Chiral symmetry restoration, eigenvalue density of Dirac operator and axial U(1) anomaly at finite temperature

We reconsider constraints on the eigenvalue density of the Dirac operator in the chiral symmetric phase of 2 flavor QCD at finite temperature. To avoid possible ultra-violet(UV) divergences, we work on a lattice, employing the overlap Dirac operator, which ensures the exact "chiral" symmetry at finite lattice spacings. Studying multi-point correlation functions in various channels and taking their thermodynamical limit (and then taking the chiral limit), we obtain stronger constraints than those found in the previous studies: both the eigenvalue density at the origin and its first and second derivatives vanish in the chiral limit of 2 flavor QCD. In addition we show that the axial U(1) anomaly becomes invisible in susceptibilities of scalar and pseudo scalar mesons, suggesting that the 2nd order chiral phase transition with the O(4) scaling is not realized in 2 flavor QCD. Possible lattice artifacts when non-chiral lattice Dirac operator is employed are briefly discussed.Comment: 39 pages, 1 figure(2 eps files), a version published in PR

Identification of hepta-histidine as a candidate drug for Huntington's disease by in silico-in vitro- in vivo-integrated screens of chemical libraries.

We identified drug seeds for treating Huntington's disease (HD) by combining in vitro single molecule fluorescence spectroscopy, in silico molecular docking simulations, and in vivo fly and mouse HD models to screen for inhibitors of abnormal interactions between mutant Htt and physiological Ku70, an essential DNA damage repair protein in neurons whose function is known to be impaired by mutant Htt. From 19,468 and 3,010,321 chemicals in actual and virtual libraries, fifty-six chemicals were selected from combined in vitro-in silico screens; six of these were further confirmed to have an in vivo effect on lifespan in a fly HD model, and two chemicals exerted an in vivo effect on the lifespan, body weight and motor function in a mouse HD model. Two oligopeptides, hepta-histidine (7H) and Angiotensin III, rescued the morphological abnormalities of primary neurons differentiated from iPS cells of human HD patients. For these selected drug seeds, we proposed a possible common structure. Unexpectedly, the selected chemicals enhanced rather than inhibited Htt aggregation, as indicated by dynamic light scattering analysis. Taken together, these integrated screens revealed a new pathway for the molecular targeted therapy of HD

Gastric Cancer with a Very High Serum CA 19-9 Level

Carbohydrate antigen 19-9 (CA 19-9) is a sensitive marker for pancreatic and hepatobiliary malignancies. The highest frequency of elevated serum CA 19-9 levels is found among patients with pancreatic cancer. CA 19-9 has recently been demonstrated to be a marker of digestive tract malignancies. We report the case of a patient with a gastric cancer and a very high serum CA 19-9 level. During laparotomy, a large mass was found in the antrum. A distal gastrectomy with D2 dissection of the lymph nodes was performed. Histological examination, including immunohistochemistry, revealed an adenocarcinoma of the stomach producing CA 19-9. To the best of our knowledge, no patient with an extremely high serum CA 19-9 level resulting from a gastric adenocarcinoma has been reported previously

Life-Detection Technologies for the Next Two Decades

Since its inception six decades ago, astrobiology has diversified immensely to encompass several scientific questions including the origin and evolution of Terran life, the organic chemical composition of extraterrestrial objects, and the concept of habitability, among others. The detection of life beyond Earth forms the main goal of astrobiology, and a significant one for space exploration in general. This goal has galvanized and connected with other critical areas of investigation such as the analysis of meteorites and early Earth geological and biological systems, materials gathered by sample-return space missions, laboratory and computer simulations of extraterrestrial and early Earth environmental chemistry, astronomical remote sensing, and in-situ space exploration missions. Lately, scattered efforts are being undertaken towards the R&D of the novel and as-yet-space-unproven life-detection technologies capable of obtaining unambiguous evidence of extraterrestrial life, even if it is significantly different from Terran life. As the suite of space-proven payloads improves in breadth and sensitivity, this is an apt time to examine the progress and future of life-detection technologies.Comment: 6 pages, the white paper was submitted to and cited by the National Academy of Sciences in support of the Astrobiology Science Strategy for the Search for Life in the Univers

Discovery, linkage disequilibrium and association analyses of polymorphisms of the immune complement inhibitor, decay-accelerating factor gene (DAF/CD55) in type 1 diabetes.

BACKGROUND: Type 1 diabetes (T1D) is a common autoimmune disease resulting from T-cell mediated destruction of pancreatic beta cells. Decay accelerating factor (DAF, CD55), a glycosylphosphatidylinositol-anchored membrane protein, is a candidate for autoimmune disease susceptibility based on its role in restricting complement activation and evidence that DAF expression modulates the phenotype of mice models for autoimmune disease. In this study, we adopt a linkage disequilibrium (LD) mapping approach to test for an association between the DAF gene and T1D. RESULTS: Initially, we used HapMap II genotype data to examine LD across the DAF region. Additional resequencing was required, identifying 16 novel polymorphisms. Combining both datasets, a LD mapping approach was adopted to test for association with T1D. Seven tag SNPs were selected and genotyped in case-control (3,523 cases and 3,817 controls) and family (725 families) collections. CONCLUSION: We obtained no evidence of association between T1D and the DAF region in two independent collections. In addition, we assessed the impact of using only HapMap II genotypes for the selection of tag SNPs and, based on this study, found that HapMap II genotypes may require additional SNP discovery for comprehensive LD mapping of some genes in common disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Association between Body Mass Index and Prognosis of Patients Hospitalized With Heart Failure

The prognostic implications of very low body mass index (BMI) values remain unclear in patients with acute decompensated heart failure (ADHF). This study aimed to investigate the prognostic impact of BMI classification based on the World Health Organization criteria in patients with ADHF. Among 3509 patients with ADHF and available BMI data at discharge in 19 participating hospitals in Japan between October 2014 and March 2016, the study population was divided into five groups; (1) Severely underweight: BMI < 16 kg/m², (2) Underweight: BMI ≥ 16 kg/m² and < 18.5 kg/m², (3) Normal weight: BMI ≥ 18.5 kg/m² and < 25 kg/m², (4) Overweight: BMI ≥ 25 kg/m² and < 30 kg/m² (5) Obese: BMI ≥ 30 kg/m². The primary outcome measure was all-cause death. The median follow-up duration was 471 days, with 96.4% follow up at 1-year. The cumulative 1-year incidence of all-cause death was higher in underweight groups, and lower in overweight groups (Severely underweight: 36.3%, Underweight: 23.9%, Normal weight: 14.4%, Overweight: 7.9%, and Obese: 9.0%, P < 0.001). After adjusting confounders, the excess mortality risk remained significant in the severely underweight group (HR, 2.32; 95%CI, 1.83–2.94; P < 0.001), and in the underweight group (HR, 1.31; 95%CI, 1.08–1.59; P = 0.005) relative to the normal weight group, while the lower mortality risk was no longer significant in the overweight group (HR, 0.82; 95%CI, 0.62–1.10; P = 0.18) and in the obese group (HR, 1.09; 95%CI, 0.65–1.85; P = 0.74). Very low BMI was associated with a higher risk for one-year mortality after discharge in patients with ADHF

Association between changes in loop diuretic dose and outcomes in acute heart failure

AIMS: Little is known about the association between the starting of or dose changes in loop diuretics during acute heart failure (AHF) hospitalization and post-discharge outcomes. We investigated the clinical impact of starting loop diuretics and changing the loop diuretics dose during hospitalization on post-discharge outcomes. METHODS AND RESULTS: From the Kyoto Congestive Heart Failure registry, 3665 consecutive patients hospitalized for HF and discharged alive were included in this study. We analysed 1906 patients without loop diuretics on admission and were discharged alive and 1759 patients who received loop diuretics on admission and were discharged alive. The primary outcome measure was all-cause death. Of the 1906 patients without loop diuretics on admission, 1366 (71.7%) patients started loop diuretics during the index AHF hospitalization. Starting loop diuretics was not associated with lower post-discharge mortality [adjusted hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.68-1.25]. Of the 1759 patients who received loop diuretics on admission, loop diuretic dose was decreased in 23.8%, unchanged in 44.6%, and increased in 31.6% of the patients. Changes in the dose at discharge compared with no change in dose were not associated with lower risk of post-discharge mortality (decrease relative to no change: adjusted HR 0.98, 95% CI 0.76-1.28; increase relative to no change: adjusted HR 1.00, 95% CI 0.78-1.27). Compared with no loop diuretics at discharge, a loop diuretics dose of ≥80 mg at discharge was associated with higher post-discharge mortality risk. CONCLUSIONS: In patients with AHF, we found no association between the starting of loop diuretics and post-discharge outcomes and between dose changes and post-discharge outcomes