Classification of the LHC BLM Ionization Chamber

The LHC beam loss monitoring (BLM) system must prevent the super conducting magnets from quenching and protect the machine components from damage. The main monitor type is an ionization chamber. About 4000 of them will be installed around the ring. The lost beam particles initiate hadronic showers through the magnets and other machine components. These shower particles are measured by the monitors installed on the outside of the accelerator equipment. For the calibration of the BLM system the signal response of the ionization chamber is simulated in GEANT4 for all relevant particle types and energies (keV to TeV range). For validation, the simulations are compared to measurements using protons, neutrons, photons and mixed radiation fields at various energies and intensities. This paper will focus on the signal response of the ionization chamber to various particle types and energies including space charge effects at high ionization densities

Characterization of DAG binding to TRPC channels by target-dependent cis–trans isomerization of OptoDArG

Azobenzene-based photochromic lipids are valuable probes for the analysis of ion channel–lipid interactions. Rapid photoisomerization of these molecules enables the analysis of lipid gating kinetics and provides information on lipid sensing. Thermal relaxation of the metastable cis conformation to the trans conformation of azobenzene photolipids is rather slow in the dark and may be modified by ligand–protein interactions. Cis photolipid-induced changes in pure lipid membranes as visualized from the morphological response of giant unilamellar vesicles indicated that thermal cis–trans isomerization of both PhoDAG-1 and OptoDArG is essentially slow in the lipid bilayer environment. While the currents activated by cis PhoDAG remained stable upon termination of UV light exposure (dark, UV-OFF), cis OptoDArG-induced TRPC3/6/7 activity displayed a striking isoform-dependent exponential decay. The deactivation kinetics of cis OptoDArG-induced currents in the dark was sensitive to mutations in the L2 lipid coordination site of TRPC channels. We conclude that the binding of cis OptoDArG to TRPC channels promotes transition of cis OptoDArG to the trans conformation. This process is suggested to provide valuable information on DAG–ion channel interactions and may enable highly selective photopharmacological interventions

Generation of 1.5 Million Beam Loss Threshold Values

CERN's Large Hadron Collider will store an unprecedented amount of energy in its circulating beams. Beamloss monitoring (BLM) is, therefore, critical for machine protection. It must protect against the consequences (equipment damage, quenches of superconducting magnets) of excessive beam loss. About 4000 monitors will be installed at critical loss locations. Each monitor has 384 beam abort thresholds associated; for 12 integrated loss durations ($40\mu$s to 83 s) and 32 energies (450GeV to 7 TeV). Depending on monitor location, the thresholds vary by orders of magnitude. For simplification, the monitors are grouped in 'families'. Monitors of one family protect similar magnets against equivalent loss scenarios. Therefore, they are given the same thresholds. The start-up calibration of the BLM system is required to be within a factor of five in accuracy; and the final accuracy should be a factor of two. Simulations (backed-up by control measurements) determine the relation between the BLM signal, the deposited energy and the critical energy deposition for damage or quench (temperature of the coil). The paper presents the strategy of determining 1.5 million threshold values

A comparative review on the well-studied GAT1 and the understudied BGT-1 in the brain

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system (CNS). Its homeostasis is maintained by neuronal and glial GABA transporters (GATs). The four GATs identified in humans are GAT1 (SLC6A1), GAT2 (SLC6A13), GAT3 (SLC6A11), and betaine/GABA transporter-1 BGT-1 (SLC6A12) which are all members of the solute carrier 6 (SLC6) family of sodium-dependent transporters. While GAT1 has been investigated extensively, the other GABA transporters are less studied and their role in CNS is not clearly defined. Altered GABAergic neurotransmission is involved in different diseases, but the importance of the different transporters remained understudied and limits drug targeting. In this review, the well-studied GABA transporter GAT1 is compared with the less-studied BGT-1 with the aim to leverage the knowledge on GAT1 to shed new light on the open questions concerning BGT-1. The most recent knowledge on transporter structure, functions, expression, and localization is discussed along with their specific role as drug targets for neurological and neurodegenerative disorders. We review and discuss data on the binding sites for Na+, Cl-, substrates, and inhibitors by building on the recent cryo-EM structure of GAT1 to highlight specific molecular determinants of transporter functions. The role of the two proteins in GABA homeostasis is investigated by looking at the transport coupling mechanism, as well as structural and kinetic transport models. Furthermore, we review information on selective inhibitors together with the pharmacophore hypothesis of transporter substrates

LHC Beam Loss Detector Design: Simulations and Measurements

The Beam Loss Monitoring (BLM) system is integrated in the active equipment protection system of the LHC. It determines the number of particles lost from the primary hadron beam by measuring the radiation field of the shower particles outside of the vacuum chamber. The LHC BLM system will use ionization chambers as its standard detectors but in the areas where very high dose rates are expected, the Secondary Emission Monitor (SEM) chambers will be additionally employed because of their high linearity, low sensitivity and fast response.The sensitivity of the SEM was modeled in Geant4 via the Photo-Absorption Ionization module together with custom parameterization of the very low energy secondary electron production. The prototypes were calibrated by proton beams. For the calibration of the BLM system the signal response of the ionization chamber is simulated in Geant4 for all relevant particle types and energies (keV to TeV range). The results are validated by comparing the simulations to measurements using protons, neutrons, photons and mixed radiation fields at various energies and intensities

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

Background The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. Methods In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. Results A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. Conclusions In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .)

Design and Implementation of Community Forum System Based on MVC Model

随着信息技术的发展以及网络的开放性，越来越多的人通过互联网进行沟通 和在线交流，而各式各样的论坛就为上网用户提供了一个很好的线上场所，通过 搜索自己感兴趣的论坛，用户可以在论坛中发表自己的见解并与志同道合的人进 行经验的交流。而随着社区的居民的沟通变得越来越频繁，能否为他们提供一个 在线的社区论坛系统就成为了很多社区管理者面临的一个重要课题。本项目就是 在这样的背景下产生的。 本文以软件工程的设计思想为指导，通过实地的调研对需求分析做了深入的 了解，并通过用例图对需求分析进行了总结，得出了系统的功能模块以及每个功 能模块的具体功能。在需求分析的基础上，通过流程图对每个功能的具体...With the opening and development of network information technology, more and more people communicate and online communication through the Internet, and every kind of forum for Internet users to provide a good online sites, search through their interest in the forum, users can be in on the altar in the opinions of their own and with like-minded people the exchange of experiences. With the resident...学位：工程硕士院系专业：软件学院_工程硕士(软件工程)学号：X201223095

The LHC Beam Loss Measurement System

An unprecedented amount of energy will be stored in the circulating beams of LHC. The loss of even a very small fraction of a beam may induce a quench in the superconducting magnets or cause physical damage to machine components. A fast (one turn) loss of 3 . 10-9 and a constant loss of 3 . 10-12 times the nominal beam intensity can quench a dipole magnet. A fast loss of 3 . 10-6 times nominal beam intensity can damage a magnet. The stored energy in the LHC beam is a factor of 200 (or more) higher than in existing hadron machines with superconducting magnets (HERA, TEVATRON, RHIC), while the quench levels of the LHC magnets are a factor of about 5 to 20 lower than the quench levels of these machines. To comply with these requirements the detectors, ionisation chambers and secondary emission monitors are designed very reliable with a large operational range. Several stages of the acquisition chain are doubled and frequent functionality tests are automatically executed. The failure probabilities of single components were identified and optimised. First measurements show the large dynamic range of the system

Preliminary study on broad-spectrum Human Papillomavirus vaccine based on L2 cross-neutralizing epitope

宫颈癌是世界范围内妇女易患的第二大癌症，HPV预防性疫苗已成为目前公认的预防宫颈癌发生的最有效手段。研究表明以HPVL1蛋白形成的HPVVLP疫苗免疫后产生的中和抗体具有型特异性，与宫颈癌有关的主要型别至少有15种。因此，扩大HPV疫苗的保护范围成为了预防性HPV疫苗的研制亟需解决的问题，所以有必要开发一种新型的，用1~2种抗原就能预防多型别HPV的广谱疫苗。 目前对HPV广谱疫苗的研究主要集中在HPVL2表位的研究，研究发现HPVL2蛋白上存在大量广谱表位，合成这些广谱表位免疫小鼠或者将广谱表位融合在蛋白免疫载体中形成嵌合蛋白免疫小鼠后，均能够产生交叉保护抗体。这些研究表明HPVL2具有发...Cervical cancer is the second most prevalent cancer among women worldwide. Recent years, with the relationship between high-risk HPV infection and cervical cancer gradually clarified, HPV prophylactic vaccine has become the most effective methods to prevent cervical cancer. Presently Merck’s Gardasil&reg; (HPV6/11/16 / 18 quadrivalent vaccine) and GlaxoSmithKline’s CervarixTM (HPV16/18 bivalent va...学位：理学硕士院系专业：生命科学学院生物化学与生物技术系_生物化学与分子生物学学号：2172009115208

Adhesion of Escherichia coli under flow conditions reveals potential novel effects of FimH mutations

FimH-mediated adhesion of Escherichia coli to bladder epithelium is a prerequisite for urinary tract infections. FimH is also essential for blood-borne bacterial dissemination, but the mechanisms are poorly understood. The purpose of this study was to assess the influence of different FimH mutations on bacterial adhesion using a novel adhesion assay, which models the physiological flow conditions bacteria are exposed to. We introduced 12 different point mutations in the mannose binding pocket of FimH in an E. coli strain expressing type 1 fimbriae only (MSC95-FimH). We compared the bacterial adhesion of each mutant across several commonly used adhesion assays, including agglutination of yeast, adhesion to mono- and tri-mannosylated substrates, and static adhesion to bladder epithelial and endothelial cells. We performed a comparison of these assays to a novel method that we developed to study bacterial adhesion to mammalian cells under flow conditions. We showed that E. coli MSC95-FimH adheres more efficiently to microvascular endothelium than to bladder epithelium, and that only endothelium supports adhesion at physiological shear stress. The results confirmed that mannose binding pocket mutations abrogated adhesion. We demonstrated that FimH residues E50 and T53 are crucial for adhesion under flow conditions. The coating of endothelial cells on biochips and modelling of physiological flow conditions enabled us to identify FimH residues crucial for adhesion. These results provide novel insights into screening methods to determine the effect of FimH mutants and potentially FimH antagonists. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10096-016-2820-8) contains supplementary material, which is available to authorized users