QCD equation of state with Tsallis statistics for heavy-ion collisions

Nonextensive statistics has attracted attention as a description of particle spectra in nuclear collisions at QCD energies. First, we construct the equation of state by incorporating Tsallis statistics based on the hadron resonance gas and parton gas models. Thermodynamic conditions are found to impose constraints on the $q$-parameter of Tsallis distribution. Next, we apply the equation of state to the relativistic hydrodynamic modeling of nuclear collisions. The Cooper-Frye prescription is consistently modified. Numerical demonstrations indicate that the model may describe charged particle spectra at Large Hadron Collider in the transverse momentum range up to 6-8 GeV. Elliptic flow, on the other hand, suggests a narrower range of applicability.Comment: 9 pages, 5 figures; revised version to appear in Physical Review

Effects of intranasal TNFα on granulocyte recruitment and activity in healthy subjects and patients with allergic rhinitis

<p>Abstract</p> <p>Background</p> <p>TNFα may contribute to the pathophysiology of airway inflammation. For example, we have recently shown that nasal administration of TNFα produces late phase co-appearance of granulocyte and plasma exudation markers on the mucosal surface. The objective of the present study was to examine indices of granulocyte presence and activity in response to intranasal TNFα challenge.</p> <p>Methods</p> <p>Healthy subjects and patients with allergic rhinitis (examined out of season) were subjected to nasal challenge with TNFα (10 μg) in a sham-controlled and crossover design. Nasal lavages were carried out prior to and 24 hours post challenge. Nasal biopsies were obtained post challenge. Nasal lavage fluid levels of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were analyzed as indices of neutrophil and eosinophil activity. Moreover, IL-8 and α₂-macroglobulin were analyzed as markers of pro-inflammatory cytokine production and plasma exudation. Nasal biopsy numbers of neutrophils and eosinophils were monitored.</p> <p>Results</p> <p>Nasal lavage fluid levels of MPO recorded 24 hours post TNFα challenge were increased in healthy subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (<it>c.f</it>. sham challenge). Similarly, α₂-macroglobulin was increased in healthy subjects (p = 0.014) and in patients with allergic rhinitis (p = 0.0034). Lavage fluid levels of ECP and IL-8 were not affected by TNFα challenge. TNFα increased the numbers of subepithelial neutrophils (p = 0.0021), but not the numbers of eosinophils.</p> <p>Conclusion</p> <p>TNFα produces a nasal inflammatory response in humans that is characterised by late phase (i.e., 24 hours post challenge) neutrophil activity and plasma exudation.</p

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe

Total Synthesis of Himastatin

I. Total Synthesis of Himastatin via Bioinspired Oxidative Dimerization The concise total synthesis of (–)-himastatin via a biomimetic final-stage dimerization is described. Our approach relies on expedient preparation of a macrocyclic depsipeptide monomer via hybrid solution/solid phase peptide synthesis, followed by a newly developed oxidative dimerization reaction to secure the C5–C5' biaryl linkage at the center of himastatin’s homodimeric structure. Application of the oxidative dimerization methodology enabled the preparation of dimeric C5–C5' cyclotryptophans, cyclotryptamines, and indolines via a radical-radical coupling pathway that was supported by mechanistic studies. II. Synthesis and Biological Study of Himastatin Derivatives The modularity and convergence of our hybrid solution/solid-phase approach to the synthesis of macrocyclic peptide monomers enabled general access to several himastatin derivatives and their comparative biological evaluation. Our findings indicate that the central C5–C5' biaryl linkage, depsipeptide linkage, and piperazic acid residue of himastatin are important for bioactivity, but that substitution of the leucine residue has negligible impact. The synthesis and biological evaluation of a series of stereochemical probes further reveal that the absolute stereochemistry of himastatin does not impact its bioactivity, consistent with primarily achiral interactions with its cellular target. Relying on our late-stage dimerization methodology for the union of complex macrocyclic peptide fragments, we also accessed a uniquely active heterodimeric fluorescent probe, TAMRA-himastatin. Confocal microscopy enabled direct observation of the antibiotic’s localization within Gram-positive bacteria, and provided evidence that himastatin targets the bacterial membrane as part of its mode of action.Ph.D

RURAL-URBAN MIGRATION AROUND YANGON CITY, MYANMAR

Labor migration is a pervasive feature of life in contemporary Myanmar, but has been the subject of only limited research to date. Furthermore, most of this work has focused on international migrants, leaving internal migration comparatively understudied. This brief addresses this gap by exploring the characteristics of migrants and migration in four townships (Kayan, Maubin, Nyaungdon, and Twantay) located close to Myanmar’s primate city, Yangon. For comparative purposes, a representative sample of 1102 households was interviewed in May 2016, in two groups of village tracts: an aquaculture cluster characterized by high concentrations of fish farms, and agriculture cluster, where crop farming is the predominant agricultural activity

RURAL-URBAN MIGRATION AROUND YANGON CITY, MYANMAR

Labor migration is a pervasive feature of life in contemporary Myanmar, but has been the subject of only limited research. Most of this work has focused on international migrants, leaving internal migration comparatively understudied

Chemoselective α-Sulfidation of Amides Using Sulfoxide Reagents.

The direct α-sulfidation of tertiary amides using sulfoxide reagents under electrophilic amide activation conditions is described. Employing convenient and readily available reagents, selective functionalization takes place to generate isolable sulfonium ions en route to α-sulfide amides. Mechanistic studies identified activated sulfoxides as promoters of the desired transformation and enabled the extension of the methodology from benzylic to aliphatic amide substrates