Miracle-dz/UniFAR-FTUs huggingface dataset:
PAR 1 Receptor / Protein Interactions 1 From Multiple PAR 1 Receptor / Protein Interactions to their Multiple Therapeutic Implications

PAR1, member of the family of protease-activated receptors, is a GPCR whose activation requires a proteolytic cleavage at its extracellular N-terminus to unveil a tethered activating ligand. Although thrombin is the main activator of this receptor, diverse other proteases can also activate and disarm PAR1. Besides, tethered activating ligand-based peptides (PAR-APs) can also activate the receptor. PAR1 mainly signals via G proteins but, it can also signal using β-arrestin pathways and by transactivation of other receptors. This complex PAR1 interactome is completed with the receptor desensitization, trafficking, and degradation. PAR1 has shown species-, cellular-, and physiological or pathological state-dependent specificity. This review try to give an overview on the complex PAR1 interactome, its therapeutic impact upon the cardiovascular, immune and nervous systems, inflammation and cancer, as well as, on its modulation with agonists and antagonists.
Dynamic cohorts : a new approach to managing detail

While it is always desirable to minimize the complexity of a model, some problems require the detailed representation of heterogeneous subgroups, where nonlinearities prevent aggregation or explicit chronological aging is needed. It is desirable to have a representation that avoids burdening the modeler or user computationally or cognitively, with excessive detail or arcane formulations. Eberlein & Thompson (2013) propose continuous cohorting, a novel solution to the cohort blending problem in population modeling, and test it against existing aging chain and cohort-shifting approaches. Continuous cohorting prevents blending of ages and other properties. However, this comes at some cost in complexity, because it creates internal states equal in number to the duration of the aging chain divided by the time step. We propose another new solution, dynamic cohorts, that prevents blending with a comparatively low computational burden. More importantly, the approach simplifies the representation of distinct age, period and cohort effects and representation of dynamics other than the aging process, like migration and attribute coflows. By encapsulating the lifecycle of a representative cohort in a single entity, rather than dispersing it across many states over time, it makes it easier to develop and explain the model structure. These innovations are not limited to population models; they also apply to other quantities, like vehicles, perishable goods or financial instruments. It makes it easy to change aggregation parametrically for empirical determination of the appropriate level of detail, and to mix detailed and aggregate elements in the same model. Background Eberlein and Thompson (2013) provide a thorough treatment of the cohort blending problem. Cohort blending arises in aging chains due to the assumption that the contents of a stock are well mixed. Surprisingly, avoiding blending in a continuous aging chain requires a very high order delay structure (Figure 1). This has long been known, and is often advantageous for representing phenomena in which events are broadly dispersed (Forrester, 1961).
Molecular diversity and distribution of arbuscular mycorrhizal fungi colonizing peach (Prunus persica) and apple (Malus pumila) trees in a sustainable small market garden

We characterized the molecular diversity and distribution of arbuscular mycorrhizal fungi (AMF) in the roots of apple and peach trees found at Grand Valley State University’s Sustainable Agriculture Project small market garden. Arbuscular mycorrhizal fungal root colonization observed in cleared and stained roots ranged from 11–43%. The molecular identity of the fungal symbionts was determined based on phylogenetic analyses of isolated small subunit ribosomal DNA sequences. Twenty-seven arbuscular mycorrhizal fungal sequences in the phylum Glomeromycota were isolated from roots of apple and peach trees with 96% of those sequences in family Glomeraceae including the genera Rhizophagus and Sclerocystis, and 4% of the sequences share identity with fungi in the family Paraglomeraceae. Four of the isolated arbuscular mycorrhizal sequences were shared between different apple and peach trees. Peach tree roots had the highest arbuscular mycorrhizal richness of trees sampled. Our analyses suggest that apple and peach trees in small gardens may form arbuscular mycorrhizal associations with different fungi than apple and peach trees of larger scale agricultural operations. Furthermore, the presence of shared AMF sequences between different fruit trees suggests the presence of common mycorrhizal networks that may serve an important function in the health and productivity of small market gardens.
Fitness determinants of repeated-sprint ability in highly trained youth football players.

UNLABELLED Variations in rates of growth and development in young football players can influence relationships among various fitness qualities. PURPOSE To investigate the relationships between repeated-sprint ability and other fundamental fitness qualities of acceleration, agility, explosive leg power, and aerobic conditioning through the age groups of U11 to U18 in highly trained junior football players. METHODS Male players (n = 119) across the age groups completed a fitness assessment battery over two testing sessions. The first session consisted of countermovement jumps without and with arm swing, 15-m sprint run, 15-m agility run, and the 20-m Shuttle Run (U11 to U15) or the Yo-Yo Intermittent Recovery Test, Level 1 (U16 to U18). The players were tested for repeated-sprint ability in the second testing session using a protocol of 6 × 30-m sprints on 30 s with an active recovery. RESULTS The correlations of repeated-sprint ability with the assorted fitness tests varied considerably between the age groups, especially for agility (r = .02 to .92) and explosive leg power (r = .04 to .84). Correlations of repeated sprint ability with acceleration (r = .48 to .93) and aerobic conditioning (r = .28 to .68) were less variable with age. CONCLUSION Repeated-sprint ability associates differently with other fundamental fitness tests throughout the teenage years in highly trained football players, although stabilization of these relationships occurs by the age of 18 y. Coaches in junior football should prescribe physical training accounting for variations in short-term disruptions or impairment of physical performance during this developmental period.
Probabilistic Hosting Capacity for Active Distribution Networks

The increased connection of distributed generation (DG), such as photovoltaic (PV) and wind turbine (WT), has shifted the current distribution networks from being passive (consuming energy) into active (consuming/producing energy). However, there is still no consensus about how to determine the maximum amount of DGs that are allowed to be connected, i.e., how to quantify a so-called “hosting capacity” (HC). Therefore, this paper proposes a novel risk assessment tool for estimating network HC by considering uncertainties associated with PV, WT, and loads. This evaluation is performed using the likelihood approximation approach. The paper, also, proposes a utilization of clearness index for localized solar irradiance prediction of PV. In addition, we propose the use of sparse grid technique as an effective means for uncertainty computation while the use of Monte Carlo technique is taken for a comparison purpose. Two actual distribution networks (11-buses and South Australian large feeder) are considered as case studies to demonstrate the usefulness of the proposed tool.
Statistical methods for detecting gene-gene and gene-environment interactions in genome-wide association studies

Despite considerable effort to elucidate the genetic architecture of multifactorial traits and diseases, there remains a gap between the estimated heritability (e.g., from twin studies) and the heritability explained by discovered genetic variants. The existence of interactions between different genes, and between genes and the environment, has frequently been hypothesized as a likely cause of this discrepancy. However, the statistical inference of interactions is plagued by limited sample sizes, high computational requirements, and incomplete knowledge of how the measurement scale and parameterization affect the analysis. This thesis addresses the major statistical, computational, and modeling issues that hamper large-scale interaction studies today. Furthermore, it investigates whether gene-gene and gene-environment interactions are significantly involved in the development of diseases linked to atherosclerosis. Firstly, I develop two statistical methods that can be used to study of genegene interactions: the first is tailored for limited sample size situations, and the second enables multiple analyses to be combined into large meta-analyses. I perform comprehensive simulation studies to determine that these methods have higher or equal statistical power than contemporary methods, scaleinvariance is required to guard against false positives, and that saturated parameterizations perform well in terms of statistical power. In two studies, I apply the two proposed methods to case/control data from myocardial infarction and associated phenotypes. In both studies, we identify putative interactions for myocardial infarction but are unable to replicate the interactions in a separate cohort. In the second study, however, we identify and replicate a putative interaction involved in Lp(a) plasma levels between two variants rs3103353 and rs9458157. Secondly, I develop a multivariate statistical method that simultaneously estimates the effects of genetic variants, environmental variables, and their interactions. I show by extensive simulations that this method achieves statistical power close to the optimal oracle method. We use this method to study the involvement of gene-environment interactions in intima-media thickness, a phenotype relevant for coronary artery disease. We identify a putative interaction between a genetic variant in the KCTD8 gene and alcohol use, thus suggesting an influence on intima-media thickness. The methods developed to support the analyses in this thesis as well as a selection of other prominent methods in the field is implemented in a software package called besiq. In conclusion, this thesis presents statistical methods, and the associated software, that allows large-scale studies of gene-gene and gene-environment interactions to be effortlessly undertaken.
Body composition and fat distribution during the first 2 weeks of gestation in ad lib.-fed and energy-restricted rats

Knowledge about changes in body composition during gestation is of interest when estimating energy requirements during pregnancy, and relevant since reproduction is often surprisingly well maintained in malnourished females. Due to difficulties in conducting such studies in humans, studies in rats are of interest. Therefore, maternal retention of fat and fat-free weight was estimated in rats during the first 2 weeks of gestation and during a corresponding time period in virgin controls. Groups fed ad lib. or 70 % of ad lib. intake during the 4 weeks preceding conception and during gestation were studied. Retention was estimated by comparing pregnant and virgin rats with rats killed at the time of conception. Body fat was analysed chemically and fat-free weight was body weight minus body fat. Each rat was divided into twelve to fourteen parts and the fat content of each part was analysed. Pregnant ad lib. -fed rats retained more fat and fat-free weight than did virgin ad lib. -fed controls. In the energy-restricted group the pregnant rats retained more fat-free weight while virgin rats retained slightly more fat than did pregnant rats. The difference between pregnant and virgin rats with respect to the amount of fat in the different body parts was small in both feeding groups. Thus, the statement that fat stored at specific sites in the maternal body represents an important source of energy for use during lactation was not supported. The findings suggest that pregnancy stimulates growth of the maternal body and that chronic moderate energy restriction curtails this growth.
The Scottish Centre for Autism Preschool Treatment Programme

This article evaluates the effectiveness of a developmentally based early intervention programme. Two groups of children were compared, a treatment group and a no-treatment control group. Standardized assessments were administered before and after the intervention period by an independent clinician. Pre-treatment comparisons revealed that the control group had a significantly higher pre-treatment IQ; but the two groups were comparable for age, mental age, socioeconomic status and number of hours of non-experimental therapy. Results demonstrated that children in the treatment group improved significantly more than those in the control group on measures of joint attention, social interaction, imitation, daily living skills, motor skills and an adaptive behaviour composite. A measure of requesting behaviour fell short of statistical significance. The total stress index reduced for treatment group parents and increased for the control group parents (but not significantly). The results of the study are considered to support the efficacy of this treatment approach.
Hedging and temporal permit issuances in cap-and-trade programs: the Market Stability Reserve under risk aversion

Abstract Cap-and-trade programs such as the European Union's Emissions Trading System (EU ETS) expose firms to considerable risks, to which the firms can respond with hedging. We develop an intertemporal stochastic equilibrium model to analyze the implications of hedging by risk-averse firms. We show that the resulting time-varying risk premium depends on the size of the permit bank. Applying the model to the EU ETS, we find that hedging can lead to a U-shaped price path, because prices initially fall due to negative risk premiums and then rise as the hedging demand declines. The Market Stability Reserve (MSR) reduces the permit bank and thus, increases the hedging value of the permits. This offers an explanation for the recent price hike, but also implies that prices may decline in the future due to more negative risk premiums. In addition, we find higher permit cancellations through the MSR than previous analyses, which do not account for hedging.
Serum levels of tenascin‐C in collagen diseases

Tenascins are a family of large multimetric extracellular matrix (ECM) proteins. Among them, large molecular weight variant tenascin‐C is known to be specifically expressed in pathological conditions. However, no link between tenascin‐C and collagen diseases has been established. The aim of our study was to determine the serum tenascin‐C levels in patients with various collagen diseases, and to evaluate the possibility that serum levels of tenascin‐C can be a useful marker for collagen diseases, correlating with the pathogenesis. Serum tenascin‐C levels of 33 patients with scleroderma (SSc), 10 patients with scleroderma spectrum disorder (SSD), 15 patients with localized scleroderma (LSc), 12 patients with dermatomyositis (DM), 10 patients with systemic lupus erythematosus (SLE) and 15 healthy controls were measured with specific enzyme‐linked immunosorbent assays. Serum tenascin‐C levels were significantly elevated in patients with SSc, SSD and LSc than in healthy controls. Significantly higher total skin thickness score or higher incidence of pitting scars/ulcers and diffuse pigmentation were observed in SSc patients with elevated tenascin‐C levels than in those with normal levels. Our study suggests that serum tenascin‐C levels are increased in fibrotic conditions, and that tenascin‐C contributes to the pathogenesis of vascular damage as well as fibrosis in SSc patients. Clarifying the role of tenascin‐C in the pathogenesis of collagen diseases may lead to a new therapeutic approach.
CS 224 N HW 4 : SQuAD Reading Comprehension Learning

The Stanford Question Answering Dataset (SQuAD) consists on more than 100000 triplets paragraph, question, answer from Wikipedia, with various answer types and length. By training a coattention-based encoder followed by a mostly linear spanning decoder and a inversion handling post processing, we are able to achieve a F1 of 56% and an exact match of 43% with a particularly good accuracy on Named entities and numerical answers.
Body Mass Index and Earnings: A Fixed Effects Approach

This paper examines the effect of body mass index (BMI) on annual earnings using an individual fixed effects approach to control for time-invariant endogeneity. Heterogeneous effects of BMI on earnings are also explored for different races and education levels. This research also conducts a preliminary investigation into relationship between BMI and job mobility as a potential mechanism mediating the effect of BMI on earnings. My findings show that white women incur a 4% annual earnings penalty per one-point increase in BMI. Overall, black and Hispanic women are insulated from this penalty. Both of these findings are relatively consistent with previous literature. However, black women with a college degree incur an annual penalty of nearly 6% per point increase in BMI, a novel finding that complicates general statements about the effect of BMI on earnings for different races. The effect of BMI on men’s earnings was either nonexistent or weakly positive. BMI does have a small, negative impact on job mobility for men, but not for women.
MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder.

OBJECTIVE Studies in nonhuman primates suggest that high levels of cortisol associated with stress have neurotoxic effects on the hippocampus, a brain structure involved in memory. The authors previously showed that patients with combat-related posttraumatic stress disorder (PTSD) had deficits in short-term memory. The purpose of this study was to compare the hippocampal volume of patients with PTSD to that of subjects without psychiatric disorder. METHOD Magnetic resonance imaging was used to measure the volume of the hippocampus in 26 Vietnam combat veterans with PTSD and 22 comparison subjects selected to be similar to the patients in age, sex, race, years of education, socioeconomic status, body size, and years of alcohol abuse. RESULTS The PTSD patients had a statistically significant 8% smaller right hippocampal volume relative to that of the comparison subjects, but there was no difference in the volume of other brain regions (caudate and temporal lobe). Deficits in short-term verbal memory as measured with the Wechsler Memory Scale were associated with smaller right hippocampal volume in the PTSD patients only. CONCLUSIONS These findings are consistent with a smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory.
Surface plasmon polariton in metal-insulator-metal configuration

The optics of the surface plasmon resonance has been known for a long time. In the configuration multilayer, the optical coupling of a wave incident to collective oscillations of electrons along an interface between a metal and a dielectric is governed by the thickness of metal and gap layers. The surface plasmon excitations excited by an electromagnetic wave in the visible band (λ= 633 nm). For the metal, in particular a frequency on their dielectric permittivity dependence and described by the Drude-Lorentz model and using the effective-index approach and an explicit expression for the propagation constant of gap surface plasmon polaritons (G-SPPs) obtained for moderate gap widths.
Honeypots for Threat Intelligence in Building Automation Systems

Direct Digital Controls (DDCs) are components of building automation systems that have a network interface. In this paper we describe how to create a honeypot for such a device. We have replicated the individual services available on the device with extensive logging mechanisms. To do this, we dealt with both protocol-specific as well as operating system-specific properties. We then conduct an experiment in which the honeypots are made publicly accessible on the Internet in order to check whether existing vulnerabilities are already being exploited in the examined devices. While analysing the data we didn’t find any specific attacks for this device. Finally, we suggest possible improvements for future experiments.
Characterization of the Metabolic Activation of Hepatitis C Virus Nucleoside Inhibitor β-d-2′-Deoxy-2′-fluoro-2′-C-methylcytidine (PSI-6130) and Identification of a Novel Active 5′-Triphosphate Species*

β-d-2′-Deoxy-2′-fluoro-2′-C-methylcytidine (PSI-6130) is a potent inhibitor of hepatitis C virus (HCV) replication in the subgenomic HCV replicon system, and its corresponding 5′-triphosphate is a potent inhibitor of the HCV RNA polymerase in vitro. In this study the formation of PSI-6130-triphosphate was characterized in primary human hepatocytes. PSI-6130 and its 5′-phosphorylated derivatives were identified, and the intracellular concentrations were determined. In addition, the deaminated derivative of PSI-6130, β-d-2′-deoxy-2′-fluoro-2′-C-methyluridine (RO2433, PSI-6026) and its corresponding phosphorylated metabolites were identified in human hepatocytes after incubation with PSI-6130. The formation of the 5′-triphosphate (TP) of PSI-6130 (PSI-6130-TP) and RO2433 (RO2433-TP) increased with time and reached steady state levels at 48 h. The formation of both PSI-6130-TP and RO2433-TP demonstrated a linear relationship with the extracellular concentrations of PSI-6130 up to 100 μm, suggesting a high capacity of human hepatocytes to generate the two triphosphates. The mean half-lives of PSI-6130-TP and RO2433-TP were 4.7 and 38 h, respectively. RO2433-TP also inhibited RNA synthesis by the native HCV replicase isolated from HCV replicon cells and the recombinant HCV polymerase NS5B with potencies comparable with those of PSI-6130-TP. Incorporation of RO2433-5′-monophosphate (MP) into nascent RNA by NS5B led to chain termination similar to that of PSI-6130-MP. These results demonstrate that PSI-6130 is metabolized to two pharmacologically active species in primary human hepatocytes.