Extended LTA, TNF, LST1 and HLA Gene Haplotypes and Their Association with Rubella Vaccine-Induced Immunity

Recent studies have suggested the importance of HLA genes in determining immune responses following rubella vaccine. The telomeric class III region of the HLA complex harbors several genes, including lymphotoxin alpha (LTA), tumor necrosis factor (TNF) and leukocyte specific transcript -1 (LST1) genes, located between the class I B and class II DRB1 loci. Apart from HLA, little is known about the effect of this extended genetic region on HLA haplotypic backgrounds as applied to immune responses.We examined the association between immune responses and extended class I-class II-class III haplotypes among 714 healthy children after two doses of rubella vaccination. These extended haplotypes were then compared to the HLA-only haplotypes. The most significant association was observed between haplotypes extending across the HLA class I region, ten-SNP haplotypes, and the HLA class II region (i.e. A-C-B-LTA-TNF-LST1-DRB1-DQA1-DQB1-DPA1-DPB1) and rubella-specific antibodies (global p-value of 0.03). Associations were found between both extended A*02-C*03-B*15-AAAACGGGGC-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 (p = 0.002) and HLA-only A*02-C*03-B*15-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 haplotypes (p = 0.009) and higher levels of rubella antibodies. The class II HLA-only haplotype DRB1*13-DQA1*01-DQB1*06-DPA1*01-DPB1*04 (p = 0.04) lacking LTA-TNF-LST1 SNPs was associated with lower rubella antibody responses. Similarly, the class I-class II HLA-only A*01-C*07-B*08-DRB1*03-DQA1*05-DQB1*02-DPA1*01-DPB1*04 haplotype was associated with increased TNF-alpha secretion levels (p = 0.009). In contrast, the extended AAAACGGGGC-DRB1*01-DQA1*01-DQB1*05-DPA1*01-DPB1*04 (p = 0.01) haplotype was found to trend with decreased rubella-specific IL-6 secretion levels.These data suggest the importance of examining both HLA genes and genes in the class III region as part of the extended haplotypes useful in understanding genomic drivers regulating immune responses to rubella vaccine

CONTENTS OF REGULATORY T-CELLS IN PERIPHERAL BLOOD AND ENDOMETRIAL TISSUE IN DYNAMIC OF MENSTRUAL CYCLE

The maintenance of CD4+CD25+/high and CD4+CD25+CD127 — regulatory T-cells in a peripheral, menstrual blood and an endometrial tissue in different phases of a menstrual cycle is investigated. It is shown that in a phase of average secretion the number of regulatory T-cells is increased. Thus quantity of CD4+CD25+increased in peripheral circulation, and in an endometrial tissue number of CD4+CD25+CD127- cells grew

Effect of Solid Dispersions on the Dissolution of Ampicillin

© 2016, Springer Science+Business Media New York.In this work, we studied water solubility of ampicillin trihydrate and its solid dispersions (SD) with polyethylene glycol-1500, polyvinylpyrrolidone-10000, and β-cyclodextrin. It was found that SD formation increases the solubility by a factor of 1.34–1.73 and the rate of ampicillin dissolution by a factor of 3.43–7.40. The results of complex physicochemical studies suggest that the improved release of ampicillin from SD is due to its micronization and solubilization by the polymer

Measurement of νˉμ\bar{\nu}_{\mu} and νμ\nu_{\mu} charged current inclusive cross sections and their ratio with the T2K off-axis near detector

We report a measurement of cross section $\sigma(\nu_{\mu}+{\rm nucleus}\rightarrow\mu^{-}+X)$ and the first measurements of the cross section $\sigma(\bar{\nu}_{\mu}+{\rm nucleus}\rightarrow\mu^{+}+X)$ and their ratio $R(\frac{\sigma(\bar \nu)}{\sigma(\nu)})$ at (anti-)neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K $\bar{\nu}/\nu$-flux, for the detector target material (mainly Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory frame kinematics of $\theta_{\mu}$500 MeV/c. The results are $\sigma(\bar{\nu})=\left( 0.900\pm0.029{\rm (stat.)}\pm0.088{\rm (syst.)}\right)\times10^{-39}$ and $\sigma(\nu)=\left( 2.41\ \pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}$in units of cm$^{2}$/nucleon and$R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)= 0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$.Comment: 18 pages, 8 figure

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA

Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 pi(0) detector

10 pages, 6 figures, Submitted to PRDhttp://journals.aps.org/prd/abstract/10.1103/PhysRevD.91.112010© 2015 American Physical Society11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PR

Search for short baseline nu(e) disappearance with the T2K near detector

8 pages, 6 figures, submitted to PRD rapid communication8 pages, 6 figures, submitted to PRD rapid communicationWe thank the J-PARC staff for superb accelerator performance and the CERN NA61 collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC and CFI, Canada; Commissariat `a l’Energie Atomique and Centre National de la Recherche Scientifique–Institut National de Physique Nucle´aire et de Physique des Particules, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; Russian Science Foundation, RFBR and Ministry of Education and Science, Russia; MINECO and European Regional Development Fund, Spain; Swiss National Science Foundation and State Secretariat for Education, Research and Innovation, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK. In addition participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; DOE Early Career program, USA

The LBNO long-baseline oscillation sensitivities with two conventional neutrino beams at different baselines

The proposed Long Baseline Neutrino Observatory (LBNO) initially consists of $\sim 20$ kton liquid double phase TPC complemented by a magnetised iron calorimeter, to be installed at the Pyh\"asalmi mine, at a distance of 2300 km from CERN. The conventional neutrino beam is produced by 400 GeV protons accelerated at the SPS accelerator delivering 700 kW of power. The long baseline provides a unique opportunity to study neutrino flavour oscillations over their 1st and 2nd oscillation maxima exploring the $L/E$ behaviour, and distinguishing effects arising from $\delta_{CP}$ and matter. In this paper we show how this comprehensive physics case can be further enhanced and complemented if a neutrino beam produced at the Protvino IHEP accelerator complex, at a distance of 1160 km, and with modest power of 450 kW is aimed towards the same far detectors. We show that the coupling of two independent sub-MW conventional neutrino and antineutrino beams at different baselines from CERN and Protvino will allow to measure CP violation in the leptonic sector at a confidence level of at least $3\sigma$ for 50\% of the true values of $\delta_{CP}$ with a 20 kton detector. With a far detector of 70 kton, the combination allows a $3\sigma$ sensitivity for 75\% of the true values of $\delta_{CP}$ after 10 years of running. Running two independent neutrino beams, each at a power below 1 MW, is more within today's state of the art than the long-term operation of a new single high-energy multi-MW facility, which has several technical challenges and will likely require a learning curve.Comment: 21 pages, 12 figure

STUDY OF THE EFFICIENCY AND SAFETY OF MYCOPHENOLATE MOFETIL THERAPY IN PATIENTSWITH SYSTEMIC SCLERODERMA

Interstitial lung disease (ILD) is one of the major causes of death in systemic scleroderma (SSD). Treatment of these patients remains difficult and controversial. Mycophenolate mofetil (MPM) has been in vitro shown to inhibit overproduction of type I collagen and hence may be effective against SSD. Objective: to study the efficiency and safety of MPM therapy in patients with SSD and clinically relevant ILD in an open-label prospective study. Subjects and methods. Ten patients with SSD (7 and 3 with its diffuse and limited forms, respectively) and ILD were given MPM in combination with glucocorticoids (mean daily dose was 10+4 mg). The mean MPM therapy duration was 11.4+1.3 months. The Rodnan total skin thickness score, flexion index, forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and European Scleroderma Study Group (EScSG) activity index were estimated and a 6-minute walk test (6MWT) was carried out before and after MPM therapy. Results. After therapy, the whole group showed a significant reduction in skin scores from 12.9+9.8 to 5.6+3.2 (p=0.036) and EScSG from 3.9+1.4 to 2.25+1.03 (p=0.015) and an increase in exercise tolerance from 446+155 to 535+78 m (p=0.03) as evidenced by 6MWT. The degree of flexion contractures decreased from 15+21 to 3.7+11.3 mm (p>0.05). FVC (77.8+18.7% versus 73.8+11.3%) and DLCO (45+14.4% versus 42+16.4%) were significantly unchanged. A 10% or more clinically significant fall was noted in FVC and DLCO in 3 and 1 patients, respectively. In the remaining patients, the lung functional test results remained stable. MPM tolerability was satisfactory. All the patients completed their course of treatment. Conclusion. Stabilization of lung function with higher exercise tolerance and significantly reduced skin density allow therapy with MPM in combination with low-dose glucocorticoids to be regarded as an effective and well-tolerated treatment in patients with ILD in the presence of SS