Miracle-dz/UniFAR-FTUs huggingface dataset:
Variational Inference of Population Structure in Large SNP Datasets

Tools for estimating population structure from genetic data are now used in a wide variety of applications in population genetics. However, inferring population structure in large modern data sets imposes severe computational challenges. Here, we develop efficient algorithms for approximate inference of the model underlying the STRUCTURE program using a variational Bayesian framework. Variational methods pose the problem of computing relevant posterior distributions as an optimization problem, allowing us to build on recent advances in optimization theory to develop fast inference tools. In addition, we propose useful heuristic scores to identify the number of populations represented in a dataset and a new hierarchical prior to detect weak population structure in the data. We test the variational algorithms on simulated data, and illustrate using genotype data from the CEPH-Human Genome Diversity Panel. The variational algorithms are almost two orders of magnitude faster than STRUCTURE and achieve accuracies comparable to those of ADMIXTURE. Furthermore, our results show that the heuristic scores for choosing model complexity provide a reasonable range of values for the number of populations represented in the data, with minimal bias towards detecting structure when it is very weak. Our algorithm, fastSTRUCTURE, is freely available online at http://pritchardlab.stanford. edu/structure.html.
The repeatability and accuracy of ultrasound in measuring backfat of cattle.

Repeatability of ultrasound backfat measurements was determined on 217 cattle, and the association of ultrasound and carcass backfat measurements was evaluated with 580 animals. The correlation (repeatability) between consecutive ultrasound measurements was . 975. Average difference between two ultrasound measures was . 72 mm and error size was directly related (P less than .001) to the amount of backfat. Ultrasound measures averaged 8% (P less than .001) less than carcass measures. The average absolute difference between these two measures was 1.57 mm. Discrepancies were (P less than .001) larger when backfat was thicker; cattle with backfat measuring less than 10 mm averaged 1.43 mm absolute difference, whereas those with backfat greater than 10 mm averaged 1.89 mm. The variance of the discrepancies was partitioned into three components: ultrasound measurement error (14%), drift related to intercept and slope (15%), and residual (71%). The residual component may have represented errors in carcass measurement. In a subsequent trial with 175 cattle, average difference between ultrasound and carcass backfat measurements was reduced to 1.19 mm. Also, the slope and intercept virtually mimicked the isopach. Ultrasound measures can be more precise (minutely exact) and accurate (close to the true value) than carcass measures for assessing absolute backfat thickness in cattle. Elements of measurement protocol that may improve ultrasound technique are imparted in the manuscript.
A simplified method of calculating cPRA for kidney allocation application in Hong Kong: a retrospective study

Calculated panel reactive antibody (cPRA) represents possibility of encountering an incompatible donor for organ transplant candidates and has gradually replaced traditional PRA as a measurement of sensitization level. We tested two cPRA calculation methods on a cohort of renal candidate (n = 613). HLA typing of 563 Chinese deceased renal donors was used to estimate allele and haplotype frequencies of Hong Kong donor pool. The OPTN formula was adopted to generate cPRA (cPRA (freq)). We also incorporated a computer script to compare unacceptable antigens of patients against HLA phenotype of donors. The cPRA based on historical donor filtering was the percentage of filter out count over total number of donors (cPRA (filter)). Values of cPRA (freq) and cPRA (filter) showed almost perfect agreement with Lin's correlation coefficient equal to 1.000. SD of bias was 0.6 cPRA point. Limit of agreement was 0.9 to −1.5 points difference. Furthermore, the poor agreement between our in‐house cPRA and values from other online calculators indicated the necessity to use local population data for accurate cPRA calculation. Built‐in donor filtering method was more practicable for Hong Kong due to factors such as cost and flexibility. An on‐going donor pool can reflect population allele frequencies and permits efficient periodic update of cPRA.
Temperature Matters! And Why It Should Matter to Tumor Immunologists

A major goal of cancer immunotherapy is to stimulate the generation of long-lasting, tumor antigen–specific immune responses that recognize and destroy tumor cells. This article discusses advances in thermal medicine with the potential to improve cancer immunotherapy. Longstanding evidence indicates that survival benefits are accorded to individuals who achieve an increase in body temperature (i.e., fever) following infection. Furthermore, accumulating evidence indicates that physiologic responses to hyperthermia affect the tumor microenvironment through temperature-sensitive checkpoints that regulate tumor vascular perfusion, lymphocyte trafficking, inflammatory cytokine expression, tumor metabolism, and innate and adaptive immune function. Nevertheless, the influence of thermal stimuli on the immune system, particularly the antitumor immune response, remains incompletely understood. In fact, temperature is still rarely considered as a critical variable in experimental immunology. We suggest that more attention should be directed to the role of temperature in the regulation of the immune response and that thermal therapy should be tested in conjunction with immunotherapy as a multi-functional adjuvant that modulates the dynamics of the tumor microenvironment. Cancer Immunol Res; 1(4); 210–6. ©2013 AACR.
Reduction of Cement Consumption by the Aid of Silica Nano-Particles (Investigation on Concrete Properties)

Abstract In this study, effects of replacing cement with colloidal amorphous silica nano-particles have been experimentally investigated on the physical and mechanical properties, durability and microstructure of concrete. Experimental results include workability, fresh concrete density, and hardened concrete properties like compressive strength at different ages of 3, 7, and 28-days, and also 28-days splitting tensile strength. Furthermore, influence of silica nano-particles on durability and microstructure of concrete for 28-days specimens was tested by conducting water absorption test, Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray Analysis (EDAX), respectively. In order to study the effect of replacement of cement with silica nano-particles, specimens with 10%, 20%, and 30% cement reduction, and addition of 1%, 2%, and 3% silica nano-particles with respect to witness specimen were fabricated. Experimental results revealed that 20% reduction of cement combining 2% silica nano-particles.
Increased Interaction With Insulin Receptor Substrate 1, a Novel Abnormality in Insulin Resistance and Type 2 Diabetes

Insulin receptor substrate 1 (IRS1) is a key mediator of insulin signal transduction. Perturbations involving IRS1 complexes may lead to the development of insulin resistance and type 2 diabetes (T2D). Surprisingly little is known about the proteins that interact with IRS1 in humans under health and disease conditions. We used a proteomic approach to assess IRS1 interaction partners in skeletal muscle from lean healthy control subjects (LCs), obese insulin-resistant nondiabetic control subjects (OCs), and participants with T2D before and after insulin infusion. We identified 113 novel endogenous IRS1 interaction partners, which represents the largest IRS1 interactome in humans and provides new targets for studies of IRS1 complexes in various diseases. Furthermore, we generated the first global picture of IRS1 interaction partners in LCs, and how they differ in OCs and T2D patients. Interestingly, dozens of proteins in OCs and/or T2D patients exhibited increased associations with IRS1 compared with LCs under the basal and/or insulin-stimulated conditions, revealing multiple new dysfunctional IRS1 pathways in OCs and T2D patients. This novel abnormality, increased interaction of multiple proteins with IRS1 in obesity and T2D in humans, provides new insights into the molecular mechanism of insulin resistance and identifies new targets for T2D drug development.
ERK signalling modulates epigenome to drive epithelial to mesenchymal transition

The series of events that allow the conversion from adherent epithelial cells into migratory cells is collectively known as epithelial-mesenchymal transition (EMT). EMT is employed during embryonic development such as for gastrulation and neural crest migration and is misused in diseases, such as cancer metastasis. ERK signalling is known to be essential for EMT, however its influence on the epigenetic and transcriptional programme underlying EMT is poorly understood. Here, using a comprehensive genome-wide analysis of H3K27ac mark and gene expression in mammary epithelial cells undergoing EMT, we found that ERK signalling is essential for the epigenetic reprogramming underlying hallmark gene expression and phenotypic changes of EMT. We show that the chemical inhibition of Erk signalling during EMT prevents the loss and gain of the H3K27ac mark at regulatory regions of epithelial and mesenchymal genes, respectively, and results in a transcriptome and epigenome closer to those of epithelial cells. Further computational analyses identified a distinct set of transcription factor motifs enriched at distal regulatory regions that are epigenetically remodelled by ERK signalling. Altogether, our findings reveal an ERK-dependent epigenetic remodelling of regulatory elements that results in a gene expression programme essential for driving EMT.
Matching exponential-based and resolvent-based centrality measures

The relative importance of nodes in a network can be quantified via functions of the adjacency matrix. Two popular choices of function are the exponential, which is parameter-free, and the resolvent function, which yields the Katz centrality measure. Katz centrality can be the more computationally efficient, especially for large directed networks, and has the benefit of generalizing naturally to time-dependent network sequences, but it depends on a parameter. We give a prescription for selecting the Katz parameter based on the objective of matching the centralities of the exponential counterpart. For our new choice of parameter the resolvent can be very ill conditioned, but we argue that the centralities computed in floating point arithmetic can nevertheless reliably be used for ranking. Experiments on \revised{six} real networks show that the new choice of Katz parameter leads to rankings of nodes that \revised{generally} match those from the exponential centralities well in practice.
FAS and FASLG Genetic Variants and Risk for Second Primary Malignancy in Patients with Squamous Cell Carcinoma of the Head and Neck

Background: Single-nucleotide polymorphisms in the promoter region of the FAS and FASLG may alter the transcriptional activity of these genes. We therefore investigated the association between the FAS and FASLG polymorphisms and risk for second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN). Methods: We used log-rank test and Cox proportional hazard models to assess the association of the four single-nucleotide polymorphisms (FAS -1377 G > A, FAS -670 A > G, FASLG -844 C > T, and FASLG -124 A > G) with the SPM-free survival and SPM risk among 1,286 incident SCCHN patients. Results: Compared with patients having the FAS -670 AA or the FASLG -844 CC genotypes, the patients having variant genotypes of FAS -670 AG/GG or FASLG -844 CT/TT genotypes had significantly increased risk for SPM, respectively. A trend for significantly increased SPM risk with increasing number of risk genotypes of the four polymorphisms was observed in a dose-response manner. Moreover, the patients with three or four combined risk genotypes had an ∼1.8- or 2.5-fold increased risk for developing SPM compared with patients with zero or one risk genotypes, respectively. Conclusions: Our results suggest a modestly increased risk for SPM after index SCCHN with FAS -670 A > G and FASLG -844 C > T polymorphisms and an even greater risk for SPM with multiple combined FAS and FASLG risk genotypes. Impact: The FAS and FASLG polymorphisms may serve as a susceptible marker for SCCHN patients at high SPM risk. Cancer Epidemiol Biomarkers Prev; 19(6); 1484–91. ©2010 AACR.
Escherichia coli Nissle 1917 protects gnotobiotic pigs against human rotavirus by modulating pDC and NK‐cell responses

Lactobacillus rhamnosus GG (LGG), a gram‐positive lactic acid bacterium, is one of the most widely used probiotics; while fewer gram‐negative probiotics including Escherichia coli Nissle 1917 (EcN) are characterized. A mechanistic understanding of their individual and interactive effects on human rotavirus (HRV) and immunity is lacking. In this study, noncolonized, EcN‐, LGG‐, and EcN + LGG‐colonized neonatal gnotobiotic (Gn) pigs were challenged with HRV. EcN colonization is associated with a greater protection against HRV, and induces the highest frequencies of plasmacytoid dendritic cells (pDCs), significantly increased NK‐cell function and decreased frequencies of apoptotic and TLR4+ mononuclear cells (MNCs). Consistent with the highest NK‐cell activity, splenic CD172+ MNCs (DC enriched fraction) of EcN‐colonized pigs produced the highest levels of IL‐12 in vitro. LGG colonization has little effect on the above parameters, which are intermediate in EcN + LGG‐colonized pigs, suggesting that probiotics modulate each other's effects. Additionally, in vitro EcN‐treated splenic or intestinal MNCs produce higher levels of innate, immunoregulatory and immunostimulatory cytokines, IFN‐α, IL‐12, and IL‐10, compared to MNCs of pigs treated with LGG. These results indicate that the EcN‐mediated greater protection against HRV is associated with potent stimulation of the innate immune system and activation of the DC‐IL‐12‐NK immune axis.
Stability of commercial glucanase and β-glucosidase preparations under hydrolysis conditions

The cost of enzymes makes enzymatic hydrolysis one of the most expensive steps in the production of lignocellulosic ethanol. Diverse studies have used commercial enzyme cocktails assuming that change in total protein concentration during hydrolysis was solely due to adsorption of endo- and exoglucanases onto the substrate. Given the sensitivity of enzymes and proteins to media conditions this assumption was tested by evaluating and modeling the protein concentration of commercial cocktails at hydrolysis conditions. In the absence of solid substrate, the total protein concentration of a mixture of Celluclast 1.5 L and Novozyme 188 decreased by as much as 45% at 50 °C after 4 days. The individual cocktails as well as a mixture of both were stable at 20 °C. At 50 °C, the protein concentration of Celluclast 1.5 was relatively constant but Novozyme 188 decreased by as much as 77%. It was hypothesized that Novozyme 188 proteins suffer a structural change at 50 °C which leads to protein aggregation and precipitation. Lyophilized β-glucosidase (P-β-glucosidase) at 50 °C exhibited an aggregation rate which was successfully modeled using first order kinetics (R2 = 0.97). By incorporating the possible presence of chaperone proteins in Novozyme 188, the protein aggregation observed for this cocktail was successfully modeled (R2 = 0.96). To accurately model the increasing protein stability observed at high cocktail loadings, the model was modified to include the presence of additives in the cocktail (R2 = 0.98). By combining the measurement of total protein concentration with the proposed Novozyme 188 protein aggregation model, the endo- and exoglucanases concentration in the solid and liquid phases during hydrolysis can be more accurately determined. This methodology can be applied to various systems leading to optimization of enzyme loading by minimizing the excess of endo- and exoglucanases. In addition, the monitoring of endo- and exoglucanases concentrations can be used to build mass balances of enzyme recycling processes and to techno-economically evaluate the viability of enzyme recycling.
Analytic tableaux calculi for KLM logics of nonmonotonic reasoning

We present tableau calculi for the logics of nonmonotonic reasoning defined by Kraus, Lehmann and Magidor (KLM). We give a tableau proof procedure for all KLM logics, namely preferential, loop-cumulative, cumulative, and rational logics. Our calculi are obtained by introducing suitable modalities to interpret conditional assertions. We provide a decision procedure for the logics considered and we study their complexity.
Voice over Internet Protocol (VoIP)

VoIP was first considered at the Federal Communications Commission more than ten years ago, and the FCC elected not to regulate it. However, by 2004 VoIP had hit the mainstream and was being welcomed by consumers and the telecommunications industry alike. Seen by many as the harbinger of a much larger movement, the convergence of all communications to IP networks, the FCC is being forced to take a new look. Because the telephone industry is heavily taxed and regulated to provide important revenue and services, a shift by the public to IP voice services must be followed by a shift in taxation and regulation if these services are to be maintained. An early proposal was to simply transfer those taxes and regulations to VoIP. Proponents of this plan argued that VoIP was delivering a substitute service that was indistinguishable to the user, and therefore should be treated the same as traditional phone service. Currently, there is a growing demand for new laws customized to fit an IP-Enabled world of services. Proponents feel that existing law was written in a different time, for a different technology, in a very different economic environment, and simply “doesn’t fit” VoIP.
CONVERGENCE OF INTEGRAL FUNCTIONALS OF STOCHASTIC PROCESSES

We investigate the convergence in distribution of integrals of stochastic processes satisfying a functional limit theorem. We allow a large class of continuous Gaussian processes in the limit. Depending on the continuity properties of the underlying process, local Lebesgue or Riemann integrability is required.We are grateful to the referees and Benedikt Pötscher for their helpful and constructive comments. The research of the first author was partially supported by OTKA grants T37668 and T43037 and NSF-OTKA grant INT-0223262. The research of the second author was partially supported by NATO grant PST.EAP. CLG 980599 and NSF-OTKA grant INT-0223262.
Positive imagery cognitive bias modification (CBM) and internet-based cognitive behavioural therapy (iCBT) versus control CBM and iCBT for depression: study protocol for a parallel-group randomised controlled trial

Introduction The current randomised controlled trial will evaluate the efficacy of an internet-delivered positive imagery cognitive bias modification (CBM) intervention for depression when compared with an active control condition and help establish the additive benefit of positive imagery CBM when delivered in combination with internet cognitive behavioural therapy for depression. Methods and analysis Patients meeting diagnostic criteria for a current major depressive episode will be recruited through the research arm of a not-for-profit clinical and research unit in Australia. The minimum sample size for each group (α set at 0.05, power at 0.80) was identified as 29, but at least 10% more will be recruited to hedge against expected attrition. We will measure the impact of CBM on primary measures of depressive symptoms (Beck Depression Inventory—second edition (BDI-II), Patient Health Questionnaire (PHQ9)) and interpretive bias (ambiguous scenarios test-depression), and on a secondary measure of psychological distress (Kessler-10 (K10)) following the 1-week CBM intervention. Secondary outcome measures of psychological distress (K10), as well as disability (WHO disability assessment schedule-II), repetitive negative thinking (repetitive thinking questionnaire), and anxiety (state trait anxiety inventory-trait version) will be evaluated following completion of the 11-week combined intervention, in addition to the BDI-II and PHQ9. Intent-to-treat marginal and mixed effect models using restricted maximum likelihood estimation will be used to evaluate the primary hypotheses. Clinically significant change will be defined as high-end state functioning (a BDI-II score <14) combined with a total score reduction greater than the reliable change index score. Maintenance of gains will be assessed at 3-month follow-up. Ethics and dissemination The current trial protocol has been approved by the Human Research Ethics Committee of St Vincent's Hospital and the University of New South Wales, Sydney. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12613000139774 and Clinicaltrials.gov: NCT01787513. This trial protocol is written in compliance with the Standard Protocol Items: recommendations for Interventional Trials (SPIRIT) guidelines.
Inhibition of TLR-4/MD-2 signaling by RP105/MD-1

Activation of Toll-like receptor (TLR) signaling by microbial and host molecular signatures is critical to the induction of immune responses. Such signaling is, perforce, kept under tight control. We recently discovered a novel endogenous inhibitor of TLR-4 — RP105. Initially identified as a B-cell-specific molecule with a role in B-cell proliferation in response to RP105 mAb and LPS, RP105 is a TLR-4 homologue. Further, like TLR-4 whose surface expression and signaling depends upon co-expression of the secreted protein MD-2, surface expression of RP105 is dependent upon co-expression of the MD2 homologue, MD-1. Unlike the TLRs, however, RP105 lacks a signaling domain, having the apparent structure of a TLR inhibitor. Further, RP105 is not B-cell-specific; its expression directly mirrors that of TLR-4 on dendritic cells and macrophages. These considerations suggested a role for RP105 as a physiological inhibitor of TLR-4 signaling. Indeed, we have recently found that: (i) RP105 is a specific inhibitor of TLR-4 signaling in HEK293 cells; (ii) RP105/MD-1 interacts directly with TLR-4/MD-2, inhibiting the ability of this signaling complex to bind LPS; (iii) RP105 regulates TLR-4 signaling in dendritic cells and macrophages; and (iv) RP105 regulates in vivo responses to LPS.
Possible role for nitric oxide releasing nerves in the regulation of ocular blood flow in the rat

AIM To investigate the role of nitrergic nerves in the regulation of ocular blood flow. METHODS Conscious, lightly restrained rats were treated with either the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI), or the non-selective inhibitor, NG-nitro-l-arginine methyl ester (L-NAME), and ocular blood flow was measured ex vivo from tissue samples, using the fully quantitative [14C]-iodoantipyrine technique. RESULTS In the peripheral circulation, L-NAME produced an increase in arterial blood pressure (+22%) while 7-NI had no effect. In contrast, both 7-NI and L-NAME produced significant decreases in ocular blood flow (−31% and −59% respectively). The ocular vascular resistance calculated from ocular blood flow and mean arterial blood pressure increased by 29% following 7-NI, but by 130% following L-NAME. CONCLUSIONS Nitric oxide releasing neurons may play an important contributory role in regulating ocular blood flow.