tweet. Using the resulting tracks, we create a list of candidates entities on which performing string similarity. The score of the matching based on string similarity is computed as the ratio of the number of tokens in common between an entity and the input tweet, and the total number of token of the entity: DISPLAYFORM0 \nIn order to exclude trivial matches, tokens within a list of stop words are not considered while performing string matching. The final score is a weighted combination of the string matching score and the time proximity of the track, aimed to enhance matches from tracks played closer to the time when the user is posting the tweet.\nThe performance of the algorithm depends, apart from the time proximity threshold t, also on other two thresholds related to the string matching, one for the Musical Work (w) and one for the Contributor (c) entities. It has been necessary for avoiding to include candidate entities matched against the schedule with a low score, often source of false positives or negatives. Consequently, as last step Contributor and Musical Work candidates entities with respectively a string matching score lower than c and w, are filtered out. In Figure 2, an example of Musical Work entity recognized in an user-generated tweet using the schedule information is presented.\nThe entities recognized from the schedule matching are joined with the ones obtained directly from the statistical models. In the joined results, the criteria is to give priority to the entities recognized from the machine learning techniques. If they do not return any entities, the entities predicted by the schedule matching are considered. Our strategy is justified by the poorer results obtained by the NER based only on the schedule matching, compared to the other models used in the experiments, to be presented in the next section.\n\nResults\nThe performances of the NER experiments are reported separately for three different parts of the system proposed.\nTable 6 presents the comparison of the various methods while performing NER on the bot-generated corpora and the user-generated corpora. Results shown that, in the first case, in the training set the F1 score is always greater than 97%, with a maximum of 99.65%. With both test sets performances decrease, varying between 94-97%. In the case of UGC, comparing the F1 score we can observe how performances significantly decrease. It can be considered a natural consequence of the complex nature of the users' informal language in comparison to the structured message created by the bot.\nIn Table 7, results of the schedule matching are reported. We can observe how the quality of the linking performed by the algorithm is correlated to the choice of the three thresholds. Indeed, the Precision score increase when the time threshold decrease, admitting less candidates as entities during the matching, and when the string similarity thresholds increase, accepting only candidates with an higher degree of similarity. The behaviour of the Recall score is inverted.\nFinally, we test the impact of using the schedule matching together with a biLSTM-CRF network. In this experiment, we consider the network trained using all the features proposed, and the embeddings not pre-trained. Table 8 reports the results obtained. We can observe how generally the system benefits from the use of the schedule information. Especially in the testing part, where the neural network recognizes with less accuracy, the explicit information contained in the schedule can be exploited for identifying the entities at which users are referring while listening to the radio and posting the tweets.\n\nTable 2. Example of entities annotated and corresponding formal forms, from the user-generated tweet (1) in Table 1.\n\nTable 3. Examples of bot-generated tweets.\n\nTable 4. Tokens’ distributions within the two datasets: user-generated tweets (top) and bot-generated tweets (bottom)\n\nTable 6. F1 score for Contributor(C) and Musical Work(MW) entities recognized from bot-generated tweets (top) and user-generated tweets (bottom)\n\nTable 8. Precision (P), Recall (R) and F1 score for Contributor (C) and Musical Work (MW) entities recognized from user-generated tweets using the biLSTM-CRF network together with the schedule matching. The thresholds used for the matching are t=1200, w=0.5, c=0.5.\n\nQuestion: What are their results on the entity recognition task?", "role": "user" }, { "content": "{\"answer\": [\"With both test sets performances decrease, varying between 94-97%\"], \"evidence\": [\"The performances of the NER experiments are reported separately for three different parts of the system proposed.\", \"Table 6 presents the comparison of the various methods while performing NER on the bot-generated corpora and the user-generated corpora. Results shown that, in the first case, in the training set the F1 score is always greater than 97%, with a maximum of 99.65%. With both test sets performances decrease, varying between 94-97%. In the case of UGC, comparing the F1 score we can observe how performances significantly decrease. It can be considered a natural consequence of the complex nature of the users\\u0027 informal language in comparison to the structured message created by the bot.\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should only include the abstract and no additional text.\n\nPaper text:\nerysipelothrix rhusiopathiae is a gram - positive , non - sporeforming , slender and straight or slightly rod - shaped bacterium that causes erysipelas in swine and a wide spectrum of diseases in other animals , like sheep , birds , reptiles , amphibians , and some fishes .\nthis bacterium is ubiquitous in environment and in reservoir of asymptomatic carriers among both domestic and wild animals . among the 23 serotypes of e. rhusiopathiae , serotypes 1a , 1b and 2 are the best known as the etiological agents affecting swine industry , , , .\ne. rhusiopathiaes vary widely in their morphology , host specificity and/or pathogenicity and little is known about the correlation of their proteins to virulence .\ne. rhusiopathiae gxby-1 , isolated from acute swine erysipelas in binyang county , guangxi province , china , exhibits high pathogenic for mouse and swine . in order to elucidate the genetic background of this pathogenic strain and get deep insights into the virulence - associated proteins of this strain , we sequenced the complete genome of e. rhusiopathiae gxby-1 .\nthe genome of e. rhusiopathiae gxby-1 was sequenced at beijing genomics institute ( bgi , shenzhen , china ) using illumina hiseq 2000 system .\na total of 300 million high - quality base pairs were produced with 62-fold coverage of the genome , and then were assembled into 11 contigs by using soap denovo software , , after which the contigs were joined into 2 scaffolds with paired - end information .\ngene predictions and annotations were performed using the glimmer software ( version 3.02 ) and trna and rrna genes were identified by trnascan and rrnammer , respectively .\nall genes were further categorized according to swissprot , go ( gene ontology ) and kegg ( kyoto ency - clopedia of genes and genomes ) .\nthe complete genome of e. rhusiopathiae gxby-1 consists of one 1,876,490 bp circular chromosome with no plasmid .\nand its chromosome contains 1734 predicted open reading frames ( orfs ) and the total length of genes is 1,668,564 bp , which makes up 88.36% of the genome .\nthe g + c content of the chromosome is 36.50% and encodes 57 trna and 27 rrna operons ( table 1 ) .\nthe gxby-1 strain genome not only enriches the genome database of e. rhusiopathiae , but also supports and extends previous studies , and provides fundamental information for further studies .\nthe genome sequence of e. rhusiopathiae gxby-1 has been deposited in ncbi genbank under accession number cp014861 .\nthe authors declare that there is no conflict of interests with respect to the work published in this paper .", "role": "user" }, { "content": "erysipelothrix rhusiopathiae ( e. rhusiopathiae ) is an important pathogenic microorganism affecting swine industry . here , \n we report the finished annotated genome sequence of e. rhusiopathiae gxby-1 , isolated from acute swine erysipelas in binyang county , guangxi , china . the gxby-1 strain , which exhibits high pathogenicity for swine , contains 1,876,490 bp with g + c content of 36.50% , and contains 1734 protein - coding genes , 57 trnas and 27 rrnas . \n the nucleotide sequence of this genome was deposited into genbank under the accession cp014861 .", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2019 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from the options provided. A short description of the datasets is also provided to help you.\n\nQuery: I want to train a supervised model for detecting fake face images from images.\n\nKeyphrases: deepfake detection images\n\nDataset description:\nFakeddit: Fakeddit is a novel multimodal dataset for fake news detection consisting of over 1 million samples from multiple categories of fake news. After being processed through several stages of review, the samples are labeled according to 2-way, 3-way, and 6-way classification categories through distant supervision.\nSNIPS: The SNIPS Natural Language Understanding benchmark is a dataset of over 16,000 crowdsourced queries distributed among 7 user intents of various complexity: SearchCreativeWork (e.g. Find me the I, Robot television show), GetWeather (e.g.\nCelebA: CelebFaces Attributes dataset contains 202,599 face images of the size 178×218 from 10,177 celebrities, each annotated with 40 binary labels indicating facial attributes like hair color, gender and age.\nConvAI2: The ConvAI2 NeurIPS competition aimed at finding approaches to creating high-quality dialogue agents capable of meaningful open domain conversation. The ConvAI2 dataset for training models is based on the PERSONA-CHAT dataset.\n\nOptions: A: Fakeddit B: SNIPS C: CelebA D: ConvAI2", "role": "user" }, { "content": "CelebA", "role": "assistant" } ]

[ { "content": "You will be presented with a citation sentence from a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nWhile there have been extensive studies on how to efficiently relocate mobile sensors to improve the area coverage of a wireless sensor network [13–17], the impact of sensor mobility on barrier coverage is yet to be explored.", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: A Survey on Data Warehouse Evolution \nChapter Title: Schema Evolution \n1. Abstract of Cited Paper (BIB001): A data warehouse (DW) is fed with data that come from external data sources that are production systems. External data sources, which are usually autonomous, often change not only their content but also their structure. The evolution of external data sources has to be reflected in a DW, that uses the sources. Traditional DW systems offer a limited support for handling dynamics in their structure and content. A promising approach to handling changes in DW structure and content is based on a multiversion data warehouse. In such a DW, each DW version describes a schema and data at certain period of time or a given business scenario, created for simulation purposes. In order to appropriately analyze multiversion data, an extension to a traditional SQL language is required. In this paper we propose an approach to querying a multiversion DW. To this end, we extended a SQL language and built a multiversion query language interface with functionality that allows: (1) expressing queries that address several DW versions and (2) presenting their results annotated with metadata information.\n\nLiterature Review:", "role": "user" }, { "content": "This approach focuses on dimensions updates BIB001 , instances updates BIB002 , facts updates and attributes updates . In BIB001 , authors proposed some operators to define dimension updates. Those operators are: -Generalize operator: it allows the creation of new level (ln) to which a pre-existent one (l) rolls up. Authors took the example of the dimension \" store \" to which they defined a new level \"type of store \" then the level \" type of store \" generalize the dimension \"store \". -Specialize operator: it allows adding a new level (ln) to a dimension. Authors choose to specialize the dimension \"day\" with the level \"hour \", and then the level \"hour\" specializes the dimension \"day \". -Relate levels operator: it allows defining a roll up function between two independent levels of the same dimension. Authors defined a relation between the level \"category\" and the level \"brand\". Those two levels were independent. -Unrelated levels operator: it allows deleting a relation between two levels. Authors deleted the relation between the levels \"company\" \"category\" and the level \"brand \". -Delete level operator: it allows to delete a level then to define new relations between levels. Authors deleted the level \"branch\" then a direct relation between the levels \"category\" and \"item\" was defined. -Add instance operator: it allows adding an instance to a level in the dimension. Authors added the instance item 5 to the level \"item \". -Delete instance operator: it allows deleting an instance of a level. Authors deleted the instance item 4 of the level \"item \". After defining operators to handle dimension updates, authors of BIB001 saw that they must handle the impact of dimension structural updates on the data cube. In fact, they proposed some data cube adaptation after the Dellevel update, Addlevel update, DelInstance update, AddInstance update by computing for each cube view an expression to maintain it. In this paper, no implementation was done to support those changes impact. In authors proposed an extension to the work presented in BIB001 and defined the WareHouse Evolution System (WHES) prototype to support dimensions and cubes update. In fact, they extended the SQL language and gave birth to the Multidimensional Data definition Language (MDL). This latter allowed defining operators for to support evolution of dimensions and cubes. For dimensions update, authors defined the following operators: -CreateDimension: this operator allows the creation of a new dimension (with its name, its properties and its levels). -DropDimension: this operator allows the deletion of an existing dimension (with its name, its properties and its levels). -RenameDimension: this operator allows changing the name of a given dimension. -AddLevel: this operator allows the add of a new level to a given dimension. -DeleteLevel: this operator allows the deletion of a level from a given dimension. -RenameLevel: this operator allows changing the name of a given level. -AddProperty: this operator allows the add of a property or attribute to a given dimension or a given level. -DeleteProperty: this operator allows the deletion of a property from a dimension or from a level. To add a level X (brand) to a dimension Y (product) using the MDL, users should respect the following syntaxes with X= brand and Y= product: For cube updates, authors defined the following operators: -CreateCube: this operator allows the creation of a new cube. -DropCube: this operator allows the deletion of a given cube. -RenameCube: this operator allows the change of the name of a given cube. -AddMeasure: this operator allows the add of a measure to a given cube. -DeleteMeasure: this operator allows the deletion of a measure from a given cube. -RenameMeasure: this operator allows the change of the name of a given measure. -AddAxis: this operator allows the add of an axis of analyse to a given cube. -DeleteAxis: this operator allows the deletion of a given axis of analyse from a cube. Let's mention that a cube is the fact table and the axis is the dimension in the relational schema. To add an axis X (city) to a cube Z (sales) using the MDL, users should respect the following syntax: Alter cube Y Alter cube sales", "role": "assistant" } ]

[ { "content": "You are provided with the abstract of a scientific paper and the abstracts of the papers it references. Your task is to write a Related Work section for the main paper. This section should concisely summarize and integrate the key points from the cited abstracts, reflecting how they relate to the main paper's contributions and context. In your summary, use numerical citation markers like [1], [2], etc., to refer to the corresponding papers.\n\nMain Abstract:\nThe 0-1 integer linear programming feasibility problem is an important NP-complete problem. This paper proposes a continuous-time dynamical system for solving that problem without getting trapped in non-solution local minima. First, the problem is transformed to an easier form in linear time. Then, we propose an \"impulse algorithm\" to escape from local traps and show its performance is better than randomization for escaping traps. Second, we present the time-to-solution distribution of the impulse algorithm and compare it with exhaustive search to see its advantages. Third, we show that the fractional size of the basin of attraction of the global minimum is significantly larger than @math , the corresponding discrete probability for exhaustive search. Finally, we conduct a case study to show that the location of the basin is independent of different dimensions. These findings reveal a better way to solve the 0-1 integer linear programming feasibility problem continuously and show that its cost could be less than discrete methods in average cases.\n\nCited Abstract(s):\n[1]: The paper presents a survey of methods and approaches solving linear integer problems, developed during the last 50 years. These problems belong to the class of NP-hard optimization problems. To find out exact optimal solutions for this class of problems requires use of considerable computational resources. The development of efficient hybrid methods, combining in a suitable way the best features of different approaches (exact or approximate) is the actual direction, in which many researchers devote their efforts to solve successfully varioushard practical problems.\n\n[2]: Author(s): Impagliazzo, R; Lovett, S; Paturi, R; Schneider, S | Abstract: We give an exact algorithm for the 0-1 Integer Linear Programming problem with a linear number of constraints that improves over exhaustive search by an exponential factor. Specifically, our algorithm runs in time @math where n is the number of variables and cn is the number of constraints. The key idea for the algorithm is a reduction to the Vector Domination problem and a new algorithm for that subproblem.\n\n[3]: \n\n[4]: In this work, we study continuous reformulations of zero–one programming problems. We prove that, under suitable conditions, the optimal solutions of a zero–one programming problem can be obtained by solving a specific continuous problem.\n\n[5]: \n\n[6]: This paper reviews the advances of mixed-integer linear programming (MILP) based approaches for the scheduling of chemical processing systems. We focus on the short-term scheduling of general network represented processes. First, the various mathematical models that have been proposed in the literature are classified mainly based on the time representation. Discrete-time and continuous-time models are presented along with their strengths and limitations. Several classes of approaches for improving the computational efficiency in the solution of MILP problems are discussed. Furthermore, a summary of computational experiences and applications is provided. The paper concludes with perspectives on future research directions for MILP based process scheduling technologies.\n\n[7]: The design of feedback (or recurrent) neural networks to produce good solutions to complex optimization problems is discussed. The theoretical basis for applying neural networks to optimization problems is reviewed, and a design rule that serves as a primitive for constructing a wide class of constraints is introduced. The use of the design rule is illustrated by developing a neural network for producing high-quality solutions to a probabilistic resource allocation task. The resulting neural network has been simulated on a high-performance parallel processor that has been optimized for neural network simulation. >", "role": "user" }, { "content": "When it comes to combinatorial problems, continuous methods have been investigated, but most of them are for solving incomplete versions of a specific problem under some special cases or for the optimization version of 0-1 ILP. For example, reviewed the use of neural networks for optimization [7] . If all of the coefficients are only 0 or 1, a Hopfield neural network is able to solve the satisfiability problem continuously (e.g. Figure (a)). In fact, following their construction, we can also build a neural network for the general 0-1 ILP feasibility problem, but the local traps (non-solution minima) and the convergence conditions largely depend on the structure of the specific problem instance (e.g. Figure (b--d)). solve the 0-1 ILP feasibility problem with exponential speedup over exhaustive search in the special case where the number of constraints is a multiple of the number of variables; this is accomplished by a reduction to the vector domination problem [2] . Other research, including 0-1 [4] integer [1] mixed [6] [5] [3] programming, have usually addressed the optimization version of the problem.", "role": "assistant" } ]

[ { "content": "You will be presented with a citation sentence from a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nGiven that normal hippocampal functioning is essential for both episodic AM and everyday memory (Vargha-Khadem et al., 1997; Isaacs et al., 2000), we also examined the effects of age and sex on everyday memory in order to determine whether\nthe results would be similar to those observed in episodic…", "role": "user" }, { "content": "Result", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a research paper and a corresponding research question. Determine the answer to the research question based on the context provided. Your answer should be one of: \"YES\", \"NO\", or \"MAYBE\".\n\nAbstract:\n(BACKGROUND AND OBJECTIVES) Extrapulmonary small cell carcinomas (EPSCC) are rare tumors where therapy remains poorly defined. We sought to determine the impact of surgical extirpation and radiation therapy for outcomes of EPSCC.\n(METHODS) The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with EPSCC which were further categorized by site and evaluated for survival by specific treatment strategy.\n(RESULTS) We identified 94,173 patients with small cell carcinoma of which 88,605 (94.1%) and 5,568 (5.9%) had pulmonary small cell carcinoma and EPSCC, respectively. EPSCC patients were subdivided by site with the following proportions: genitourinary (24.1%), gastrointestinal (22.1%), head and neck (7.1%), breast (4%), and miscellaneous (42.7%). Overall EPSSC and specifically gastrointestinal disease had significantly improved median, 5- and 10-year survival with surgery and/or radiation for all stages and sizes. For all EPSCCs multivariate analysis revealed age (>50), gender (female), stage (regional, distant), radiation, and surgery to be independent predictors of survival.\n\nQuestion:\nDoes surgery or radiation therapy impact survival for patients with extrapulmonary small cell cancers?\n\nAnswer:", "role": "user" }, { "content": "YES", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nthe multiplicity of stars is influenced by the specific characteristics of the star formation process , and thus has been the subject of extensive measurements .\nsimilarly , in an attempt to gain insight into the formation of brown dwarfs , recent studies have heavily scrutinized the binary properties of objects near and below the hydrogen burning mass limit in the solar neighborhood @xcite , open clusters @xcite , and young clusters and associations @xcite .\nmost of the binary low - mass stars and brown dwarfs in these surveys exhibit maximum separations of @xmath7 au , which is consistent with the predictions of the embryo ejection scenario for the formation of low - mass bodies @xcite .\nhowever , a small but growing number of low - mass binaries have been found at wider projected separations that range from 33 - 41 au @xcite to beyond 200 au @xcite . because these wide binaries are weakly bound and extremely fragile , it is unlikely they that have been subjected to violent dynamical interactions , indicating that some low - mass stars and brown dwarfs are able to form without the involvement of ejection .\nin fact , the role of ejection may be minor based on other aspects of the multiplicity of low - mass objects @xcite . to fully utilize multiplicity as a probe of the formation of low - mass bodies\n, it is necessary to consider populations spanning a range of ages and star - forming conditions .\nob associations represent an area of this phase space that remained unexplored until @xcite obtained @xmath8 images of low - mass members of upper scorpius , which has an age of 5 myr @xcite and is the nearest ob association at a distance 145 pc @xcite . among their 12 targets\n, they discovered three binaries , all with projected separations less than 18 au .\n@xcite tentatively suggested that this absence of wide systems in upper sco relative to lower density clusters like chamaeleon i and tw hya @xcite might indicate a variation in the formation process of low - mass binaries with star - forming environment . in this letter ,\ni report the discovery of a widely - separated low - mass binary star in upper sco , which was found serendipitously during a spectroscopic survey of the low - mass members of this association .\ni present near - infrared ( ir ) images and spectroscopy of the components of the pair , measure their spectral types and assess their membership in a binary system , and discuss the implications of this new pair .\nwhile conducting a spectroscopic survey of known low - mass members of the upper sco association on 2005 june 16 with spex @xcite at the nasa infrared telescope facility ( irtf ) , i found that one of the targets , denis - p j161833.2 - 251750.4 @xcite , appeared as a @xmath9 double on the slit - viewing camera .\nto further investigate the nature of this pair , i performed the imaging and spectroscopy described in this section . to measure the flux ratio of the components of denis - p j161833.2 - 251750.4 ( hereafter denis 1618 - 2517 )\n, i used the slit - viewing camera on spex .\nthis camera contained a @xmath10 aladdin 2 insb array and had a plate scale of @xmath11 pixel@xmath12 @xcite . through a @xmath0 filter\n, i obtained 18 dithered one - second exposures .\nthese images were median combined to produce a flat field image , which was then divided into each original exposure .\nthe 12 frames with the best image quality were registered and combined . a @xmath13 subsection of the resulting image surrounding denis 1618 - 2517 is shown in figure [ fig : image ] .\nthe components of this pair exhibit fwhm@xmath14 in this image .\ni extracted photometry for each object with the task phot under the iraf package apphot using a radius of three pixels , arriving at a magnitude difference of @xmath15 mag . to measure astrometry for the pair , i first determined the rotation between the cardinal directions and the array axes using the 2mass coordinates of denis 1618 - 2517 and the one other 2mass source appearing in the image ( 2mass 16183428 - 2518067 ) . with this information , i measured a position angle of @xmath16 for the secondary relative to the primary .\nusing the plate scale from @xcite , i then measured a separation of @xmath17 for the pair .\nspectra were obtained of the components of denis 1618 - 2517 using spex in the prism mode with a @xmath18 slit .\nthis configuration produced a wavelength coverage of 0.8 - 2.5 and a resolution of @xmath19 .\nafter adjusting the position angle of the slit to align it with the axis connecting the pair , i selected an integration time of 30 sec and obtained a total of 18 exposures during a sequence of dithers between two positions on the slit .\nthe 10 frames with the best image quality were reduced with the spextool package @xcite .\nthe data were corrected for telluric absorption with the method described by @xcite .\ni now use the photometry and spectroscopy from the previous section to examine the spectral types and extinctions of the components of denis 1618 - 2517 .\n@xcite found that the h@xmath20 emission and na i absorption in an unresolved optical spectrum of the pair were indicative of youth and thus membership in upper sco . in the spex data ,\ni find evidence of youth in both objects .\nas shown in figure [ fig : spec ] , each spectrum exhibits a triangular @xmath3-band continuum , which is a distinguishing characteristic of cool pre - main - sequence objects @xcite .\nthe depths of the optical and ir molecular absorption bands , primarily tio , vo , and h@xmath21o , are also very similar between the two objects , demonstrating that the two objects have the same spectral type to within @xmath22 subclass . in comparison , two young low - mass stars at the same age with a @xmath0-band magnitude difference of 0.42\nare predicted to have @xmath23 k @xcite , which corresponds to @xmath22 subclass @xcite .\nthus , the relative spectral types and magnitudes of the components of denis 1618 - 2517 are consistent with the coevality expected for a binary system . although the absorption band strengths agree between the two objects , the secondary is redder beyond 1.7 .\nthis is difficult to explain as a difference in spectral type or extinction , and instead probably is due to excess emission from circumstellar material around the secondary , an imperfect separation of the light from the two objects during extraction of their spectra , or the combination of misalignment of the slit along the binary axis and differential refraction .\nmeanwhile , the ir spectra of both denis 1618 - 2517 a and b are significantly redder than most of the other low - mass members of upper sco that were observed during the same run .\nthe same trend is present in the 2mass @xmath24 and @xmath25 colors of these objects and is consistent with extinction .\nrelative to the bluest ( i.e. , unreddened ) spex data of members of upper sco and other young clusters at m5-m6 @xcite , the spectrum of denis 1618 - 2517 a+b exhibits an extinction of @xmath26 .\nthe presence of significant reddening is additional evidence that these objects are not foreground field dwarfs .\nbased on the strength of the molecular absorption bands , denis 1618 - 2517 a and b are earlier than most of the other upper sco members observed in this run , which have optical spectral types that range from m5 to m9 @xcite .\nthis suggests that denis 1618 - 2517 a+b may be closer to m5 than the value of m6 measured by @xcite .\ni find the same result when i compare the pair to optically - classified members of other young clusters .\nfor instance , as shown in figure [ fig : spec ] , the molecular absorption bands of denis 1618 - 2517 a+b agree better with those of mho 6 than with mho 5 , which have optical types of m4.75 and m6 , respectively @xcite .\nthe relatively large reddening toward denis 1618 - 2517 may have caused @xcite to arrive at a spectral type that was slightly too late . combining a spectral type of m5 with the temperature scale of @xcite and the evolutionary models of @xcite implies a mass of @xmath4 @xmath27 for each component of denis 1618 - 2517 .\nthe results from the previous section and from @xcite demonstrated that the components of denis 1618 - 2517 are young members of upper sco .\ni now examine if they are likely to comprise a true binary system rather than a pair of unrelated members of the association that happen to have a small projected separation .\nthe surface density of m - type members of upper sco is @xmath28 deg@xmath29 and the total area of the association is @xmath30 deg@xmath31 @xcite . across the entire association , the probability of finding\na pair of m - type members with a projected separation of @xmath32 is @xmath33 .\nthe observations that discovered this pair considered only a small fraction of the membership ( a few dozen ) and were not designed to detect close pairs . as a result , the relevant probability for denis 1618 - 2517 is lower by at least an order of magnitude .\nbased on the very low value of this probability , i conclude that denis 1618 - 2517 a and b comprise a binary system rather than two unrelated members of upper sco . using the average distance of 145 pc for the association @xcite , the projected separation of @xmath1 of this pair corresponds to 140 au . demonstrating a common proper motion for a pair of stars is the conventional method of conclusively establishing binarity in the solar neighborhood , but it is less useful for young populations because even unrelated cluster members are comoving at the level of precision typically available for these measurements .\nfor instance , the common proper motions measurements for the recently discovered substellar companions to gq lup @xcite and 2 m 1207 - 3932 @xcite are not precise enough to distinguish between true binaries and comoving unbound cluster members seen in projection near each other .\nthus , for gq lup , 2 m 1207 - 3932 , previously known pairs in upper sco @xcite , and indeed the vast majority of visual doubles in young clusters and associations , available evidence of binarity is based on the same statistical considerations presented in this work for denis 1618 - 2517 .\nonly the value of the probability differs among these binaries , which depends on the separation of a given pair and the surface density of cluster members .\nthe probability of unrelated clusters members with small separations is exceedingly low for sparse populations like upper sco , chamaeleon , lupus , and tw hya @xcite but non - negligible for dense clusters like the trapezium in orion @xcite .\nas with the brown dwarf pair in chamaeleon from @xcite , the binarity of denis 1618 - 2517 was discovered serendipitously and thus can not be used at this time in a multiplicity measurement for low - mass members of upper sco . however , the mere existence of this binary system has important implications .\nfirst , denis 1618 - 2517 is one of only a few known low - mass binaries with very wide separations ( @xmath34 au , * ? ? ?\n* ; * ? ? ?\n* ; * ? ? ?\nthese wide pairs are fragile and easily disrupted , and thus demonstrate that some low - mass stars and brown dwarfs can form without the assistance of ejection .\nin addition , with these observations of denis 1618 - 2517 , wide low - mass binaries are now known across a wider range of star - forming conditions , from small , sparse clusters ( chamaeleon ) and to rich ob associations ( upper sco ) .\nthus , in the measurements available to date , the formation of wide low - mass binaries has no discernible dependence on star - forming environment .", "role": "user" }, { "content": "using the near - infrared spectrometer spex and its slit - viewing camera at the irtf , i have resolved a low - mass member of the upper scorpius ob association into a double star . from @xmath0-band images of the pair , denis - p j161833.2 - 251750.4 a and b \n , i measure a separation of @xmath1 and a magnitude difference of @xmath2 mag . \n i present resolved 0.8 - 2.5 spectroscopy of the two objects , both of which exhibit signatures of youth in the shape of their @xmath3- and @xmath0-band continua , demonstrating that both are members of upper scorpius rather than field stars . \n in addition , through a comparison to optically - classified pre - main - sequence objects , i derive a spectral type near m5 for each component , corresponding to a mass of @xmath4 @xmath5 with the evolutionary models of chabrier and baraffe . \n the probability that this pair is composed of unrelated m - type members of upper scorpius is @xmath6 . \n when added to the recent discoveries of other wide , easily disrupted low - mass binaries , this new system further establishes that the formation of low - mass stars and brown dwarfs does not require ejection from multiple systems . \n these observations also indicate that wide low - mass binaries can form in ob associations as well as in smaller clusters where the previously known wide pairs have been found . \n thus , the available data show no perceptible effect of star - forming environment on the prevalence of loosely bound low - mass systems .", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\", \"Protein\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\" : [\"Dexamethasone\", ...], \"Protein\" : [\"BRCA-1\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nEfficacy and safety of tamsulosin in the treatment of urological diseases.\nThe alpha(1)-adrenoceptor antagonist, tamsulosin, is selective for alpha(1A)- and alpha(1D)- over alpha(1B)-adrenoceptors. Both placebo-controlled and comparative studies with other agents have demonstrated tamsulosin to be an effective treatment for patients with lower urinary symptoms suggestive of benign prostatic hyperplasia. Its effectiveness appears to be maintained over many years. Tamsulosin may also effectively reduce lower urinary tract symptoms in other urological diseases. A dose of tamsulosin 0.4 mg/day has a tolerability close to that of placebo and has little, if any, blood pressure lowering effects. Tolerability and lack of blood pressure lowering are maintained even in high-risk patients such as those with cardiovascular comorbidity and/or comedication. Apart from adrenoceptor subtype-selectivity, a smooth pharmacokinetic profile of its modified-release formulation and a selective accumulation in target tissues may contribute to an excellent efficacy:tolerability ratio.", "role": "user" }, { "content": "{\"Chemical\": [\"Tamsulosin\", \"tamsulosin\"], \"Protein\": [\"alpha(1)-adrenoceptor\", \"alpha(1A)- and alpha(1D)- over alpha(1B)-adrenoceptors\", \"adrenoceptor\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nSystematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.\nAbstract 1:\nPelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer, but the clinical impact of lymphadenectomy has not been addressed in randomized studies. We conducted a randomized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to standard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival.\n From October 1, 1996, through March 31, 2006, 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were randomly assigned to undergo pelvic systematic lymphadenectomy (n = 264) or no lymphadenectomy (n = 250). Patients' clinical data, pathological tumor characteristics, and operative and early postoperative data were recorded at discharge from hospital. Late postoperative complications, adjuvant therapy, and follow-up data were collected 6 months after surgery. Survival was analyzed by use of the log-rank test and a Cox multivariable regression analysis. All statistical tests were two-sided.\n The median number of lymph nodes removed was 30 (interquartile range = 22-42) in the pelvic systematic lymphadenectomy arm and 0 (interquartile range = 0-0) in the no-lymphadenectomy arm (P < .001). Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy (81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm, P = .001). Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm (13.3% vs 3.2%, difference = 10.1%, 95% confidence interval [CI] = 5.3% to 14.9%, P < .001). At a median follow-up of 49 months, 78 events (ie, recurrence or death) had been observed and 53 patients had died. The unadjusted risks for first event and death were similar between the two arms (hazard ratio [HR] for first event = 1.10, 95% CI = 0.70 to 1.71, P = .68, and HR for death = 1.20, 95% CI = 0.70 to 2.07, P = .50). The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms (81.0% and 85.9% in the lymphadenectomy arm and 81.7% and 90.0% in the no-lymphadenectomy arm, respectively).\n Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging, it did not improve disease-free or overall survival.\n\n\nTitle 2:\nEfficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study.\nAbstract 2:\nHysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer.\n From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884.\n After a median follow-up of 37 months (IQR 24-58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1.16 (95% CI 0.87-1.54; p=0.31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI -4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1.35 (1.06-1.73; p=0.017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1-12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1.04 (0.74-1.45; p=0.83) and for recurrence-free survival was 1.25 (0.93-1.66; p=0.14).\n Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials.", "role": "user" }, { "content": "We found no evidence that lymphadenectomy decreases the risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. The evidence on serious adverse events suggests that women who receive lymphadenectomy are more likely to experience surgically related systemic morbidity or lymphoedema/lymphocyst formation.", "role": "assistant" } ]

[ { "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nFabrication of Glyconanoparticle Microarrays\n\nPaper sections:\n\n<p>Microarrays, which allow simultaneous interrogation of ligand-receptor interactions in high throughput and at low sample consumption, have significantly increased the efficiencies of bioassays and greatly facilitated the fundamental studies as well as the development of therapeutic and diagnostic tools.1–5 Carbohydrate microarrays,6–15 for example, have been widely used to study glycan-lectin interactions which play an important role in a variety of biological processes, including cell-cell communications, immune responses, and the progression of tumor cells. Carbohydrate microarrays are generally fabricated by spotting and immobilizing glycans on a solid surface either by physical adsorption or covalent coupling.9,16–19 The arrays are then probed with lectins and the affinity of the interactions presented as a physical readout, for example, fluorescence intensity when a fluorescently-tagged lectin is used.</p><p>It has been shown that glycans immobilized on surfaces with proper ligand presentation can significantly amplify their binding affinities to lectins.15,20–21 In these cases, the solid surface acts as the multivalent scaffold having multiple copies of ligands when interacting with lectins. On flat surfaces, however, the affinity reaches a limit when the ligand density becomes saturated.15,22 Efforts have been devoted to fabricate 3D glycan surfaces to increase the ligand density.15 For example, Bertozzi and co-workers fabricated glycopolymer microarrays where glycans were covalently attached to a polymer scaffold.23 Pieters et al. fabricated glycodendrimer arrays and studied the binding affinity to lectins with regard to multivalency.24 Miura and coworkers presented dendritic sugar microarrays where glycodendrimers were immobilzed on gold substrate via the click chemistry.25 Gildersleeve and coworkers used bovine serum albumin (BSA)-glycan conjugates to generate arrays and evaluated the affinity to lectins as a function of glycan density.26 Rubina et al. presented a 3D hydrogel glycan microarray where saccharides were immobilized inside a porous polymer gel.27</p><p>Here we report a new type of glycan microarray based on glyconanoparticles. The GNP microarrays are fabricated by printing GNPs on a photoactive surface followed by covalent immobilization by light activation. The GNP microarrays were then probed with lectins labeled with fluorescein (FITC) or FITC-doped silica nanoparticles.</p><p>GNPs (diameter 118 nm, see Figure S1, Supporting Information) were synthesized following a previously reported procedure.28 Five carbohydrates, 3,6-di-O-(α-D-mannopyranosyl)-D-mannopyranose (Man 3), 2-O-α-D-mannopyranosyl-D-mannopyranose (Man 2), D-mannose (Man), D-glucose (Glc), and D-fructose (Fru) (Scheme 1) were conjugated onto silica nanoparticles using the photocoupling chemistry developed in our laboratory.11 Briefly, silica nanopartilces prepared by the Stöber method were functionalized with perfluorophenyl azide (PFPA), and carbohydrates were then coupled to the nanoparticles via the CH insertion reaction of the perfluorophenylnitrene generated by photoactivation of PFPA (see Supporting Information for experimental details).29–31 The densities of the immobilized carbohydrates were determined using the colorimetric assay of anthrone/sulfuric acid, from which the coupling yields were also calculated (see Table S1, Supporting Information for results and calculations).</p><p>GNP microarrays were fabricated using the same photocoupling chemistry, however, poly(allyl amine) (PAAm)-PFPA was used in this case (Scheme 1). The polymer matrix is necessary as it ensures the conformal contact with solid materials such as nanoparticles, which is critical in the immobilization of solid materials.32 The process was carried out as shown in Scheme 1 (see Supporting Information for detailed experimental procedures). The epoxy-functionalized wafers33 were first treated with PAAm-PFPA,32 and aqueous solutions of GNPs were then printed on the PAAm-PFPA-functionalized wafers using a robotic printer. A polymer film, polystyrene (PS) or poly(2-ethyl-2-oxazoline) (PEOX), was subsequently introduced by spin-coating the polymer from its chloroform solution. Chloroform was used since GNPs were insoluble and therefore the printed GNPs would remain intact. Subsequent light activation covalently attached both GNPs and the polymer via the surface PFPA (Scheme 1). GNP microarrays were obtained after excess GNPs and the polymer were removed by sonication in chloroform followed by water.</p><p>To test the optimal array conditions, Man-conjugated GNPs (Man-GNPs) were printed with varying particle concentrations. The microarray was then treated with Concanavalin A (Con A), a plant lectin that binds specifically to carbohydrates having α-Man and α-Glc structures.34 In the present studies, Con A was labeled with either FSNPs (FSNP-Con A) or FITC (FITC-Con A) to facilitate the visualization of the interactions. FSNP-Con A was prepared by treating FSNPs35 with 3-glycidyloxytrimethoxysilane followed by Con A (see Supporting Information for experimental details). To reduce the non-specific adsorption of the labeled Con A on the microarray, polymer thin films were used as the background coatings. Hydrophilic polymers such as PEOX were highly effective in resisting the adsorption of proteins including FITC-Con A.36–37 For FSNPs, however, the result was the opposite. FNSPs adsorbed strongly on hydrophilic polymers whereas minimal adsorption was observed on hydrophobic polymers such as PS.</p><p>After the Man-GNP microarrays were treated with FSNP-Con A or FITC-Con A, fluorescence signals were clearly visible (Figure S2a, Supporting Information). Additionally, the fluorescence intensity increased with increasing Man-GNP concentration (I, II, Figure 1). Because the photocoupling chemistry occurs at the interface between surface PFPA and GNPs, in principle, only a monolayer of GNPs should result. The binding would therefore saturate and the fluorescence intensity would plateau. However, the signal continued to increase with the Man-GNP printing concentration. A closer examination of the arrayed spots by AFM revealed that the particle density increased with the GNP printing concentration. At 20 mg/mL, agglomerated particles were clearly visible (Figure S3, Supporting Information). The agglomeration increased the GNP density and therefore the binding signals.</p><p>To evaluate the effectiveness of PS and PEOX in reducing the non-specific adsorption, Man-GNP microarrays without the polymer coating were incubated with BSA, a commonly used blocking agent in microarray assays, before they were treated with FSNP-Con A or FITC-Con A. In both cases, lower signals were obtained at all GNP concentrations in comparison to those with the polymer coating (III vs. I, and IV vs. II, Figure 1). Especially at higher GNP concentrations of 10 mg/mL or above, the signals were significantly higher on arrays when the polymer coating was used. The enhanced array sensitivity resulted from the markedly reduced background noises when PS (for FSNP-Con A) or PEOX (for FITC-Con A)36 was used as the antifouling coating. In addition, the signals from FSNP-Con A were higher than those from FITC-Con A. This is consistent with the results from others38–41 and our previous study35 that FSNPs exhibit high fluorescence intensity by entrapping multiple dye molecules inside the silica nanoparticles.</p><p>GNP microarrays were next prepared following the procedures and conditions developed above. Five different GNPs were printed on PAAm-PFPA surface at 10 mg/mL particle concentration. PS was then spin-coated and the GNP microarray was obtained after excess GNPs and the polymer were removed by sonication in chloroform followed by water. Figure 2i is the fluorescence image of the GNP microarrays after treating with FSNP-Con A. Man3-GNP showed the highest fluorescence intensity followed by Man2-GNP and Man-GNP. Only weak fluorescence was detected from Glc-GNP, and for Fru-GNP, the signal was minimal. These results are consistent with the affinity rank order of the corresponding free ligands with Con A (Table S2, Supporting Information).42–43</p><p>GNP microarrays were then compared with carbohydrate microarrays that were prepared by printing the corresponding free carbohydrate ligands on the PAAm-PFPA surface. Spin-coating PS followed by UV irradiation and solvent extraction gave the carbohydrate microarray. The array was then treated with FSNP-Con A. It can be clearly seen that the signals for the higher affinity ligands Man 3 and Man 2 were higher on the GNP microarray (Figure 2i) than those on the carbohydrate microarray (Figure 2ii). Since the background coating (PS) and the probe (FSNP-Con A) were the same for both arrays, the signal enhancement should come from GNPs as compared to the carbohydrate ligands.44–46 For the weaker ligands Man and Glc, on the other hand, the signals were lower on the GNP microarray (Figure 2i) than those on the carbohydrate microarray (Figure 2ii). This selective affinity amplification for high affinity ligands was observed previously on Au NPs21,47–48 as well as on dendrimers49 and neoglycopolymers.50 Note that Fru, a non-binding ligand, showed a relatively high fluorescence on the carbohydrate microarray (Figure 2ii). This could be due to the non-specific adsorption of FSNP-Con A nanoparticles on the hydrophilic Fru surface.</p><p>The GNP and carbohydrate microarrays were further evaluated using FITC-Con A. In this case, PEOX was used as the polymer coating to reduce the non-specific adsorption of FITC-Con A. The overall signal intensities were lower in this case (Figure 2iii) than when FSNP-Con A was used (Figure 2iv), similar to the result shown in Figure 1. Again, GNP microarray displayed higher signals for Man 3 and Man 2, and lower signals for Man and Glc (Figure 2iii) than the carbohydrate microarray (Figure 2iv). Also, higher residual fluorescence was seen for the Fru spots on carbohydrate microarray (Figure 2iv).</p>\n\nCONCLUSIONS\n<p>In summary, a new microarray platform, based on glyconanoparticles, was developed to study glycan-lectin interactions. The GNP microarrays were fabricated using a general photocoupling chemistry whereby the printed GNPs were covalently immobilized on the substrates with high efficiency. The GNP microarrays, when probed with FNSP-labeled lectin, gave higher signals as compared to FITC-labeled lectin or carbohydrate microarrays. In addition, the signal enhancement was greater for higher affinity ligands than for the lower affinity ones. This new GNP microarray platform should find a wide range of applications in bioanalysis facilitating the development of new diagnostic and therapeutic tools.</p>", "role": "user" }, { "content": "We report a new type of microarray, based on glyconanoparticles (GNPs), to study glycan-lectin interactions. GNPs, synthesized by conjugating carbohydrate ligands on silica nanoparticles, were printed on a photoactive surface followed by covalent immobilization by light activation. The GNP microarrays could be probed by lectins labeled with fluorescein as well as fluorescein-doped silica nanoparticles (FSNPs). Results showed that FSNP as the label enhanced the signals for the higher affinity ligands than the lower ones.", "role": "assistant" } ]

[ { "content": "You will be shown a claim related to the COVID-19 pandemic, and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\".\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract.\n\nFor instance, if the model were given the claim \"the COVID vaccine is safe for healthy adults\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that the risks of severe COVID vaccine side effects are low for healthy adults.\"]\n}\n\nClaim: Identification of unique mutations in sars-cov-2 strains isolated from brazil suggests its attenuated pathotype\n\nAbstract:\nSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses.\nStudies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat.\nGenomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2.\nRNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance.\nIn this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology.\nIn addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2.\nOur results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission.\nThe results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology.\", \"In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2.\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nEvaluation of estrogenic effects of polychlorinated biphenyls and organochlorinated pesticides using immature rat uterotrophic assay. In this study, we investigated the effects of polychlorinated biphenyls (PCBs) and organochlorinated pesticides on the serum levels of luteinising hormone (LH), follicle stimulating hormone (FSH) and weights and histomorphometry of uterine tissue in immature female rats using uterotrophic assay. A total of 36 rats were randomly divided into six groups (n = 6 per group) as control, oestradiol (E2, 100 μg/kg), PCB 180, Aroclor 1221, endosulfan and mirex at 10 mg/kg dosage. After 3 days of injections (subcutaneous), animals were decapitated and blood samples were collected. Uteri were dissected, weighed out and then fixed in 10% formaldehyde. They were processed for histomorphometry. The serum levels of LH and FSH were determined by enzyme immunoassay.Uterine weight was significantly increased by E2 and reduced by mirex (p < 0.001 and p < 0.05, respectively). Total volume of uterus was significantly raised by E2, Aroclor 1221 and endosulfan compared with that of the control group (p < 0.01). The ratio of epithelium was significantly increased by E2, PCBs and pesticides (p < 0.01). The uterine cavity ratio was decreased by aroclor (p < 0.01), PCB 180 and mirex (p < 0.05). The serum levels of LH did not significantly differ among the groups but the levels of FSH were decreased by PCB 180 and endosulfan (p < 0.05 and p < 0.01, respectively). These findings suggest that PCB 180, Aroclor 1221 and endosulfan may be estrogenic in immature uterotrophic assay.", "role": "user" }, { "content": "{\"Chemical\": [\"mirex\", \"oestradiol\", \"PCB 180\", \"polychlorinated biphenyls\", \"PCBs\", \"formaldehyde\", \"Aroclor 1221\", \"organochlorinated\", \"endosulfan\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nexperiments\n\nContext before the citation:\nHere, the PET and GR kernel perform similar: this is different from the results of (Nguyen et al., 2009) where GR performed much worse than PET for ACE data. As in the undersampled system, when the data is balanced, SqGRW (sequence kernel on dependency tree in which grammatical relations are inserted as intermediate nodes) achieves the best recall. As in the baseline system, a combination of structures performs best.\n\nCitation Sentence:\nHere , the PET and GR kernel perform similar : this is different from the results of ( Nguyen et al. , 2009 ) where GR performed much worse than PET for ACE data .\n\nContext after the citation:\nThis exemplifies the difference in the nature of our event annotations from that of ACE relations. Since the average distance between target entities in the surface word order is higher for our events, the phrase structure trees are bigger. This means that implicit feature space is much sparser and thus not the best representation. for relation detection.", "role": "user" }, { "content": "CompareOrContrast", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"AnatomicalEntity\"].\n\nPlease return the output as a JSON object of the format: {\"AnatomicalEntity\": [\"tumor cells\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be an empty JSON array \"[]\".\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nMEK5/ERK5 signaling modulates endothelial cell migration and focal contact turnover.\nThe formation of new blood vessels from pre-existing ones requires highly coordinated restructuring of endothelial cells (EC) and the surrounding extracellular matrix. Directed EC migration is a central step in this process and depends on cellular signaling cascades that initiate and control the structural rearrangements. On the basis of earlier findings that ERK5 deficiency in mouse EC results in massive defects in vessel architecture, we focused on the impact of the MEK5/ERK5 signaling pathway on EC migration. Using a retroviral gene transfer approach, we found that constitutive activation of MEK5/ERK5 signaling strongly inhibits EC migration and results in massive morphological changes. The area covered by spread EC was dramatically enlarged, accompanied by an increase in focal contacts and altered organization of actin filaments. Consequently, cells were more rigid and show reduced motility. This phenotype was most likely based on decreased focal contact turnover caused by reduced expression of p130Cas, a key player in directed cell migration. We demonstrate for the first time that ERK5 signaling not only is involved in EC survival and stress response but also controls migration and morphology of EC.", "role": "user" }, { "content": "{\"AnatomicalEntity\": [\"EC\", \"focal contact\", \"endothelial cells\", \"focal contacts\", \"cells\", \"cell\", \"endothelial cell\", \"cellular\", \"filaments\", \"blood vessels\", \"vessel architecture\", \"extracellular matrix\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nintroduction\n\nContext before the citation:\nCross-lingual Textual Entailment (CLTE) has been proposed by (Mehdad et al., 2010) as an extension of Textual Entailment (Dagan and Glickman, 2004) that consists in deciding, given two texts T and H in different languages, if the meaning of H can be inferred from the meaning of T.\n\nCitation Sentence:\nCross-lingual Textual Entailment ( CLTE ) has been proposed by ( Mehdad et al. , 2010 ) as an extension of Textual Entailment ( Dagan and Glickman , 2004 ) that consists in deciding , given two texts T and H in different languages , if the meaning of H can be inferred from the meaning of T .\n\nContext after the citation:\nThe task is inherently difficult, as it adds issues related to the multilingual dimension to the complexity of semantic inference at the textual level. For instance, the reliance of current monolingual TE systems on lexical resources (e.g. WordNet, VerbOcean, FrameNet) and deep processing components (e.g. syntactic and semantic parsers, co-reference resolution tools, temporal expressions recognizers and normalizers) has to confront, at the cross-lingual level, with the limited availability of lexical/semantic resources covering multiple languages, the limited coverage of the existing ones, and the burden of integrating languagespecific components into the same cross-lingual architecture. As a first step to overcome these problems, (Mehdad et al., 2010) proposes a “basic solution”, that brings CLTE back to the monolingual scenario by translating H into the language of T. Despite the advantages in terms of modularity and portability of the architecture, and the promising experimental results, this approach suffers from one main limitation which motivates the investigation on alternative solutions. Decoupling machine translation (MT) and TE, in fact, ties CLTE performance to the availability of MT components, and to the quality of the translations.", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: I want to use an image-text matching system for generic image retrieval.\n\nKeyphrases: image-sentence matching images sentences\n\nDataset description:\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\nFashion IQ: Fashion IQ support and advance research on interactive fashion image retrieval. Fashion IQ is the first fashion dataset to provide human-generated captions that distinguish similar pairs of garment images together with side-information consisting of real-world product descriptions and derived visual attribute labels for these images.\nFlickr30k: The Flickr30k dataset contains 31,000 images collected from Flickr, together with 5 reference sentences provided by human annotators.\nLakh MIDI Dataset: The Lakh MIDI dataset is a collection of 176,581 unique MIDI files, 45,129 of which have been matched and aligned to entries in the Million Song Dataset. Its goal is to facilitate large-scale music information retrieval, both symbolic (using the MIDI files alone) and audio content-based (using information extracted from the MIDI files as annotations for the matched audio files).\nRecipeQA: RecipeQA is a dataset for multimodal comprehension of cooking recipes. It consists of over 36K question-answer pairs automatically generated from approximately 20K unique recipes with step-by-step instructions and images.\nCTC: A dataset that allows exploration of cross-modal retrieval where images contain scene-text instances.\n\nOptions:- A: COCO B: Fashion IQ C: Flickr30k D: Lakh MIDI Dataset E: RecipeQA F: CTC", "role": "user" }, { "content": "[\"COCO\", \"Flickr30k\"]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\", \"Protein\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\" : [\"Dexamethasone\", ...], \"Protein\" : [\"BRCA-1\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nSelective inhibitors and tailored activity probes for lipoprotein-associated phospholipase A(2).\nLipoprotein-associated phospholipase A(2) (Lp-PLA(2) or PLA(2)G7) binds to low-density lipoprotein (LDL) particles, where it is thought to hydrolyze oxidatively truncated phospholipids. Lp-PLA(2) has also been implicated as a pro-tumorigenic enzyme in human prostate cancer. Several inhibitors of Lp-PLA(2) have been described, including darapladib, which is currently in phase 3 clinical development for the treatment of atherosclerosis. The selectivity that darapladib and other Lp-PLA(2) inhibitors display across the larger serine hydrolase family has not, however, been reported. Here, we describe the use of both general and tailored activity-based probes for profiling Lp-PLA(2) and inhibitors of this enzyme in native biological systems. We show that both darapladib and a novel class of structurally distinct carbamate inhibitors inactivate Lp-PLA(2) in mouse tissues and human cell lines with high selectivity. Our findings thus identify both inhibitors and chemoproteomic probes that are suitable for investigating Lp-PLA(2) function in biological systems.", "role": "user" }, { "content": "{\"Chemical\": [\"serine\", \"carbamate\", \"darapladib\"], \"Protein\": [\"serine hydrolase\", \"Lp-PLA(2)\", \"lipoprotein-associated phospholipase A(2)\", \"low-density lipoprotein\", \"LDL\", \"PLA(2)G7)\", \"Lipoprotein-associated phospholipase A(2)\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with a sentence from biomedical research text. Extract all terms that correspond to chemical entities of biological interest (ChEBI).\nReturn your identified terms in a JSON array, formatted like this: [\"Entity1\", \"Entity2\", ...].\nIf no such entities are detected, respond by providing an empty JSON array [].\n\nBiomedical context:\n(A)Shownare21-d-oldlittermates.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "You will be presented with a paragraph from a COVID-19 literature. Your task is to classify the topics of this piece of text by choosing from the following categories:\n\n- Epidemic Forecasting: The content relates to predictions about the spread of COVID-19.\n- Treatment: The paragraph discusses therapeutic methods or medication for COVID-19.\n- Prevention: The content covers measures to prevent the spread of COVID-19.\n- Mechanism: The paragraph explains the biological mechanisms of the virus.\n- Case Report: The content is a report of a COVID-19 case.\n- Transmission: The paragraph discusses how COVID-19 is transmitted.\n- Diagnosis: The content is about diagnosing COVID-19 in individuals.\n\nYour classification should be provided as an element within a JSON array. The array should be formatted with topics enclosed in double quotes and separated by commas, following the JSON format, for example: [\"Topic1\", \"Topic2\", ...]. Include all applicable categories within the array. \nYour output should be a valid JSON array, and no additional text should be included in your response.\n\nArticle:\n\nCoronavirus disease-2019 (COVID-19) pandemic has become a global threat and death tolls are increasing worldwide. The SARS-CoV-2 though shares similarities with SARS-CoV and MERS-CoV, immunopathology of the novel virus is not understood properly. Previous reports from SARS and MERS-CoV documents that preexisting, non-neutralizing or poorly neutralizing antibodies developed as a result of vaccine or infection enhance subsequent infection, a phenomenon called as antibody-dependent enhancement (ADE). Since immunotherapy has been implicated for COVID-19 treatment and vaccine is under development, due consideration has to be provided on ADE to prevent untoward reactions. ADE mitigation strategies like the development of vaccine or immunotherapeutics targeting receptor binding motif can be designed to minimize ADE of SARS-CoV-2 since full-length protein-based approach can lead to ADE as reported in MERS-CoV. The present mini-review aims to address the phenomenon of ADE of SARS-CoV-2 through the lessons learned from SARS-CoV and MERS-CoV and ways to mitigate them so as to develop better vaccines and immunotherapeutics against SARS-CoV-2.", "role": "user" }, { "content": "[\"Treatment\", \"Mechanism\"]", "role": "assistant" } ]

[ { "content": "You will be given an abstract from a computer science research paper. Given the abstract, your task is to extract all unique relationships between entities of the following, and ONLY the following, types:\n\n- \"USED-FOR\": For instance, \"Our method models user proficiency\" -> [\"method\", \"user proficiency\", \"USED-FOR\"].\n- \"EVALUATE-FOR\": For instance, \"We evaluate our method using F1-measure\" -> [\"F1-measure\", \"method\", \"EVALUATE-FOR\"].\n- \"FEATURE-OF\": For instance, \"prior knowledge of the model\" -> [\"prior knowledge\", \"model\", \"FEATURE-OF\"].\n- \"HYPONYM-OF\": For instance, \"TUIT is a software library\" -> [\"TUIT\", \"software library\", \"HYPONYM-OF\"].\n- \"PART-OF\": For instance, \"We incorporate NLU module into the system\" -> [\"NLU module\", \"system\", \"PART-OF\"].\n- \"COMPARE\": For instance, \"Unlike the quantitative prior, the qualitative prior is often ignored\" -> [\"quantitative prior\", \"qualitative prior\", \"COMPARE\"].\n- \"CONJUNCTION\": For instance, \"obtained from human expert or knowledge base\" -> [\"human expert\", \"knowledge base\", \"CONJUNCTION\"].\n\nFormat your output as a JSON array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<Entity_B>\", \"<RELATION_A_B>\"]. An example output might look like:\n\n[[\"neural networks\", \"classification\", \"USED-FOR\"], [\"neuron\", \"neural network\", \"PART-OF\"]].\n\nIf no relations are found, please return an empty JSON array \"[]\".\n\nAbstract:\n\nThis paper proposes a method for learning joint embed-dings of images and text using a two-branch neural network with multiple layers of linear projections followed by nonlinearities. The network is trained using a large-margin objective that combines cross-view ranking constraints with within-view neighborhood structure preservation constraints inspired by metric learning literature. Extensive experiments show that our approach gains significant improvements in accuracy for image-to-text and text-to-image retrieval. Our method achieves new state-of-the-art results on the Flickr30K and MSCOCO image-sentence datasets and shows promise on the new task of phrase lo-calization on the Flickr30K Entities dataset.", "role": "user" }, { "content": "[[\"cross-view ranking constraints\", \"large-margin objective\", \"FEATURE-OF\"], [\"cross-view ranking constraints\", \"within-view neighborhood structure preservation constraints\", \"CONJUNCTION\"], [\"Flickr30K and MSCOCO image-sentence datasets\", \"method\", \"EVALUATE-FOR\"], [\"multiple layers of linear projections\", \"nonlinearities\", \"CONJUNCTION\"], [\"Flickr30K Entities dataset\", \"phrase lo-calization\", \"USED-FOR\"], [\"phrase lo-calization\", \"method\", \"EVALUATE-FOR\"], [\"method\", \"joint embed-dings of images and text\", \"USED-FOR\"], [\"nonlinearities\", \"two-branch neural network\", \"PART-OF\"], [\"multiple layers of linear projections\", \"two-branch neural network\", \"PART-OF\"], [\"image-to-text and text-to-image retrieval\", \"method\", \"EVALUATE-FOR\"], [\"two-branch neural network\", \"method\", \"USED-FOR\"], [\"within-view neighborhood structure preservation constraints\", \"large-margin objective\", \"FEATURE-OF\"], [\"large-margin objective\", \"two-branch neural network\", \"USED-FOR\"], [\"accuracy\", \"method\", \"EVALUATE-FOR\"]]", "role": "assistant" } ]

[ { "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSpectral Studies of UV and Solar Photocatalytic Degradation of AZO Dye and Textile Dye Effluents Using Green Synthesized Silver Nanoparticles\n\nPaper sections:\n1. Introduction\n<p>The emission of effluents from textile industries has been a major concern of the modern world, due to the great pollution that these effluents promote on the water resources [1]. In the synthetic dyes released in effluents from textile industries, AZO dye is one of the more detrimental classes because of its high persistent nature in the aquatic environment, due to its chemical compositions, involving aromatic rings, azoic linkages, and amino groups [2]. The dye industry effluents are a major problem worldwide. The dye industry effluents not only disturb the aquatic ecosystem but also the biota and human beings.</p><p>The dyes are used to modify the colour characteristics of different substrates, such as fibre products, fabric, leather, plastic, wood products, and paper. The dyes were extracted from natural sources, mainly from animals and plant materials, and used much before the nineteenth century [3]. After the nineteenth century the natural dyes were replaced by synthetic dyes. Every day new synthetic dyes are developed for new colours and this eliminates the use of natural dye. These synthetic dyes are inorganic substances to pollute the water bodies. The dye effluent can induce oxidative stress [4], mutagenic activity [5–8], and carcinogenic activity and it can also generate DNA adducts and so forth in living organisms. Nowadays, the dyestuffs and textile effluents were treated using various physical, chemical, and biological methods [9–14]. In the dye effluents treatment, the use of green synthesized nanoparticles is less understood. So in the present study silver nanoparticles synthesized using plant material were tested to treat dye effluents.</p>\n\n2.1. Synthesis and Characterization of Silver Nanoparticles (AgNPs)\n<p>The green synthesized silver nanoparticles were prepared using the crude extract of coconut tree inflorescence fraction (EA : M (40 : 60)) as per technology developed [15]. These synthesized nanoparticles were 22 nm, spherical sized particles. The characteristics of AgNPs were studied using UV/visible spectroscopy, FTIR, and TEM assays.</p>\n\n2.2. Preparation of AZO Dye\n<p>The commercially available AZO dye was purchased from Merck, India. One gram of AZO dye was dissolved in 1000 mL of double distilled water carefully in dark bottles. The dye concentration was 0.1%. The prepared dye was used for further studies.</p>\n\n2.3. Collection of Dye Industry Effluents\n<p>The textile mill effluent was collected from the sewage tank in a textile factory in Tiruppur, Tamil Nadu, India.</p>\n\n2.4. Photocatalytic Based Degradation\n<p>The photocatalytic degradation of AZO dye and textile industry effluents was investigated using green synthesized silver nanoparticles as a photocatalyst under solar light and UV light. The dye degradation was tested by UV/visible double beam spectroscopy 2203 and kinetic measurement was performed at room temperature for UV radiated dye degradation and at outside room temperature for solar radiation. The concentration of the dye was (Optical Density) measured at 200–1000 nm wavelength. The progress of the photocatalytic reaction was observed by recording optical density at regular time intervals. The temperature and PH were also measured at regular time intervals.</p>\n\n3. Result and Discussion\n<p>AZO dyes are compounds characterized by the presence of one or more AZO groups (-N=N-) [2]. This was confirmed by the presence of two absorption bands at 568–737 nm and another at 404–475 nm. These two absorption bands are responsible for n → π\n∗ electron transition. The effluents have two major absorption peaks and were noted at 227 nm and 214 nm. These two peak values always correspond with n → π\n∗ electron transition.</p>\n\n3.1. Photodegradation Process for AZO Dye\n<p>The photodegradation process was carried out under solar and UV light irradiation using green synthesized silver nanoparticles as photocatalysts. The absorption spectra of AZO dye (Figures 1(a) and 1(b)) degradation under solar light irradiation were observed regularly at time intervals. The solar and UV light irradiation, the intimacy between dye molecules and a semiconductor material, and the presence of oxygen are indispensable for an efficient photosensitized degradation reaction.</p><p>The results were shown in Figures 1(a), 1(b), 2(a), and 2(b). The excitation of AZO molecules also depends on the PH and temperature. The excited molecules were absorbed by the Ag nanoparticles. It was confirmed by the absorption spectrum at the regular time intervals (Figures 1(b) and 2(b)). The time taken for dye degradation and PH changed irregularly (Figure 3). The efficacy of light source has changed the electron transition in AZO molecules.</p><p>As the dye molecules were largely seen on the sample surface, the degradation reaction proceeds predominantly through the monochromatic UV light irradiation as reflected by the drastic shift in absorption spectra as shown in Figures 2(a) and 2(b). The comparison of solar and UV light irradiation showed that the UV light has degraded the AZO dyes more effectively than the solar sources.</p>\n\n3.2. Photodegradation Process for Textile Industry Effluents\n<p>The photodegradation process was carried out under solar and ultraviolet irradiation using green synthesized silver nanoparticles as the photocatalyst. Figures 5(a) and 5(b) indicate the absorption spectra of effluent degradation under solar light irradiation. The solar light irradiation induced the electrons (nanoparticles) and is excited from n → π\n∗ electron transition. The absorption rate at regular time intervals and the PH sequentially increased (Figure 6) based on the light intensity (light energy).</p><p>In this reaction also the solar and UV light irradiation, the intimacy between the dye molecule's and a semiconductor material, and the presence of oxygen are indispensable for an efficient photosensitized degradation reaction.</p><p>The results shown in Figures 4(a) and 5(a) show the excitation of dye molecule's in the effluents. The excitation of electrons depends on PH, light intensity (light energy), and temperature. The excited electrons bound to the dye molecules. Then the effluent got changed in their physical, chemical, and biological properties and binding capability. This was confirmed by the absorption spectrum at the regular time intervals (Figures 4(b) and 5(b)). PH got increased with the increase of the duration of dye degradation (Figure 6).</p>\n\n4. Conclusion\n<p>Presence of AZO dyes and other dyes in the textile mill effluents threatens the aquatic food chain. In order to degrade the dyes, UV and solar light irradiation in the presence of green synthesized silver nanoparticles were tested. The presence of green synthesized AgNPs promoted the degradation fast. Hence the coconut tree inflorescence extract mediated silver nanoparticles were found to enhance the photocatalytic dye degradation effectively.</p>", "role": "user" }, { "content": "The photocatalytic degradation of the chemical dye AZO and dye effluents in different time duration has been investigated using biologically synthesized silver nanoparticles. Dye industry effluents and AZO dye undergo degradation to form harmless intermediate and colourless products following irradiation by UV and solar light in the presence of green synthesized silver nanoparticles. The degree of degradation was tested under the experimental conditions such as PH, temperature, and absorbance of the dye in UV and solar light was measured. The degradation was higher in the UV light source than in the solar light source. Green synthesized silver nanoparticles in the UV light source were found to expedite the dye degradation process.", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a research paper and a corresponding research question. Determine the answer to the research question based on the context provided. Your answer should be one of: \"YES\", \"NO\", or \"MAYBE\".\n\nAbstract:\n(OBJECTIVE) Bladder catheterisation is a routine part of major abdominal surgery. Transurethral catheterisation is the most common method of bladder drainage but is also notorious for its discomfort and increased risk of urinary tract infection. The present study aimed to establish patient satisfaction with transurethral catheterisation and to assess the incidence of clinically significant urinary tract infections after transurethral catheterisation through survey.\n(METHODS) All patients who underwent major open abdominal surgery between October 2006 and December 2008 and required standard transurethral bladder catheterisation, were asked to participate in the study. Fifty patients were recruited.\n(RESULTS) Male patients were more dissatisfied than their female counterparts with transurethral catheterisation (satisfaction score: 4.18/10 vs. 2.75/10; p = 0.05). Male patients had more than double the score for pain at the urinary meatus with the catheter in situ (p =0.012) and during urine catheter removal (p = 0.013). Half the patients in the study also had symptoms of urinary tract infection after catheter removal.\n\nQuestion:\nIs transurethral catheterisation the ideal method of bladder drainage?\n\nAnswer:", "role": "user" }, { "content": "NO", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2019 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from the options provided. A short description of the datasets is also provided to help you.\n\nQuery: A simple yet effective and efficient approach for video object segmentation.\n\nKeyphrases: video object segmentation images optical flow\n\nDataset description:\nCaltech-101: The Caltech101 dataset contains images from 101 object categories (e.g., “helicopter”, “elephant” and “chair” etc.) and a background category that contains the images not from the 101 object categories.\nDocBank: A benchmark dataset that contains 500K document pages with fine-grained token-level annotations for document layout analysis. DocBank is constructed using a simple yet effective way with weak supervision from the \\LaTeX{} documents available on the arXiv.com.\nIMDB-BINARY: IMDB-BINARY is a movie collaboration dataset that consists of the ego-networks of 1,000 actors/actresses who played roles in movies in IMDB. In each graph, nodes represent actors/actress, and there is an edge between them if they appear in the same movie.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\n\nOptions: A: Caltech-101 B: DocBank C: IMDB-BINARY D: COCO", "role": "user" }, { "content": "COCO", "role": "assistant" } ]