Miracle-dz/UniFAR-FTUs huggingface dataset:
Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry

The envelope of HSV-1 contains a number of glycoproteins, four of which are essential for virus entry. Virus particles lacking gB, gD, gH or gL are entry-defective, although these viruses retain the ability to bind to the plasma membrane via the remaining glycoproteins. Soluble forms of gD have been shown to trigger the nuclear translocation of the NF-κB transcriptional complex in addition to stimulating the production of Type I interferon. By taking advantage of the entry-defective phenotype of glycoprotein-deficient HSV-1 virus particles, the results presented here show that binding of virions to cellular receptors on the plasma membrane is sufficient to stimulate a change in cellular gene expression. Preliminary microarray studies, validated by quantitative real-time PCR, identified the differential expression of cellular genes associated with the NF-κB, PI3K/Akt, Jak/Stat and related Jak/Src pathways by virions lacking gB or gH but not gD. Gene induction occurred at a few particles per cell, corresponding to physiological conditions during primary infection. Reporter assay studies determined that NF-κB transcriptional activity is stimulated within an hour of HSV-1 binding, peaks between two and three hours post-binding and declines to background levels by five hours after induction. The immediate, transient nature of these signalling events suggests that HSV-1 glycoproteins, particularly gD, may alter the cellular environment pre-entry so as to condition the cell for viral replication.
Multiple extended target tracking based on GLMB filter and gibbs sampler

In this paper, a new multiple extended target tracking learning algorithm based on labelled random finite sets (L-RFS) framework is proposed to estimate the number, shape and state of extended targets under clutter conditions. The algorithm mainly includes two aspects: multi-extended target dynamic modeling and multi-extended target tracking estimates. Firstly, a finite mixture model (FMM) of extended target is established under the generalized labelled multi-bernoulli (GLMB) filter. Learning the parameters of finite mixture model by Gibbs sampling and Bayesian information criterion (BIC), and then equivalent point target measurements are used in place of the actual extended target measurements. Finally, the proposed ellipse approximation model is used to realize the estimation of the extended target shape. The simulation results show that the proposed algorithm can effectively track the multiple extended targets and obtain the shape of extended target.
Constructing Imperfect Recall Abstractions to Solve Large Extensive-Form Games

Extensive-form games are an important model of finite sequential interaction between players. The size of the extensive-form representation is, however, often prohibitive and it is the most common cause preventing deployment of game-theoretic solution concepts to real-world scenarios. The state-of-the-art approach to solve this issue is the information abstraction methodology. The majority of existing information abstraction approaches create abstracted games where players remember all their actions and all the information they obtained in the abstracted game -- a property denoted as a perfect recall. Remembering all the actions, however, causes the number of decision points of the player (and hence also the size of his strategy) to grow exponentially with the number of actions taken in the past. On the other hand, relaxing the perfect recall requirement (resulting in so-called imperfect recall abstractions) can significantly increase the computational complexity of solving the resulting abstracted game. In this work, we introduce two domain-independent algorithms FPIRA and CFR+IRA which are able to start with an arbitrary imperfect recall abstraction of the solved two-player zero-sum perfect recall extensive-form game. The algorithms simultaneously solve the abstracted game, detect the missing information causing problems and return it to the players. This process is repeated until provable convergence to the desired approximation of the Nash equilibrium of the original game. We experimentally demonstrate that even when the algorithms start with trivial coarse imperfect recall abstraction, they are capable of approximating Nash equilibrium of large games using abstraction with as little as 0.9% of information sets of the original game.
Marital Status and Mortality among Middle Age and Elderly Men and Women in Urban Shanghai

Background Previous studies have suggested that marital status is associated with mortality, but few studies have been conducted in China where increasing aging population and divorce rates may have major impact on health and total mortality. Methods We examined the association of marital status with mortality using data from the Shanghai Women's Health Study (1996–2009) and Shanghai Men's Health Study (2002–2009), two population-based cohort studies of 74,942 women aged 40–70 years and 61,500 men aged 40–74 years at the study enrollment. Deaths were identified by biennial home visits and record linkage with the vital statistics registry. Marital status was categorized as married, never married, divorced, widowed, and all unmarried categories combined. Cox regression models were used to derive hazard ratios (HR) and 95% confidence interval (CI). Results Unmarried and widowed women had an increased all-cause HR = 1.11, 95% CI: 1.03, 1.21 and HR = 1.10, 95% CI: 1.02, 1.20 respectively) and cancer (HR = 1.17, 95% CI: 1.04, 1.32 and HR = 1.18, 95% CI: 1.04, 1.34 respectively) mortality. Never married women had excess all-cause mortality (HR = 1.46, 95% CI: 1.03, 2.09). Divorce was associated with elevated cardiovascular disease (CVD) mortality in women (HR = 1.47, 95% CI: 1.01, 2.13) and elevated all-cause mortality (HR = 2.45, 95% CI: 1.55, 3.86) in men. Amongst men, not being married was associated with excess all-cause (HR = 1.45, 95% CI: 1.12, 1.88) and CVD (HR = 1.65, 95% CI: 1.07, 2.54) mortality. Conclusions Marriage is associated with decreased all cause mortality and CVD mortality, in particular, among both Chinese men and women.
Investigation on optical properties of BSA protein on single-layer graphene using terahertz spectroscopy technology

Terahertz (THz) spectroscopy is sensitive to probe several aspects of biological systems. In THz frequency, electrically controllable Drude-like intraband absorption makes graphene a promising platform for building graphene-based optoelectronic devices such as THz biosensor. In this work, BSA protein thin films were spin-coated and incubated on single-layer graphene. IR lasers with different power were used as the pump light to stimulate the sandwich-like sample respectively. The graphene monolayer complex conductivity was calculated using the transmission method. The novel optical properties of single-layer graphene and BSA protein on graphene in the THz range will be discussed in this paper.
Frequent Use of Paracetamol and Risk of Allergic Disease Among Women in an Ethiopian Population

Introduction The hypothesis that paracetamol might increase the risk of asthma and other allergic diseases have gained support from a range of independent studies. However, in studies based in developed countries, the possibility that paracetamol and asthma are associated through aspirin avoidance is difficult to exclude. Objectives To explore this hypothesis among women in a developing country, where we have previously reported aspirin avoidance to be rare. Methods In 2005/6 a population based cohort of 1065 pregnant women was established in Butajira, Ethiopia and baseline demographic data collected. At 3 years post birth, an interview-based questionnaire administered to 945 (94%) of these women collected data on asthma, eczema, and hay fever in the past 12 month, frequency of paracetamol use and potential confounders. Allergen skin tests to Dermatophagoides pteronyssinus and cockroach were also performed. The independent effects of paracetamol use on allergic outcomes were determined using multiple logistic regression analysis. Findings The prevalence of asthma, eczema and hay fever was 1.7%, 0.9% and 3.8% respectively; of any one of these conditions 5.5%, and of allergen sensitization 7.8%. Paracetamol use in the past month was reported by 29%, and associations of borderline significance were seen for eczema (adjusted OR (95% CI) = 8.51 (1.68 to 43.19) for 1–3 tablets and 2.19 (0.36 to 13.38) for ≥4 tablets, compared to no tablets in the past month; overall p = 0.055) and for ‘any allergic condition’ (adjusted OR (95% CI) = 2.73 (1.22 to 6.11) for 1–3 tablets and 1.35 (0.67 to 2.70) for ≥4 tablets compared to 0 in the past month; overall p = 0.071). Conclusions This study provides further cross-sectional evidence that paracetamol use increases the risk of allergic disease.
A Simple Approach to Determine a Curve Fitting Model with a Correct Weighting Function for Calibration Curves in Quantitative Ligand Binding Assays

In ligand binding assays (LBA), the concentration to response data is a nonlinear relationship driven by the law of mass action. Four parameter logistic (4PL) and five parameter logistic (5PL) curve fitting models are two widely accepted and validated models for LBA calibration curve data. Selection of the appropriate regression model and weighting function are key components of LBA development. Assessment of selected model and weighting function should be performed during assay development and confirmed later during validation. There has been limited published work on practical approaches to determining an appropriate weighting function and selection of a regression model for ligand binding assays. Herein, a structured scheme is presented to determine both. By applying commonly available software, assay performance data were analyzed to determine weighting functions and associated choice of a curve fitting model in three presented case studies. As a result, assay ranges of quantification were improved by reducing lower limit of quantification (from 1.00 to 0.317 ng/mL in one case study and from 2.06 to 1.37 ng/mL in another) or extending both low and upper limits of quantification(e.g., 1.04 to 48.3 ng/mL improved to 0.602 to 145 ng/mL). In addition, assay calibration curve performance demonstrated improved assay accuracy (%RE) and precision (%CV). Recommendations on decision flow when determining appropriate weighting function and curve fit model are presented.
Volatility in the effective size of a freshwater gastropod population

Abstract Despite the utility of gastropod models for the study of evolutionary processes of great generality and importance, their effective population size has rarely been estimated in the field. Here, we report allele frequency variance at three allozyme‐encoding loci monitored over 7 years in a population of the invasive freshwater pulmonate snail Physa acuta (Draparnaud 1805), estimating effective population size with both single‐sample and two‐sample approaches. Estimated N e declined from effectively infinite in 2009 to approximately 40–50 in 2012 and then rose back to infinity in 2015, corresponding to a striking fluctuation in the apparent census size of the population. Such volatility in N e may reflect cryptic population subdivision.
A Pharmacokinetic/Viral Kinetic Model to Evaluate Treatment of Chronic HCV Infection with a Non-Nucleoside Polymerase Inhibitor

Background Viral kinetic models have proven useful in characterizing treatment effectiveness during HCV therapy with interferon (IFN) as well as with direct-acting antivirals (DAAs). Methods Here we use a pharmacokinetic/viral kinetic (PK/VK) model to describe HCV RNA kinetics during treatment with setrobuvir, a non-nucleosidic inhibitor of the HCV NS5B polymerase enzyme. Using PK data from three studies in healthy volunteers and PK and VK data from a Phase I study, where setrobuvir was administered for 3 days, we fitted a two-compartment PK model with first-order absorption and lag-time, an Emax pharmacodynamics model and a standard biphasic VK model. Results Setrobuvir's EC50 and Hill coefficient and the viral clearance rate were significantly different (P=0.014, P<0.001 and P=0.004, respectively) between patients infected with HCV subtypes 1b and 1a, leading to an increased viral load decline in patients infected with genotype 1b virus. Conclusions Understanding the combined effects of PK/VK on the performance of a non-nucleoside polymerase inhibitor such as setrobuvir could provide valuable insights into their use in combination with other DAAs as well as to optimize future therapy. Further, our work suggests that patients infected with subtype 1a would need higher doses than those infected with subtype 1b to achieve the same effectiveness. Whether this is true for other non-nucleoside polymerase inhibitors needs to be examined.
Paternal Exposure to Environmental Chemical Stress Affects Male Offspring’s Hepatic Mitochondria

Preconceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3× per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age. Analysis of the liver proteome by 2D-gel electrophoresis and mass spectrometry indicated that proteins involved in mitochondrial function were significantly downregulated in the offspring of exposed fathers. This down-regulation of mitochondrial proteins was paralleled by a reduction in mitochondrial DNA copy number and reduced activity of citrate synthase and β-hydroxyacyl-CoA dehydrogenase, but in male offspring only. Surprisingly, analysis of hepatic mRNA expression revealed a male-specific up-regulation of the genes, whose proteins were downregulated, including Aldh2 and Ogg1. This discrepancy could be related to several selected microRNA (miRNA)'s that regulate the translation of these proteins; miRNA-122, miRNA-129-2-5p, and miRNA-1941 were upregulated in a gender-specific manner. Since mitochondria are thought to be a source of intracellular reactive oxygen species, we additionally assessed oxidatively-induced DNA damage. Both 8-hydroxy-deoxyguanosine and malondialdehyde-dG adduct levels were significantly reduced in male offspring of exposed fathers. In conclusion, we show that paternal exposure to B[a]P can regulate mitochondrial metabolism in offspring, which may have profound implications for our understanding of health and disease risk inherited from fathers.
The Application of Non-Cooperative Stackelberg Game Theory in Behavioral Science: Social Optimality with any Number of Players

Here we present a ground-breaking new postulate for game theory. The first part of this postulate contains the axiomatic observation that all games are created by a designer, whether they are: e.g., (dynamic/static) or (stationary/non-stationary) or (sequential/one-shot) non-cooperative games, and importantly, whether or not they are intended to represent a non-cooperative Stackelberg game, they can be mapped to a Stackelberg game. I.e., the game designer is the leader who is totally rational and honest, and the followers are mapped to the players of the designed game. If now the game designer, or "the leader" in the Stackelberg context, adopts a pure strategy, we postulate the following second part following from axiomatic observation of ultimate game leadership, where empirical insight leads to the second part of this postulate. Importantly, implementing a non-cooperative Stackelberg game, with a very honest and rational leader results in social optimality for all players (followers), assuming pure strategy across all followers and leader, and that the leader is totally rational, honest, and is able to achieve a minimum amount of competency in leading this game, with any finite number of iterations of leading this finite game.
The unfolded protein response in neurodegenerative disorders – therapeutic modulation of the PERK pathway

The unfolded protein response (UPR) is a highly conserved protein quality control mechanism, activated in response to Endoplasmic Reticulum (ER) stress. Signalling is mediated through three branches, PERK, IRE1, and ATF6, respectively, that together provide a coordinated response that contributes to overcoming disrupted proteostasis. PERK branch activation predominantly causes a rapid reduction in global rates of translation, while the IRE1 and ATF6 branch signalling induce a transcriptional response resulting in expression of chaperones and components of the protein degradation machinery. Protein misfolding neurodegenerative diseases show disruption of proteostasis as a biochemical feature. In the brains of animal models of disease and in human post mortem tissue from many of these disorders, markers of UPR induction, particularly, the PERK pathway can be observed in close association with disease progression. Recent research has revealed dysregulated UPR signalling to be a major pathogenic mechanism in neurodegeneration, and that genetic and pharmacological modulation of the PERK pathway results in potent neuroprotection. Targeting aberrant UPR signalling is the focus of new therapeutic strategies, which importantly could be beneficial across the broad spectrum of neurodegenerative diseases.
Measuring Childhood Adversity in Life Course Cardiovascular Research: A Systematic Review

Objective Identifying the life course health effects of childhood adversity is a burgeoning area of research, particularly in relation to cardiovascular disease (CVD). However, adversity measurement varies widely across studies, which may hamper our ability to make comparisons across studies and identify mechanisms linking adversity to CVD. The purposes of this review are to summarize adversity measurement approaches in the context of CVD, identify gaps, and make recommendations for future research. Methods PubMed and PsycINFO searches were conducted through June 2016. Studies were selected if CVD end point or predisease risk markers were investigated in association with a measure of childhood adversity. Forty-three studies were reviewed. A meta-analysis was not conducted because of the variation in exposures and outcomes assessed. Results Adversity measurement was heterogeneous across studies. Metrics included different sets of adverse events, relational factors, and socioeconomic indicators. Thirty-seven percent measured childhood adversity prospectively, 23% examined a CVD end point, and 77% treated adversity as an unweighted summary score. Despite the heterogeneity in measurement, most studies found a positive association between childhood adversity and CVD risk, and the association seems to be dose–response. Conclusions The literature on childhood adversity and CVD would benefit from improving consistency of measurement, using weighted adversity composites, modeling adversity trajectories over time, and considering socioeconomic status as an antecedent factor instead of a component part of an adversity score. We suggest conceptual and analytic strategies to enhance, refine, and replicate the observed association between childhood adversity and CVD risk.
A Faster Algorithm Solving a Generalization of Isotonic Median Regression and a Class of Fused Lasso Problems

Many applications in the areas of production, signal processing, economics, bioinformatics, and statistical learning involve a given partial order on certain parameters and a set of noisy observations of the parameters. The goal is to derive estimated values of the parameters that satisfy the partial order that minimize the loss of deviations from the given observed values. A prominent application of this setup is the well-known isotonic regression problem where the partial order is a total order. A commonly studied isotonic regression problem is the isotonic median regression (IMR) where the loss function is a sum of absolute value functions on the deviations of the estimated values from the observation values. We present here the most efficient algorithm to date for a generalization of IMR with any convex piecewise linear loss function as well as for variant models that include $\ell_1$ norm penalty separation/regularization functions in the objective on the violation of the total order constraints. Suc.
Evaluation of a Sensor System for Detecting Humans Trapped under Rubble: A Pilot Study

Rapid localization of injured survivors by rescue teams to prevent death is a major issue. In this paper, a sensor system for human rescue including three different types of sensors, a CO2 sensor, a thermal camera, and a microphone, is proposed. The performance of this system in detecting living victims under the rubble has been tested in a high-fidelity simulated disaster area. Results show that the CO2 sensor is useful to effectively reduce the possible concerned area, while the thermal camera can confirm the correct position of the victim. Moreover, it is believed that the use of microphones in connection with other sensors would be of great benefit for the detection of casualties. In this work, an algorithm to recognize voices or suspected human noise under rubble has also been developed and tested.
Metabolomic Profiling of Drug Responses in Acute Myeloid Leukaemia Cell Lines

Combined bezafibrate (BEZ) and medroxyprogesterone acetate (MPA) exert unexpected antileukaemic activities against acute myeloid leukaemia (AML) and these activities are associated with the generation of reactive oxygen species (ROS) within the tumor cells. Although the generation of ROS by these drugs is supported by preceding studies including our own, the interrelationship between the cellular effects of the drugs and ROS generation is not well understood. Here we report the use of NMR metabolomic profiling to further study the effect of BEZ and MPA on three AML cell lines and to shed light on the underlying mechanism of action. For this we focused on drug effects induced during the initial 24 hours of treatment prior to the onset of overt cellular responses and examined these in the context of basal differences in metabolic profiles between the cell lines. Despite their ultimately profound cellular effects, the early changes in metabolic profiles engendered by these drugs were less pronounced than the constitutive metabolic differences between cell types. Nonetheless, drug treatments engendered common metabolic changes, most markedly in the response to the combination of BEZ and MPA. These responses included changes to TCA cycle intermediates consistent with recently identified chemical actions of ROS. Notable amongst these was the conversion of α-ketoglutarate to succinate which was recapitulated by the treatment of cell extracts with exogenous hydrogen peroxide. These findings indicate that the actions of combined BEZ and MPA against AML cells are indeed mediated downstream of the generation of ROS rather than some hitherto unsuspected mechanism. Moreover, our findings demonstrate that metabolite profiles represent highly sensitive markers for genomic differences between cells and their responses to external stimuli. This opens new perspectives to use metabolic profiling as a tool to study the rational redeployment of drugs in new disease settings.