Deuteron and antideuteron production in Au+Au collisions at sqrt(s_NN)=200 GeV

The production of deuterons and antideuterons in the transverse momentum range 1.1 < p_T < 4.3 GeV/c at mid-rapidity in Au + Au collisions at sqrt(s_NN)=200 GeV has been studied by the PHENIX experiment at RHIC. A coalescence analysis comparing the deuteron and antideuteron spectra with those of protons and antiprotons, has been performed. The coalescence probability is equal for both deuterons and antideuterons and increases as a function of p_T, which is consistent with an expanding collision zone. Comparing (anti)proton yields p_bar/p = 0.73 +/- 0.01, with (anti)deuteron yields: d_bar/d = 0.47 +/- 0.03, we estimate that n_bar/n = 0.64 +/- 0.04.Comment: 326 authors, 6 pages text, 5 figures, 1 Table. Submitted to PRL. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Acetylcholinesterase Inhibitor Pyridostigmine Bromide Attenuates Gut Pathology and Bacterial Dysbiosis in a Murine Model of Ulcerative Colitis

Abstract Background Ulcerative colitis (UC) is a Th2 infammatory bowel disease characterized by increased IL-5 and IL-13 expression, eosinophilic/neutrophilic infltration, decreased mucus production, impaired epithelial barrier, and bacterial dysbiosis of the colon. Acetylcholine and nicotine stimulate mucus production and suppress Th2 infammation through nicotinic receptors in lungs but UC is rarely observed in smokers and the mechanism of the protection is unclear. Methods In order to evaluate whether acetylcholine can ameliorate UC-associated pathologies, we employed a mouse model of dextran sodium sulfate (DSS)-induced UC-like conditions, and a group of mice were treated with Pyridostigmine bromide (PB) to increase acetylcholine availability. The efects on colonic tissue morphology, Th2 infammatory factors, MUC2 mucin, and gut microbiota were analyzed. Results DSS challenge damaged the murine colonic architecture, reduced the MUC2 mucin and the tight-junction protein ZO-1. The PB treatment signifcantly attenuated these DSS-induced responses along with the eosinophilic infltration and the pro-Th2 infammatory factors. Moreover, PB inhibited the DSS-induced loss of commensal Clostridia and Flavobacteria, and the gain of pathogenic Erysipelotrichia and Fusobacteria. Conclusions Together, these data suggest that in colons of a murine model, PB promotes MUC2 synthesis, suppresses Th2 infammation and attenuates bacterial dysbiosis therefore, PB has a therapeutic potential in UC

Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV

The invariant differential cross section for inclusive electron production in p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4 <= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the inclusive electron spectrum from semileptonic decays of hadrons carrying heavy flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via three independent methods. The resulting electron spectrum from heavy flavor decays is compared to recent leading and next-to-leading order perturbative QCD calculations. The total cross section of charm quark-antiquark pair production is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Measurement of Transverse Single-Spin Asymmetries for Mid-rapidity Production of Neutral Pions and Charged Hadrons in Polarized p+p Collisions at sqrt(s) = 200 GeV

The transverse single-spin asymmetries of neutral pions and non-identified charged hadrons have been measured at mid-rapidity in polarized proton-proton collisions at sqrt(s) = 200 GeV. The data cover a transverse momentum (p_T) range 0.5-5.0 GeV/c for charged hadrons and 1.0-5.0 GeV/c for neutral pions, at a Feynman-x (x_F) value of approximately zero. The asymmetries seen in this previously unexplored kinematic region are consistent with zero within statistical errors of a few percent. In addition, the inclusive charged hadron cross section at mid-rapidity from 0.5 < p_T < 7.0 GeV/c is presented and compared to NLO pQCD calculations. Successful description of the unpolarized cross section above ~2 GeV/c using NLO pQCD suggests that pQCD is applicable in the interpretation of the asymmetry results in the relevant kinematic range.Comment: 331 authors, 6 pages text, 2 figures, 3 tables. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Translocation-coupled DNA cleavage by the Type ISP restriction-modification enzymes

Endonucleolytic double-strand DNA break production requires separate strand cleavage events. Although catalytic mechanisms for simple dimeric endonucleases are available, there are many complex nuclease machines which are poorly understood in comparison. Here we studied the single polypeptide Type ISP restriction-modification (RM) enzymes, which cleave random DNA between distant target sites when two enzymes collide following convergent ATP-driven translocation. We report the 2.7 Angstroms resolution X-ray crystal structure of a Type ISP enzyme-DNA complex, revealing that both the helicase-like ATPase and nuclease are unexpectedly located upstream of the direction of translocation, inconsistent with simple nuclease domain-dimerization. Using single-molecule and biochemical techniques, we demonstrate that each ATPase remodels its DNA-protein complex and translocates along DNA without looping it, leading to a collision complex where the nuclease domains are distal. Sequencing of single cleavage events suggests a previously undescribed endonuclease model, where multiple, stochastic strand nicking events combine to produce DNA scission

The social biography of antibiotic use in smallholder dairy farms in India

Background Antimicrobial resistance (AMR) has been identified as one of the major threats to global health, food security and development today. While there has been considerable attention about the use and misuse of antibiotics amongst human populations in both research and policy environments, there is no definitive estimate of the extent of misuse of antibiotics in the veterinary sector and its contribution to AMR in humans. In this study, we explored the drivers ofirrational usage of verterinary antibiotics in the dairy farming sector in peri-urban India. Methods and materials The study was conducted in the peri-urban belts of Ludhiana, Guwahati and Bangalore. A total of 54 interviews (formal and non-formal) were carried out across these three sites. Theme guides were developed to explore different drivers of veterinary antimicrobial use. Data was audio recorded and transcribed. Analysis of the coded data set was carried out using AtlasTi. Version 7. Themes emerged inductively from the set of codes. Results Findings were presented based on concept of ‘levels of analyses’. Emergent themes were categorised as individual, health systems, and policy level drivers. Low level of knowledge related to antibiotics among farmers, active informal service providers, direct marketing of drugs to the farmers and easily available antibiotics, dispensed without appropriate prescriptions contributed to easy access to antibiotics, and were identified to be the possible drivers contributing to the non-prescribed and self-administered use of antibiotics in the dairy farms. Conclusions Smallholding dairy farmers operated within very small margins of profits. The paucity of formal veterinary services at the community level, coupled with easy availability of antibiotics and the need to ensure profits and minimise losses, promoted non-prescribed antibiotic consumption. It is essential that these local drivers of irrational antibiotic use are understood in order to develop interventions and policies that seek to reduce antibiotic misuse

Launching a Novel Preclinical Infrastructure: Comparative Oncology Trials Consortium Directed Therapeutic Targeting of TNFα to Cancer Vasculature

Background: Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC). The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. Methodology/Principal Findings: Through this established infrastructure, the first trial of the COTC (COTC001) evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF) to αV integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24) determined an optimal safe dose (5 x 1012 transducing units intravenous) of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%), stable disease in six (43%), and disease progression in six (43%) via Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions/Significance: The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies