The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

Blocking FSH induces thermogenic adipose tissue and reduces body fat

Functional Genomics of Systemic Disorder

Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines

HBV DNA Integration and Clonal Hepatocyte Expansion in Chronic Hepatitis B Patients Considered Immune Tolerant

BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is characterized clinically by progression through disease phases. The first, labeled immune tolerant (IT), is perceived to lack disease activity. Here, we examined HBV-DNA integration, clonal hepatocyte expansion, HBV antigen expression and HBV-specific immunity in patients considered IT to assess whether this designation is appropriate, or if pathological changes may be present. METHODS: HBV-DNA integration, clonal hepatocyte expansion, HBsAg and HBcAg expression were studied in liver tissue from CHB patients, (age 14–39 years; median=24.5). These included 9 HBeAg(+) IT patients. Ten HBeAg(+) and 7 HBeAg(−) age-matched patients with active disease served as controls. HBV-specific T cells were quantified in paired peripheral blood lymphocytes. RESULTS: HBV antigen expression differed between the patient groups. However, unexpectedly high numbers of HBV-DNA integrations, randomly distributed across most chromosomes, were detectable in all patient groups. Patients considered IT also displayed significant clonal hepatocyte expansion, potentially in response to active HBV-specific T cell immunity. HBV-specific T cell responses were also confirmed in the periphery of these patients. CONCLUSIONS: A high level of HBV DNA integration and clonal hepatocyte expansion in patients considered IT suggests that events in hepatocarcinogenesis are underway even in the early stages of CHB. The concept that the IT phase is devoid of markers of disease progression and is immunologically inert is unsupported; instead, we propose that high replicative low inflammatory (HRLI) CHB more accurately reflects this early disease phase. The timing of therapeutic intervention to minimize further genetic damage to the hepatocyte population should be reconsidered

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Principles of Bioimage Informatics: Focus on Machine Learning of Cell Patterns

Abstract. The field of bioimage informatics concerns the development and use of methods for computational analysis of biological images. Traditionally, analysis of such images has been done manually. Manual annotation is, however, slow, expensive, and often highly variable from one expert to another. Furthermore, with modern automated microscopes, hundreds to thousands of images can be collected per hour, making manual analysis infeasible. This field borrows from the pattern recognition and computer vision literature (which contain many techniques for image processing and recognition), but has its own unique challenges and tradeoffs. Fluorescence microscopy images represent perhaps the largest class of biological images for which automation is needed. For this modality, typical problems include cell segmentation, classification of phenotypical response, or decisions regarding differentiated responses (treatment vs. control setting). This overview focuses on the problem of subcellular location determination as a running example, but the techniques discussed are often applicable to other problems.

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society