Mckeerivas9908

Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with disease pathogenesis. Nonsynonymous single-nucleotide polymorphisms encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis identified that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2 = 0.99). read more Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma tissues combined resulted in the quantitation of 62 pAIMs that correlate with patient race and genotype-confirmed ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. pAIMs will support generalized proteoancestry assessment as well as efforts investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.We design a "wisdom-of-the-crowds" GRN inference pipeline and couple it to complex network analysis to understand the organizational principles governing gene regulation in long-lived glp-1/Notch Caenorhabditis elegans. The GRN has three layers (input, core, and output) and is topologically equivalent to bow-tie/hourglass structures prevalent among metabolic networks. To assess the functional importance of structural layers, we screened 80% of regulators and discovered 50 new aging genes, 86% with human orthologues. Genes essential for longevity-including ones involved in insulin-like signaling (ILS)-are at the core, indicating that GRN's structure is predictive of functionality. We used in vivo reporters and a novel functional network covering 5,497 genetic interactions to make mechanistic predictions. We used genetic epistasis to test some of these predictions, uncovering a novel transcriptional regulator, sup-37, that works alongside DAF-16/FOXO. We present a framework with predictive power that can accelerate discovery in C. elegans and potentially humans.Dynamic tuning of terahertz (THz) wave is vital for the development of next generation THz devices. Utilization of solar energy for tuning THz waves is a promising, eco-friendly, and sustainable way to expand THz application scenarios. Ti2O3 with an ultranarrow bandgap of 0.1eV exhibits intriguing thermal-induced metal-insulator transition (MIT), and possesses excellent photothermal conversion efficiency. Herein, Ti2O3 film was fabricated by a two-step magnetron sputtering method, and exhibited an excellent photothermal conversion efficiency of 90.45% and demonstrated temperature-dependent THz transmission characteristics with a wideband at 0.1-1 THz. We supposed to combine photothermal conversion characteristics with temperature-dependent THz transmission properties of Ti2O3 film, which could introduce solar light as the energy source for tuning THz waves. Our work will provide new sight for investigating MIT characteristics of Ti2O3 at THz regime and exhibit huge potential in the application of tuning terahertz waves in outdoor scenarios in the future.The Polyomaviridae is a family of ubiquitous dsDNA viruses that establish persistent infection early in life. Screening for human polyomaviruses (HPyVs), which comprise 14 diverse species, relies upon species-specific qPCRs whose validity may be challenged by accelerating genomic exploration of the virosphere. Using this reasoning, we tested 64 published HPyV qPCR assays in silico against the 1781 PyV genome sequences that were divided in targets and nontargets, based on anticipated species specificity of each qPCR. We identified several cases of problematic qPCR performance that were confirmed in vitro and corrected through using degenerate oligos. Furthermore, our study ranked 8 out of 52 tested BKPyV qPCRs as remaining of consistently high quality in the wake of recent PyV discoveries and showed how sensitivity of most other qPCRs could be rescued by annealing temperature adjustment. This study establishes an efficient framework for ensuring confidence in available HPyV qPCRs in the genomic era.We propose CX-ToM, short for counterfactual explanations with theory-of-mind, a new explainable AI (XAI) framework for explaining decisions made by a deep convolutional neural network (CNN). In contrast to the current methods in XAI that generate explanations as a single shot response, we pose explanation as an iterative communication process, i.e., dialogue between the machine and human user. More concretely, our CX-ToM framework generates a sequence of explanations in a dialogue by mediating the differences between the minds of the machine and human user. To do this, we use Theory of Mind (ToM) which helps us in explicitly modeling the human's intention, the machine's mind as inferred by the human, as well as human's mind as inferred by the machine. Moreover, most state-of-the-art XAI frameworks provide attention (or heat map) based explanations. In our work, we show that these attention-based explanations are not sufficient for increasing human trust in the underlying CNN model. In CX-ToM, we instead use counterfactual explanations called fault-lines which we define as follows given an input image I for which a CNN classification model M predicts class c pred , a fault-line identifies the minimal semantic-level features (e.g., stripes on zebra), referred to as explainable concepts, that need to be added to or deleted from I to alter the classification category of I by M to another specified class c alt . Extensive experiments verify our hypotheses, demonstrating that our CX-ToM significantly outperforms the state-of-the-art XAI models.Impressive global efforts have identified both rare and common gene variants associated with severe COVID-19 using sequencing technologies. However, these studies lack the sensitivity to accurately detect several classes of variants, especially large structural variants (SVs), which account for a substantial proportion of genetic diversity including clinically relevant variation. We performed optical genome mapping on 52 severely ill COVID-19 patients to identify rare/unique SVs as decisive predisposition factors associated with COVID-19. We identified 7 SVs involving genes implicated in two key host-viral interaction pathways innate immunity and inflammatory response, and viral replication and spread in nine patients, of which SVs in STK26 and DPP4 genes are the most intriguing candidates. This study is the first to systematically assess the potential role of SVs in the pathogenesis of COVID-19 severity and highlights the need to evaluate SVs along with sequencing variants to comprehensively associate genomic information with interindividual variability in COVID-19 phenotypes.Think tanks play a fundamental role in shaping policy agendas in Western countries, especially in the US. As international biosecurity is turning from a moderate to a serious concern, the convergence of biosecurity subjects and think tanks is evidently increasing. Examining the involvement and implication of think tanks in biosecurity policy formulation domestically and internationally is, therefore, of great value. This article takes a brief look at the intellectual output of over 30 think tanks during the last five years, before and after the outbreak of COVID-19, and tries to build an understanding of the extent to which these think tanks informed strategic, operational, and tactical decisions, with the aim of providing a better basis for dealing with sophisticated biological threats.The recent global COVID-19 pandemic has had profound economic and social impacts on the world. It has highlighted an urgent need to strengthen existing international biosecurity governance mechanisms to prevent the misuse and malicious abuse of life science research and maintain international biological arms control norms. Biologists are at the front line of biotechnology development and are key to maintaining biosecurity awareness and moral self-discipline. As an important first step, biologists need to actively participate in the formulation and implementation of relevant biosecurity policies and measures to ensure their effectiveness and sustainability. Furthermore, efforts should be made to advocate for and promote the establishment of an ethical code of conduct for biologists to share safety responsibilities for global biosecurity. To maximize the impact of this ethical code of conduct, an effective approach to implementing codes of conduct for biologists at both national and international levels should be established under the framework of the Biological and Toxin Weapons Convention (BTWC).Drug development for specific antiviral agents against coronavirus disease 2019 (COVID-19) is still an unmet medical need as the pandemic continues to spread globally. Although huge efforts for drug repurposing and compound screens have been put forth, only a few compounds are in late-stage clinical trials. New approaches and assays are needed to accelerate COVID-19 drug discovery and development. Here, we report a time-resolved fluorescence resonance energy transfer-based assay that detects the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (NP) produced in infected cells. It uses two specific anti-NP monoclonal antibodies conjugated to donor and acceptor fluorophores that produce a robust ratiometric signal for high throughput screening of large compound collections. Using this assay, we measured a half maximal inhibitory concentration (IC50) for remdesivir of 9.3 μM against infection with SARS-CoV-2 USA/WA1/2020 (WA-1). The assay also detected SARS-CoV-2 South African (Beta, β), Brazilian/Japanese P.1 (Gamma, γ), and Californian (Epsilon, ε) variants of concern (VoC). Therefore, this homogeneous SARS-CoV-2 NP detection assay can be used for accelerating lead compound discovery for drug development and for evaluating drug efficacy against emerging SARS-CoV-2 VoC.While perceptions of animal welfare have been assessed in veterinary students and students internationally, there remains a gap in research concerning undergraduate and graduate student perspectives of animal welfare in animal science programs at colleges and universities across the United States. A survey was developed to assess current animal science student perspectives of the importance of animal welfare as part of their education, their knowledge of available educational opportunities, and resources they think should be included in animal welfare curricula. An online survey was distributed to a national listserv of university administrators of animal science programs in the United States. A total of 624 survey responses were statistically summarized. Most respondents were undergraduate students (78.0%, n = 487), between the ages of 18 and 24 (85.9%, n = 536), and female (86.1%, n = 537). Results indicated that despite most respondents not taking an animal welfare course previously (60.7%, n = 379), most s currently enrolled in animal science departments will become the future stakeholders in animal-focused industries.