Science.gov

Sample records for based gp collider

  1. A Photon Collider Experiment based on SLC

    SciTech Connect

    Gronberg, J

    2003-11-01

    Technology for a photon collider experiment at a future TeV-scale linear collider has been under development for many years. The laser and optics technology has reached the point where a GeV-scale photon collider experiment is now feasible. We report on the photon-photon luminosities that would be achievable at a photon collider experiment based on a refurbished Stanford Linear Collider.

  2. Laser-plasma-based linear collider using hollow plasma channels

    DOE PAGES

    Schroeder, C. B.; Benedetti, C.; Esarey, E.; ...

    2016-03-03

    A linear electron–positron collider based on laser-plasma accelerators using hollow plasma channels is considered. Laser propagation and energy depletion in the hollow channel is discussed, as well as the overall efficiency of the laser-plasma accelerator. Example parameters are presented for a 1-TeV and 3-TeV center-of-mass collider based on laser-plasma accelerators.

  3. Eliciting Neutralizing Antibodies with gp120 Outer Domain Constructs Based on M-Group Consensus Sequence

    PubMed Central

    Qin, Yali; Banasik, Marisa; Kim, SoonJeung; Penn-Nicholson, Adam; Habte, Habtom H; Labranche, Celia; Montefiori, David C; Wang, Chong; Cho, Michael W

    2014-01-01

    One strategy being evaluated for HIV-1 vaccine development is focusing immune responses towards neutralizing epitopes on the gp120 outer domain (OD) by removing the immunodominant, but non-neutralizing, inner domain. Previous OD constructs have not elicited strong neutralizing antibodies (nAbs). We constructed two immunogens, a monomeric gp120-OD and a trimeric gp120-OD×3, based on an M group consensus sequence (MCON6). Their biochemical and immunological properties were compared with intact gp120. Results indicated better preservation of critical neutralizing epitopes on gp120-OD×3. In contrast to previous studies, our immunogens induced potent, cross-reactive nAbs in rabbits. Although nAbs primarily targeted Tier 1 viruses, they exhibited significant breadth. Epitope mapping analyses indicated that nAbs primarily targeted conserved V3 loop elements. Although the potency and breadth of nAbs were similar for all three immunogens, nAb induction kinetics indicated that gp120-OD×3 was superior to gp120-OD, suggesting that gp120-OD×3 is a promising prototype for further gp120 OD-based immunogen development. PMID:25046154

  4. Structural Analysis of a Highly Glycosylated and Unliganded gp120-Based Antigen Using Mass Spectrometry

    SciTech Connect

    L Wang; Y Qin; S Ilchenko; J Bohon; W Shi; M Cho; K Takamoto; M Chance

    2011-12-31

    Structural characterization of the HIV-1 envelope protein gp120 is very important for providing an understanding of the protein's immunogenicity and its binding to cell receptors. So far, the crystallographic structure of gp120 with an intact V3 loop (in the absence of a CD4 coreceptor or antibody) has not been determined. The third variable region (V3) of the gp120 is immunodominant and contains glycosylation signatures that are essential for coreceptor binding and entry of the virus into T-cells. In this study, we characterized the structure of the outer domain of gp120 with an intact V3 loop (gp120-OD8) purified from Drosophila S2 cells utilizing mass spectrometry-based approaches. We mapped the glycosylation sites and calculated the glycosylation occupancy of gp120-OD8; 11 sites from 15 glycosylation motifs were determined as having high-mannose or hybrid glycosylation structures. The specific glycan moieties of nine glycosylation sites from eight unique glycopeptides were determined by a combination of ECD and CID MS approaches. Hydroxyl radical-mediated protein footprinting coupled with mass spectrometry analysis was employed to provide detailed information about protein structure of gp120-OD8 by directly identifying accessible and hydroxyl radical-reactive side chain residues. Comparison of gp120-OD8 experimental footprinting data with a homology model derived from the ligated CD4-gp120-OD8 crystal structure revealed a flexible V3 loop structure in which the V3 tip may provide contacts with the rest of the protein while residues in the V3 base remain solvent accessible. In addition, the data illustrate interactions between specific sugar moieties and amino acid side chains potentially important to the gp120-OD8 structure.

  5. Structural analysis of a highly glycosylated and unliganded gp120-based antigen using mass spectrometry†

    PubMed Central

    Wang, Liwen; Qin, Yali; Ilchenko, Serguei; Bohon, Jen; Shi, Wuxian; Cho, Michael W.; Takamoto, Keiji; Chance, Mark R.

    2010-01-01

    Structural characterization of the HIV envelope protein gp120 is very important to provide an understanding of the protein's immunogenicity and it's binding to cell receptors. So far, crystallographic structure determination of gp120 with an intact V3 loop (in the absence of CD4 co-receptor or antibody) has not been achieved. The third variable region (V3) of the gp120 is immunodominant and contains glycosylation signatures that are essential for co-receptor binding and viral entry to T-cells. In this study, we characterized the structure of the outer domain of gp120 with an intact V3 loop (gp120-OD8) purified from Drosophila S2 cells utilizing mass spectrometry-based approaches. We mapped the glycosylation sites and calculated glycosylation occupancy of gp120-OD8; eleven sites from fifteen glycosylation motifs were determined as having high mannose or hybrid glycosylation structures. The specific glycan moieties of nine glycosylation sites from eight unique glycopeptides were determined by a combination of ECD and CID MS approaches. Hydroxyl radical-mediated protein footprinting coupled with mass spectrometry analysis was employed to provide detailed information on protein structure of gp120-OD8 by directly identifying accessible and hydroxyl radical-reactive side chain residues. Comparison of gp120-OD8 experimental footprinting data with a homology model derived from the ligated CD4/ gp120-OD8 crystal structure revealed a flexible V3 loop structure where the V3 tip may provide contacts with the rest of the protein while residues in the V3 base remain solvent accessible. In addition, the data illustrate interactions between specific sugar moieties and amino acid side chains potentially important to the gp120-OD8 structure. PMID:20825246

  6. Accelerator physics in ERL based polarized electron ion collider

    SciTech Connect

    Hao, Yue

    2015-05-03

    This talk will present the current accelerator physics challenges and solutions in designing ERL-based polarized electron-hadron colliders, and illustrate them with examples from eRHIC and LHeC designs. These challenges include multi-pass ERL design, highly HOM-damped SRF linacs, cost effective FFAG arcs, suppression of kink instability due to beam-beam effect, and control of ion accumulation and fast ion instabilities.

  7. Beam-Based Feedback System for the International Linear Collider

    NASA Astrophysics Data System (ADS)

    Ivanov, Valentin

    The algorithms and computer codes for linac Feedback system were developed at SLAC during 1991-2004. The efficiency of that system have been demonstrated for the SLC, CLIC, TESLA and NLC projects. International Linear Collider (ILC) has its own features. Ground motion (GM) oscillations play a dominant role here. It forced to implement a new version of the Linac Feedback Simulation Code based on the previous developments. A set of benchmark tests and realistic simulations for the whole ILC structure have been performed. The effects of different GM models, BPM resolution, time intervals, initial misalignments, a dispersion-free steering (DFS), and a quad jitter have been studied.

  8. Does variation in general practitioner (GP) practice matter for the length of sick leave? A multilevel analysis based on Norwegian GP-patient data.

    PubMed

    Aakvik, Arild; Holmås, Tor Helge; Kamrul Islam, M

    2010-05-01

    In Norway, as in many countries, the national insurance system is under economic stress from demographic change impacting on the pensions versus contributions balance, and an increasing number of disability and sickness benefit claimants. The general practitioner (GP) is responsible for assessing work capacity and issuing certificates for sick leave based on an evaluation of the patient. Although many studies have analyzed certified sickness absence and predictive factors, no studies assess its variation between patients, GPs or geographical areas within a multilevel framework. Using a rich Norwegian matched patient-GP data set and employing a multilevel random intercept model, the study attempts to disentangle patient, GP and municipality-level variation in the certified sickness absence length for Norwegian workers in 2003. We find that most observed patient and GP characteristics are significantly associated with the length of sick leave (LSL) and medical diagnosis is an important observed factor explaining certified sickness durations. However, 98% of the unexplained variation in the LSL is attributed to patient factors rather than influenced by variation in GP practice or differences in municipality-level characteristics. Our findings indicate that GPs practice variation does not matter much for the patients' LSL. Our results are compatible with a high degree of patient involvement in current general practice. Based on this understanding one may infer that GPs play an advocate role for their patients in Norway, where the patients' own wishes are important when decisions are made.

  9. Ingot Nb based SRF technology for the International Linear Collider

    SciTech Connect

    Yamamoto, Akira; Yamanaka, Masashi; Myneni, Ganapati

    2015-12-04

    The International Linear Collider (ILC) is anticipated to be built as the next energy-frontier electron-positron colliding accelerator with a global effort in particle physics. Niobium based Superconducting Radio-Frequency (SRF) technology is required to provide beam-accelerating structure with elliptical cavity strings to linearly accelerate the electron and positron beams up to 250 GeV and to realize a center-of-mass energy of 500 GeV in collisions. The accelerator design and R&D efforts progressed, and the ILC Technical Design Report (ILC-TDR) was published in 2013. Niobium will take a critical role to generate electric field gradient with a frequency of 1.3 GHz, for accelerating the beam with the best efficiency, in energy balance, using RF superconductivity. This paper discusses a technical approach to provide Nb material (ingot) and thin disks for producing the elliptical cavity structure, with direct slicing from Nb ingot having sufficiently optimized purity and residual resistance ration (RRR) necessary for the ILC SRF cavities.

  10. Luminosity Limitations of Linear Colliders Based on Plasma Acceleration

    SciTech Connect

    Lebedev, Valeri; Burov, Alexey; Nagaitsev, Sergei

    2016-01-01

    Particle acceleration in plasma creates a possibility of exceptionally high accelerating gradients and appears as a very attractive option for future linear electron-positron and/or photon-photon colliders. These high accelerating gradients were already demonstrated in a number of experiments. Furthermore, a linear collider requires exceptionally high beam brightness which still needs to be demonstrated. In this article we discuss major phenomena which limit the beam brightness of accelerated beam and, consequently, the collider luminosity.

  11. Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the diagest 3-GP motivation study

    PubMed Central

    2012-01-01

    Background Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs) were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs’ attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. Methods We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs’ level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF) was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Results Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152) of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. Conclusions When a hospital-led study explores issues in primary

  12. BEAM-BASED NON-LINEAR OPTICS CORRECTIONS IN COLLIDERS.

    SciTech Connect

    PILAT, R.; LUO, Y.; MALITSKY, N.; PTITSYN, V.

    2005-05-16

    A method has been developed to measure and correct operationally the non-linear effects of the final focusing magnets in colliders, that gives access to the effects of multi-pole errors by applying closed orbit bumps, and analyzing the resulting tune and orbit shifts. This technique has been tested and used during 4 years of RHIC (the Relativistic Heavy Ion Collider at BNL) operations. I will discuss here the theoretical basis of the method, the experimental set-up, the correction results, the present understanding of the machine model, the potential and limitations of the method itself as compared with other non-linear correction techniques.

  13. Partnerships in purchasing: development of consortium-based purchasing among GP fundholders.

    PubMed

    Laing, A; Cotton, S

    1997-11-01

    In the last few years there have been considerable changes in the National Health Service (NHS) in the UK. Arguably the most significant of these has been the introduction of competition. Central to this development has been the introduction of general practice (GP) fundholding, whereby practices purchase health care for their patients directly from competing suppliers. Those practices which have become fundholders have faced considerable challenges in developing their purchasing function, given the complexities of contracting within the context of the NHS internal market. Although one of the original aims of GP fundholding was to facilitate locally responsive purchasing, such have been the complexities of contracting that many fundholding practices have attempted to reduce the managerial demands of purchasing through membership of purchasing consortia. Based on an in-depth study of GP fundholders across Scotland, this paper explores the development of consortium-based purchasing. Specifically, this paper seeks to address three issues central to the evolution of such consortium-based purchasing. Firstly, the patterns of organizational structure and the operational dynamics of such consortia. Secondly, the impact of such consortia on the process of fundholder purchasing. Thirdly, the managerial implications of purchasing through such consortia for the participating practices. In addressing these issues, it will examine whether such patterns of purchaser development have impacted on the evolution of locally responsive purchasing.

  14. Color octet electron search potential of FCC based e–p colliders

    NASA Astrophysics Data System (ADS)

    Acar, Y. C.; Kaya, U.; Oner, B. B.; Sultansoy, S.

    2017-04-01

    Resonant production of color octet electrons, e 8, at the FCC based e–p colliders is analyzed. It is shown that e-FCC will cover much a wider region of e 8 masses compared to the LHC. Moreover, with the highest electron beam energy, the e 8 search potential of the e-FCC exceeds that of the FCC p–p collider. If e 8 is discovered earlier by the FCC p–p collider, e-FCC will give an opportunity to handle very important additional information. For example, the compositeness scale can be probed up to the hundreds of TeV region.

  15. A DSP based data acquisition module for colliding beam accelerators

    SciTech Connect

    Mead, J.A.; Shea, T.J.

    1995-10-01

    In 1999, the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory will accelerate and store two beams of gold ions. The ions will then collide head on at a total energy of nearly 40 trillion electron volts. Attaining these conditions necessitates real-time monitoring of beam parameters and for this purpose a flexible data acquisition platform has been developed. By incorporating a floating point digital signal processor (DSP) and standard input/output modules, this system can acquire and process data from a variety of beam diagnostic devices. The DSP performs real time corrections, filtering, and data buffering to greatly reduce control system computation and bandwidth requirements. We will describe the existing hardware and software while emphasizing the compromises required to achieve a flexible yet cost effective system. Applications in several instrumentation systems currently construction will also be presented.

  16. ALV-J GP37 molecular analysis reveals novel virus-adapted sites and three tyrosine-based Env species.

    PubMed

    Ye, Jianqiang; Fan, Zhonglei; Shang, Jianjun; Tian, Xiaoyan; Yang, Jialiang; Chen, Hongjun; Shao, Hongxia; Qin, Aijian

    2015-01-01

    Compared to other avian leukosis viruses (ALV), ALV-J primarily induces myeloid leukemia and hemangioma and causes significant economic loss for the poultry industry. The ALV-J Env protein is hypothesized to be related to its unique pathogenesis. However, the molecular determinants of Env for ALV-J pathogenesis are unclear. In this study, we compared and analyzed GP37 of ALV-J Env and the EAV-HP sequence, which has high homology to that of ALV-J Env. Phylogenetic analysis revealed five groups of ALV-J GP37 and two novel ALV-J Envs with endemic GP85 and EAV-HP-like GP37. Furthermore, at least 15 virus-adapted mutations were detected in GP37 compared to the EAV-HP sequence. Further analysis demonstrated that three tyrosine-based motifs (YxxM, ITIM (immune tyrosine-based inhibitory motif) and ITAM-like (immune tyrosine-based active motif like)) associated with immune disease and oncogenesis were found in the cytoplasmic tail of GP37. Based on the potential function and distribution of these motifs in GP37, ALV-J Env was grouped into three species, inhibitory Env, bifunctional Env and active Env. Accordingly, 36.91%, 61.74% and 1.34% of ALV-J Env sequences from GenBank are classified as inhibitory, bifunctional and active Env, respectively. Additionally, the Env of the ALV-J prototype strain, HPRS-103, and 17 of 18 EAV-HP sequences belong to the inhibitory Env. And models for signal transduction of the three ALV-J Env species were predicted. Our findings and models provide novel insights for identifying the roles and molecular mechanism of ALV-J Env in the unique pathogenesis of ALV-J.

  17. Derivative Trade Optimizing Model Utilizing GP Based on Behavioral Finance Theory

    NASA Astrophysics Data System (ADS)

    Matsumura, Koki; Kawamoto, Masaru

    This paper proposed a new technique which makes the strategy trees for the derivative (option) trading investment decision based on the behavioral finance theory and optimizes it using evolutionary computation, in order to achieve high profitability. The strategy tree uses a technical analysis based on a statistical, experienced technique for the investment decision. The trading model is represented by various technical indexes, and the strategy tree is optimized by the genetic programming(GP) which is one of the evolutionary computations. Moreover, this paper proposed a method using the prospect theory based on the behavioral finance theory to set psychological bias for profit and deficit and attempted to select the appropriate strike price of option for the higher investment efficiency. As a result, this technique produced a good result and found the effectiveness of this trading model by the optimized dealings strategy.

  18. [Calorimeter based detectors for high energy hadron colliders]. [Progress report

    SciTech Connect

    Not Available

    1992-08-04

    This document provides a progress report on research that has been conducted under DOE Grant DEFG0292ER40697 for the past year, and describes proposed work for the second year of this 8 year grant starting November 15, 1992. Personnel supported by the contract include 4 faculty, 1 research faculty, 4 postdocs, and 9 graduate students. The work under this grant has in the past been directed in two complementary directions -- DO at Fermilab, and the second SSC detector GEM. A major effort has been towards the construction and commissioning of the new Fermilab Collider detector DO, including design, construction, testing, the commissioning of the central tracking and the central calorimeters. The first DO run is now underway, with data taking and analysis of the first events. Trigger algorithms, data acquisition, calibration of tracking and calorimetry, data scanning and analysis, and planning for future upgrades of the DO detector with the advent of the FNAL Main Injector are all involved. The other effort supported by this grant has been towards the design of GEM, a large and general-purpose SSC detector with special emphasis on accurate muon measurement over a large solid angle. This effort will culminate this year in the presentation to the SSC laboratory of the GEM Technical Design Report. Contributions are being made to the detector design, coordination, and physics simulation studies with special emphasis on muon final states. Collaboration with the RD5 group at CERN to study muon punch through and to test cathode strip chamber prototypes was begun.

  19. NEUTRINO FACTORY BASED ON MUON-STORAGE-RINGS TO MUON COLLIDERS: PHYSICS AND FACILITIES.

    SciTech Connect

    PARSA,Z.

    2001-06-18

    Intense muon sources for the purpose of providing intense high energy neutrino beams ({nu} factory) represents very interesting possibilities. If successful, such efforts would significantly advance the state of muon technology and provides intermediate steps in technologies required for a future high energy muon collider complex. High intensity muon: production, capture, cooling, acceleration and multi-turn muon storage rings are some of the key technology issues that needs more studies and developments, and will briefly be discussed here. A muon collider requires basically the same number of muons as for the muon storage ring neutrino factory, but would require more cooling, and simultaneous capture of both {+-} {mu}. We present some physics possibilities, muon storage ring based neutrino facility concept, site specific examples including collaboration feasibility studies, and upgrades to a full collider.

  20. Immunogenicity of multi-epitope-based vaccine candidates administered with the adjuvant Gp96 against rabies.

    PubMed

    Niu, Yange; Liu, Ye; Yang, Limin; Qu, Hongren; Zhao, Jingyi; Hu, Rongliang; Li, Jing; Liu, Wenjun

    2016-04-01

    Rabies, a zoonotic disease, causes > 55,000 human deaths globally and results in at least 500 million dollars in losses every year. The currently available rabies vaccines are mainly inactivated and attenuated vaccines, which have been linked with clinical diseases in animals. Thus, a rabies vaccine with high safety and efficacy is urgently needed. Peptide vaccines are known for their low cost, simple production procedures and high safety. Therefore, in this study, we examined the efficacy of multi-epitope-based vaccine candidates against rabies virus. The ability of various peptides to induce epitope-specific responses was examined, and the two peptides that possessed the highest antigenicity and conservation, i.e., AR16 and hPAB, were coated with adjuvant canine-Gp96 and used to prepare vaccines. The peptides were prepared as an emulsion of oil in water (O/W) to create three batches of bivalent vaccine products. The vaccine candidates possessed high safety. Virus neutralizing antibodies were detected on the day 14 after the first immunization in mice and beagles, reaching 5-6 IU/mL in mice and 7-9 IU/mL in beagles by day 28. The protective efficacy of the vaccine candidates was about 70%-80% in mice challenged by a virulent strain of rabies virus. Thus, a novel multi-epitope-based rabies vaccine with Gp96 as an adjuvant was developed and validated in mice and dogs. Our results suggest that synthetic peptides hold promise for the development of novel vaccines against rabies.

  1. Performance-Based Seismic Design of Steel Frames Utilizing Colliding Bodies Algorithm

    PubMed Central

    Veladi, H.

    2014-01-01

    A pushover analysis method based on semirigid connection concept is developed and the colliding bodies optimization algorithm is employed to find optimum seismic design of frame structures. Two numerical examples from the literature are studied. The results of the new algorithm are compared to the conventional design methods to show the power or weakness of the algorithm. PMID:25202717

  2. A laser system for the TESLA photon collider based on an external ring resonator

    NASA Astrophysics Data System (ADS)

    Will, I.; Quast, T.; Redlin, H.; Sandner, W.

    2001-10-01

    We present a concept of a laser system for a photon collider at the TESLA linac. It is based on an external optical ring cavity which is pumped by a short-pulse laser. A detailed discussion of the geometry of the external cavity is given.

  3. Operational plasma density and laser parameters for future colliders based on laser-plasma accelerators

    SciTech Connect

    Schroeder, C. B.; Esarey, E.; Leemans, W. P.

    2012-12-21

    The operational plasma density and laser parameters for future colliders based on laser-plasma accelerators are discussed. Beamstrahlung limits the charge per bunch at low plasma densities. Reduced laser intensity is examined to improve accelerator efficiency in the beamstrahlung-limited regime.

  4. Performance-based seismic design of steel frames utilizing colliding bodies algorithm.

    PubMed

    Veladi, H

    2014-01-01

    A pushover analysis method based on semirigid connection concept is developed and the colliding bodies optimization algorithm is employed to find optimum seismic design of frame structures. Two numerical examples from the literature are studied. The results of the new algorithm are compared to the conventional design methods to show the power or weakness of the algorithm.

  5. SDA-based diagnostic and analysis tools for Collider Run II

    SciTech Connect

    Bolshakov, T.B.; Lebrun, P.; Panacek, S.; Papadimitriou, V.; Slaughter, J.; Xiao, A.; /Fermilab

    2005-05-01

    Operating and improving the understanding of the Fermilab Accelerator Complex for the colliding beam experiments requires advanced software methods and tools. The Shot Data Analysis (SDA) has been developed to fulfill this need. Data from the Fermilab Accelerator Complex is stored in a relational database, and is served to programs and users via Web-based tools. Summary tables are systematically generated during and after a store. These tables (the Supertable, the Recomputed Emittances, the Recomputed Intensities and other tables) are discussed here.

  6. Feedback scheme for kink instability in ERL based electron ion collider

    SciTech Connect

    Hao, Y.; Litvinenko, V.N.; Ptitsyn, V.

    2011-03-28

    Kink instability presents one of the limiting factors from achieving higher luminosity in ERL based electron ion collider (EIC). However, we can take advantage of the flexibility of the linac and design a feedback system to cure the instability. This scheme raises the threshold of kink instability dramatically and provides opportunity for higher luminosity. We studied the effectiveness of this system and its dependence on the amplitude and phase of the feedback. In this paper we present results of theses studies of this scheme and describe its theoretical and practical limitations. The main advantage of an energy recovery linac (ERL) based electron ion collider (EIC) over a ring-ring type counterpart is the higher achievable luminosity. In ERL-based version, one electron beam collides with the opposing ion beam only once so that the beam-beam parameter can largely exceed the usual limitation in an electron collider ring, while the beam-beam parameter for the ion beam remains small values. The resulting luminosity may be enhanced by one order of magnitude. The beam dynamics related challenges also arise as the luminosity boost in ERL based EIC due to the significant beam-beam effect on the electron beam. The effects on the electron beam include the additional large beam-beam tune shift and nonlinear emittance growth, which are discussed. The ion beam may develop a head-tail type instability, referred as 'kink instability', through the interaction with the electron beam. In this paper, we discuss the feasibility of an active feedback system to mitigate the kink instability, by taking advantage of the flexibility of ERL. Throughout the paper, we will discuss the collision between proton and electron beam. Any other ion species can be scaled by its charge Z and ion mass A.

  7. Intrinsic acid-base properties of a hexa-2'-deoxynucleoside pentaphosphate, d(ApGpGpCpCpT): neighboring effects and isomeric equilibria.

    PubMed

    Domínguez-Martín, Alicia; Johannsen, Silke; Sigel, Astrid; Operschall, Bert P; Song, Bin; Sigel, Helmut; Okruszek, Andrzej; González-Pérez, Josefa María; Niclós-Gutiérrez, Juan; Sigel, Roland K O

    2013-06-17

    The intrinsic acid-base properties of the hexa-2'-deoxynucleoside pentaphosphate, d(ApGpGpCpCpT) [=(A1∙G2∙G3∙C4∙C5∙T6)=(HNPP)⁵⁻] have been determined by ¹H NMR shift experiments. The pKa values of the individual sites of the adenosine (A), guanosine (G), cytidine (C), and thymidine (T) residues were measured in water under single-strand conditions (i.e., 10% D₂O, 47 °C, I=0.1 M, NaClO₄). These results quantify the release of H⁺ from the two (N7)H⁺ (G∙G), the two (N3)H⁺ (C∙C), and the (N1)H⁺ (A) units, as well as from the two (N1)H (G∙G) and the (N3)H (T) sites. Based on measurements with 2'-deoxynucleosides at 25 °C and 47 °C, they were transferred to pKa values valid in water at 25 °C and I=0.1 M. Intramolecular stacks between the nucleobases A1 and G2 as well as most likely also between G2 and G3 are formed. For HNPP three pKa clusters occur, that is those encompassing the pKa values of 2.44, 2.97, and 3.71 of G2(N7)H⁺, G3(N7)H⁺, and A1(N1)H⁺, respectively, with overlapping buffer regions. The tautomer populations were estimated, giving for the release of a single proton from five-fold protonated H₅(HNPP)(±) , the tautomers (G2)N7, (G3)N7, and (A1)N1 with formation degrees of about 74, 22, and 4%, respectively. Tautomer distributions reveal pathways for proton-donating as well as for proton-accepting reactions both being expected to be fast and to occur practically at no "cost". The eight pKa values for H₅(HNPP)(±) are compared with data for nucleosides and nucleotides, revealing that the nucleoside residues are in part affected very differently by their neighbors. In addition, the intrinsic acidity constants for the RNA derivative r(A1∙G2∙G3∙C4∙C5∙U6), where U=uridine, were calculated. Finally, the effect of metal ions on the pKa values of nucleobase sites is briefly discussed because in this way deprotonation reactions can easily be shifted to the physiological pH range. Copyright © 2013 WILEY

  8. Comment on ``Beamstrahlung considerations in laser-plasma-accelerator-based linear colliders''

    NASA Astrophysics Data System (ADS)

    Lebedev, Valeri; Nagaitsev, Sergei

    2013-10-01

    Schroeder, Esarey, Geddes, Benedetti, and Leemans [Phys. Rev. ST Accel. Beams 13, 101301 (2010)PRABFM1098-440210.1103/PhysRevSTAB.13.101301 and Phys. Rev. ST Accel. Beams 15, 051301 (2012)PRABFM1098-440210.1103/PhysRevSTAB.15.051301] have proposed a set of parameters for a TeV-scale collider based on plasma wakefield accelerator principles. In particular, it is sugested that the luminosities greater than 1034cm-2s-1 are attainable for an electron-positron collider. In this Comment we dispute this set of parameters on the basis of first principles. The interactions of accelerating beam with plasma impose fundamental limitations on beam properties and, thus, on attainable luminosity values.

  9. Computational Design of Hypothetical New Peptides Based on a Cyclotide Scaffold as HIV gp120 Inhibitor.

    PubMed

    Sangphukieo, Apiwat; Nawae, Wanapinun; Laomettachit, Teeraphan; Supasitthimethee, Umaporn; Ruengjitchatchawalya, Marasri

    2015-01-01

    Cyclotides are a family of triple disulfide cyclic peptides with exceptional resistance to thermal/chemical denaturation and enzymatic degradation. Several cyclotides have been shown to possess anti-HIV activity, including kalata B1 (KB1). However, the use of cyclotides as anti-HIV therapies remains limited due to the high toxicity in normal cells. Therefore, grafting anti-HIV epitopes onto a cyclotide might be a promising approach for reducing toxicity and simultaneously improving anti-HIV activity. Viral envelope glycoprotein gp120 is required for entry of HIV into CD4+ T cells. However, due to a high degree of variability and physical shielding, the design of drugs targeting gp120 remains challenging. We created a computational protocol in which molecular modeling techniques were combined with a genetic algorithm (GA) to automate the design of new cyclotides with improved binding to HIV gp120. We found that the group of modified cyclotides has better binding scores (23.1%) compared to the KB1. By using molecular dynamic (MD) simulation as a post filter for the final candidates, we identified two novel cyclotides, GA763 and GA190, which exhibited better interaction energies (36.6% and 22.8%, respectively) when binding to gp120 compared to KB1. This computational design represents an alternative tool for modifying peptides, including cyclotides and other stable peptides, as therapeutic agents before the synthesis process.

  10. Availability modeling approach for future circular colliders based on the LHC operation experience

    NASA Astrophysics Data System (ADS)

    Niemi, Arto; Apollonio, Andrea; Gutleber, Johannes; Sollander, Peter; Penttinen, Jussi-Pekka; Virtanen, Seppo

    2016-12-01

    Reaching the challenging integrated luminosity production goals of a future circular hadron collider (FCC-hh) and high luminosity LHC (HL-LHC) requires a thorough understanding of today's most powerful high energy physics research infrastructure, the LHC accelerator complex at CERN. FCC-hh, a 4 times larger collider ring aims at delivering 10 - 20 ab-1 of integrated luminosity at 7 times higher collision energy. Since the identification of the key factors that impact availability and cost is far from obvious, a dedicated activity has been launched in the frame of the future circular collider study to develop models to study possible ways to optimize accelerator availability. This paper introduces the FCC reliability and availability study, which takes a fresh new look at assessing and modeling reliability and availability of particle accelerator infrastructures. The paper presents a probabilistic approach for Monte Carlo simulation of the machine operational cycle, schedule and availability for physics. The approach is based on best-practice, industrially applied reliability analysis methods. It relies on failure rate and repair time distributions to calculate impacts on availability. The main source of information for the study is coming from CERN accelerator operation and maintenance data. Recent improvements in LHC failure tracking help improving the accuracy of modeling of LHC performance. The model accuracy and prediction capabilities are discussed by comparing obtained results with past LHC operational data.

  11. Exotic colliders

    SciTech Connect

    Chattopadhyay, S.

    1994-11-01

    The motivation, feasibility and potential for two unconventional collider concepts - the Gamma-Gamma Collider and the Muon Collider - are described. The importance of the development of associated technologies such as high average power, high repetition rate lasers and ultrafast phase-space techniques are outlined.

  12. Structure-based design of a protein immunogen that displays an HIV-1 gp41 neutralizing epitope.

    PubMed

    Stanfield, Robyn L; Julien, Jean-Philippe; Pejchal, Robert; Gach, Johannes S; Zwick, Michael B; Wilson, Ian A

    2011-12-02

    Antibody Z13e1 is a relatively broadly neutralizing anti-human immunodeficiency virus type 1 antibody that recognizes the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Based on the crystal structure of an MPER epitope peptide in complex with Z13e1 Fab, we identified an unrelated protein, interleukin (IL)-22, with a surface-exposed region that is structurally homologous in its backbone to the gp41 Z13e1 epitope. By grafting the gp41 Z13e1 epitope sequence onto the structurally homologous region in IL-22, we engineered a novel protein (Z13-IL22-2) that contains the MPER epitope sequence for use as a potential immunogen and as a reagent for the detection of Z13e1-like antibodies. The Z13-IL22-2 protein binds Fab Z13e1 with a K(d) of 73 nM. The crystal structure of Z13-IL22-2 in complex with Fab Z13e1 shows that the epitope region is faithfully replicated in the Fab-bound scaffold protein; however, isothermal calorimetry studies indicate that Fab binding to Z13-IL22-2 is not a lock-and-key event, leaving open the question of whether conformational changes upon binding occur in the Fab, in Z13-IL-22, or in both.

  13. Structure-Based Design of a Protein Immunogen that Displays an HIV-1 gp41 Neutralizing Epitope

    SciTech Connect

    Stanfield, Robyn L.; Julien, Jean-Philippe; Pejchal, Robert; Gach, Johannes S.; Zwick, Michael B.; Wilson, Ian A.

    2012-06-27

    Antibody Z13e1 is a relatively broadly neutralizing anti-human immunodeficiency virus type 1 antibody that recognizes the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Based on the crystal structure of an MPER epitope peptide in complex with Z13e1 Fab, we identified an unrelated protein, interleukin (IL)-22, with a surface-exposed region that is structurally homologous in its backbone to the gp41 Z13e1 epitope. By grafting the gp41 Z13e1 epitope sequence onto the structurally homologous region in IL-22, we engineered a novel protein (Z13-IL22-2) that contains the MPER epitope sequence for use as a potential immunogen and as a reagent for the detection of Z13e1-like antibodies. The Z13-IL22-2 protein binds Fab Z13e1 with a K{sub d} of 73 nM. The crystal structure of Z13-IL22-2 in complex with Fab Z13e1 shows that the epitope region is faithfully replicated in the Fab-bound scaffold protein; however, isothermal calorimetry studies indicate that Fab binding to Z13-IL22-2 is not a lock-and-key event, leaving open the question of whether conformational changes upon binding occur in the Fab, in Z13-IL-22, or in both.

  14. Simulation Studies of Beam-Beam Effects of a Ring-Ring Electron-Ion Collider Based on CEBAF

    SciTech Connect

    Yuhong Zhang,Ji Qiang

    2009-05-01

    The collective beam-beam effect can potentially cause a rapid growth of beam sizes and reduce the luminosity of a collider to an unacceptably low level. The ELIC, a proposed ultra high luminosity electron-ion collider based on CEBAF, employs high repetition rate crab crossing colliding beams with very small bunch transverse sizes and very short bunch lengths, and collides them at up to 4 interaction points with strong final focusing. All of these features can make the beam-beam effect challenging. In this paper, we present simulation studies of the beam-beam effect in ELIC using a self-consistent strong-strong beam-beam simulation code developed at Lawrence Berkeley National Laboratory. This simulation study is used for validating the ELIC design and for searching for an optimal parameter set.

  15. Concepts for ELIC - A High Luminosity CEBAF Based Electron-Light Ion Collider

    SciTech Connect

    Ya. Derbenev, A. Bogacz, G. Krafft, R. Li, L. Merminga, B. Yunn, Y. Zhang

    2006-09-01

    A CEBAF accelerator based electron-light ion collider (ELIC) of rest mass energy from 20 to 65 GeV and luminosity from 10^33 to 10^35 cm6-2s^-1 with both beams polarized is envisioned as a future upgrade to CEBAF. A two step upgrade scenario is under study: CEBAF accelerator-ring-ring scheme (CRR) as the first step, and a multi-turn ERL-ring as the second step, to attain a better electron emittance and maximum luminosity. In this paper we report results of our studies of the CRR version of ELIC.

  16. Induction of HIV neutralizing antibodies against the MPER of the HIV envelope protein by HA/gp41 chimeric protein-based DNA and VLP vaccines.

    PubMed

    Ye, Ling; Wen, Zhiyuan; Dong, Ke; Wang, Xi; Bu, Zhigao; Zhang, Huizhong; Compans, Richard W; Yang, Chinglai

    2011-01-01

    Several conserved neutralizing epitopes have been identified in the HIV Env protein and among these, the MPER of gp41 has received great attention and is widely recognized as a promising target. However, little success has been achieved in eliciting MPER-specific HIV neutralizing antibodies by a number of different vaccine strategies. We investigated the ability of HA/gp41 chimeric protein-based vaccines, which were designed to enhance the exposure of the MPER in its native conformation, to induce MPER-specific HIV neutralizing antibodies. In characterization of the HA/gp41 chimeric protein, we found that by mutating an unpaired Cys residue (Cys-14) in its HA1 subunit to a Ser residue, the modified chimeric protein HA-C14S/gp41 showed increased reactivity to a conformation-sensitive monoclonal antibody against HA and formed more stable trimers in VLPs. On the other hand, HA-C14S/gp41 and HA/gp41 chimeric proteins expressed on the cell surfaces exhibited similar reactivity to monoclonal antibodies 2F5 and 4E10. Immunization of guinea pigs using the HA-C14S/gp41 DNA or VLP vaccines induced antibodies against the HIV gp41 as well as to a peptide corresponding to a segment of MPER at higher levels than immunization by standard HIV VLPs. Further, sera from vaccinated guinea pigs were found to exhibit HIV neutralizing activities. Moreover, sera from guinea pigs vaccinated by HA-C14S/gp41 DNA and VLP vaccines but not the standard HIV VLPs, were found to neutralize HIV pseudovirions containing a SIV-4E10 chimeric Env protein. The virus neutralization could be blocked by a MPER-specific peptide, thus demonstrating induction of MPER-specific HIV neutralizing antibodies by this novel vaccine strategy. These results show that induction of MPER-specific HIV neutralizing antibodies can be achieved through a rationally designed vaccine strategy.

  17. High Energy Photon Beam Generation For QCD Explorer Based γP Colliders

    NASA Astrophysics Data System (ADS)

    Ciftci, A. K.; Aksakal, H.; Nergiz, Z.

    2007-04-01

    Combination of two linear accelerator projects, namely CLIC (Compact Linear Collider) and ILC (International Linear Collider) with LHC(Large Hadron Collider) offer an opportunity to build γp collider. High energy photons are produced by the Compton backscattering of the laser photons off high energy electrons at the conversion region. Then, Compton backscattered photons are collided with protons at the interaction region. In this study, conversion properties and optimum laser and electron beam parameters for CLIC and ILC are determined using CAIN simulation program.

  18. Mixed nanomicelles as potential carriers for systemic delivery of Z-GP-Dox, an FAPα-based doxorubicin prodrug: formulation and pharmacokinetic evaluation

    PubMed Central

    Zhang, Yuchen; Zhang, Xingwang; Liu, Hongming; Cai, Shaohui; Wu, Baojian

    2015-01-01

    Z-GP-Dox, the FAPα (fibroblast activation protein-α)-based doxorubicin prodrug, demonstrates excellent tumor targeting effects and a favorable toxicokinetic profile. However, the insoluble nature of Z-GP-Dox becomes a significant barrier to drug administration, particularly when it comes to the clinical stage. Here we developed a nanomicelle system to facilitate the systemic delivery of Z-GP-Dox, and evaluated its disposition in rats following administration of the micelles using a physiologically-based pharmacokinetic model. Z-GP-Dox-loaded mixed nanomicelles (ZGD-MNs) were prepared by dispersion of an ethanol solution of Z-GP-Dox, lecithin, and sodium oleate in water. The obtained ZGD-MNs were 86.6 nm in size with a drug loading of 14.03%. ZGD-MNs were fairly stable in phosphate-buffered saline and showed satisfactory physical and chemical stability over a 2-week observation period. Accumulative drug release was more than 56% within 24 hours. Further, the physiologically-based pharmacokinetic rat model consisting of various organs (ie, heart, liver, spleen, lung, kidney, and intestine) was fitted to the experimental data following administration of ZGD-loaded cosolvent (control) or micelles. Derived partition coefficient values revealed that the nanomicelles significantly altered the biodistribution of Z-GP-Dox. Of note, drug distribution to the lung, liver, and spleen was greatly enhanced and the fold change ranged from 2.4 to 33. In conclusion, this is the first report of a mixed micelle system being a viable carrier for delivery of Z-GP-Dox. Also, the pharmacokinetic behavior of Z-GP-Dox was satisfactorily described by the physiologically-based pharmacokinetic model. PMID:25759584

  19. A competency based selection procedure for Dutch postgraduate GP training: a pilot study on validity and reliability.

    PubMed

    Vermeulen, Margit I; Tromp, Fred; Zuithoff, Nicolaas P A; Pieters, Ron H M; Damoiseaux, Roger A M J; Kuyvenhoven, Marijke M

    2014-12-01

    Abstract Background: Historically, semi-structured interviews (SSI) have been the core of the Dutch selection for postgraduate general practice (GP) training. This paper describes a pilot study on a newly designed competency-based selection procedure that assesses whether candidates have the competencies that are required to complete GP training. The objective was to explore reliability and validity aspects of the instruments developed. The new selection procedure comprising the National GP Knowledge Test (LHK), a situational judgement tests (SJT), a patterned behaviour descriptive interview (PBDI) and a simulated encounter (SIM) was piloted alongside the current procedure. Forty-seven candidates volunteered in both procedures. Admission decision was based on the results of the current procedure. Study participants did hardly differ from the other candidates. The mean scores of the candidates on the LHK and SJT were 21.9 % (SD 8.7) and 83.8% (SD 3.1), respectively. The mean self-reported competency scores (PBDI) were higher than the observed competencies (SIM): 3.7(SD 0.5) and 2.9(SD 0.6), respectively. Content-related competencies showed low correlations with one another when measured with different instruments, whereas more diverse competencies measured by a single instrument showed strong to moderate correlations. Moreover, a moderate correlation between LHK and SJT was found. The internal consistencies (intraclass correlation, ICC) of LHK and SJT were poor while the ICC of PBDI and SIM showed acceptable levels of reliability. Findings on content validity and reliability of these new instruments are promising to realize a competency based procedure. Further development of the instruments and research on predictive validity should be pursued.

  20. Muon colliders

    SciTech Connect

    Palmer, R.B. |; Sessler, A.; Skrinsky, A.

    1996-01-01

    Muon Colliders have unique technical and physics advantages and disadvantages when compared with both hadron and electron machines. They should thus be regarded as complementary. Parameters are given of 4 TeV and 0.5 TeV high luminosity {micro}{sup +}{micro}{sup {minus}}colliders, and of a 0.5 TeV lower luminosity demonstration machine. We discuss the various systems in such muon colliders, starting from the proton accelerator needed to generate the muons and proceeding through muon cooling, acceleration and storage in a collider ring. Problems of detector background are also discussed.

  1. Muon colliders

    NASA Astrophysics Data System (ADS)

    Palmer, R. B.; Sessler, A.; Skrinsky, A.; Tollestrup, A.; Baltz, A. J.; Chen, P.; Cheng, W.-H.; Cho, Y.; Courant, E.; Fernow, R. C.; Gallardo, J. C.; Garren, A.; Green, M.; Kahn, S.; Kirk, H.; Lee, Y. Y.; Mills, F.; Mokhov, N.; Morgan, G.; Neuffer, D.; Noble, R.; Norem, J.; Popovic, M.; Schachinger, L.; Silvestrov, G.; Summers, D.; Stumer, I.; Syphers, M.; Torun, Y.; Trbojevic, D.; Turner, W.; Van Ginneken, A.; Vsevolozhskaya, T.; Weggel, R.; Willen, E.; Winn, D.; Wurtele, J.

    1996-05-01

    Muon Colliders have unique technical and physics advantages and disadvantages when compared with both hadron and electron machines. They should thus be regarded as complementary. Parameters are given of 4 TeV and 0.5 TeV high luminosity μ+μ- colliders, and of a 0.5 TeV lower luminosity demonstration machine. We discuss the various systems in such muon colliders, starting from the proton accelerator needed to generate the muons and proceeding through muon cooling, acceleration and storage in a collider ring. Problems of detector background are also discussed.

  2. Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif

    PubMed Central

    Molinos-Albert, Luis M.; Bilbao, Eneritz; Agulló, Luis; Marfil, Silvia; García, Elisabet; Concepción, Maria Luisa Rodríguez de la; Izquierdo-Useros, Nuria; Vilaplana, Cristina; Nieto-Garai, Jon A.; Contreras, F.-Xabier; Floor, Martin; Cardona, Pere J.; Martinez-Picado, Javier; Clotet, Bonaventura; Villà-Freixa, Jordi; Lorizate, Maier; Carrillo, Jorge; Blanco, Julià

    2017-01-01

    The HIV-1 gp41 Membrane Proximal External Region (MPER) is recognized by broadly neutralizing antibodies and represents a promising vaccine target. However, MPER immunogenicity and antibody activity are influenced by membrane lipids. To evaluate lipid modulation of MPER immunogenicity, we generated a 1-Palmitoyl-2-oleoylphosphatidylcholine (POPC)-based proteoliposome collection containing combinations of phosphatidylserine (PS), GM3 ganglioside, cholesterol (CHOL), sphingomyelin (SM) and the TLR4 agonist monophosphoryl lipid A (MPLA). A recombinant gp41-derived miniprotein (gp41-MinTT) exposing the MPER and a tetanus toxoid (TT) peptide that favors MHC-II presentation, was successfully incorporated into lipid mixtures (>85%). Immunization of mice with soluble gp41-MinTT exclusively induced responses against the TT peptide, while POPC proteoliposomes generated potent anti-gp41 IgG responses using lower protein doses. The combined addition of PS and GM3 or CHOL/SM to POPC liposomes greatly increased gp41 immunogenicity, which was further enhanced by the addition of MPLA. Responses generated by all proteoliposomes targeted the N-terminal moiety of MPER overlapping the 2F5 neutralizing epitope. Our data show that lipids impact both, the epitope targeted and the magnitude of the response to membrane-dependent antigens, helping to improve MPER-based lipid carriers. Moreover, the identification of immunodominant epitopes allows for the redesign of immunogens targeting MPER neutralizing determinants. PMID:28084464

  3. Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif.

    PubMed

    Molinos-Albert, Luis M; Bilbao, Eneritz; Agulló, Luis; Marfil, Silvia; García, Elisabet; Concepción, Maria Luisa Rodríguez de la; Izquierdo-Useros, Nuria; Vilaplana, Cristina; Nieto-Garai, Jon A; Contreras, F-Xabier; Floor, Martin; Cardona, Pere J; Martinez-Picado, Javier; Clotet, Bonaventura; Villà-Freixa, Jordi; Lorizate, Maier; Carrillo, Jorge; Blanco, Julià

    2017-01-13

    The HIV-1 gp41 Membrane Proximal External Region (MPER) is recognized by broadly neutralizing antibodies and represents a promising vaccine target. However, MPER immunogenicity and antibody activity are influenced by membrane lipids. To evaluate lipid modulation of MPER immunogenicity, we generated a 1-Palmitoyl-2-oleoylphosphatidylcholine (POPC)-based proteoliposome collection containing combinations of phosphatidylserine (PS), GM3 ganglioside, cholesterol (CHOL), sphingomyelin (SM) and the TLR4 agonist monophosphoryl lipid A (MPLA). A recombinant gp41-derived miniprotein (gp41-MinTT) exposing the MPER and a tetanus toxoid (TT) peptide that favors MHC-II presentation, was successfully incorporated into lipid mixtures (>85%). Immunization of mice with soluble gp41-MinTT exclusively induced responses against the TT peptide, while POPC proteoliposomes generated potent anti-gp41 IgG responses using lower protein doses. The combined addition of PS and GM3 or CHOL/SM to POPC liposomes greatly increased gp41 immunogenicity, which was further enhanced by the addition of MPLA. Responses generated by all proteoliposomes targeted the N-terminal moiety of MPER overlapping the 2F5 neutralizing epitope. Our data show that lipids impact both, the epitope targeted and the magnitude of the response to membrane-dependent antigens, helping to improve MPER-based lipid carriers. Moreover, the identification of immunodominant epitopes allows for the redesign of immunogens targeting MPER neutralizing determinants.

  4. The ERL-based Design of Electron-Hadron Collider eRHIC

    SciTech Connect

    Ptitsyn, Vadim

    2016-06-01

    Recent developments of the ERL-based design of future high-luminosity electron-hadron collider eRHIC focused on balancing technological risks present in the design versus the design cost. As a result a lower risk design has been adopted at moderate cost increase. The modifications include a change of the main linac RF frequency, reduced number of SRF cavity types and modified electron spin transport using a spin rotator. A luminosity-staged approach is being explored with a Nominal design ($L \\sim 10^{33} {\\rm cm}^2 {\\rm s}^{-1}$) that employs reduced electron current and could possibly be based on classical electron cooling, and then with the Ultimate design ($L \\gt 10^{34} {\\rm cm}^{-2} {\\rm s}^{-1}$) that uses higher electron current and an innovative cooling technique (CeC). The paper describes the recent design modifications, and presents the full status of the eRHIC ERL-based design.

  5. Project Nuclotron-based Ion Collider fAcility at JINR

    NASA Astrophysics Data System (ADS)

    Kekelidze, V. D.; Matveev, V. A.; Meshkov, I. N.; Sorin, A. S.; Trubnikov, G. V.

    2017-09-01

    The project of Nuclotron-based Ion Collider fAcility (NICA) that is under development at JINR (Dubna) is presented. The general goals of the project are experimental studies of both hot and dense baryonic matter and spin physics (in collisions of polarized protons and deuterons). The first program requires providing of heavy ion collisions in the energy range of √ {{s_{NN}}} = 4-11 Gev at average luminosity of L = 1 × 1027 cm-2 s-1 for 197Au79+ nuclei. The polarized beams mode is proposed to be used in energy range of √ {{s_{NN}}} = 12-27 Gev (protons at luminosity of L ≥ 1 × 1030 cm-2 s-1. The report contains description of the facility scheme and its characteristics in heavy ion operation mode. The Collider will be equipped with two detectors—MultiPurpose Detector (MPD), which is in an active stage of construction, and Spin Physics Detector (SPD) that is in the stage of conceptual design. Fixed target experiment "Baryonic matter at Nuclotron" (BM@N) will be performed in very beginning of the project. The wide program of applied researches at NICA facility is being developed as well.

  6. Thallium-based high-temperature superconductors for beam impedance mitigation in the Future Circular Collider

    NASA Astrophysics Data System (ADS)

    Calatroni, S.; Bellingeri, E.; Ferdeghini, C.; Putti, M.; Vaglio, R.; Baumgartner, T.; Eisterer, M.

    2017-07-01

    CERN has recently started a design study for a possible next-generation high-energy hadron-hadron collider (Future Circular Collider—FCC-hh). The FCC-hh study calls for an unprecedented center-of-mass collision energy of 100 TeV, achievable by colliding counter-rotating proton beams with an energy of 50 TeV steered in a 100 km circumference tunnel by superconducting magnets which produce a dipole field of 16 T. The beams emit synchrotron radiation at high power levels, which, to optimize cryogenic efficiency, is absorbed by a beam-facing screen, coated with copper, and held at 50 K in the current design. The surface impedance of this screen has a strong impact on beam stability, and copper at 50 K allows for a limited beam stability margin only. This motivates the exploration of whether high-temperature superconductors (HTS), the only known materials possibly having a surface impedance lower than copper under the required operating conditions, would represent a viable alternative. This paper summarizes the FCC-hh requirements and focuses on identifying the best possible HTS material for this purpose. It reviews in particular the properties of Tl-based HTS, and discusses the consequent motivation for developing a deposition process for such compounds, which should be scalable to the size of the FCC components.

  7. Egg envelope glycoprotein gp37 as a Xenopus homolog of mammalian ZP1, based on cDNA cloning.

    PubMed

    Kubo, H; Kawano, T; Tsubuki, S; Kotani, M; Kawasaki, H; Kawashima, S

    2000-08-01

    The egg envelope is a kind of extracellular matrix, which surrounds growing oocytes, ovulated eggs and early embryos. Among the glycoprotein components of the Xenopus laevis egg envelope, gp43/gp41 and gp69/64 have already been shown to be frog homologs of the mammalian zona pellucida components ZP3 and ZP2, respectively. To determine the structure of another major component of egg envelope, gp37, the peptides isolated from the lysyl endopeptidase digests of gp37 were sequenced for amino acids to design degenerate primers for polymerase chain reaction. By reverse transcription-polymerase chain reaction with a poly(A)+ RNA from the ovary of a postovulated female Xenopus, a specifically amplified band was obtained and sequenced. The upstream and downstream sequences of the sequenced region were completed by 5'- and 3'-rapid amplification of cDNA ends, respectively. The gp37 cDNA comprises 1674 bp and contains one open reading frame encoding a polypeptide with 543 amino acids. The predicted amino acid sequence of the gp37 cDNA has a close similarity to that of mammalian ZP1. Northern blot and in situ hybridization studies indicated that the transcript (1.8 kb) is exclusively expressed in the oocytes, particularly in the previtellogenic young oocytes, just like the expression pattern of gp43 mRNA, suggesting a coordinate transcription of the gp43 and gp37 genes in Xenopus.

  8. Positron source investigation by using CLIC drive beam for Linac-LHC based e+p collider

    NASA Astrophysics Data System (ADS)

    Arιkan, Ertan; Aksakal, Hüsnü

    2012-08-01

    Three different methods which are alternately conventional, Compton backscattering and Undulator based methods employed for the production of positrons. The positrons to be used for e+p collisions in a Linac-LHC (Large Hadron Collider) based collider have been studied. The number of produced positrons as a function of drive beam energy and optimum target thickness has been determined. Three different targets have been used as a source investigation which are W75-Ir25, W75-Ta25, and W75-Re25 for three methods. Estimated number of the positrons has been performed with FLUKA simulation code. Then, these produced positrons are used for following Adiabatic matching device (AMD) and capture efficiency is determined. Then e+p collider luminosity corresponding to the methods mentioned above have been calculated by CAIN code.

  9. Expression of an immunogenic LTB-based chimeric protein targeting Zaire ebolavirus epitopes from GP1 in plant cells.

    PubMed

    Ríos-Huerta, Regina; Monreal-Escalante, Elizabeth; Govea-Alonso, Dania O; Angulo, Carlos; Rosales-Mendoza, Sergio

    2017-02-01

    An antigenic protein targeting two epitopes from the Zaire ebolavirus GP1 protein was expressed in plant cells rendering an antigen capable of inducing humoral responses in mouse when administered subcutaneously or orally. The 2014 Ebola outbreak made clear that new treatments and prophylactic strategies to fight this disease are needed. Since vaccination is an intervention that could achieve the control of this epidemic disease, exploring the production of new low-cost vaccines is a key path to consider; especially in developing countries. In this context, plants are attractive organisms for the synthesis and delivery of subunit vaccines. This study aimed at producing a chimeric protein named LTB-EBOV, based on the B subunit of the Escherichia coli heat-labile enterotoxin as an immunogenic carrier and two epitopes from the Zaire ebolavirus GP1 protein recognized by neutralizing antibodies. The LTB-EBOV protein was expressed in plant tissues at levels up to 14.7 µg/g fresh leaf tissue and proven to be immunogenic in BALB/c mice when administered by either subcutaneous or oral routes. Importantly, IgA and IgG responses were induced following the oral immunization. The potential use of the plant-made LTB-EBOV protein against EBOV is discussed.

  10. Immunogenic properties of a trimeric gp41-based immunogen containing an exposed membrane-proximal external region

    PubMed Central

    Habte, Habtom H.; Banerjee, Saikat; Shi, Heliang; Qin, Yali; Cho, Michael W

    2015-01-01

    The membrane-proximal external region (MPER) of HIV-1 gp41 is an attractive target for vaccine development. Thus, better understanding of its immunogenic properties in various structural contexts is important. We previously described the crystal structure of a trimeric protein complex named gp41-HR1-54Q, which consists of the heptad repeat regions 1 and 2 and the MPER. The protein was efficiently recognized by broadly neutralizing antibodies. Here, we describe its immunogenic properties in rabbits. The protein was highly immunogenic, especially the C-terminal end of the MPER containing 4E10 and 10E8 epitopes (671NWFDITNWLWYIK683). Although antibodies exhibited strong competition activity against 4E10 and 10E8, neutralizing activity was not detected. Detailed mapping analyses indicated that amino acid residues critical for recognition resided on faces of the alpha helix that are either opposite of or perpendicular to the epitopes recognized by 4E10 and 10E8. These results provide critical information for designing the next generation of MPER-based immunogens. PMID:26454663

  11. Immunogenic properties of a trimeric gp41-based immunogen containing an exposed membrane-proximal external region.

    PubMed

    Habte, Habtom H; Banerjee, Saikat; Shi, Heliang; Qin, Yali; Cho, Michael W

    2015-12-01

    The membrane-proximal external region (MPER) of HIV-1 gp41 is an attractive target for vaccine development. Thus, better understanding of its immunogenic properties in various structural contexts is important. We previously described the crystal structure of a trimeric protein complex named gp41-HR1-54Q, which consists of the heptad repeat regions 1 and 2 and the MPER. The protein was efficiently recognized by broadly neutralizing antibodies. Here, we describe its immunogenic properties in rabbits. The protein was highly immunogenic, especially the C-terminal end of the MPER containing 4E10 and 10E8 epitopes ((671)NWFDITNWLWYIK(683)). Although antibodies exhibited strong competition activity against 4E10 and 10E8, neutralizing activity was not detected. Detailed mapping analyses indicated that amino acid residues critical for recognition resided on faces of the alpha helix that are either opposite of or perpendicular to the epitopes recognized by 4E10 and 10E8. These results provide critical information for designing the next generation of MPER-based immunogens.

  12. Commercial associative memory performance for applications in track-based triggers at the Large Hadron Collider

    NASA Astrophysics Data System (ADS)

    Webster, Jordan

    2017-01-01

    Dense track environments in pp collisions at the Large Hadron Collider (LHC) motivate the use of triggers with dedicated hardware for fast track reconstruction. The ATLAS Collaboration is in the process of implementing a Fast Tracker (FTK) trigger upgrade, in which Content Addressable Memories (CAMs) will be used to rapidly match hit patterns with large banks of simulated tracks. The FTK CAMs are produced primarily at the University of Pisa. However, commercial CAM technology is rapidly developing due to applications in computer networking devices. This poster presents new studies comparing FTK CAMs to cutting-edge ternary CAMs developed by Cavium. The comparison is intended to guide the design of future track-based trigger systems for the next Phase at the LHC.

  13. Monte-Carlo-based studies of a polarized positron source for International Linear Collider (ILC)

    NASA Astrophysics Data System (ADS)

    Dollan, Ralph; Laihem, Karim; Schälicke, Andreas

    2006-04-01

    The full exploitation of the physics potential of an International Linear Collider (ILC) requires the development of a polarized positron beam. New concepts of polarized positron sources are based on the development of circularly polarized photon sources. The polarized photons create electron-positron pairs in a thin target and transfer their polarization state to the outgoing leptons. To achieve a high level of positron polarization the understanding of the production mechanisms in the target is crucial. Therefore, a general framework for the simulation of polarized processes with GEANT4 is under development. In this contribution the current status of the project and its application to a study of the positron production process for the ILC is presented.

  14. An FEL design for gamma-gamma colliders based on chirped pulse amplification techniques

    SciTech Connect

    Kim, K.J.; Xie, M.; Sessler, A.M.

    1995-12-31

    A next generation e{sup +}-e{sup -} linear collider in the TeV range can be converted into a {gamma}-{gamma} collider by converting it to e{sup -}-e{sup -} operation and then generating {gamma}-rays via Compton backscattering with optical beams. This provides unique access to some areas of fundamental physics as well as highly desirable redundancy to the collisions. The required optical beam (with a wavelength of about 1 micron) must have very high peak power, (about 1 TW) as well as average power (about 10 kW). To achieve a 1 : 1 conversion from an electron to {gamma}-quantum, each micropulse must contain about one Joule and must be about one picosecond long, the micropulse peak power being about one Terawatt. To match the electron beam pulse structure, a macropulse consists of a sequence of about one hundred micropulses separated by about one nanosecond, and the macropulses am repeated at a rate of about 100 Hz. Thus, the time average power is about 10 kW propose and analyze a promising scheme to produce the required optical beam based on the chirped pulse amplification technique. In this scheme, a low power optical beam of the same time structure required for the {gamma}-{gamma} collider is passed through a grating pair to stretch and chirp the picosecond micropulses to about one nanosecond, so that each macropulse will be an almost continuous, 100 nanosecond long pulse, but with chirps (from red to blue) within each nanosecond. The optical beam is then amplified in an FEL, driven by an intense electron beam from an induction linac. The amplified beam is then passed through another grating pair to compress the micropulses, thus recovering the original time structure, but containing about one Joule per micropulse. The requirements for electron beams, about 100 MeV energy, 1 kA current, 50 mm-mrad rms emittance, 10{sup -3} energy spread, are consistent with the state-of-the-art induction linac technology.

  15. AAV-Based RNAi Silencing of NADPH Oxidase gp91phox Attenuates Cold-Induced Cardiovascular Dysfunction

    PubMed Central

    Wang, Xiuqing; Skelley, Lucille; Wang, Bo; Mejia, Ayesha; Sapozhnikov, Val

    2012-01-01

    Abstract Clinical observations and epidemiological surveys indicated that the prevalence of hypertension and heart diseases is increased in cold regions or during winter. Cold exposure increased NADPH oxidase gp91phox protein expression in heart, kidneys, and aorta in rats. The aim of this study was to investigate if RNA interference (RNAi) silencing of gp91phox would attenuate cold-induced hypertension and cardiovascular and renal damage. The recombinant adeno-associated virus serotype 2 (AAV-2) vector carrying gp91phox-shRNA (gp91-shRNA) was constructed for inhibiting gp91phox protein expression in cold-exposed rats. Blood pressure (BP) was monitored using a telemetry system. BP was increased in the Control-shRNA and PBS groups within 1 week of exposure to moderate cold (5°C) and reached a plateau after 7 weeks. The cold-induced increase in BP was attenuated significantly by intravenous delivery of gp91-shRNA (1.25×1010 particles/rat, 0.5 mL). One single dose of gp91-shRNA controlled hypertension for up to 10 weeks. In addition, gp91-shRNA reversed cold-induced vascular dysfunction. gp91-shRNA abolished the cold-induced up-regulation of gp91phox protein expression in heart, kidneys, and aorta, confirming effective silencing of gp91phox. The cold-induced increases in NADPH oxidase activity and superoxide production were eliminated by silencing of gp91phox, suggesting that the cold-induced up-regulation of NADPH oxidase activity may be attributed to the increased gp91phox protein expression. RNAi silencing of gp91phox abolished cold-induced cardiac and renal hypertrophy and attenuated aortic, coronary, and renal remodeling. The up-regulation of gp91phox may play a critical role in cold-induced cardiovascular dysfunction and organ damage. AAV delivery of gp91-shRNA may be a new and effective therapeutic approach for cold-related cardiovascular disorders. PMID:22888847

  16. Ion colliders

    SciTech Connect

    Fischer, W.

    2011-12-01

    Ion colliders are research tools for high-energy nuclear physics, and are used to test the theory of Quantum Chromo Dynamics (QCD). The collisions of fully stripped high-energy ions create matter of a temperature and density that existed only microseconds after the Big Bang. Ion colliders can reach higher densities and temperatures than fixed target experiments although at a much lower luminosity. The first ion collider was the CERN Intersecting Storage Ring (ISR), which collided light ions [77Asb1, 81Bou1]. The BNL Relativistic Heavy Ion Collider (RHIC) is in operation since 2000 and has collided a number of species at numerous energies. The CERN Large Hadron Collider (LHC) started the heavy ion program in 2010. Table 1 shows all previous and the currently planned running modes for ISR, RHIC, and LHC. All three machines also collide protons, which are spin-polarized in RHIC. Ion colliders differ from proton or antiproton colliders in a number of ways: the preparation of the ions in the source and the pre-injector chain is limited by other effects than for protons; frequent changes in the collision energy and particle species, including asymmetric species, are typical; and the interaction of ions with each other and accelerator components is different from protons, which has implications for collision products, collimation, the beam dump, and intercepting instrumentation devices such a profile monitors. In the preparation for the collider use the charge state Z of the ions is successively increased to minimize the effects of space charge, intrabeam scattering (IBS), charge change effects (electron capture and stripping), and ion-impact desorption after beam loss. Low charge states reduce space charge, intrabeam scattering, and electron capture effects. High charge states reduce electron stripping, and make bending and acceleration more effective. Electron stripping at higher energies is generally more efficient. Table 2 shows the charge states and energies in the

  17. Pharmacophore refinement of gpIIb/IIIa antagonists based on comparative studies of antiadhesive cyclic and acyclic RGD peptides

    NASA Astrophysics Data System (ADS)

    Müller, Gerhard; Gurrath, Marion; Kessler, Horst

    1994-12-01

    Structurally guided design approaches to low-molecular-weight platelet aggregation antagonists addressing the platelet-associated heterodimeric cell surface receptor gpIIb/IIIa rely on comparative studies of an ensemble of conformationally and biologically characterized compounds, since no high-resolution structure of the receptor system is available. We report a classical indirect and comparative pharmacophore refinement approach based on a series of small cyclic Arg-Gly-Asp (RGD) peptides as gpIIb/IIIa-fibrinogen interaction antagonists. These peptides have previously been investigated as potent and selective tumor cell adhesion inhibitors. The definition of geometrical descriptors classifying the RGD peptide conformations and their subsequent analysis over selected RGD- and RXD-containing protein structures allows for a correlation of distinct structural features for platelet aggregation inhibition. An almost parallel alignment of the Arg and Asp side chains was identified by a vector analysis as being present in all active cyclic hexa-and pentapeptides. This orientation is induced mainly by the constraint of backbone cyclization and is not of any covalent tripeptide-inherent origin, which was rationalized by a 500 ps high-energy MD simulation of a sequentially related linear model peptide. The incorporation of the recognition tripeptide Arg-Gly-Asp into the cyclic peptide templates acted as a filter mechanism, restricting the otherwise free torsional relation of both side chains to a parallel orientation. Based on the derived results, several detailed features of the receptor binding site could be deduced in terms of receptor complementarity. These findings should govern the design of next-generation compounds with enhanced activities. Furthermore, the complementary stereochemical characteristics of the substrate can be used as boundary conditions for pseudoreceptor modelling studies that are capable of reconstructing a hypothetical binding pocket

  18. In silico vaccine design based on molecular simulations of rhinovirus chimeras presenting HIV-1 gp41 epitopes.

    PubMed

    Lapelosa, Mauro; Gallicchio, Emilio; Arnold, Gail Ferstandig; Arnold, Eddy; Levy, Ronald M

    2009-01-16

    A cluster of promising epitopes for the development of human immunodeficiency virus (HIV) vaccines is located in the membrane-proximal external region (MPER) of the gp41 subunit of the HIV envelope spike structure. The crystal structure of the peptide corresponding to the so-called ELDKWA epitope (HIV-1 HxB2 gp41 residues 662-668), in complex with the corresponding broadly neutralizing human monoclonal antibody 2F5, provides a target for structure-based vaccine design strategies aimed at finding macromolecular carriers that are able to present this MPER-derived epitope with optimal antigenic activity. To this end, a series of replica exchange molecular dynamics computer simulations was conducted to characterize the distributions of conformations of ELDKWA-based epitopes inserted into a rhinovirus carrier and to identify those with the highest fraction of conformations that are able to bind 2F5. The length, hydrophobic character, and precise site of insertion were found to be critical for achieving structural similarity to the target crystal structure. A construct with a high degree of complementarity to the corresponding determinant region of 2F5 was obtained. This construct was employed to build a high-resolution structural model of the complex between the 2F5 antibody and the chimeric human rhinovirus type 14:HIV-1 ELDKWA virus particle. Additional simulations, which were conducted to study the conformational propensities of the ELDKWA region in solution, confirm the hypothesis that the ELDKWA region of gp41 is highly flexible and capable of assuming helical conformations (as in the postfusion helical bundle structure) and beta-turn conformations (as in the complex with the 2F5 antibody). These results also suggest that the ELDKWA epitope can be involved in intramolecular--and likely intermolecular--hydrophobic interactions. This tendency offers an explanation for the observation that mutations decreasing the hydrophobic character of the MPER in many cases result

  19. Towards future circular colliders

    NASA Astrophysics Data System (ADS)

    Benedikt, Michael; Zimmermann, Frank

    2016-09-01

    The Large Hadron Collider (LHC) at the European Organization for Nuclear Research (CERN) presently provides proton-proton collisions at a center-of-mass (c.m.) energy of 13 TeV. The LHC design was started more than 30 years ago, and its physics program will extend through the second half of the 2030's. The global Future Circular Collider (FCC) study is now preparing for a post-LHC project. The FCC study focuses on the design of a 100-TeV hadron collider (FCC-hh) in a new ˜100 km tunnel. It also includes the design of a high-luminosity electron-positron collider (FCCee) as a potential intermediate step, and a lepton-hadron collider option (FCC-he). The scope of the FCC study comprises accelerators, technology, infrastructure, detectors, physics, concepts for worldwide data services, international governance models, and implementation scenarios. Among the FCC core technologies figure 16-T dipole magnets, based on Nb3 S n superconductor, for the FCC-hh hadron collider, and a highly-efficient superconducting radiofrequency system for the FCC-ee lepton collider. Following the FCC concept, the Institute of High Energy Physics (IHEP) in Beijing has initiated a parallel design study for an e + e - Higgs factory in China (CEPC), which is to be succeeded by a high-energy hadron collider (SPPC). At present a tunnel circumference of 54 km and a hadron collider c.m. energy of about 70 TeV are being considered. After a brief look at the LHC, this article reports the motivation and the present status of the FCC study, some of the primary design challenges and R&D subjects, as well as the emerging global collaboration.

  20. Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

    PubMed Central

    Joseph, Joan; Fernández-Lloris, Raquel; Pezzat, Elías; Saubi, Narcís; Cardona, Pere-Joan; Mothe, Beatriz; Gatell, Josep Maria

    2010-01-01

    Mycobacterium bovis Bacillus Calmette-Guérin (BCG) as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261) and Mycobacteria spp. α-antigen promoter (in plasmid pJH222). Among 14 rBCG:HIV-1gp120 (pMV261) colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222) colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors. PMID:20617151

  1. Kunjin virus replicon-based vaccines expressing Ebola virus glycoprotein GP protect the guinea pig against lethal Ebola virus infection.

    PubMed

    Reynard, O; Mokhonov, V; Mokhonova, E; Leung, J; Page, A; Mateo, M; Pyankova, O; Georges-Courbot, M C; Raoul, H; Khromykh, A A; Volchkov, V E

    2011-11-01

    Pre- or postexposure treatments against the filoviral hemorrhagic fevers are currently not available for human use. We evaluated, in a guinea pig model, the immunogenic potential of Kunjin virus (KUN)-derived replicons as a vaccine candidate against Ebola virus (EBOV). Virus like particles (VLPs) containing KUN replicons expressing EBOV wild-type glycoprotein GP, membrane anchor-truncated GP (GP/Ctr), and mutated GP (D637L) with enhanced shedding capacity were generated and assayed for their protective efficacy. Immunization with KUN VLPs expressing full-length wild-type and D637L-mutated GPs but not membrane anchor-truncated GP induced dose-dependent protection against a challenge of a lethal dose of recombinant guinea pig-adapted EBOV. The surviving animals showed complete clearance of the virus. Our results demonstrate the potential for KUN replicon vectors as vaccine candidates against EBOV infection.

  2. In silico Analysis of HIV-1 Env-gp120 Reveals Structural Bases for Viral Adaptation in Growth-Restrictive Cells

    PubMed Central

    Yokoyama, Masaru; Nomaguchi, Masako; Doi, Naoya; Kanda, Tadahito; Adachi, Akio; Sato, Hironori

    2016-01-01

    Variable V1/V2 and V3 loops on human immunodeficiency virus type 1 (HIV-1) envelope-gp120 core play key roles in modulating viral competence to recognize two infection receptors, CD4 and chemokine-receptors. However, molecular bases for the modulation largely remain unclear. To address these issues, we constructed structural models for a full-length gp120 in CD4-free and -bound states. The models showed topologies of gp120 surface loop that agree with those in reported structural data. Molecular dynamics simulation showed that in the unliganded state, V1/V2 loop settled into a thermodynamically stable arrangement near V3 loop for conformational masking of V3 tip, a potent neutralization epitope. In the CD4-bound state, however, V1/V2 loop was rearranged near the bound CD4 to support CD4 binding. In parallel, cell-based adaptation in the absence of anti-viral antibody pressures led to the identification of amino acid substitutions that individually enhance viral entry and growth efficiencies in association with reduced sensitivity to CCR5 antagonist TAK-779. Notably, all these substitutions were positioned on the receptors binding surfaces in V1/V2 or V3 loop. In silico structural studies predicted some physical changes of gp120 by substitutions with alterations in viral replication phenotypes. These data suggest that V1/V2 loop is critical for creating a gp120 structure that masks co-receptor binding site compatible with maintenance of viral infectivity, and for tuning a functional balance of gp120 between immune escape ability and infectivity to optimize HIV-1 replication fitness. PMID:26903989

  3. Photon collider at TESLA

    NASA Astrophysics Data System (ADS)

    Telnov, Valery

    2001-10-01

    High energy photon colliders ( γγ, γe) based on backward Compton scattering of laser light is a very natural addition to e +e - linear colliders. In this report, we consider this option for the TESLA project. Recent study has shown that the horizontal emittance in the TESLA damping ring can be further decreased by a factor of four. In this case, the γγ luminosity in the high energy part of spectrum can reach about (1/3) Le +e -. Typical cross-sections of interesting processes in γγ collisions are higher than those in e +e - collisions by about one order of magnitude, so the number of events in γγ collisions will be more than that in e +e - collisions. Photon colliders can, certainly, give additional information and they are the best for the study of many phenomena. The main question is now the technical feasibility. The key new element in photon colliders is a very powerful laser system. An external optical cavity is a promising approach for the TESLA project. A free electron laser is another option. However, a more straightforward solution is "an optical storage ring (optical trap)" with a diode pumped solid state laser injector which is today technically feasible. This paper briefly reviews the status of a photon collider based on the linear collider TESLA, its possible parameters and existing problems.

  4. FEL-based coherent electron cooling for high-energy hadron colliders

    SciTech Connect

    Litvinenko,V.N.; Derbenev, Y.S.

    2008-06-23

    Cooling intense high-energy hadron beams is a major challenge in modern accelerator physics. Synchrotron radiation is too feeble and two common methods--stochastic and electron cooling--are not efficient in providing significant cooling for high energy, high intensity proton colliders. In this paper they discuss a practical scheme of Coherent Electron Cooling (CeC), which promises short cooling times (below one hour) for intense proton beams in RHIC at 250 GeV or in LHC at 7 TeV. A possibility of CeC using various microwave instabilities was discussed since 1980s. In this paper, they present first evaluation of specific CeC scheme based on capabilities of present-day accelerator technology, ERLs, and high-gain Free-Electron lasers (FELs). They discuss the principles, the main limitations of this scheme and present some predictions for Coherent Electron Cooling in RHIC and the LHC operating with ions or protons, summarized in Table 1.

  5. HIGGS PHYSICS WITH A GAMMA GAMMA COLLIDER BASED ON CLIC 1*.

    SciTech Connect

    ASNER,D.; BURKHARDT,H.; DE ROECK,A.; ELLIS,J.; GRONBERG,J.; HEINEMEYER,S.; SCHMITT,M.; SCHULTE,D.; VELASCO,M.; ZIMMERMAN,F.

    2001-11-01

    We present the machine parameters and physics capabilities of the CLIC Higgs Experiment (CLICHE), a low-energy {gamma}{gamma} collider based on CLIC 1, the demonstration project for the higher-energy two-beam accelerator CLIC. CLICHE is conceived as a factory capable of producing around 20,000 light Higgs bosons per year. We discuss the requirements for the CLIC 1 beams and a laser backscattering system capable of producing a {gamma}{gamma} total (peak) luminosity of 2.0 (0.36) x 10{sup 34} cm{sup -2} s{sup -1} with E{sub CM}({gamma}{gamma}) 115 GeV. We show how CLICHE could be used to measure accurately the mass, {bar b}b, WW and {gamma}{gamma} decays of a light Higgs boson. We illustrate how these measurements may distinguish between the Standard Model Higgs boson and those in supersymmetric and more general two-Higgs-doublet models, complementing the measurements to be made with other accelerators. We also comment on other prospects in {gamma}{gamma} and e{sup -}{gamma} physics with CLICHE.

  6. Future colliders

    SciTech Connect

    Palmer, R.B.; Gallardo, J.C.

    1996-10-01

    The high energy physics advantages, disadvantages and luminosity requirements of hadron (pp, pp), of lepton (e{sup +}e{sup {minus}}, {mu}{sup +} {mu}{sup {minus}}) and photon-photon colliders are considered. Technical arguments for increased energy in each type of machine are presented. Their relative size, and the implications of size on cost are discussed.

  7. Projects of Nuclotron modernization and Nuclotron-based ion collider facility (NICA) at JINR

    SciTech Connect

    Lednicky, R.

    2008-09-15

    One of the basic facilities at the Joint Institute for Nuclear Research (JINR) in Dubna is the 6 A GeV Nuclotron, which has replaced the old weak focusing 10-GeV proton accelerator Synchrophasotron. The first relativistic nuclear beams with the energy of 4.2 A GeV were obtained at the Synchrophasotron in 1971. Since that time, relativistic nuclear physics has been one of the main directions of the JINR research program. In the coming years, the new JINR flagship program assumes the experimental study of hot and dense strongly interacting QCD matter at the new JINR facility. This goal is proposed to be reached by (i) development of the existing Nuclotron accelerator facility as a basis for generation of intense beams over atomic mass range from protons to uranium and light polarized ions, (ii) design and construction of the Nuclotron-based heavy Ion Collider fAcility (NICA) with the maximum nucleon-nucleon center-of-mass collision energy of {radical}s{sub NN} = 9 GeV and averaged luminosity 10{sup 27} cm{sup -2} s{sup -1}, and (iii) design and construction of the Multipurpose Particle Detector (MPD) at intersecting beams. Realization of the project will lead to unique conditions for research activity of the world community. The NICA energy region is of major interest because the highest nuclear (baryonic) density under laboratory conditions can be reached there. Generation of intense polarized light nuclear beams aimed at investigation of polarization phenomena at the Nuclotron is foreseen.

  8. Employees’ views on home-based, after-hours telephone triage by Dutch GP cooperatives

    PubMed Central

    2013-01-01

    Background Dutch out-of-hours (OOH) centers find it difficult to attract sufficient triage staff. They regard home-based triage as an option that might attract employees. Specially trained nurses are supposed to conduct triage by telephone from home for after-hours medical care. The central aim of this research is to investigate the views of employees of OOH centers in The Netherlands on home-based telephone triage in after-hours care. Methods The study is a Q methodology study. Triage nurses, general practitioners (GPs) and managers of OOH centers ranked 36 opinion statements on home-based triage. We interviewed 10 participants to help develop and validate the statements for the Q sort, and 77 participants did the Q sort. Results We identified four views on home-based telephone triage. Two generally favor home-based triage, one highlights some concerns and conditions, and one opposes it out of concern for quality. The four views perceive different sources of credibility for nurse triagists working from home. Conclusion Home-based telephone triage is a controversial issue among triage nurses, GPs and managers of OOH centers. By identifying consensus and dissension among GPs, triagists, managers and regulators, this study generates four perspectives on home-based triage. In addition, it reveals the conditions considered important for home-based triage. PMID:24188407

  9. Comparison of Two Widely Used Human Papillomavirus Detection and Genotyping Methods, GP5+/6+-Based PCR Followed by Reverse Line Blot Hybridization and Multiplex Type-Specific E7-Based PCR

    PubMed Central

    Vaccarella, Salvatore; Franceschi, Silvia; Tenet, Vanessa; Umulisa, M. Chantal; Tshomo, Ugyen; Dondog, Bolormaa; Vorsters, Alex; Tommasino, Massimo; Heideman, Daniëlle A. M.; Snijders, Peter J. F.; Gheit, Tarik

    2016-01-01

    GP5+/6+-based PCR followed by reverse line blot hybridization (GP5+/6+RLB) and multiplex type-specific PCR (E7-MPG) are two human papillomavirus (HPV) genotyping methodologies widely applied in epidemiological research. We investigated their relative analytical performance in 4,662 samples derived from five studies in Bhutan, Rwanda, and Mongolia coordinated by the International Agency for Research on Cancer (IARC). A total of 630 samples were positive by E7-MPG only (13.5%), 24 were positive by GP5+/6+RLB only (0.5%), and 1,014 were positive (21.8%) by both methods. Ratios of HPV type-specific positivity of the two tests (E7-MPG:GP5+/6+RLB ratio) were calculated among 1,668 samples that were HPV positive by one or both tests. E7-MPG:GP5+/6+RLB ratios were >1 for all types and highly reproducible across populations and sample types. E7-MPG:GP5+/6+RLB ratios were highest for HPV53 (7.5) and HPV68 (7.1). HPV16 (1.6) and HPV18 (1.7) had lower than average E7-MPG:GP5+/6+RLB ratios. Among E7-MPG positive infections, median mean fluorescence intensity (MFI; a semiquantitative measure of viral load) tended to be higher among samples positive for the same virus type by GP5+/6+RLB than for those negative for the same type by GP5+/6+RLB. Exceptions, however, included HPV53, -59, and -82, for which the chances of being undetected by GP5+/6+RLB appeared to be MFI independent. Furthermore, the probability of detecting an additional type by E7-MPG was higher when another type was already detected by GP5+/6+RLB, suggesting the existence of masking effects due to competition for GP5+/6+ PCR primers. In conclusion, this analysis is not an evaluation of clinical performance but may inform choices for HPV genotyping methods in epidemiological studies, when the relative merits and dangers of sensitivity versus specificity for individual types should be considered, as well as the potential to unmask nonvaccine types following HPV vaccination. PMID:27225411

  10. Comparison of Two Widely Used Human Papillomavirus Detection and Genotyping Methods, GP5+/6+-Based PCR Followed by Reverse Line Blot Hybridization and Multiplex Type-Specific E7-Based PCR.

    PubMed

    Clifford, Gary M; Vaccarella, Salvatore; Franceschi, Silvia; Tenet, Vanessa; Umulisa, M Chantal; Tshomo, Ugyen; Dondog, Bolormaa; Vorsters, Alex; Tommasino, Massimo; Heideman, Daniëlle A M; Snijders, Peter J F; Gheit, Tarik

    2016-08-01

    GP5+/6+-based PCR followed by reverse line blot hybridization (GP5+/6+RLB) and multiplex type-specific PCR (E7-MPG) are two human papillomavirus (HPV) genotyping methodologies widely applied in epidemiological research. We investigated their relative analytical performance in 4,662 samples derived from five studies in Bhutan, Rwanda, and Mongolia coordinated by the International Agency for Research on Cancer (IARC). A total of 630 samples were positive by E7-MPG only (13.5%), 24 were positive by GP5+/6+RLB only (0.5%), and 1,014 were positive (21.8%) by both methods. Ratios of HPV type-specific positivity of the two tests (E7-MPG:GP5+/6+RLB ratio) were calculated among 1,668 samples that were HPV positive by one or both tests. E7-MPG:GP5+/6+RLB ratios were >1 for all types and highly reproducible across populations and sample types. E7-MPG:GP5+/6+RLB ratios were highest for HPV53 (7.5) and HPV68 (7.1). HPV16 (1.6) and HPV18 (1.7) had lower than average E7-MPG:GP5+/6+RLB ratios. Among E7-MPG positive infections, median mean fluorescence intensity (MFI; a semiquantitative measure of viral load) tended to be higher among samples positive for the same virus type by GP5+/6+RLB than for those negative for the same type by GP5+/6+RLB. Exceptions, however, included HPV53, -59, and -82, for which the chances of being undetected by GP5+/6+RLB appeared to be MFI independent. Furthermore, the probability of detecting an additional type by E7-MPG was higher when another type was already detected by GP5+/6+RLB, suggesting the existence of masking effects due to competition for GP5+/6+ PCR primers. In conclusion, this analysis is not an evaluation of clinical performance but may inform choices for HPV genotyping methods in epidemiological studies, when the relative merits and dangers of sensitivity versus specificity for individual types should be considered, as well as the potential to unmask nonvaccine types following HPV vaccination. Copyright © 2016, American Society for

  11. Static beam-based alignment for the Ring-To-Main-Linac of the Compact Linear Collider

    NASA Astrophysics Data System (ADS)

    Han, Y.; Latina, A.; Ma, L.; Schulte, D.

    2017-06-01

    The Compact Linear Collider (CLIC) is a future multi-TeV collider for the post-Large Hadron Collider era. It features high-gradient acceleration and ultra-low emittance to achieve its ambitious goals of high collision energy and peak luminosity. Beam-based alignment (BBA) techniques are mandatory for CLIC to preserve the ultra-low emittances from the damping rings to the interaction point. In this paper, a detailed study of BBA techniques has been carried out for the entire 27 km long ``Ring-To-Main-Linac'' (RTML) section of the CLIC, to correct realistic static errors such as element position offsets, angle, magnetic strength and dynamic magnetic centre shifts. The correction strategy is proved to be very effective and leads to a relaxation of the pre-alignment tolerances for the component installation in the tunnel. This is the first time such a large scale and complex lattice has been corrected to match the design budgets. The techniques proposed could be applied to similarly sized facilities, such as the International Linear Collider, where a similar RTML section is used, or free-electron lasers, which, being equipped with linacs and bunch compressors, present challenges similar to those of the CLIC RTML. Moreover, a new technique is investigated for the emittance tuning procedure: the direct measurement of the interactions between the beams and a set of a few consecutive laser wires. The speed of this technique can be faster comparing to the traditional techniques based on emittance reconstructed from beam size measurements at several positions.

  12. Student perceptions of GP teachers' role in community-based undergraduate surgical education: a qualitative study.

    PubMed

    Powell, Sian; Easton, Graham

    2012-08-01

    To evaluate medical students' perceptions of a new community-based surgical module being delivered as part of a third-year clinical methods teaching (CMT) course at Imperial College, London. A qualitative study using focus group interviews with medical students who had recently completed the surgical module. Focus group discussions were recorded, transcribed and analysed to identify key categories that reflected the positive and negative aspects of the student's perspectives. Imperial College, London Two groups of fourth-year medical students were invited to participate in the focus groups. The first group consisted of seven students from the surgery and Anaesthesia BSc course. The second group consisted of a random sample of five students from other BSc courses at Imperial College. These were not defined pre-study as the purpose of the study was to obtain student perceptions of the surgical module. Facilitators were given guide questions to aid consistency and prompted discussion where required using an inductive approach to the topics discussed by the students. Student opinions of surgical teaching delivered in the community compared favourably with the surgical teaching delivered in hospitals. Students identified the key benefits as: having protected time to learn, regular access to suitable patients, and teaching that was more learner-centred. Challenges identified by students included the GPs' lack of specialist knowledge and teaching that was dictated by individual interests rather than the syllabus. Community-based teaching has been widely used to deliver teaching traditionally taught in hospital settings. However, surgical skills are still taught largely by surgical specialists within hospitals. Our study suggests that students are receptive to GPs teaching surgical topics in the community and perceive GPs as competent teachers. This study suggests that there may be benefits in delivering traditional surgical modules in community settings. Providing

  13. Scintillator Based Tracking Detectors for a Muon System at Future Colliders

    NASA Astrophysics Data System (ADS)

    Denisov, Dmitri; Evdokimov, Valery; Lukic, Strahinja; Ujic, Predrag

    2017-01-01

    Extruded scintilator +WLS strips with SiPM readout for large muon detection systems were tested in the muon beam of the Fermilab Test Beam Facility. Light yield of up to 140 photoelectrons per muon per strip has been observed, as well as time resolution of 330 ps and position resolution along the strip of 5.4 cm. With such excellent performance parameters this detector is natural option for large scale future colliders muon systems.

  14. Final Report for the UNIVERSITY-BASED DETECTOR RESEARCH AND DEVELOPMENT FOR THE INTERNATIONAL LINEAR COLLIDER

    SciTech Connect

    Brau, James E

    2013-04-22

    The U.S Linear Collider Detector R&D program, supported by the DOE and NSF umbrella grants to the University of Oregon, made significant advances on many critical aspects of the ILC detector program. Progress advanced on vertex detector sensor development, silicon and TPC tracking, calorimetry on candidate technologies, and muon detection, as well as on beamline measurements of luminosity, energy, and polarization.

  15. Sublingual Priming with a HIV gp41-Based Subunit Vaccine Elicits Mucosal Antibodies and Persistent B Memory Responses in Non-Human Primates

    PubMed Central

    Bekri, Selma; Bourdely, Pierre; Luci, Carmelo; Dereuddre-Bosquet, Nathalie; Su, Bin; Martinon, Frédéric; Braud, Véronique M.; Luque, Irene; Mateo, Pedro L.; Crespillo, Sara; Conejero-Lara, Francisco; Moog, Christiane; Le Grand, Roger; Anjuère, Fabienne

    2017-01-01

    Persistent B cell responses in mucosal tissues are crucial to control infection against sexually transmitted pathogens like human immunodeficiency virus 1 (HIV-1). The genital tract is a major site of infection by HIV. Sublingual (SL) immunization in mice was previously shown to generate HIV-specific B cell immunity that disseminates to the genital tract. We report here the immunogenicity in female cynomolgus macaques of a SL vaccine based on a modified gp41 polypeptide coupled to the cholera toxin B subunit designed to expose hidden epitopes and to improve mucosal retention. Combined SL/intramuscular (IM) immunization with such mucoadhesive gp41-based vaccine elicited mucosal HIV-specific IgG and IgA antibodies more efficiently than IM immunization alone. This strategy increased the number and duration of gp41-specific IgA secreting cells. Importantly, combined immunization improved the generation of functional antibodies 3 months after vaccination as detected in HIV-neutralizing assays. Therefore, SL immunization represents a promising vaccine strategy to block HIV-1 transmission. PMID:28203239

  16. Sublingual Priming with a HIV gp41-Based Subunit Vaccine Elicits Mucosal Antibodies and Persistent B Memory Responses in Non-Human Primates.

    PubMed

    Bekri, Selma; Bourdely, Pierre; Luci, Carmelo; Dereuddre-Bosquet, Nathalie; Su, Bin; Martinon, Frédéric; Braud, Véronique M; Luque, Irene; Mateo, Pedro L; Crespillo, Sara; Conejero-Lara, Francisco; Moog, Christiane; Le Grand, Roger; Anjuère, Fabienne

    2017-01-01

    Persistent B cell responses in mucosal tissues are crucial to control infection against sexually transmitted pathogens like human immunodeficiency virus 1 (HIV-1). The genital tract is a major site of infection by HIV. Sublingual (SL) immunization in mice was previously shown to generate HIV-specific B cell immunity that disseminates to the genital tract. We report here the immunogenicity in female cynomolgus macaques of a SL vaccine based on a modified gp41 polypeptide coupled to the cholera toxin B subunit designed to expose hidden epitopes and to improve mucosal retention. Combined SL/intramuscular (IM) immunization with such mucoadhesive gp41-based vaccine elicited mucosal HIV-specific IgG and IgA antibodies more efficiently than IM immunization alone. This strategy increased the number and duration of gp41-specific IgA secreting cells. Importantly, combined immunization improved the generation of functional antibodies 3 months after vaccination as detected in HIV-neutralizing assays. Therefore, SL immunization represents a promising vaccine strategy to block HIV-1 transmission.

  17. Characterization of gp70 and Anti-gp70 Monoclonal Antibodies in Paracoccidioides brasiliensis Pathogenesis

    PubMed Central

    de Mattos Grosso, Daniela; de Almeida, Sandro Rogério; Mariano, Mario; Lopes, Jose Daniel

    2003-01-01

    Paracoccidioidomycosis (PCM) is a systemic granulomatous mycosis whose agent is Paracoccidioides brasiliensis. In the culture supernatant, the fungus expresses glycoproteins of from 13 to 148 kDa. A cell surface glycoprotein of 43 kDa is the major antigenic component of P. brasiliensis. Another expressed glycoprotein, gp70, is recognized by 96% of sera from PCM patients and is able to induce lymphoproliferation. Since, little is known about this glycoprotein, we produced monoclonal antibodies (MAbs) against gp70 to isolate the molecule from total fungus extracts and to investigate its possible role in the pathogenesis of PCM. Using these MAbs, it was observed by confocal microscopy that gp70 is located mainly in the intracellular compartment of the fungus, although it was also detected in the culture supernatant. Based on observations showing that gp43 has a down-regulatory effect on mouse peritoneal macrophages, we tested the effects of gp70 on their phagocytic ability. Purified gp70 was able to inhibit the activity of macrophages through the mannose receptors and also through the Fc receptors; the latter effect was not observed with gp43. gp70 inhibits NO and H2O2 liberation by peritoneal macrophages in vitro, as does gp43. Results obtained with gp43 led us to hypothesize that gp70 could act as an escape mechanism for fungal establishment in primary infections. To corroborate this hypothesis, we analyzed the effect of passive immunization of mice during infection with P. brasiliensis using anti-gp70 MAbs. This treatment almost completely abolished granuloma formation in the lungs, suggesting that the protein facilitates fungal establishment and progression of lesions in primary infection. PMID:14573675

  18. Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans

    PubMed Central

    Julien, Jean-Philippe; Sok, Devin; Khayat, Reza; Lee, Jeong Hyun; Doores, Katie J.; Walker, Laura M.; Ramos, Alejandra; Diwanji, Devan C.; Pejchal, Robert; Cupo, Albert; Katpally, Umesh; Depetris, Rafael S.; Stanfield, Robyn L.; McBride, Ryan; Marozsan, Andre J.; Paulson, James C.; Sanders, Rogier W.; Moore, John P.; Burton, Dennis R.; Poignard, Pascal; Ward, Andrew B.; Wilson, Ian A.

    2013-01-01

    New broad and potent neutralizing HIV-1 antibodies have recently been described that are largely dependent on the gp120 N332 glycan for Env recognition. Members of the PGT121 family of antibodies, isolated from an African donor, neutralize ∼70% of circulating isolates with a median IC50 less than 0.05 µg ml−1. Here, we show that three family members, PGT121, PGT122 and PGT123, have very similar crystal structures. A long 24-residue HCDR3 divides the antibody binding site into two functional surfaces, consisting of an open face, formed by the heavy chain CDRs, and an elongated face, formed by LCDR1, LCDR3 and the tip of the HCDR3. Alanine scanning mutagenesis of the antibody paratope reveals a crucial role in neutralization for residues on the elongated face, whereas the open face, which accommodates a complex biantennary glycan in the PGT121 structure, appears to play a more secondary role. Negative-stain EM reconstructions of an engineered recombinant Env gp140 trimer (SOSIP.664) reveal that PGT122 interacts with the gp120 outer domain at a more vertical angle with respect to the top surface of the spike than the previously characterized antibody PGT128, which is also dependent on the N332 glycan. We then used ITC and FACS to demonstrate that the PGT121 antibodies inhibit CD4 binding to gp120 despite the epitope being distal from the CD4 binding site. Together, these structural, functional and biophysical results suggest that the PGT121 antibodies may interfere with Env receptor engagement by an allosteric mechanism in which key structural elements, such as the V3 base, the N332 oligomannose glycan and surrounding glycans, including a putative V1/V2 complex biantennary glycan, are conformationally constrained. PMID:23658524

  19. Preservation of Ultra Low Emittances Using Adiabatic Matching in Future Plasma Wakefield-based Colliders

    SciTech Connect

    Gholizadeh, Reza; Muggli, Patric; Katsouleas, Tom; Mori, Warren

    2009-01-22

    The Plasma Wakefield Accelerator is a promising technique to lower the cost of the future high energy colliders by offering orders of magnitude higher gradients than the conventional accelerators. It has been shown that ion motion is an important issue to account for in the extreme regime of ultra high energies and ultra low emittances, characteristics of future high energy collider beams. In this regime, the transverse electric field of the beam is so high that in simulations, the plasma ions cannot be considered immobile at the time scale of electron plasma oscillation, thereby leading to a nonlinear focusing force. Therefore, the transverse emittance of a beam will not be preserved under these circumstances. However, we show that matched profile in case of a nonlinear focusing force still exists and can be derived from Vlasov equation. Furthermore, we introduce a plasma section that can reduce the emittance growth by adiabatically reducing the ion mass and hence increasing the nonlinear term in the focusing force. Simulation results are presented.

  20. RF system for a 30 GHz, 5 TeV linear collider based on conventional technology

    SciTech Connect

    Wilson, P.B.; Raubenheimer, T.; Ruth, R.D.

    1997-07-01

    In order that it may be built within a reasonable length and with reasonable ac power consumption, a 5 TeV linear collider must employ an accelerating gradient and rf frequency which are both higher than for present 1 TeV collider designs. The required rf power per meter, which will also be higher than for 1 TeV designs, can be provided either by relatively conventional rf technology or by a two-beam scheme such as that proposed for CLIC. In this paper the first alternative, a 30 GHz rf system employing microwave tube power sources together with rf pulse compression, is described which produces an accelerating gradient on the order of 200 MV per meter. Limitations on the peak power that can be obtained from conventional klystrons as a function of frequency are discussed; it is found that such klystrons are only marginally adequate as a power source at 30 GHz. Several alternative rf sources, such as multiple-beam klystrons, sheet-beam klystrons, gyroklystrons and annular-beam ubitrons are described which are capable of providing the required power, after pulse compression, of about 600 MW per meter.

  1. Half-day release in vocational GP training: a case study of redesign based on qualitative evaluation.

    PubMed

    Rigby, Carolyn

    2010-11-01

    Mindful of the changes to general practice (GP) and GP training over recent years, one vocational training scheme (VTS) decided to thoroughly evaluate its long-running half-day release scheme to decide if it remained fit for purpose, and to plan and implement changes in the light of findings. A literature review was first carried out to ascertain what is known about the contribution that day release and half-day release (HDR) programmes make to GP training. Little has been published on content or evaluation but there is varied experience of incorporating release training into hospital training. This case study reports the views of trainers and trainees on the HDR at Tees Valley Vocational Training Scheme, and the resultant changes made to this HDR programme by the participants. Trainers mostly valued their commitment to HDR small group teaching for their personal development as teachers and for the opportunity to 'keep in touch' with trainees during their hospital posts. Trainees were positive about the HDR programme, but requested more continuity. The plan that evolved is to continue weekly HDR throughout the training programme, keeping trainees in the same small group for three years. In ST1 and ST3 years one programme director per group facilitates each session, maintaining consistency over the year, and liaising with specialists around content. Trainers each teach two sessions in ST2 year. Elective sessions are planned for extended training.

  2. Cystein 402 of HIV gp 120 is essential for CD4-binding and resistance of gp 120 to intracellular degradation.

    PubMed

    Hemming, A; Bolmstedt, A; Flodby, P; Lundberg, L; Gidlund, M; Wigzell, H; Olofsson, S

    1989-01-01

    A DNA fragment encoding the CD4-binding region of human immunodeficiency virus type 1 (HIV) gp 120 was excised from an SV40-based expression vector containing gp 160, and subcloned into phage M13 for site-directed mutagenesis. Mutant vectors were constructed and CV-1 cells were transfected with constructs, where Cys402 was substituted for a serine, and metabolically labelled with [3H]-N-acetylglucosamine (GlcN). Radioimmunoprecipitation with an hyperimmunserum, specific for gp 120/gp 160, and subsequent SDS-polyacrylamide gel electrophoresis demonstrated presence of gp 160, whereas gp 120 was replaced by [3H]-GlcN-labelled material, migrating as a diffuse band corresponding to 80-105k, suggesting increased sensitivity of mutant env gene products to proteolysis after cleavage to gp 120. Wild type gp 120 and gp 160 bound to CD4, whereas neither gp 160 nor gp 120 from mutant-transfected cell lysates did bind to CD4. Altogether the results indicated that Cys402, probably by participating in a disulfide bridge, is essential for (i) the CD4-binding ability of env gene products and for (ii) the physical stability of gp 120.

  3. An injection system for PEP-based asymmetric storage ring collider for the copious production of B mesons

    SciTech Connect

    Barletta, W.A.

    1989-09-18

    The proposed asymmetric energy B-factory utilizing PEP will require high energy, low emittance sources of positrons and electrons suitable for filling the storage rings. Proposed characteristics of this collider operating at a luminosity of 10{sup 34} cm{sup -2}s{sup -1} have been studied by LBL (Apiary-III). The design consists of two rings, a large 9 GeV ring (PEP or a modification thereof) plus a smaller 3.1 GeV ring, each with a circulating current of 3 Amperes. Ideally the fill time should be much shorter than the luminosity life-time of the rings (set by the size of the low energy ring). As the luminosity lifetime of the collider is not expected to be very high, the PEP-based B-factory should have a powerful, dedicated injector. For the purpose of estimating the characteristics of the injection system the maximum time for a complete fill of the positron ring is taken to be {approx}100 seconds. The design of the injection system is discussed in this paper. 1 ref., 9 figs., 4 tabs.

  4. Clinical evaluation of a GP5+/6+-based luminex assay having full high-risk human papillomavirus genotyping capability and an internal control.

    PubMed

    Geraets, D T; Cuschieri, K; de Koning, M N C; van Doorn, L J; Snijders, P J F; Meijer, C J L M; Quint, W G V; Arbyn, M

    2014-11-01

    The LMNX genotyping kit HPV GP (LMNX) is based on the clinically validated GP5+/6+ PCR, with a genotyping readout as an alternative for the more established enzyme immunoassay (EIA) detection of 14 targeted high-risk human papillomavirus (HPV) types. LMNX is additionally provided with an internal control probe. Here, we present an analysis of the clinical performance of the LMNX using a sample panel and infrastructure provided by the international VALGENT (Validation of Genotyping Tests) project. This panel consisted of cervical specimens from approximately 1,000 women attending routine screening, "enriched" with 300 women with abnormal cytology. Cases were defined as women classified with cervical intraepithelial neoplasia (CIN) grade 2+ (CIN2+) (n = 102) or CIN3+ (n = 55) within the previous 18 months. Controls were women who had normal cytology results over two subsequent screening rounds at a 3-year interval (n = 746). The GP5+/6+-PCR EIA (EIA) was used as a comparator assay and showed sensitivities of 94.1% and 98.2% for CIN2+ and CIN3+, respectively, with a clinical specificity of 92.4% among women aged ≥ 30 years. The LMNX demonstrated clinical sensitivities of 96.1% for CIN2+ and of 98.2% for CIN3+ and a clinical specificity of 92.6% for women aged ≥ 30 years. The LMNX and EIA were in high agreement (Cohen's kappa = 0.969) for the detection of 14 hrHPVs in aggregate, and no significant difference was observed (McNemar's P = 0.629). The LMNX internal control detected 0.6% inadequate specimens. Based on our study results, we consider the LMNX, similarly to the EIA, useful for HPV-based cervical cancer screening.

  5. Clinical Evaluation of a GP5+/6+-Based Luminex Assay Having Full High-Risk Human Papillomavirus Genotyping Capability and an Internal Control

    PubMed Central

    Cuschieri, K.; de Koning, M. N. C.; van Doorn, L. J.; Snijders, P. J. F.; Meijer, C. J. L. M.; Quint, W. G. V.; Arbyn, M.

    2014-01-01

    The LMNX genotyping kit HPV GP (LMNX) is based on the clinically validated GP5+/6+ PCR, with a genotyping readout as an alternative for the more established enzyme immunoassay (EIA) detection of 14 targeted high-risk human papillomavirus (HPV) types. LMNX is additionally provided with an internal control probe. Here, we present an analysis of the clinical performance of the LMNX using a sample panel and infrastructure provided by the international VALGENT (Validation of Genotyping Tests) project. This panel consisted of cervical specimens from approximately 1,000 women attending routine screening, “enriched” with 300 women with abnormal cytology. Cases were defined as women classified with cervical intraepithelial neoplasia (CIN) grade 2+ (CIN2+) (n = 102) or CIN3+ (n = 55) within the previous 18 months. Controls were women who had normal cytology results over two subsequent screening rounds at a 3-year interval (n = 746). The GP5+/6+-PCR EIA (EIA) was used as a comparator assay and showed sensitivities of 94.1% and 98.2% for CIN2+ and CIN3+, respectively, with a clinical specificity of 92.4% among women aged ≥30 years. The LMNX demonstrated clinical sensitivities of 96.1% for CIN2+ and of 98.2% for CIN3+ and a clinical specificity of 92.6% for women aged ≥30 years. The LMNX and EIA were in high agreement (Cohen's kappa = 0.969) for the detection of 14 hrHPVs in aggregate, and no significant difference was observed (McNemar's P = 0.629). The LMNX internal control detected 0.6% inadequate specimens. Based on our study results, we consider the LMNX, similarly to the EIA, useful for HPV-based cervical cancer screening. PMID:25210073

  6. Diagnostic value of anti-gp210 antibodies in primary biliary cirrhosis: a case-based review.

    PubMed

    Valour, Florent; Durupt, Stéphane; Khenifer, Safia; Durieu, Isabelle

    2013-06-26

    Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterised by chronic cholestasis usually associated with antimitochondrial antibodies. Moreover, several types of antinuclear antibodies have been associated with primary biliary cirrhosis. We describe an 83-year-old man, in whom the exploration of a chronic cholestasis led to the diagnosis of primary biliary cirrhosis despite negative antimitochondrial antibodies, regarding the presence of anti-gp210 antibodies. Found in 25% of patients, these antinuclear antibodies must be sought before a strong suspicion of primary biliary cirrhosis with antimitochondrial antibodies negative, as they are highly specific of the disease. They are generally associated with a more aggressive form of PBC.

  7. GP consultations for common mental disorders and subsequent sickness certification: register-based study of the employed population in Norway.

    PubMed

    Gjesdal, Sturla; Holmaas, Tor Helge; Monstad, Karin; Hetlevik, Øystein

    2016-12-01

    Challenges related to work are in focus when employed people with common mental disorders (CMDs) consult their GPs. Many become sickness certified and remain on sick leave over time. To investigate the frequency of new CMD episodes among employed patients in Norwegian general practice and subsequent sickness certification. Using a national claims register, employed persons with a new episode of CMD were included. Sickness certification, sick leave over 16 days and length of absences were identified. Patient- and GP-related predictors for the different outcomes were assessed by means of logistic regression. During 1 year 2.6% of employed men and 4.2% of employed women consulted their GP with a new episode of CMD. Forty-five percent were sickness certified, and 24 percent were absent over 16 days. Thirty-eight percent had depression and 19% acute stress reaction, which carried the highest risk for initial sickness certification, 75%, though not for prolonged absence. Men and older patients had lower risk for sickness certification, but higher risk for long-term absence. Better knowledge of factors at the workplace detrimental to mental health, and better treatment for depression and stress reactions might contribute to timely return of sickness absentees. © The Author 2016. Published by Oxford University Press.

  8. GP consultations for common mental disorders and subsequent sickness certification: register-based study of the employed population in Norway

    PubMed Central

    Gjesdal, Sturla; Holmaas, Tor Helge; Monstad, Karin; Hetlevik, Øystein

    2016-01-01

    Background. Challenges related to work are in focus when employed people with common mental disorders (CMDs) consult their GPs. Many become sickness certified and remain on sick leave over time. Objectives. To investigate the frequency of new CMD episodes among employed patients in Norwegian general practice and subsequent sickness certification. Methods. Using a national claims register, employed persons with a new episode of CMD were included. Sickness certification, sick leave over 16 days and length of absences were identified. Patient- and GP-related predictors for the different outcomes were assessed by means of logistic regression. Results. During 1 year 2.6% of employed men and 4.2% of employed women consulted their GP with a new episode of CMD. Forty-five percent were sickness certified, and 24 percent were absent over 16 days. Thirty-eight percent had depression and 19% acute stress reaction, which carried the highest risk for initial sickness certification, 75%, though not for prolonged absence. Men and older patients had lower risk for sickness certification, but higher risk for long-term absence. Conclusion. Better knowledge of factors at the workplace detrimental to mental health, and better treatment for depression and stress reactions might contribute to timely return of sickness absentees. PMID:27535329

  9. Identification of the paired basic convertases implicated in HIV gp160 processing based on in vitro assays and expression in CD4(+) cell lines.

    PubMed

    Decroly, E; Wouters, S; Di Bello, C; Lazure, C; Ruysschaert, J M; Seidah, N G

    1996-11-29

    The human immunodeficiency virus HIV envelope glycoprotein gp160 is synthesized as an inactive precursor, which is processed into its fusiogenic form gp120/gp41 by host cell proteinases during its intracellular trafficking. Kexin/subtilisin-related endoproteases have been proposed to be enzyme candidates for this maturation process. In the present study, 1) we examined the ability of partially purified precursor convertases and their isoforms to cleave gp160 in vitro. The data demonstrate that all the convertases tested specifically cleave the HIV envelope glycoprotein into gp120 and gp41. 2) We demonstrated that a 19-amino acid model peptide spanning the gp120/gp41 junction is cleaved by all convertases at the same gp160 site as that recognized in HIV-infected cells. 3) In an effort to evaluate specific convertase inhibitors, we showed that the alpha1-antitrypsin variant, alpha1-PDX, inhibits equally well the ability of the tested convertases to cleave gp160 in vitro. 4) Three lymphocyte cell lines were screened by reverse transcription polymerase chain reaction in an effort to identify which are the convertases expressed in the most common HIV target, the CD4(+) lymphocytes. The data demonstrate that furin, PC5/6, and the newly cloned PC7 are the main transcribed convertases, suggesting that these proteinases are the major gp160-converting enzymes in T4 lymphocytes.

  10. High Energy Colliders

    NASA Astrophysics Data System (ADS)

    Palmer, R. B.; Gallardo, J. C.

    INTRODUCTION PHYSICS CONSIDERATIONS GENERAL REQUIRED LUMINOSITY FOR LEPTON COLLIDERS THE EFFECTIVE PHYSICS ENERGIES OF HADRON COLLIDERS HADRON-HADRON MACHINES LUMINOSITY SIZE AND COST CIRCULAR e^{+}e^- MACHINES LUMINOSITY SIZE AND COST e^{+}e^- LINEAR COLLIDERS LUMINOSITY CONVENTIONAL RF SUPERCONDUCTING RF AT HIGHER ENERGIES γ - γ COLLIDERS μ ^{+} μ^- COLLIDERS ADVANTAGES AND DISADVANTAGES DESIGN STUDIES STATUS AND REQUIRED R AND D COMPARISION OF MACHINES CONCLUSIONS DISCUSSION

  11. (Calorimeter based detectors for high energy hadron colliders). [State Univ. of New York

    SciTech Connect

    Not Available

    1992-08-04

    This document provides a progress report on research that has been conducted under DOE Grant DEFG0292ER40697 for the past year, and describes proposed work for the second year of this 8 year grant starting November 15, 1992. Personnel supported by the contract include 4 faculty, 1 research faculty, 4 postdocs, and 9 graduate students. The work under this grant has in the past been directed in two complementary directions -- DO at Fermilab, and the second SSC detector GEM. A major effort has been towards the construction and commissioning of the new Fermilab Collider detector DO, including design, construction, testing, the commissioning of the central tracking and the central calorimeters. The first DO run is now underway, with data taking and analysis of the first events. Trigger algorithms, data acquisition, calibration of tracking and calorimetry, data scanning and analysis, and planning for future upgrades of the DO detector with the advent of the FNAL Main Injector are all involved. The other effort supported by this grant has been towards the design of GEM, a large and general-purpose SSC detector with special emphasis on accurate muon measurement over a large solid angle. This effort will culminate this year in the presentation to the SSC laboratory of the GEM Technical Design Report. Contributions are being made to the detector design, coordination, and physics simulation studies with special emphasis on muon final states. Collaboration with the RD5 group at CERN to study muon punch through and to test cathode strip chamber prototypes was begun.

  12. Does integrated training in evidence-based medicine (EBM) in the general practice (GP) specialty training improve EBM behaviour in daily clinical practice? A cluster randomised controlled trial.

    PubMed

    Kortekaas, M F; Bartelink, M E L; Zuithoff, N P A; van der Heijden, G J M G; de Wit, N J; Hoes, A W

    2016-09-13

    Evidence-based medicine (EBM) is an important element in the general practice (GP) specialty training. Studies show that integrating EBM training into clinical practice brings larger benefits than stand-alone modules. However, these studies have neither been performed in GP nor assessed EBM behaviour of former trainees in daily clinical practice. GP specialty training in the Netherlands. All 82 third year GP trainees who started their final third year in 2011 were approached for inclusion, of whom 79 (96%) participated: 39 in the intervention group and 40 in the control group. Integrated EBM training, in which EBM is embedded closely within the clinical context by joint assignments for the trainee and supervisor in daily practice, and teaching sessions based on dilemmas from actual patient consultations. Stand-alone EBM training at the institute only. Our primary outcome was EBM behaviour, assessed by measuring guideline adherence (incorporating rational, motivated deviation) and information-seeking behaviour. Our secondary outcomes were EBM attitude and EBM knowledge. Data were acquired using logbooks and questionnaires, respectively. Analyses were performed using mixed models. Logbook data were available from 76 (96%) of the participating trainees at baseline (7614 consultations), 60 (76%) at the end of the third year (T1, 4973 consultations) and 53 (67%) 1 year after graduation (T2, 3307 consultations). We found no significant differences in outcomes between the 2 groups, with relative risks for guideline adherence varying between 0.96 and 0.99 (95% CI 0.86 to 1.11) at T1, and 0.99 and 1.10 (95% CI 0.92 to 1.25) at T2, and for information-seeking behaviour between 0.97 and 1.16 (95% CI 0.70 to 1.91) and 0.90 and 1.10 (95% CI 0.70 to 1.32), respectively. Integrated EBM training compared with stand-alone EBM training does not improve EBM behaviour, attitude or knowledge of (future) GPs. Published by the BMJ Publishing Group Limited. For permission to use (where

  13. Does integrated training in evidence-based medicine (EBM) in the general practice (GP) specialty training improve EBM behaviour in daily clinical practice? A cluster randomised controlled trial

    PubMed Central

    Kortekaas, M F; Bartelink, M E L; Zuithoff, N P A; van der Heijden, G J M G; de Wit, N J; Hoes, A W

    2016-01-01

    Objectives Evidence-based medicine (EBM) is an important element in the general practice (GP) specialty training. Studies show that integrating EBM training into clinical practice brings larger benefits than stand-alone modules. However, these studies have neither been performed in GP nor assessed EBM behaviour of former trainees in daily clinical practice. Setting GP specialty training in the Netherlands. Participants All 82 third year GP trainees who started their final third year in 2011 were approached for inclusion, of whom 79 (96%) participated: 39 in the intervention group and 40 in the control group. Intervention Integrated EBM training, in which EBM is embedded closely within the clinical context by joint assignments for the trainee and supervisor in daily practice, and teaching sessions based on dilemmas from actual patient consultations. Comparison Stand-alone EBM training at the institute only. Primary and secondary outcomes Our primary outcome was EBM behaviour, assessed by measuring guideline adherence (incorporating rational, motivated deviation) and information-seeking behaviour. Our secondary outcomes were EBM attitude and EBM knowledge. Data were acquired using logbooks and questionnaires, respectively. Analyses were performed using mixed models. Results Logbook data were available from 76 (96%) of the participating trainees at baseline (7614 consultations), 60 (76%) at the end of the third year (T1, 4973 consultations) and 53 (67%) 1 year after graduation (T2, 3307 consultations). We found no significant differences in outcomes between the 2 groups, with relative risks for guideline adherence varying between 0.96 and 0.99 (95% CI 0.86 to 1.11) at T1, and 0.99 and 1.10 (95% CI 0.92 to 1.25) at T2, and for information-seeking behaviour between 0.97 and 1.16 (95% CI 0.70 to 1.91) and 0.90 and 1.10 (95% CI 0.70 to 1.32), respectively. Conclusions Integrated EBM training compared with stand-alone EBM training does not improve EBM behaviour, attitude

  14. Vorticity in heavy-ion collisions at the JINR Nuclotron-based Ion Collider fAcility

    NASA Astrophysics Data System (ADS)

    Ivanov, Yu. B.; Soldatov, A. A.

    2017-05-01

    Vorticity of matter generated in noncentral heavy-ion collisions at energies of the Nuclotron-based Ion Collider fAcility (NICA) at the Joint Institute for Nuclear Research (JINR) in Dubna is studied. Simulations are performed within the model of the three-fluid dynamics (3FD) which reproduces the major part of bulk observables at these energies. Comparison with earlier calculations is done. The qualitative pattern of the vorticity evolution is analyzed. It is demonstrated that the vorticity is mainly located at the border between participants and spectators. In particular, this implies that the relative Λ -hyperon polarization should be stronger at rapidities of the fragmentation regions than that in the midrapidity region.

  15. Beam-based measurements of long-range transverse wakefields in the Compact Linear Collider main-linac accelerating structure

    DOE PAGES

    Zha, Hao; Latina, Andrea; Grudiev, Alexej; ...

    2016-01-20

    The baseline design of CLIC (Compact Linear Collider) uses X-band accelerating structures for its main linacs. In order to maintain beam stability in multibunch operation, long-range transverse wakefields must be suppressed by 2 orders of magnitude between successive bunches, which are separated in time by 0.5 ns. Such strong wakefield suppression is achieved by equipping every accelerating structure cell with four damping waveguides terminated with individual rf loads. A beam-based experiment to directly measure the effectiveness of this long-range transverse wakefield and benchmark simulations was made in the FACET test facility at SLAC using a prototype CLIC accelerating structure. Furthermore,more » the experiment showed good agreement with the simulations and a strong suppression of the wakefields with an unprecedented minimum resolution of 0.1 V/(pC mm m).« less

  16. Development of high-resolution GEM-based detector for the extracted electron beam facility at the VEPP-4M collider

    NASA Astrophysics Data System (ADS)

    Bobrovnikov, V. S.; Kudryavtsev, V. N.; Maltsev, T. V.; Shekhtman, L. I.

    2017-07-01

    The goal of the extracted beam facility at the VEPP-4M collider is to test prototypes of new detectors for particle physics. Measurements taken at this installation require high-resolution low-mass tracking detectors to precisely determine particle trajectories. The high-resolution GEM-based tracking detector developed for this facility is described in this paper.

  17. Molecular docking guided structure based design of symmetrical N,N'-disubstituted urea/thiourea as HIV-1 gp120-CD4 binding inhibitors.

    PubMed

    Sivan, Sree Kanth; Vangala, Radhika; Manga, Vijjulatha

    2013-08-01

    Induced fit molecular docking studies were performed on BMS-806 derivatives reported as small molecule inhibitors of HIV-1 gp120-CD4 binding. Comprehensive study of protein-ligand interactions guided in identification and design of novel symmetrical N,N'-disubstituted urea and thiourea as HIV-1 gp120-CD4 binding inhibitors. These molecules were synthesized in aqueous medium using microwave irradiation. Synthesized molecules were screened for their inhibitory ability by HIV-1 gp120-CD4 capture enzyme-linked immunosorbent assay (ELISA). Designed compounds were found to inhibit HIV-1 gp120-CD4 binding in micromolar (0.013-0.247 μM) concentrations.

  18. Electronic GP information

    NASA Astrophysics Data System (ADS)

    The Geomagnetism and Paleomagnetism Section's Executive Committee is instituting an e-mail list of active GP members. Only those members who would like to receive informal information about current topics, events, or happenings in geomagnetism and paleomagnetism will be on the list. The e-mail list promises to be well-used as we have already received requests for inclusion from several geomagnetists and paleomagnetists.If you wish to be included, send your name, address, and e-mail address to Sue Beske-Diehl, Secretary—GP Section of AGU, Dept. of Geological Engineering, Geology, Geophysics, Michigan Technological University, 1400 Townshend Dr., Houghton, MI 49931—1295 fax 906-487-3371; e-mail sbeske-d@mtu.edu.

  19. The E166 experiment: Development of an Undulator-Based Polarized Positron Source for the International Linear Collider

    SciTech Connect

    Kovermann, J.; Stahl, A.; Mikhailichenko, A.A.; Scott, D.; Moortgat-Pick, G.A.; Gharibyan, V.; Pahl, P.; Poschl, R.; Schuler, K.P.; Laihem, K.; Riemann, S.; Schalicke, A.; Dollan, R.; Kolanoski, H.; Lohse, T.; Schweizer, T.; McDonald, K.T.; Batygin, Y.; Bharadwaj, V.; Bower, G.; Decker, F.J.; /SLAC /Tel Aviv U. /Tennessee U.

    2011-11-14

    A longitudinal polarized positron beam is foreseen for the international linear collider (ILC). A proof-of-principle experiment has been performed in the final focus test beam at SLAC to demonstrate the production of polarized positrons for implementation at the ILC. The E166 experiment uses a 1 m long helical undulator in a 46.6 GeV electron beam to produce a few MeV photons with a high degree of circular polarization. These photons are then converted in a thin target to generate longitudinally polarized e{sup +} and e{sup -}. The positron polarization is measured using a Compton transmission polarimeter. The data analysis has shown asymmetries in the expected vicinity of 3.4% and {approx}1% for photons and positrons respectively and the expected positron longitudinal polarization is covering a range from 50% to 90%. The full exploitation of the physics potential of an international linear collider (ILC) will require the development of polarized positron beams. Having both e{sup +} and e{sup -} beams polarized will provide new insight into structures of couplings and thus give access to physics beyond the standard model [1]. The concept for a polarized positron source is based on circularly polarized photon sources. These photons are then converted to longitudinally polarized e{sup +} and e{sup -} pairs. While in an experiment at KEK [1a], Compton backscattering is used [2], the E166 experiment uses a helical undulator to produce polarized photons. An undulator-based positron source for the ILC has been proposed in [3,4]. The proposed scheme for an ILC positron source is illustrated in figure 1. In this scheme, a 150 GeV electron beam passes through a 120 m long helical undulator to produce an intense photon beam with a high degree of circular polarization. These photons are converted in a thin target to e{sup +} e{sup -} pairs. The polarized positrons are then collected, pre-accelerated to the damping ring and injected to the main linac. The E166 experiment is

  20. Transcytosis-blocking abs elicited by an oligomeric immunogen based on the membrane proximal region of HIV-1 gp41 target non-neutralizing epitopes.

    PubMed

    Matoba, Nobuyuki; Griffin, Tagan A; Mittman, Michele; Doran, Jeffrey D; Alfsen, Annette; Montefiori, David C; Hanson, Carl V; Bomsel, Morgane; Mor, Tsafrir S

    2008-05-01

    CTB-MPR(649-684), a translational fusion protein consisting of cholera toxin B subunit (CTB) and residues 649 684 of gp41 membrane proximal region (MPR), is a candidate vaccine aimed at blocking early steps of HIV-1 mucosal transmission. Bacterially produced CTB MPR(649-684) was purified to homogeneity by two affinity chromatography steps. Similar to gp41 and derivatives thereof, the MPR domain can specifically and reversibly self-associate. The affinities of the broadly-neutralizing monoclonal Abs 4E10 and 2F5 to CTB MPR(649-684) were equivalent to their nanomolar affinities toward an MPR peptide. The fusion protein's affinity to GM1 ganglioside was comparable to that of native CTB. Rabbits immunized with CTB-MPR(649-684) raised only a modest level of anti-MPR(649-684) Abs. However, a prime-boost immunization with CTB-MPR(649-684) and a second MPR(649-684)-based immunogen elicited a more productive anti-MPR(649-684) antibody response. These Abs strongly blocked the epithelial transcytosis of a primary subtype B HIV-1 isolate in a human tight epithelial model, expanding our previously reported results using a clade D virus. The Abs recognized epitopes at the N-terminal portion of the MPR peptide, away from the 2F5 and 4E10 epitopes and were not effective in neutralizing infection of CD4+ cells. These results indicate distinct vulnerabilities of two separate interactions of HIV-1 with human cells - Abs against the C-terminal portion of the MPR can neutralize CD4+-dependent infection, while Abs targeting the MPR's N-terminal portion can effectively block galactosyl ceramide dependent transcytosis. We propose that Abs induced by MPR(649-684)-based immunogens may provide broad protective value independent of infection neutralization.

  1. Exploratory study of a novel low occupancy vertex detector architecture based on high precision timing for high luminosity particle colliders

    NASA Astrophysics Data System (ADS)

    Orel, Peter; Varner, Gary S.; Niknejadi, Pardis

    2017-06-01

    Vertex detectors provide space-time coordinates for the traversing charged particle decay products closest to the interaction point. Resolving these increasingly intense particle fluences at high luminosity particle colliders, such as SuperKEKB, is an ever growing challenge. This results in a non-negligible occupancy of the vertex detector using existing low material budget techniques. Consequently, new approaches are being studied that meet the vertexing requirements while lowering the occupancy. In this paper, we introduce a novel vertex detector architecture. Its design relies on an asynchronous digital pixel matrix in combination with a readout based on high precision time-of-flight measurement. Denoted the Timing Vertex Detector (TVD), it consists of a binary pixel array, a transmission line for signal collection, and a readout ASIC. The TVD aims to have a spatial resolution comparable to the existing Belle2 vertex detector. At the same time it offers a reduced occupancy by a factor of ten while decreasing the channel count by almost three orders of magnitude. Consequently, reducing the event size from about 1 MB/event to about 5.9 kB/event.

  2. Exclusive reactions and the PbWO4-based Inner Calorimeter for the Electron-Ion Collider

    NASA Astrophysics Data System (ADS)

    Trotta, Richard; Horn, Tanja; Vargas, Andres; Carmignotto, Marco; Ali, Salina; Uniyal, Rishabh

    2017-01-01

    One of the main goals of the Electron-Ion Collider (EIC) is the three-dimensional imaging of nucleon and nuclei and unveiling the role of orbital angular motion of sea quarks and gluons in forming the nucleon spin. These studies are made possible through a new framework developed to explore nucleon structure through the Generalized Parton Distributions (GPDs) and the Transverse Momentum-Dependent parton distributions (TMDs). To carry out the scientific program, a specialized detector is needed. The particle identification requirements are driven by semi-inclusive and exclusive scattering processes like DVCS. For the latter an elimination or reduction of background events is mandatory. This requires good resolution in angle to distinguish between clusters, good energy resolution for measurements of the cluster energy, and the ability to withstand radiation. The small Moliere radius of the PbWO4 crystals makes them an ideal solution for the EIC inner crystal calorimeter. In this talk we will discuss what needs to be done to build a PbWO4-based inner calorimeter, the importance of PbWO4 quality, and results from ongoing crystal characterization efforts.

  3. When craft and science collide: Improving therapeutic practices through evidence-based innovations.

    PubMed

    Justice, Laura M

    2010-04-01

    Evidence-based practice (EBP) is a model of clinical decision-making that is increasingly being advocated for use in the field of speech-language pathology. With the increased emphasis on scientific evidence as a form of knowledge important to EBP, clinicians may wonder whether their craft-based knowledge (i.e., knowledge derived from theory and practice), remains a legitimate form of knowledge for use in clinician decisions. This article describes forms of knowledge that may be used to address clinical questions, to include both craft and science. Additionally, the steps used when engaging in EBP are described so that clinicians understand when and how craft comes into play. The major premise addressed within this article is that craft is a legitimate form of knowledge and that engagement in EBP requires one to employ craft-based knowledge.

  4. Challenges in future linear colliders

    SciTech Connect

    Swapan Chattopadhyay; Kaoru Yokoya

    2002-09-02

    For decades, electron-positron colliders have been complementing proton-proton colliders. But the circular LEP, the largest e-e+ collider, represented an energy limit beyond which energy losses to synchrotron radiation necessitate moving to e-e+ linear colliders (LCs), thereby raising new challenges for accelerator builders. Japanese-American, German, and European collaborations have presented options for the Future Linear Collider (FLC). Key accelerator issues for any FLC option are the achievement of high enough energy and luminosity. Damping rings, taking advantage of the phenomenon of synchrotron radiation, have been developed as the means for decreasing beam size, which is crucial for ensuring a sufficiently high rate of particle-particle collisions. Related challenges are alignment and stability in an environment where even minute ground motion can disrupt performance, and the ability to monitor beam size. The technical challenges exist within a wider context of socioeconomic and political challenges, likely necessitating continued development of international collaboration among parties involved in accelerator-based physics.

  5. Developing the content of two behavioural interventions: Using theory-based interventions to promote GP management of upper respiratory tract infection without prescribing antibiotics #1

    PubMed Central

    Hrisos, Susan; Eccles, Martin; Johnston, Marie; Francis, Jill; Kaner, Eileen FS; Steen, Nick; Grimshaw, Jeremy

    2008-01-01

    Background Evidence shows that antibiotics have limited effectiveness in the management of upper respiratory tract infection (URTI) yet GPs continue to prescribe antibiotics. Implementation research does not currently provide a strong evidence base to guide the choice of interventions to promote the uptake of such evidence-based practice by health professionals. While systematic reviews demonstrate that interventions to change clinical practice can be effective, heterogeneity between studies hinders generalisation to routine practice. Psychological models of behaviour change that have been used successfully to predict variation in behaviour in the general population can also predict the clinical behaviour of healthcare professionals. The purpose of this study was to design two theoretically-based interventions to promote the management of upper respiratory tract infection (URTI) without prescribing antibiotics. Method Interventions were developed using a systematic, empirically informed approach in which we: selected theoretical frameworks; identified modifiable behavioural antecedents that predicted GPs intended and actual management of URTI; mapped these target antecedents on to evidence-based behaviour change techniques; and operationalised intervention components in a format suitable for delivery by postal questionnaire. Results We identified two psychological constructs that predicted GP management of URTI: "Self-efficacy," representing belief in one's capabilities, and "Anticipated consequences," representing beliefs about the consequences of one's actions. Behavioural techniques known to be effective in changing these beliefs were used in the design of two paper-based, interactive interventions. Intervention 1 targeted self-efficacy and required GPs to consider progressively more difficult situations in a "graded task" and to develop an "action plan" of what to do when next presented with one of these situations. Intervention 2 targeted anticipated

  6. Search for top quark at Fermilab Collider

    SciTech Connect

    Sliwa, K.; The CDF Collaboration

    1991-10-01

    The status of a search for the top quark with Collider Detector at Fermilab (CDF), based on a data sample recorded during the 1988--1989 run is presented. The plans for the next Fermilab Collider run in 1992--1993 and the prospects of discovering the top quark are discussed. 19 refs., 4 figs., 2 tabs.

  7. The development of colliders

    SciTech Connect

    Sessler, A.M.

    1997-03-01

    During the period of the 50`s and the 60`s colliders were developed. Prior to that time there were no colliders, and by 1965 a number of small devices had worked, good understanding had been achieved, and one could speculate, as Gersh Budker did, that in a few years 20% of high energy physics would come from colliders. His estimate was an under-estimate, for now essentially all of high energy physics comes from colliders. The author presents a brief review of that history: sketching the development of the concepts, the experiments, and the technological advances which made it all possible.

  8. Muon collider design

    NASA Astrophysics Data System (ADS)

    Palmer, R.; Sessler, A.; Skrinsky, A.; Tollestrup, A.; Baltz, A.; Caspi, S.; P., Chen; W-H., Cheng; Y., Cho; Cline, D.; Courant, E.; Fernow, R.; Gallardo, J.; Garren, A.; Gordon, H.; Green, M.; Gupta, R.; Hershcovitch, A.; Johnstone, C.; Kahn, S.; Kirk, H.; Kycia, T.; Y., Lee; Lissauer, D.; Luccio, A.; McInturff, A.; Mills, F.; Mokhov, N.; Morgan, G.; Neuffer, D.; K-Y., Ng; Noble, R.; Norem, J.; Norum, B.; Oide, K.; Parsa, Z.; Polychronakos, V.; Popovic, M.; Rehak, P.; Roser, T.; Rossmanith, R.; Scanlan, R.; Schachinger, L.; Silvestrov, G.; Stumer, I.; Summers, D.; Syphers, M.; Takahashi, H.; Torun, Y.; Trbojevic, D.; Turner, W.; van Ginneken, A.; Vsevolozhskaya, T.; Weggel, R.; Willen, E.; Willis, W.; Winn, D.; Wurtele, J.; Zhao, Y.

    1996-11-01

    Muon Colliders have unique technical and physics advantages and disadvantages when compared with both hadron and electron machines. They should thus be regarded as complementary. Parameters are given of 4 TeV and 0.5 TeV high luminosity \\mu^+ \\mu^- colliders, and of a 0.5 TeV lower luminosity demonstration machine. We discuss the various systems in such muon colliders, starting from the proton accelerator needed to generate the muons and proceeding through muon cooling, acceleration and storage in a collider ring. Detector background, polarization, and nonstandard operating conditions are discussed.

  9. Reconstruction of an active SOCS3-based E3 ubiquitin ligase complex in vitro: identification of the active components and JAK2 and gp130 as substrates.

    PubMed

    Kershaw, Nadia J; Laktyushin, Artem; Nicola, Nicos A; Babon, Jeffrey J

    2014-02-01

    SOCS3 (suppressor of cytokine signaling 3) inhibits the intracellular signaling cascade initiated by exposure of cells to cytokines. SOCS3 regulates signaling via two distinct mechanisms: directly inhibiting the catalytic activity of Janus kinases (JAKs) that initiate the intracellular signaling cascade and catalysing the ubiquitination of signaling components by recruiting components of an E3 ubiquitin ligase complex. Here we investigate the latter mode-of-action biochemically by reconstructing a SOCS3-based E3 ubiquitin ligase complex in vitro using fully purified, recombinant components and examining its ability to promote the ubiquitination of molecules involved in the cytokine signaling cascade. We show that SOCS3 is an active substrate recruitment module for a Cullin5-based E3 ligase and have defined the core protein components required for ubiquitination. SOCS3-induced polyubiquitination was rapid and could proceed through a number of different ubiquitin lysines. SOCS3 catalyzed the ubiquitination of both the IL-6 receptor common chain (gp130) and JAK2.

  10. Reconstruction of an active SOCS3-based E3 ubiquitin ligase complex in vitro: Identification of the active components and JAK2 and gp130 as substrates

    PubMed Central

    Kershaw, Nadia J.; Laktyushin, Artem; Nicola, Nicos A.; Babon, Jeffrey J.

    2014-01-01

    SOCS3 (Suppressor of Cytokine Signaling 3) inhibits the intracellular signaling cascade initiated by exposure of cells to cytokines. SOCS3 regulates signaling via two distinct mechanisms: directly inhibiting the catalytic activity of Janus Kinases (JAKs) that initiate the intracellular signaling cascade and catalysing the ubiquitination of signaling components by recruiting components of an E3 ubiquitin ligase complex. Here we investigate the latter mode-of-action biochemically by reconstructing a SOCS3-based E3 ubiquitin ligase complex in vitro using fully purified, recombinant components and examining its ability to promote the ubiquitination of molecules involved in the cytokine signaling cascade. We show that SOCS3 is an active substrate recruitment module for a Cullin5-based E3 ligase and have defined the core protein components required for ubiquitination. SOCS3-induced poly-ubiquitination was rapid and could proceed through a number of different ubiquitin lysines. SOCS3 catalysed the ubiquitination of both the IL-6 receptor common chain (gp130) and JAK2. PMID:24438103

  11. Higgs boson and Z physics at the first muon collider

    SciTech Connect

    Demarteau, M.; Han, T.

    1998-01-01

    The potential for the Higgs boson and Z-pole physics at the first muon collider is summarized, based on the discussions at the ``Workshop on the Physics at the First Muon Collider and at the Front End of a Muon Collider``.

  12. SLAC Linear Collider

    SciTech Connect

    Richter, B.

    1985-12-01

    A report is given on the goals and progress of the SLAC Linear Collider. The status of the machine and the detectors are discussed and an overview is given of the physics which can be done at this new facility. Some ideas on how (and why) large linear colliders of the future should be built are given.

  13. Anti-HIV-1 Activity Prediction of Novel Gp41 Inhibitors Using Structure-Based Virtual Screening and Molecular Dynamics Simulation.

    PubMed

    Sepehri, Saghi; Saghaie, Lotfollah; Fassihi, Afshin

    2017-03-01

    The fusion of viral and host cell membranes is mediated using gp41 subunit of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein. As the HIV-1 enters the host cells, the two helical regions (HR1 and HR2) in the ectodomain of gp41 form a six-helix bundle, which carries the target and viral cell membranes to close proximity. Steps of this process serve as attractive targets for developing HIV-1 fusion inhibitors. Identification of some novel HIV fusion inhibitors with the goal of blocking the formation of the six-helix bundle was accomplished by computer-aided drug design techniques. A virtual screening strategy was employed to recognize small molecules presumably able to bind the gp41 at the internal interface of the NHR helices at the core native viral six-helix. This study was carried out in two stages. In the first stage, a library of more than seven thousand compounds was collected from ZINC, PubChem and BindingDB databases and protein data bank. Key contacts of known inhibitors with gp41 binding site residues were considered as the collecting criteria. In the second stage series of filtering processes were performed on this library in subsequent steps to find the potential gp41 inhibitors. The filtering criteria included pharmacokinetic and ADMET properties as well as in silico anti-HIV-1 prediction. Molecular docking simulation was carried out to identify interactions of the filtered molecules with the key residues in the gp41 binding site. Finally, molecular dynamics simulation indicates the superior inhibitory ability of three selected compounds over the known gp41inhibitor, NB-64.

  14. On the Future High Energy Colliders

    SciTech Connect

    Shiltsev, Vladimir

    2015-09-28

    High energy particle colliders have been in the forefront of particle physics for more than three decades. At present the near term US, European and international strategies of the particle physics community are centered on full exploitation of the physics potential of the Large Hadron Collider (LHC) through its high-luminosity upgrade (HL-LHC). A number of the next generation collider facilities have been proposed and are currently under consideration for the medium and far-future of accelerator-based high energy physics. In this paper we offer a uniform approach to evaluation of various accelerators based on the feasibility of their energy reach, performance potential and cost range.

  15. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

    PubMed Central

    Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

    2010-01-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

  16. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

    PubMed

    Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

    2011-02-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Frequency of GP communication addressing the patient's resources and coping strategies in medical interviews: a video-based observational study.

    PubMed

    Mjaaland, Trond A; Finset, Arnstein

    2009-07-01

    There is increasing focus on patient-centred communicative approaches in medical consultations, but few studies have shown the extent to which patients' positive coping strategies and psychological assets are addressed by general practitioners (GPs) on a regular day at the office. This study measures the frequency of GPs' use of questions and comments addressing their patients' coping strategies or resources. Twenty-four GPs were video-recorded in 145 consultations. The consultations were coded using a modified version of the Roter Interaction Analysis System. In this study, we also developed four additional coding categories based on cognitive therapy and solution-focused therapy: attribution, resources, coping, and solution-focused techniques.The reliability between coders was established, a factor analysis was applied to test the relationship between the communication categories, and a tentative validating exercise was performed by reversed coding. Cohen's kappa was 0.52 between coders. Only 2% of the utterances could be categorized as resource or coping oriented. Six GPs contributed 59% of these utterances. The factor analysis identified two factors, one task oriented and one patient oriented. The frequency of communication about coping and resources was very low. Communication skills training for GPs in this field is required. Further validating studies of this kind of measurement tool are warranted.

  18. Preliminary design report of a relativistic-Klystron two-beam-accelerator based power source for a 1 TeV center-of-mass next linear collider

    SciTech Connect

    Yu, S.; Goffeney, N.; Henestroza, E.

    1995-02-22

    A preliminary point design for an 11.4 GHz power source for a 1 TeV center-of-mass Next Linear Collider (NLC) based on the Relativistic-Klystron Two-Beam-Accelerator (RK-TBA) concept is presented. The present report is the result of a joint LBL-LLNL systems study. consisting of three major thrust areas: physics, engineering, and costing. The new RK-TBA point design, together with our findings in each of these areas, are reported.

  19. A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120

    SciTech Connect

    Beddows, Simon; Franti, Michael; Dey, Antu K.; Kirschner, Marc; Iyer, Sai Prasad N.; Fisch, Danielle C.; Ketas, Thomas; Yuste, Eloisa; Desrosiers, Ronald C.; Klasse, Per Johan; Maddon, Paul J.; Olson, William C.; Moore, John P. . E-mail: jpm2003@med.cornell.edu

    2007-04-10

    The human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein (Env) complex, a homotrimer containing gp120 surface glycoprotein and gp41 transmembrane glycoprotein subunits, mediates the binding and fusion of the virus with susceptible target cells. The Env complex is the target for neutralizing antibodies (NAbs) and is the basis for vaccines intended to induce NAbs. Early generation vaccines based on monomeric gp120 subunits did not confer protection from infection; one alternative approach is therefore to make and evaluate soluble forms of the trimeric Env complex. We have directly compared the immunogenicity in rabbits of two forms of soluble trimeric Env and monomeric gp120 based on the sequence of HIV-1{sub JR-FL}. Both protein-only and DNA-prime, protein-boost immunization formats were evaluated, DNA-priming having little or no influence on the outcome. One form of trimeric Env was made by disrupting the gp120-gp41 cleavage site by mutagenesis (gp140{sub UNC}), the other contains an intramolecular disulfide bond to stabilize the cleaved gp120 and gp41 moieties (SOSIP.R6 gp140). Among the three immunogens, SOSIP.R6 gp140 most frequently elicited neutralizing antibodies against the homologous, neutralization-resistant strain, HIV-1{sub JR-FL}. All three proteins induced NAbs against more sensitive strains, but the breadth of activity against heterologous primary isolates was limited. When antibodies able to neutralize HIV-1{sub JR-FL} were detected, antigen depletion studies showed they were not directed at the V3 region but were targeted at other, undefined gp120 and also non-gp120 epitopes.

  20. Linear collider: a preview

    SciTech Connect

    Wiedemann, H.

    1981-11-01

    Since no linear colliders have been built yet it is difficult to know at what energy the linear cost scaling of linear colliders drops below the quadratic scaling of storage rings. There is, however, no doubt that a linear collider facility for a center of mass energy above say 500 GeV is significantly cheaper than an equivalent storage ring. In order to make the linear collider principle feasible at very high energies a number of problems have to be solved. There are two kinds of problems: one which is related to the feasibility of the principle and the other kind of problems is associated with minimizing the cost of constructing and operating such a facility. This lecture series describes the problems and possible solutions. Since the real test of a principle requires the construction of a prototype I will in the last chapter describe the SLC project at the Stanford Linear Accelerator Center.

  1. Virological and Immunological Characterization of Novel NYVAC-Based HIV/AIDS Vaccine Candidates Expressing Clade C Trimeric Soluble gp140(ZM96) and Gag(ZM96)-Pol-Nef(CN54) as Virus-Like Particles

    PubMed Central

    Perdiguero, Beatriz; Gómez, Carmen Elena; Cepeda, Victoria; Sánchez-Sampedro, Lucas; García-Arriaza, Juan; Mejías-Pérez, Ernesto; Jiménez, Victoria; Sánchez, Cristina; Sorzano, Carlos Óscar S.; Oliveros, Juan Carlos; Delaloye, Julie; Roger, Thierry; Calandra, Thierry; Asbach, Benedikt; Wagner, Ralf; Kibler, Karen V.; Jacobs, Bertram L.; Pantaleo, Giuseppe

    2014-01-01

    ABSTRACT The generation of vaccines against HIV/AIDS able to induce long-lasting protective immunity remains a major goal in the HIV field. The modest efficacy (31.2%) against HIV infection observed in the RV144 phase III clinical trial highlighted the need for further improvement of HIV vaccine candidates, formulation, and vaccine regimen. In this study, we have generated two novel NYVAC vectors, expressing HIV-1 clade C gp140(ZM96) (NYVAC-gp140) or Gag(ZM96)-Pol-Nef(CN54) (NYVAC-Gag-Pol-Nef), and defined their virological and immunological characteristics in cultured cells and in mice. The insertion of HIV genes does not affect the replication capacity of NYVAC recombinants in primary chicken embryo fibroblast cells, HIV sequences remain stable after multiple passages, and HIV antigens are correctly expressed and released from cells, with Env as a trimer (NYVAC-gp140), while in NYVAC-Gag-Pol-Nef-infected cells Gag-induced virus-like particles (VLPs) are abundant. Electron microscopy revealed that VLPs accumulated with time at the cell surface, with no interference with NYVAC morphogenesis. Both vectors trigger specific innate responses in human cells and show an attenuation profile in immunocompromised adult BALB/c and newborn CD1 mice after intracranial inoculation. Analysis of the immune responses elicited in mice after homologous NYVAC prime/NYVAC boost immunization shows that recombinant viruses induced polyfunctional Env-specific CD4 or Gag-specific CD8 T cell responses. Antibody responses against gp140 and p17/p24 were elicited. Our findings showed important insights into virus-host cell interactions of NYVAC vectors expressing HIV antigens, with the activation of specific immune parameters which will help to unravel potential correlates of protection against HIV in human clinical trials with these vectors. IMPORTANCE We have generated two novel NYVAC-based HIV vaccine candidates expressing HIV-1 clade C trimeric soluble gp140 (ZM96) and Gag(ZM96)-Pol

  2. A high-efficiency recombineering system with PCR-based ssDNA in Bacillus subtilis mediated by the native phage recombinase GP35.

    PubMed

    Sun, Zhaopeng; Deng, Aihua; Hu, Ting; Wu, Jie; Sun, Qinyun; Bai, Hua; Zhang, Guoqiang; Wen, Tingyi

    2015-06-01

    Bacillus subtilis and its closely related species are important strains for industry, agriculture, and medicine. However, it is difficult to perform genetic manipulations using the endogenous recombination machinery. In many bacteria, phage recombineering systems have been employed to improve recombineering frequencies. To date, an efficient phage recombineering system for B. subtilis has not been reported. Here, we, for the first time, identified that GP35 from the native phage SPP1 exhibited a high recombination activity in B. subtilis. On this basis, we developed a high-efficiency GP35-meditated recombineering system. Taking single-stranded DNA (ssDNA) as a recombineering substrate, ten recombinases from diverse sources were investigated in B. subtilis W168. GP35 showed the highest recombineering frequency (1.71 ± 0.15 × 10(-1)). Besides targeting the purine nucleoside phosphorylase gene (deoD), we also demonstrated the utility of GP35 and Beta from Escherichia coli lambda phage by deleting the alpha-amylase gene (amyE) and uracil phosphoribosyltransferase gene (upp). In all three genetic loci, GP35 exhibited a higher frequency than Beta. Moreover, a phylogenetic tree comparing the kinship of different recombinase hosts with B. subtilis was constructed, and the relationship between the recombineering frequency and the kinship of the host was further analyzed. The results suggested that closer kinship to B. subtilis resulted in higher frequency in B. subtilis. In conclusion, the recombinase from native phage or prophage can significantly promote the genetic recombineering frequency in its host, providing an effective genetic tool for constructing genetically engineered strains and investigating bacterial physiology.

  3. The VCSEL-based array optical transmitter (ATx) development towards 120-Gbps link for collider detector: development update

    NASA Astrophysics Data System (ADS)

    Guo, D.; Liu, C.; Chen, J.; Chramowicz, J.; Gong, D.; Hou, S.; Huang, D.; Jin, G.; Li, X.; Liu, T.; Prosser, A.; Teng, P. K.; Ye, J.; Zhou, Y.; You, Y.; Xiang, A. C.; Liang, H.

    2015-01-01

    A compact radiation-tolerant array optical transmitter module (ATx) is developed to provide data transmission up to 10Gbps per channel with 12 parallel channels for collider detector applications. The ATx integrates a Vertical Cavity Surface-Emitting Laser (VCSEL) array and driver circuitry for electrical to optical conversion, an edge warp substrate for the electrical interface and a micro-lens array for the optical interface. This paper reports the continuing development of the ATx custom package. A simple, high-accuracy and reliable active-alignment method for the optical coupling is introduced. The radiation-resistance of the optoelectronic components is evaluated and the inclusion of a custom-designed array driver is discussed.

  4. The E166 experiment: Development of an undulator-based polarized positron source for the international linear collider

    NASA Astrophysics Data System (ADS)

    Kovermann, J.; Stahl, A.; Mikhailichenko, A. A.; Scott, D.; Moortgat-Pick, G. A.; Gharibyan, V.; Pahl, P.; Põschl, R.; Schüler, K. P.; Laihem, K.; Riemann, S.; Schälicke, A.; Dollan, R.; Kolanoski, H.; Lohse, T.; Schweizer, T.; McDonald, K. T.; Batygin, Y.; Bharadwaj, V.; Bower, G.; Decker, F.-J.; Hast, C.; Iverson, R.; Sheppard, J. C.; Szalata, Z.; Walz, D.; Weidemann, A.; Alexander, G.; Reinherz-Aronis, E.; Berridge, S.; Bugg, W.; Efrimenko, Y.

    2007-12-01

    A longitudinal polarized positron beam is foreseen for the international linear collider (ILC). A proof-of-principle experiment has been performed in the final focus test beam at SLAC to demonstrate the production of polarized positrons for implementation at the ILC. The E166 experiment uses a 1 m long helical undulator in a 46.6 GeV electron beam to produce a few MeV photons with a high degree of circular polarization. These photons are then converted in a thin target to generate longitudinally polarized e^+ and e^-. The positron polarization is measured using a Compton transmission polarimeter. The data analysis has shown asymmetries in the expected vicinity of 3.4% and ˜1% for photons and positrons respectively and the expected positron longitudinal polarization is covering a range from 50% to 90%.

  5. Functional properties of extracellular domains of transducer receptor gp130.

    PubMed

    Kostjukova, M N; Tupitsyn, N N

    2011-04-01

    Cytokine receptor molecules have been shown to have extracellular domains of complex structure and a multi-step activation system. Glycoprotein gp130 is a typical transducer of cytokine signal; it functions by forming multicomponent receptor complexes and transferring signals of tens of cytokines from the IL-6 family. Structural organization and basic functioning principles of gp130 are well known, as well as related signal pathways, which function during normal differentiation and are involved in pathogenesis of many tumors. The role of gp130 in IL-6-dependent tumors is best studied. In this review, based on extensive accumulated data, we examine the functional significance of certain parts of gp130 extracellular domains. Potentials of a recently developed method for estimation of receptor activation at the level of epitope structure are discussed.

  6. The development of colliders

    SciTech Connect

    Sessler, A.M.

    1993-02-01

    Don Kerst, Gersh Budker, and Bruno Touschek were the individuals, and the motivating force, which brought about the development of colliders, while the laboratories at which it happened were Stanford, MURA, the Cambridge Electron Accelerator, Orsay, Frascati, CERN, and Novosibirsk. These laboratories supported, during many years, this rather speculative activity. Of course, many hundreds of physicists contributed to the development of colliders but the men who started it, set it in the right direction, and forcefully made it happen, were Don, Gersh, and Bruno. Don was instrumental in the development of proton-proton colliders, while Bruno and Gersh spearheaded the development of electron-positron colliders. In this brief review of the history, I will sketch the development of the concepts, the experiments, and the technological developments which made possible the development of colliders. It may look as if the emphasis is on theoretical concepts, but that is really not the case, for in this field -- the physics of beams -- the theory and experiment go hand in hand; theoretical understanding and advances are almost always motivated by the need to explain experimental results or the desire to construct better experimental devices.

  7. Covalent Conjugation of a Peptide Triazole to HIV-1 gp120 Enables Intramolecular Binding Site Occupancy

    PubMed Central

    2015-01-01

    the PT–gp120 conjugate to the noncovalent PT–gp120 complex support the orientation of binding of PT to gp120 predicted in the molecular dynamics simulation model of the PT–gp120 noncovalent complex. The conformationally stabilized covalent conjugate can be used to expand the structural definition of the PT-induced “off” state of gp120, for example, by high-resolution structural analysis. Such structures could provide a guide for improving the subsequent structure-based design of inhibitors with the peptide triazole mode of action. PMID:24801282

  8. Considerations on Energy Frontier Colliders after LHC

    SciTech Connect

    Shiltsev, Vladimir

    2016-11-15

    Since 1960’s, particle colliders have been in the forefront of particle physics, 29 total have been built and operated, 7 are in operation now. At present the near term US, European and international strategies of the particle physics community are centered on full exploitation of the physics potential of the Large Hadron Collider (LHC) through its high-luminosity upgrade (HL-LHC). The future of the world-wide HEP community critically depends on the feasibility of possible post-LHC colliders. The concept of the feasibility is complex and includes at least three factors: feasibility of energy, feasibility of luminosity and feasibility of cost. Here we overview all current options for post-LHC colliders from such perspective (ILC, CLIC, Muon Collider, plasma colliders, CEPC, FCC, HE-LHC) and discuss major challenges and accelerator R&D required to demonstrate feasibility of an energy frontier accelerator facility following the LHC. We conclude by taking a look into ultimate energy reach accelerators based on plasmas and crystals, and discussion on the perspectives for the far future of the accelerator-based particle physics. This paper largely follows previous study [1] and the presenta ion given at the ICHEP’2016 conference in Chicago [2].

  9. The Muon Collider

    SciTech Connect

    Zisman, Michael S.

    2011-01-05

    We describe the scientific motivation for a new type of accelerator, the muon collider. This accelerator would permit an energy-frontier scientific program and yet would fit on the site of an existing laboratory. Such a device is quite challenging, and requires a substantial R&D program. After describing the ingredients of the facility, the ongoing R&D activities of the Muon Accelerator Program are discussed. A possible U.S. scenario that could lead to a muon collider at Fermilab is briefly mentioned.

  10. The Muon Collider

    SciTech Connect

    Zisman, Michael S

    2010-05-17

    We describe the scientific motivation for a new type of accelerator, the muon collider. This accelerator would permit an energy-frontier scientific program and yet would fit on the site of an existing laboratory. Such a device is quite challenging, and requires a substantial R&D program. After describing the ingredients of the facility, the ongoing R&D activities of the Muon Accelerator Program are discussed. A possible U.S. scenario that could lead to a muon collider at Fermilab is briefly mentioned.

  11. Black Holes Collide

    NASA Image and Video Library

    2017-09-28

    When two black holes collide, they release massive amounts of energy in the form of gravitational waves that last a fraction of a second and can be "heard" throughout the universe - if you have the right instruments. Today we learned that the #LIGO project heard the telltale chirp of black holes colliding, fulfilling Einstein's General Theory of Relativity. NASA's LISA mission will look for direct evidence of gravitational waves. go.nasa.gov/23ZbqoE This video illustrates what that collision might look like.

  12. Structures of Ebola Virus GP and sGP in Complex with Therapeutic Antibodies

    PubMed Central

    Pallesen, Jesper; Murin, Charles D.; de Val, Natalia; Cottrell, Christopher A.; Hastie, Kathryn M.; Turner, Hannah L.; Fusco, Marnie L.; Flyak, Andrew I.; Zeitlin, Larry; Crowe, James E.; Andersen, Kristian G.; Saphire, Erica Ollmann; Ward, Andrew B.

    2016-01-01

    The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein termed sGP that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein termed GP. GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-EM structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. Further, we provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses toward differently structured products of the GP gene. PMID:27562261

  13. Design considerations for a laser-plasma linear collider

    SciTech Connect

    Schroeder, C. B.; Esarey, E.; Geddes, C. G. R.; Toth, Cs.; Leemans, W. P.

    2009-01-22

    Design considerations for a next-generation electron-positron linear collider based on laser-plasma-accelerators are discussed. Several of the advantages and challenges of laser-plasma-based accelerator technology are addressed. An example of the parameters for a 1 TeV laser-plasma-based collider is presented.

  14. Design considerations for a laser-plasma linear collider

    SciTech Connect

    Schroeder, C. B.; Esarey, E.; Geddes, C. G. R.; Toth, Cs.; Leemans, W. P.

    2008-08-01

    Design considerations for a next-generation electron-positron linear collider based on laser-plasma-accelerators are discussed. Several of the advantages and challenges of laser-plasma based accelerator technology are addressed. An example of the parameters for a 1 TeV laser-plasma based collider is presented.

  15. Linear Collider Diagnostics

    SciTech Connect

    Ross, Marc

    2000-05-17

    Each major step toward higher energy particle accelerators relies on new technology. Linear colliders require beams of unprecedented brightness and stability. Instrumentation and control technology is the single most critical tool that enables linear colliders to extend the energy reach. In this paper the authors focus on the most challenging aspects of linear collider instrumentation systems. In the Next Linear Collider (NLC), high brightness multibunch e{sup +}/e{sup {minus}} beams, with I{sub {+-}} = 10{sup 12} particles/pulse and sigma{sub x,y} {approximately} 50 x 5 mu-m, originate in damping rings and are subsequently accelerated to several hundred GeV in 2 X-band 11,424 MHz linacs from which they emerge with typical sigma{sub x,y} {approximately} 7 x 1 mu-m. Following a high power collimation section the e{sup +}/e{sup {minus}} beams are focused to sigma{sub x,y} {approximately} 300 x 5 nm at the interaction point. In this paper they review the beam intensity, position and profile monitors (x,y,z), mechanical vibration sensing and stabilization systems, long baseline RF distribution systems and beam collimation hardware.

  16. Hadron collider physics

    SciTech Connect

    Pondrom, L.

    1991-10-03

    An introduction to the techniques of analysis of hadron collider events is presented in the context of the quark-parton model. Production and decay of W and Z intermediate vector bosons are used as examples. The structure of the Electroweak theory is outlined. Three simple FORTRAN programs are introduced, to illustrate Monte Carlo calculation techniques. 25 refs.

  17. High energy colliders

    SciTech Connect

    Palmer, R.B.; Gallardo, J.C.

    1997-02-01

    The authors consider the high energy physics advantages, disadvantages and luminosity requirements of hadron (pp, p{anti p}), lepton (e{sup +}e{sup {minus}}, {mu}{sup +}{mu}{sup {minus}}) and photon-photon colliders. Technical problems in obtaining increased energy in each type of machine are presented. The machines relative size are also discussed.

  18. High luminosity particle colliders

    SciTech Connect

    Palmer, R.B.; Gallardo, J.C.

    1997-03-01

    The authors consider the high energy physics advantages, disadvantages and luminosity requirements of hadron (pp, p{anti p}), lepton (e{sup +}e{sup {minus}}, {mu}{sup +}{mu}{sup {minus}}) and photon-photon colliders. Technical problems in obtaining increased energy in each type of machine are presented. The machines relative size are also discussed.

  19. Transverse emittance-preserving arc compressor for high-brightness electron beam-based light sources and colliders

    NASA Astrophysics Data System (ADS)

    Di Mitri, S.; Cornacchia, M.

    2015-03-01

    Bunch length magnetic compression is used in high-brightness linacs driving free-electron lasers (FELs) and particle colliders to increase the peak current of the injected beam. To date, it is performed in dedicated insertions made of few degrees bending magnets and the compression factor is limited by the degradation of the beam transverse emittance owing to emission of coherent synchrotron radiation (CSR). We reformulate the known concept of CSR-driven optics balance for the general case of varying bunch length and demonstrate, through analytical and numerical results, that a 500 pC charge beam can be time-compressed in a periodic 180 deg arc at 2.4 GeV beam energy and lower, by a factor of up to 45, reaching peak currents of up to 2 kA and with a normalized emittance growth at the 0.1 μ \\text{m} rad level. The proposed solution offers new schemes of beam longitudinal gymnastics; an application to an energy recovery linac driving FEL is discussed.

  20. Enzymatic removal of mannose moieties can increase the immune response to HIV-1 gp120 in vivo

    PubMed Central

    Banerjee, Kaustuv; Andjelic, Sofija; Klasse, Per Johan; Kang, Yun; Sanders, Rogier W.; Michael, Elizabeth; Durso, Robert J.; Ketas, Thomas J.; Olson, William C.; Moore, John P.

    2009-01-01

    The Env glycoproteins gp120 and gp41 are used in humoral immunity-based vaccines against human immunodeficiency virus (HIV-1) infection. One among many obstacles to such a vaccine is the structural defenses of Env glycoproteins that limit their immunogenicity. For example, gp120 mannose residues can induce immunosuppressive responses in vitro, including IL-10 expression, via mannose C-type lectin receptors on antigen-presenting cells. Here, we have investigated whether mannose removal alters gp120 immunogenicity in mice. Administering demannosylated gp120 (D-gp120) in the TH2-skewing adjuvant Alum induced ~50-fold higher titers of anti-gp120 IgG, compared to unmodified gp120. While the IgG subclass profile was predominantly TH2-associated IgG1, Abs of the TH1-associated IgG2a and IgG3 subclasses were also detectable in D-gp120 recipients. Immunizing with D-gp120 also improved T-cell responses. Giving an IL-10 receptor blocking MAb together with unmodified gp120 in Alum increased the anti-gp120 IgG titer, implicating IL-10 as a possible mediator of auto-suppressive responses to gp120. PMID:19410272

  1. Increased expression of Gp96 by HBx-induced NF-κB activation feedback enhances hepatitis B virus production.

    PubMed

    Fan, Hongxia; Yan, Xiaoli; Zhang, Yu; Zhang, Xiaojun; Gao, Yanzhou; Xu, Yaxing; Wang, Fusheng; Meng, Songdong

    2013-01-01

    Elevated expression of heat shock protein gp96 in hepatitis B virus (HBV)-infected patients is positively correlated with the progress of HBV-induced diseases, but little is known regarding the molecular mechanism of virus-induced gp96 expression and its impact on HBV infection. In this study, up-regulation of gp96 by HBV replication was confirmed both in vitro and in vivo. Among HBV components, HBV x protein (HBx) was found to increase gp96 promoter activity and enhance gp96 expression by using a luciferase reporter system, and western blot analysis. Further, we found that HBx-mediated regulation of gp96 expression requires a NF-κB cis-regulatory element on the gp96 promoter, and chromatin immunoprecipitation results demonstrated that HBx promotes the binding of NF-κB to the gp96 promoter. Significantly, both gain- and loss-of-function studies showed that gp96 enhances HBV production in HBV-transfected cells and a mouse model based on hydrodynamic transfection. Moreover, up-regulated gp96 expression was observed in HBV-infected patients, and gp96 levels were correlated with serum viral loads. Thus, our work demonstrates a positive feedback regulatory pathway involving gp96 and HBV, which may contribute to persistent HBV infection. Our data also indicate that modulation of gp96 function may represent a novel strategy for the intervention of HBV infection.

  2. Enzymatic removal of mannose moieties can increase the immune response to HIV-1 gp120 in vivo.

    PubMed

    Banerjee, Kaustuv; Andjelic, Sofija; Klasse, Per Johan; Kang, Yun; Sanders, Rogier W; Michael, Elizabeth; Durso, Robert J; Ketas, Thomas J; Olson, William C; Moore, John P

    2009-06-20

    The Env glycoproteins gp120 and gp41 are used in humoral immunity-based vaccines against human immunodeficiency virus (HIV-1) infection. One among many obstacles to such a vaccine is the structural defenses of Env glycoproteins that limit their immunogenicity. For example, gp120 mannose residues can induce immunosuppressive responses in vitro, including IL-10 expression, via mannose C-type lectin receptors on antigen-presenting cells. Here, we have investigated whether mannose removal alters gp120 immunogenicity in mice. Administering demannosylated gp120 (D-gp120) in the T(H)2-skewing adjuvant Alum induced approximately 50-fold higher titers of anti-gp120 IgG, compared to unmodified gp120. While the IgG subclass profile was predominantly T(H)2-associated IgG1, Abs of the T(H)1-associated IgG2a and IgG3 subclasses were also detectable in D-gp120 recipients. Immunizing with D-gp120 also improved T-cell responses. Giving an IL-10 receptor blocking MAb together with unmodified gp120 in Alum increased the anti-gp120 IgG titer, implicating IL-10 as a possible mediator of auto-suppressive responses to gp120.

  3. Comparative functional role of PC7 and furin in the processing of the HIV envelope glycoprotein gp160.

    PubMed

    Decroly, E; Benjannet, S; Savaria, D; Seidah, N G

    1997-03-17

    The intracellular proteolytic processing of HIV envelope glycoprotein gp160 into gp120/gp41 is an essential step for virus infectivity. Several convertases, belonging to the pro-protein convertase family, have been proposed as candidate gp160 processing enzymes. Here we demonstrate using RT-PCR that resting human T4 lymphocytes weakly express PC7, furin, and PC5 mRNA whereas lymphocytes activated under conditions favoring HIV replication express 5-10-fold higher levels of furin and PC7. In this report, we examined the capability of the newly cloned convertase PC7 to cleave gp160 into gp120/gp41 and compared it to furin. This was carried out in a cell-based assay whereby both gp160 and the cognate convertase were co-expressed in the constitutively secreting BSC40 cells and in the regulated AtT20 cells, as well as using two in vitro assays which examined the cleavage of gp160 or of a synthetic peptide spanning the cleavage site. The data demonstrate that PC7 can cleave specifically and in a cell-type specific manner gp160 into gp120gp41, suggesting that both furin and PC7 are so far the major PC-like candidate gp160 convertase in T4 lymphocytes.

  4. Accelarators, Colliders and Their Application

    NASA Astrophysics Data System (ADS)

    Wilson, E.

    This document is part of Subvolume C 'Accelerators and Colliders' of Volume 21 'Elementary Particles' of Landolt-Börnstein - Group I 'Elementary Particles, Nuclei and Atoms'. It contains the Chapter '1 Accelarators, Colliders and Their Application' with the content:

  5. Introductory Lectures on Collider Physics

    NASA Astrophysics Data System (ADS)

    Tait, Tim M. P.; Wang, Lian-Tao

    2013-12-01

    These are elementary lectures about collider physics. They are aimed at graduate students who have some background in computing Feynman diagrams and the Standard Model, but assume no particular sophistication with the physics of high energy colliders.

  6. Tau anomalous magnetic moment in γγ colliders

    NASA Astrophysics Data System (ADS)

    Peressutti, Javier; Sampayo, Oscar A.

    2012-08-01

    We investigate the possibility of setting model independent limits for a nonstandard anomalous magnetic moment aτNP of the tau lepton, in future γγ colliders based on Compton backscattering. For a hypothetical collider we find that, at various levels of confidence, the limits for aτNP could be improved, compared to previous studies based on LEP1, LEP2 and SLD data. We show the results for a realistic range of the center of mass energy of the e+e- collider. As a more direct application, we also present the results of the simulation for the photon collider at the TESLA project.

  7. Infiltration of Neutrophils and Eosinophils during Allergic Inflammation is Regulated by the Inhibitory Receptor gp-49B

    USDA-ARS?s Scientific Manuscript database

    gp49B, an Ig-like receptor, negatively regulates the activity of mast cells and neutrophils through cytoplasmic immuno-receptor tyrosine-based inhibition motifs (ITIM). To further characterize the role of gp49B in vivo, gp49B-deficient mice were tested in two allergic models. Responses to ragweed (R...

  8. Synaptic membrane glycoproteins gp65 and gp55 are new members of the immunoglobulin superfamily.

    PubMed

    Langnaese, K; Beesley, P W; Gundelfinger, E D

    1997-01-10

    Glycoproteins gp65 and gp55 are major components of synaptic membranes prepared from rat forebrain. Both are recognized by the monoclonal antibody SMgp65. We have used SMgp65 to screen a rat brain cDNA expression library. Two sets of overlapping cDNAs that contain open reading frames of 397 and 281 amino acids were isolated. The deduced proteins are members of the immunoglobulin (Ig) superfamily containing three and two Ig domains, respectively. The common part has approximately 40% sequence identity with neurothelin/basigin. The identity of the proteins as gp65 and gp55 was confirmed by production of new antisera against a common recombinant protein fragment. These antisera immunoprecipitate gp65 and gp55. Furthermore, expression of gp65 and gp55 cDNAs in human 293 cells treated with tunicamycin results in the production of unglycosylated core proteins of identical size to deglycosylated gp65 and gp55. Northern analysis revealed that gp65 transcripts are brain-specific, whereas gp55 is expressed in most tissues and cell lines examined. The tissue distribution was confirmed at the protein level though the pattern of glycosylation of gp55 varies between tissues. In situ hybridization experiments with a common and a gp65-specific probe suggest differential expression of gp65 and gp55 transcripts in the rat brain.

  9. The SPL7013 dendrimer destabilizes the HIV-1 gp120-CD4 complex

    NASA Astrophysics Data System (ADS)

    Nandy, Bidisha; Saurabh, Suman; Sahoo, Anil Kumar; Dixit, Narendra M.; Maiti, Prabal K.

    2015-11-01

    The poly (l-lysine)-based SPL7013 dendrimer with naphthalene disulphonate surface groups blocks the entry of HIV-1 into target cells and is in clinical trials for development as a topical microbicide. Its mechanism of action against R5 HIV-1, the HIV-1 variant implicated in transmission across individuals, remains poorly understood. Using docking and fully atomistic MD simulations, we find that SPL7013 binds tightly to R5 gp120 in the gp120-CD4 complex but weakly to gp120 alone. Further, the binding, although to multiple regions of gp120, does not occlude the CD4 binding site on gp120, suggesting that SPL7013 does not prevent the binding of R5 gp120 to CD4. Using MD simulations to compute binding energies of several docked structures, we find that SPL7013 binding to gp120 significantly weakens the gp120-CD4 complex. Finally, we use steered molecular dynamics (SMD) to study the kinetics of the dissociation of the gp120-CD4 complex in the absence of the dendrimer and with the dendrimer bound in each of the several stable configurations to gp120. We find that SPL7013 significantly lowers the force required to rupture the gp120-CD4 complex and accelerates its dissociation. Taken together, our findings suggest that SPL7013 compromises the stability of the R5 gp120-CD4 complex, potentially preventing the accrual of the requisite number of gp120-CD4 complexes across the virus-cell interface, thereby blocking virus entry.The poly (l-lysine)-based SPL7013 dendrimer with naphthalene disulphonate surface groups blocks the entry of HIV-1 into target cells and is in clinical trials for development as a topical microbicide. Its mechanism of action against R5 HIV-1, the HIV-1 variant implicated in transmission across individuals, remains poorly understood. Using docking and fully atomistic MD simulations, we find that SPL7013 binds tightly to R5 gp120 in the gp120-CD4 complex but weakly to gp120 alone. Further, the binding, although to multiple regions of gp120, does not occlude

  10. Fast feedback for linear colliders

    SciTech Connect

    Hendrickson, L.; Adolphsen, C.; Allison, S.; Gromme, T.; Grossberg, P.; Himel, T.; Krauter, K.; MacKenzie, R.; Minty, M.; Sass, R.

    1995-05-01

    A fast feedback system provides beam stabilization for the SLC. As the SLC is in some sense a prototype for future linear colliders, this system may be a prototype for future feedbacks. The SLC provides a good base of experience for feedback requirements and capabilities as well as a testing ground for performance characteristics. The feedback system controls a wide variety of machine parameters throughout the SLC and associated experiments, including regulation of beam position, angle, energy, intensity and timing parameters. The design and applications of the system are described, in addition to results of recent performance studies.

  11. Grafting of abciximab to a microbubble-based ultrasound contrast agent for targeting to platelets expressing GP IIb/IIIa - characterization and in vitro testing.

    PubMed

    Della Martina, A; Allémann, E; Bettinger, T; Bussat, P; Lassus, A; Pochon, S; Schneider, M

    2008-03-01

    Abciximab-grafted ultrasound sensitive microbubbles were developed for the diagnosis of stroke. The antibody fragment abciximab, which binds to the GP IIb/IIIa and alpha v beta 3 receptors expressed by activated platelets, was chosen because most ischemic strokes are due to arterial thrombi that are mainly composed of platelets. The abciximab antibody fragment was activated by reduction of the disulfide bond for grafting on the microbubbles. The suspension was freeze-dried after the grafting was performed directly on the formed microbubbles. Quantification of the amounts of abciximab present on the surface of the microbubbles was assessed semi-quantitatively by flow cytometry, and quantitatively using radio-labeled abciximab. A protocol for human and rat platelets deposition and fixation was implemented and the expression of the GP IIb/IIIa receptor was validated by immunostaining. The abciximab-grafted microbubbles showed high static and dynamic binding to fixed platelets. Detection by ultrasonography of microbubbles bound on white and red clots gave higher signals compared to Sono Vue microbubbles.

  12. The Very Large Hadron Collider: The farthest energy frontier

    SciTech Connect

    Barletta, William A.

    2001-06-21

    The Very Large Hadron Collider (or Eloisatron) represents what may well be the final step on the energy frontier of accelerator-based high energy physics. While an extremely high luminosity proton collider at 100-200 TeV center of mass energy can probably be built in one step with LHC technology, that machine would cost more than what is presently politically acceptable. This talk summarizes the strategies of collider design including staged deployment, comparison with electron-positron colliders, opportunities for major innovation, and the technical challenges of reducing costs to manageable proportions. It also presents the priorities for relevant R and D for the next few years.

  13. Comparing Tsallis and Boltzmann temperatures from relativistic heavy ion collider and large hadron collider heavy-ion data

    NASA Astrophysics Data System (ADS)

    Gao, Y.-Q.; Liu, F.-H.

    2016-03-01

    The transverse momentum spectra of charged particles produced in Au + Au collisions at the relativistic heavy ion collider and in Pb + Pb collisions at the large hadron collider with different centrality intervals are described by the multisource thermal model which is based on different statistic distributions for a singular source. Each source in the present work is described by the Tsallis distribution and the Boltzmann distribution, respectively. Then, the interacting system is described by the (two-component) Tsallis distribution and the (two-component) Boltzmann distribution, respectively. The results calculated by the two distributions are in agreement with the experimental data of the Solenoidal Tracker At Relativistic heavy ion collider, Pioneering High Energy Nuclear Interaction eXperiment, and A Large Ion Collider Experiment Collaborations. The effective temperature parameters extracted from the two distributions on the descriptions of heavy-ion data at the relativistic heavy ion collider and large hadron collider are obtained to show a linear correlation.

  14. Bouncing and Colliding Branes

    SciTech Connect

    Lehners, Jean-Luc

    2007-11-20

    In a braneworld description of our universe, we must allow for the possibility of having dynamical branes around the time of the big bang. Some properties of such domain walls in motion are discussed here, for example the ability of negative-tension domain walls to bounce off spacetime singularities and the consequences for cosmological perturbations. In this context, we will also review a colliding branes solution of heterotic M-theory that has been proposed as a model for early universe cosmology.

  15. Accelerators, Colliders, and Snakes

    NASA Astrophysics Data System (ADS)

    Courant, Ernest D.

    2003-12-01

    The author traces his involvement in the evolution of particle accelerators over the past 50 years. He participated in building the first billion-volt accelerator, the Brookhaven Cosmotron, which led to the introduction of the "strong-focusing" method that has in turn led to the very large accelerators and colliders of the present day. The problems of acceleration of spin-polarized protons are also addressed, with discussions of depolarizing resonances and "Siberian snakes" as a technique for mitigating these resonances.

  16. Colliding crystalline beams

    SciTech Connect

    Wei, J.; Sessler, A.M.

    1998-08-01

    The understanding of crystalline beams has advanced to the point where one can now, with reasonable confidence, undertake an analysis of the luminosity of colliding crystalline beams. Such a study is reported here. It is necessary to observe the criteria, previously stated, for the creation and stability of crystalline beams. This requires, firstly, the proper design of a lattice. Secondly, a crystal must be formed, and this can usually be done at various densities. Thirdly, the crystals in a colliding-beam machine are brought into collision. The authors study all of these processes using the molecular dynamics (MD) method. The work parallels what was done previously, but the new part is to study the crystal-crystal interaction in collision. They initially study the zero-temperature situation. If the beam-beam force (or equivalent tune shift) is too large then overlapping crystals can not be created (rather two spatially separated crystals are formed). However, if the beam-beam force is less than but comparable to that of the space-charge forces between the particles, they find that overlapping crystals can be formed and the beam-beam tune shift can be of the order of unity. Operating at low but non-zero temperature can increase the luminosity by several orders of magnitude over that of a usual collider. The construction of an appropriate lattice, and the development of adequately strong cooling, although theoretically achievable, is a challenge in practice.

  17. Estradiol and progesterone-mediated regulation of P-gp in P-gp overexpressing cells (NCI-ADR-RES) and placental cells (JAR).

    PubMed

    Coles, Lisa D; Lee, Insong J; Voulalas, Pamela J; Eddington, Natalie D

    2009-01-01

    The effect of progesterone and estrogen treatment on the expression and function of P-glycoprotein (P-gp) was evaluated in JAR cells and a P-gp overexpressing cell line, NCI-ADR-RES. Western blot analysis and real-time Q-PCR were used to evaluate P-gp protein and MDR1 mRNA expression respectively in the cells following incubation with progesterone (P4) and/or beta-estradiol (E2). Cellular uptake studies of the P-gp substrates, saquinavir and paclitaxel, were performed to evaluate function. Treatment with either E2 or P4 resulted in a significant increase in P-gp protein levels in the NCI-ADR-RES cells at concentrations of or greater than 100 nM or 10 nM, respectively. JAR cells also had increased levels of P-gp with 100 nM of P4 but were much more sensitive to E2 showing increased P-gp at a concentration of 1 nM. Furthermore, E2 or P4 treatment resulted in a significant decrease in cellular uptake of the P-gp substrates tested in these cells lines. Based on mRNA quantitation, a transient increase (2-fold) in MDR1 levels was observed at 8 h postincubation with either E2 or P4, while MDR1 levels remained high in the JAR cells treated with E2 for 72 h postincubation. The addition of actinomycin D, a transcription inhibitor negated the increase in P-gp by P4 and E2. P4 and E2 increase P-gp expression and function in NCI-ADR-RES and JAR cells with the ERalpha-expressing cells (JAR) much more sensitive to E2. Furthermore, transcriptional regulation by E2 and P4 likely contributes to the modulation of P-gp levels.

  18. The consequence of regional gradients of P-gp and CYP3A4 for drug-drug interactions by P-gp inhibitors and the P-gp/CYP3A4 interplay in the human intestine ex vivo.

    PubMed

    Li, Ming; de Graaf, Inge A M; van de Steeg, Evita; de Jager, Marina H; Groothuis, Geny M M

    2017-04-01

    Intestinal P-gp and CYP3A4 work coordinately to reduce the intracellular concentration of drugs, and drug-drug interactions (DDIs) based on this interplay are of clinical importance and require pre-clinical investigation. Using precision-cut intestinal slices (PCIS) of human jejunum, ileum and colon, we investigated the P-gp/CYP3A4 interplay and related DDIs with P-gp inhibitors at the different regions of the human intestine with quinidine (Qi), dual substrate of P-gp and CYP3A4, as probe. All the P-gp inhibitors increased the intracellular concentrations of Qi by 2.1-2.6 fold in jejunum, 2.6-3.8 fold in ileum but only 1.2-1.3 fold in colon, in line with the different P-gp expression in these intestinal regions. The selective P-gp inhibitors (CP100356 and PSC833) enhanced 3-hydroxy-quinidine (3OH-Qi) in jejunum and ileum, while dual inhibitors of P-gp and CYP3A4 (verapamil and ketoconazole) decreased the 3OH-Qi production, despite of the increased intracellular Qi concentration, due to inhibition of CYP3A4. The outcome of DDIs based on P-gp/CYP3A4 interplay, shown as remarkable changes in the intracellular concentration of both the parent drug and the metabolite, varied among the intestinal regions, probably due to the different expression of P-gp and CYP3A4, and were different from those found in rat PCIS, which may have important implications for the disposition and toxicity of drugs and their metabolites.

  19. Lattice of the NICA Collider Rings

    SciTech Connect

    Sidorin, Anatoly; Kozlov, Oleg; Meshkov, Igor; Mikhaylov, Vladimir; Trubnikov, Grigoriy; Lebedev, Valeri Nagaitsev, Sergei; Senichev, Yurij; /Julich, Forschungszentrum

    2010-05-01

    The Nuclotron-based Ion Collider fAcility (NICA) is a new accelerator complex being constructed at JINR. It is designed for collider experiments with ions and protons and has to provide ion-ion (Au{sup 79+}) and ion-proton collisions in the energy range 1 {divided_by} 4.5 GeV/n and collisions of polarized proton-proton and deuteron-deuteron beams. Collider conceptions with constant {gamma}{sub tr} and with possibility of its variation are considered. The ring has the racetrack shape with two arcs and two long straight sections. Its circumference is about 450m. The straight sections are optimized to have {beta}* {approx} 35cm in two IPs and a possibility of final betatron tune adjustment.

  20. Educational expectations of GP trainers. A EURACT needs analysis.

    PubMed

    Guldal, Dilek; Windak, Adam; Maagaard, Roar; Allen, Justin; Kjaer, Niels K

    2012-12-01

    In this background paper, we discuss the educational needs of family medicine teachers and trainers in the light of a EURACT (European Academy of Teachers in General Practice) project aimed at the development of a European framework for the professional development of general practice (GP) educators. There is evidence that the ideal GP educator would benefit from systematic training in teaching skills. Although international literature indicates that such skills training should be in supervision, feedback, assessment and educational management, it is not clear if these needs vary between trainers who teach general practice in different settings and environments. Needs assessment: Recently EURACT, in collaboration with partners from five EU countries and Turkey, set up a project aimed at the development of a comprehensive 'training the trainers' programme. The project included a baseline survey of perceived educational needs and wants among both novice and expert European GP educators. The survey demonstrated that the educational needs of GP educators did not vary much in the content areas in which training was required throughout Europe but did vary in the level and depth of knowledge needed; this depended on their experience and level of expertise as teachers. Based on the information gathered and experience gained from previous EURACT courses, a Leonardo da Vinci project has developed and launched a comprehensive programme with courses at three levels of participant expertise, to address the personal learning needs of GP educators.

  1. A fusion intermediate gp41 immunogen elicits neutralizing antibodies to HIV-1.

    PubMed

    Lai, Rachel P J; Hock, Miriam; Radzimanowski, Jens; Tonks, Paul; Hulsik, David Lutje; Effantin, Gregory; Seilly, David J; Dreja, Hanna; Kliche, Alexander; Wagner, Ralf; Barnett, Susan W; Tumba, Nancy; Morris, Lynn; LaBranche, Celia C; Montefiori, David C; Seaman, Michael S; Heeney, Jonathan L; Weissenhorn, Winfried

    2014-10-24

    The membrane-proximal external region (MPER) of the human immunodeficiency virus, type 1 (HIV-1) envelope glycoprotein subunit gp41 is targeted by potent broadly neutralizing antibodies 2F5, 4E10, and 10E8. These antibodies recognize linear epitopes and have been suggested to target the fusion intermediate conformation of gp41 that bridges viral and cellular membranes. Anti-MPER antibodies exert different degrees of membrane interaction, which is considered to be the limiting factor for the generation of such antibodies by immunization. Here we characterize a fusion intermediate conformation of gp41 (gp41(int)-Cys) and show that it folds into an elongated ∼ 12-nm-long extended structure based on small angle x-ray scattering data. Gp41(int)-Cys was covalently linked to liposomes via its C-terminal cysteine and used as immunogen. The gp41(int)-Cys proteoliposomes were administered alone or in prime-boost regimen with trimeric envelope gp140(CA018) in guinea pigs and elicited high anti-gp41 IgG titers. The sera interacted with a peptide spanning the MPER region, demonstrated competition with broadly neutralizing antibodies 2F5 and 4E10, and exerted modest lipid binding, indicating the presence of MPER-specific antibodies. Although the neutralization potency generated solely by gp140(CA018) was higher than that induced by gp41(int)-Cys, the majority of animals immunized with gp41(int)-Cys proteoliposomes induced modest breadth and potency in neutralizing tier 1 pseudoviruses and replication-competent simian/human immunodeficiency viruses in the TZM-bl assay as well as responses against tier 2 HIV-1 in the A3R5 neutralization assay. Our data thus demonstrate that liposomal gp41 MPER formulation can induce neutralization activity, and the strategy serves to improve breadth and potency of such antibodies by improved vaccination protocols.

  2. Designing a soluble near full-length HIV-1 gp41 trimer.

    PubMed

    Gao, Guofen; Wieczorek, Lindsay; Peachman, Kristina K; Polonis, Victoria R; Alving, Carl R; Rao, Mangala; Rao, Venigalla B

    2013-01-04

    The HIV-1 envelope spike is a trimer of heterodimers composed of an external glycoprotein gp120 and a transmembrane glycoprotein gp41. gp120 initiates virus entry by binding to host receptors, whereas gp41 mediates fusion between viral and host membranes. Although the basic pathway of HIV-1 entry has been extensively studied, the detailed mechanism is still poorly understood. Design of gp41 recombinants that mimic key intermediates is essential to elucidate the mechanism as well as to develop potent therapeutics and vaccines. Here, using molecular genetics and biochemical approaches, a series of hypotheses was tested to overcome the extreme hydrophobicity of HIV-1 gp41 and design a soluble near full-length gp41 trimer. The two long heptad repeat helices HR1 and HR2 of gp41 ectodomain were mutated to disrupt intramolecular HR1-HR2 interactions but not intermolecular HR1-HR1 interactions. This resulted in reduced aggregation and improved solubility. Attachment of a 27-amino acid foldon at the C terminus and slow refolding channeled gp41 into trimers. The trimers appear to be stabilized in a prehairpin-like structure, as evident from binding of a HR2 peptide to exposed HR1 grooves, lack of binding to hexa-helical bundle-specific NC-1 mAb, and inhibition of virus neutralization by broadly neutralizing antibodies 2F5 and 4E10. Fusion to T4 small outer capsid protein, Soc, allowed display of gp41 trimers on the phage nanoparticle. These approaches for the first time led to the design of a soluble gp41 trimer containing both the fusion peptide and the cytoplasmic domain, providing insights into the mechanism of entry and development of gp41-based HIV-1 vaccines.

  3. HIV Subtypes B and C gp120 and Methamphetamine Interaction: Dopaminergic System Implicates Differential Neuronal Toxicity.

    PubMed

    Samikkannu, Thangavel; Rao, Kurapati V K; Salam, Abdul Ajees Abdul; Atluri, Venkata S R; Kaftanovskaya, Elena M; Agudelo, Marisela; Perez, Suray; Yoo, Changwon; Raymond, Andrea D; Ding, Hong; Nair, Madhavan P N

    2015-06-09

    HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, DAT, CaMKs and CREBP transcription. Both the structural sequence and modeling studies demonstrated that clade B gp120 in V1-V4, α -2 and N-glycosylated sites are distinct from clade C gp120. The distinct structure and sequence variation of clade B gp120 differentially impact DRD-2, DAT, CaMK II and CaMK IV mRNA, protein and intracellular expression compared to clade C gp120. However, CREB transcription is upregulated by both clade B and C gp120, and METH co-treatment potentiated these effects. In conclusion, distinct structural sequences of HIV-1 clade B and C gp120 differentially regulate the dopaminergic pathway and METH potentiates neurotoxicity.

  4. Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes

    PubMed Central

    Garry, Courtney E; Garry, Robert F

    2008-01-01

    Background Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV) form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP) encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. Results Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G), were established for Thogoto virus (THOV) GP and Autographa california multiple NPV (AcMNPV) GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. Conclusion These results suggest that proteins in the GP64 superfamily are class III penetrenes. PMID:18282283

  5. The Stanford Linear Collider

    SciTech Connect

    Seeman, J.T.

    1990-10-01

    The Stanford Linear Collider (SLC) has been in operation for several years with the initial and accelerator physics experiments just completed. A synopsis of these results is included. The second round of experiments is now under preparation to install the new physics detector (SLD) in Fall 1990 and to increase the luminosity significantly by late 1991. Collisions at high intensity and with polarized electrons are planned. Many beam dynamics and technological advances are in progress to meet these goals. 10 refs., 15 figs., 1 tab.

  6. Muon Colliders and Neutrino Factories

    SciTech Connect

    Geer, Steve; /Fermilab

    2009-11-01

    Over the past decade, there has been significant progress in developing the concepts and technologies needed to produce, capture, and accelerate {Omicron}(10{sup 21}) muons per year. These developments have paved the way for a new type of neutrino source (neutrino factory) and a new type of very high energy lepton-antilepton collider (muon collider). This article reviews the motivation, design, and research and development for future neutrino factories and muon colliders.

  7. Muon colliders and neutrino factories

    SciTech Connect

    Geer, S.; /Fermilab

    2010-09-01

    Over the last decade there has been significant progress in developing the concepts and technologies needed to produce, capture and accelerate {Omicron}(10{sup 21}) muons/year. This development prepares the way for a new type of neutrino source (Neutrino Factory) and a new type of very high energy lepton-antilepton collider (Muon Collider). This article reviews the motivation, design and R&D for Neutrino Factories and Muon Colliders.

  8. Physics at a photon collider

    SciTech Connect

    Stefan Soldner-Rembold

    2002-09-30

    A Photon Collider will provide unique opportunities to study the SM Higgs boson and to determine its properties. MSSM Higgs bosons can be discovered at the Photon Collider for scenarios where they might escape detection at the LHC. As an example for the many other physics topics which can be studied at a Photon Collider, recent results on Non-Commutative Field Theories are also discussed.

  9. The Next Linear Collider: NLC2001

    SciTech Connect

    D. Burke et al.

    2002-01-14

    Recent studies in elementary particle physics have made the need for an e{sup +}e{sup -} linear collider able to reach energies of 500 GeV and above with high luminosity more compelling than ever [1]. Observations and measurements completed in the last five years at the SLC (SLAC), LEP (CERN), and the Tevatron (FNAL) can be explained only by the existence of at least one particle or interaction that has not yet been directly observed in experiment. The Higgs boson of the Standard Model could be that particle. The data point strongly to a mass for the Higgs boson that is just beyond the reach of existing colliders. This brings great urgency and excitement to the potential for discovery at the upgraded Tevatron early in this decade, and almost assures that later experiments at the LHC will find new physics. But the next generation of experiments to be mounted by the world-wide particle physics community must not only find this new physics, they must find out what it is. These experiments must also define the next important threshold in energy. The need is to understand physics at the TeV energy scale as well as the physics at the 100-GeV energy scale is now understood. This will require both the LHC and a companion linear electron-positron collider. A first Zeroth-Order Design Report (ZDR) [2] for a second-generation electron-positron linear collider, the Next Linear Collider (NLC), was published five years ago. The NLC design is based on a high-frequency room-temperature rf accelerator. Its goal is exploration of elementary particle physics at the TeV center-of-mass energy, while learning how to design and build colliders at still higher energies. Many advances in accelerator technologies and improvements in the design of the NLC have been made since 1996. This Report is a brief update of the ZDR.

  10. Majorana Higgses at colliders

    NASA Astrophysics Data System (ADS)

    Nemevšek, Miha; Nesti, Fabrizio; Vasquez, Juan Carlos

    2017-04-01

    Collider signals of heavy Majorana neutrino mass origin are studied in the minimal Left-Right symmetric model, where their mass is generated spontaneously together with the breaking of lepton number. The right-handed triplet Higgs boson Δ, responsible for such breaking, can be copiously produced at the LHC through the Higgs portal in the gluon fusion and less so in gauge mediated channels. At Δ masses below the opening of the V V decay channel, the two observable modes are pair-production of heavy neutrinos via the triplet gluon fusion gg → Δ → NN and pair production of triplets from the Higgs h → ΔΔ → 4 N decay. The latter features tri- and quad same-sign lepton final states that break lepton number by four units and have no significant background. In both cases up to four displaced vertices may be present and their displacement may serve as a discriminating variable. The backgrounds at the LHC, including the jet fake rate, are estimated and the resulting sensitivity to the Left-Right breaking scale extends well beyond 10 TeV. In addition, sub-dominant radiative modes are surveyed: the γγ, Zγ and lepton flavour violating ones. Finally, prospects for Δ signals at future e + e - colliders are presented.

  11. Correlation femtoscopy study at energies available at the JINR Nuclotron-based Ion Collider fAcility and the BNL Relativistic Heavy Ion Collider within a viscous hydrodynamic plus cascade model

    NASA Astrophysics Data System (ADS)

    Batyuk, P.; Karpenko, Iu.; Lednicky, R.; Malinina, L.; Mikhaylov, K.; Rogachevsky, O.; Wielanek, D.

    2017-08-01

    Correlation femtoscopy allows one to measure the space-time characteristics of particle production in relativistic heavy-ion collisions due to the effects of quantum statistics (QS) and final state interactions (FSIs). The main features of the femtoscopy measurements at top RHIC and LHC energies are considered as a manifestation of strong collective flow and are well interpreted within hydrodynamic models employing equation of state (EoS) with a crossover type transition between quark-gluon plasma (QGP) and hadron gas phases. The femtoscopy at lower energies was intensively studied at AGS and SPS accelerators and is being studied now in the Beam Energy Scan program (BES) at the BNL Relativistic Heavy Ion Collider in the context of exploration of the QCD phase diagram. In this article we present femtoscopic observables calculated for Au-Au collisions at √{sN N}=7.7 -62.4 GeV in a viscous hydro + cascade model vHLLE+UrQMD and their dependence on the EoS of thermalized matter.

  12. Structural and Functional Properties of Peptides Based on the N-terminus of HIV-1 gp41 and the C-terminus of the Amyloid-Beta Protein

    PubMed Central

    Gordon, Larry M.; Nisthal, Alex; Lee, Andy B.; Eskandari, Sepehr; Ruchala, Piotr; Jung, Chun-Ling; Waring, Alan J.; Mobley, Patrick W.

    2008-01-01

    Given their high alanine and glycine levels, plaque formation, α-helix to β-sheet interconversion and fusogenicity, FP (i.e., the N-terminal fusion peptide of HIV-1 gp41; 23 residues) and amyloids were proposed as belonging to the same protein superfamily. Here, we further test whether FP may exhibit ‘amyloid-like’ characteristics, by contrasting its structural and functional properties with those of Aβ(26–42), a 17-residue peptide from the C-terminus of the amyloid-beta protein responsible for Alzheimer’s. FTIR spectroscopy, electron microscopy, light scattering and predicted amyloid structure aggregation (PASTA) indicated that aqueous FP and Aβ(26–42) formed similar networked β-sheet fibrils, although the FP fibril interactions were weaker. FP and Aβ(26–42) both lysed and aggregated human erythrocytes, with the hemolysis-onsets correlated with the conversion of α-helix to β-sheet for each peptide in liposomes. Congo red (CR), a marker of amyloid plaques in situ, similarly inhibited either FP- or Aβ(26–42)-induced hemolysis, and surface plasmon resonance indicated that this may be due to direct CR-peptide binding. These findings suggest that membrane-bound β-sheets of FP may contribute to the cytopathicity of HIV in vivo through an amyloid-type mechanism, and support the classification of HIV-1 FP as an ‘amyloid homolog’ (or ‘amylog’). PMID:18515070

  13. Project of the Nuclotron-based Ion Collider fAcility (NICA) at JINR, Dubna: Perspectives of heavy ion and spin physics

    SciTech Connect

    Lednicky, Richard

    2009-08-04

    One of the main directions of the research program at the Joint Institute for Nuclear Research (JINR) in Dubna is the relativistic nuclear and spin physics. The present basic facility for this research is the 6 A GeV superconducting synchrotron--Nuclotron. In the coming years, the new JINR flagship program assumes the experimental study of hot and dense strongly interacting QCD matter and polarization phenomena at the new JINR facility. This goal is proposed to be reached by (i) development of the existing Nuclotron accelerator facility as a basis for generation of intense beams over atomic mass range from protons to uranium and light polarized ions, (ii) design and construction of the Nuclotron-based Heavy Ion Collider fAcility (NICA) with the maximum nucleon-nucleon center-of-mass energy of {radical}(S{sub NN}) = 9 GeV and averaged luminosity 10{sup 27} cm{sup -2} s{sup -1} for U+U collisions, and (iii) design and construction of the Multipurpose Particle Detector (MPD) and Spin Physics Detector (SPD) at intersecting beams. Realization of the project will lead to unique conditions for research activity of the world community.

  14. The future of the Large Hadron Collider and CERN.

    PubMed

    Heuer, Rolf-Dieter

    2012-02-28

    This paper presents the Large Hadron Collider (LHC) and its current scientific programme and outlines options for high-energy colliders at the energy frontier for the years to come. The immediate plans include the exploitation of the LHC at its design luminosity and energy, as well as upgrades to the LHC and its injectors. This may be followed by a linear electron-positron collider, based on the technology being developed by the Compact Linear Collider and the International Linear Collider collaborations, or by a high-energy electron-proton machine. This contribution describes the past, present and future directions, all of which have a unique value to add to experimental particle physics, and concludes by outlining key messages for the way forward.

  15. Connecting, Supporting, Colliding: The Work-Based Interactions of Young LGBQ-Identifying Workers and Older Queer Colleagues

    ERIC Educational Resources Information Center

    Willis, Paul

    2010-01-01

    While attention has been given to older employees' experiences of sexuality-based discrimination and harassment, this paper explores young lesbian, gay, bisexual, and queer identifying employees' (18-26 years old) accounts of working with queer coworkers and managers in Australian workplaces. Two sets of relationships are evidenced and discussed:…

  16. Connecting, Supporting, Colliding: The Work-Based Interactions of Young LGBQ-Identifying Workers and Older Queer Colleagues

    ERIC Educational Resources Information Center

    Willis, Paul

    2010-01-01

    While attention has been given to older employees' experiences of sexuality-based discrimination and harassment, this paper explores young lesbian, gay, bisexual, and queer identifying employees' (18-26 years old) accounts of working with queer coworkers and managers in Australian workplaces. Two sets of relationships are evidenced and discussed:…

  17. Collider Signal I :. Resonance

    NASA Astrophysics Data System (ADS)

    Tait, Tim M. P.

    2010-08-01

    These TASI lectures were part of the summer school in 2008 and cover the collider signal associated with resonances in models of physics beyond the Standard Model. I begin with a review of the Z boson, one of the best-studied resonances in particle physics, and review how the Breit-Wigner form of the propagator emerges in perturbation theory and discuss the narrow width approximation. I review how the LEP and SLAC experiments could use the kinematics of Z events to learn about fermion couplings to the Z. I then make a brief survey of models of physics beyond the Standard Model which predict resonances, and discuss some of the LHC observables which we can use to discover and identify the nature of the BSM physics. I finish up with a discussion of the linear moose that one can use for an effective theory description of a massive color octet vector particle.

  18. Positrons for linear colliders

    SciTech Connect

    Ecklund, S.

    1987-11-01

    The requirements of a positron source for a linear collider are briefly reviewed, followed by methods of positron production and production of photons by electromagnetic cascade showers. Cross sections for the electromagnetic cascade shower processes of positron-electron pair production and Compton scattering are compared. A program used for Monte Carlo analysis of electromagnetic cascades is briefly discussed, and positron distributions obtained from several runs of the program are discussed. Photons from synchrotron radiation and from channeling are also mentioned briefly, as well as positron collection, transverse focusing techniques, and longitudinal capture. Computer ray tracing is then briefly discussed, followed by space-charge effects and thermal heating and stress due to showers. (LEW)

  19. ALPs at colliders

    NASA Astrophysics Data System (ADS)

    Mimasu, Ken; Sanz, Verónica

    2015-06-01

    New pseudo-scalars, often called axion-like particles (ALPs), abound in model-building and are often associated with the breaking of a new symmetry. Traditional searches and indirect bounds are limited to light axions, typically in or below the KeV range for ALPs coupled to photons. We present collider bounds on ALPs from mono-γ, tri-γ and mono-jet searches in a model independent fashion, as well as the prospects for the LHC and future machines. We find that they are complementary to existing searches, as they are sensitive to heavier ALPs and have the capability to cover an otherwise inaccessible region of parameter space. We also show that, assuming certain model dependent correlations between the ALP coupling to photons and gluons as well as considering the validity of the effective description of ALP interactions, mono-jet searches are in fact more suitable and effective in indirectly constraining ALP scenarios.

  20. Soviet Hadron Collider

    NASA Astrophysics Data System (ADS)

    Kotchetkov, Dmitri

    2017-01-01

    Rapid growth of the high energy physics program in the USSR during 1960s-1970s culminated with a decision to build the Accelerating and Storage Complex (UNK) to carry out fixed target and colliding beam experiments. The UNK was to have three rings. One ring was to be built with conventional magnets to accelerate protons up to the energy of 600 GeV. The other two rings were to be made from superconducting magnets, each ring was supposed to accelerate protons up to the energy of 3 TeV. The accelerating rings were to be placed in an underground tunnel with a circumference of 21 km. As a 3 x 3 TeV collider, the UNK would make proton-proton collisions with a luminosity of 4 x 1034 cm-1s-1. Institute for High Energy Physics in Protvino was a project leading institution and a site of the UNK. Accelerator and detector research and development studies were commenced in the second half of 1970s. State Committee for Utilization of Atomic Energy of the USSR approved the project in 1980, and the construction of the UNK started in 1983. Political turmoil in the Soviet Union during late 1980s and early 1990s resulted in disintegration of the USSR and subsequent collapse of the Russian economy. As a result of drastic reduction of funding for the UNK, in 1993 the project was restructured to be a 600 GeV fixed target accelerator only. While the ring tunnel and proton injection line were completed by 1995, and 70% of all magnets and associated accelerator equipment were fabricated, lack of Russian federal funding for high energy physics halted the project at the end of 1990s.

  1. GP-B error modeling and analysis

    NASA Technical Reports Server (NTRS)

    Hung, J. C.

    1982-01-01

    Individual source errors and their effects on the accuracy of the Gravity Probe B (GP-B) experiment were investigated. Emphasis was placed on: (1) the refinement of source error identification and classifications of error according to their physical nature; (2) error analysis for the GP-B data processing; and (3) measurement geometry for the experiment.

  2. Insight derived from molecular dynamics simulations into molecular motions, thermodynamics and kinetics of HIV-1 gp120.

    PubMed

    Sang, Peng; Yang, Li-Quan; Ji, Xing-Lai; Fu, Yun-Xin; Liu, Shu-Qun

    2014-01-01

    Although the crystal structures of the HIV-1 gp120 core bound and pre-bound by CD4 are known, the details of dynamics involved in conformational equilibrium and transition in relation to gp120 function have remained elusive. The homology models of gp120 comprising the N- and C-termini and loops V3 and V4 in the CD4-bound and CD4-unbound states were built and subjected to molecular dynamics (MD) simulations to investigate the differences in dynamic properties and molecular motions between them. The results indicate that the CD4-bound gp120 adopted a more compact and stable conformation than the unbound form during simulations. For both the unbound and bound gp120, the large concerted motions derived from essential dynamics (ED) analyses can influence the size/shape of the ligand-binding channel/cavity of gp120 and, therefore, were related to its functional properties. The differences in motion direction between certain structural components of these two forms of gp120 were related to the conformational interconversion between them. The free energy calculations based on the metadynamics simulations reveal a more rugged and complex free energy landscape (FEL) for the unbound than for the bound gp120, implying that gp120 has a richer conformational diversity in the unbound form. The estimated free energy difference of ∼-6.0 kJ/mol between the global minimum free energy states of the unbound and bound gp120 indicates that gp120 can transform spontaneously from the unbound to bound states, revealing that the bound state represents a high-probability "ground state" for gp120 and explaining why the unbound state resists crystallization. Our results provide insight into the dynamics-and-function relationship of gp120, and facilitate understandings of the thermodynamics, kinetics and conformational control mechanism of HIV-1 gp120.

  3. Insights into vaccine development for acquired immune deficiency syndrome from crystal structures of human immunodeficiency virus-1 gp41 and equine infectious anemia virus gp45.

    PubMed

    Duan, Liangwei; Du, Jiansen; Liu, Xinqi

    2015-10-01

    An effective vaccine against acquired immune deficiency syndrome is still unavailable after dozens of years of striving. The glycoprotein gp41 of human immunodeficiency virus is a good candidate as potential immunogen because of its conservation and relatively low glycosylation. As a reference of human immunodeficiency virus gp41, gp45 from equine infectious anemia virus (EIAV) could be used for comparison because both wild-type and vaccine strain of EIAV have been extensively studied. From structural studies of these proteins, the conformational changes during viral invasion could be unveiled, and a more effective acquired immune deficiency syndrome vaccine immunogen might be designed based on this information.

  4. Screening and Identification of ssDNA Aptamer for Human GP73

    PubMed Central

    Du, Jingchun; Hong, Jianming; Xu, Chun; Cai, Yuanyuan; Xiang, Bo; Zhou, Chengbo; Xu, Xia

    2015-01-01

    As one tumor marker of HCC, Golgi Protein 73 (GP73) is given more promise in the early diagnosis of HCC, and aptamers have been developed to compete with antibodies as biorecognition probes in different detection system. In this study, we utilized GP73 to screen specific ssDNA aptamers by SELEX technique. First, GP73 proteins were expressed and purified by prokaryotic expression system and Nickle ion affinity chromatography, respectively. At the same time, the immunogenicity of purified GP73 was confirmed by Western blotting. The enriched ssDNA library with high binding capacity for GP73 was obtained after ten rounds of SELEX. Then, thirty ssDNA aptamers were sequenced, in which two ssDNA aptamers with identical DNA sequence were confirmed, based on the alignment results, and designated as A10-2. Furthermore, the specific antibody could block the binding of A10-2 to GP73, and the specific binding of A10-2 to GP73 was also supported by the observation that several tumor cell lines exhibited variable expression level of GP73. Significantly, the identified aptamer A10-2 could distinguish normal and cancerous liver tissues. So, our results indicate that the aptamer A10-2 might be developed into one molecular probe to detect HCC from normal liver specimens. PMID:26583119

  5. A single amino acid substitution modulates low-pH-triggered membrane fusion of GP64 protein in Autographa californica and Bombyx mori nucleopolyhedroviruses

    SciTech Connect

    Katou, Yasuhiro; Yamada, Hayato; Ikeda, Motoko; Kobayashi, Michihiro

    2010-09-01

    We have previously shown that budded viruses of Bombyx mori nucleopolyhedrovirus (BmNPV) enter the cell cytoplasm but do not migrate into the nuclei of non-permissive Sf9 cells that support a high titer of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) multiplication. Here we show, using the syncytium formation assay, that low-pH-triggered membrane fusion of BmNPV GP64 protein (Bm-GP64) is significantly lower than that of AcMNPV GP64 protein (Ac-GP64). Mutational analyses of GP64 proteins revealed that a single amino acid substitution between Ac-GP64 H155 and Bm-GP64 Y153 can have significant positive or negative effects on membrane fusion activity. Studies using bacmid-based GP64 recombinant AcMNPV harboring point-mutated ac-gp64 and bm-gp64 genes showed that Ac-GP64 H155Y and Bm-GP64 Y153H substitutions decreased and increased, respectively, the multiplication and cell-to-cell spread of progeny viruses. These results indicate that Ac-GP64 H155 facilitates the low-pH-triggered membrane fusion reaction between virus envelopes and endosomal membranes.

  6. Topics in Collider Physics

    SciTech Connect

    Petriello, Frank J

    2003-08-27

    It is an exciting time for high energy physics. Several experiments are currently exploring uncharted terrain; the next generation of colliders will begin operation in the coming decade. These experiments will together help us understand some of the most puzzling issues in particle physics: the mechanism of electroweak symmetry breaking and the generation of flavor physics. It is clear that the primary goal of theoretical particle physics in the near future is to support and guide this experimental program. These tasks can be accomplished in two ways: by developing experimental signatures for new models which address outstanding problems, and by improving Standard Model predictions for precision observables. We present here several results which advance both of these goals. We begin with a study of non-commutative field theories. It has been suggested that TeV-scale non-commutativity could explain the origin of CP violation in the SM. We identify several distinct signatures of non-commutativity in high energy processes. We also demonstrate the one-loop quantum consistency of a simple spontaneously broken non-commutative U(1) theory; this result is an important preface to any attempt to embed the SM within a non-commutative framework. We then investigate the phenomenology of extra-dimensional theories, which have been suggested recently as solutions to the hierarchy problem of particle physics. We first examine the implications of allowing SM fields to propagate in the full five-dimensional spacetime of the Randall-Sundrum model, which solves the hierarchy problem via an exponential ''warping'' of the Planck scale induced by a five-dimensional anti de-Sitter geometry. In an alternative extra-dimensional theory, in which all SM fields are permitted to propagate in flat extra dimensions, we show that properties of the Higgs boson are significantly modified. Finally, we discuss the next-to-next-to leading order QCD corrections to the dilepton rapidity distribution in

  7. Physics at future hadron colliders

    SciTech Connect

    U. Baur et al.

    2002-12-23

    We discuss the physics opportunities and detector challenges at future hadron colliders. As guidelines for energies and luminosities we use the proposed luminosity and/or energy upgrade of the LHC (SLHC), and the Fermilab design of a Very Large Hadron Collider (VLHC). We illustrate the physics capabilities of future hadron colliders for a variety of new physics scenarios (supersymmetry, strong electroweak symmetry breaking, new gauge bosons, compositeness and extra dimensions). We also investigate the prospects of doing precision Higgs physics studies at such a machine, and list selected Standard Model physics rates.

  8. Hadron collider physics at UCR

    SciTech Connect

    Kernan, A.; Shen, B.C.

    1997-07-01

    This paper describes the research work in high energy physics by the group at the University of California, Riverside. Work has been divided between hadron collider physics and e{sup +}-e{sup {minus}} collider physics, and theoretical work. The hadron effort has been heavily involved in the startup activities of the D-Zero detector, commissioning and ongoing redesign. The lepton collider work has included work on TPC/2{gamma} at PEP and the OPAL detector at LEP, as well as efforts on hadron machines.

  9. Muon collider interaction region design

    DOE PAGES

    Alexahin, Y. I.; Gianfelice-Wendt, E.; Kashikhin, V. V.; ...

    2011-06-02

    Design of a muon collider interaction region (IR) presents a number of challenges arising from low β* < 1 cm, correspondingly large beta-function values and beam sizes at IR magnets, as well as the necessity to protect superconducting magnets and collider detectors from muon decay products. As a consequence, the designs of the IR optics, magnets and machine-detector interface are strongly interlaced and iterative. A consistent solution for the 1.5 TeV center-of-mass muon collider IR is presented. It can too provide an average luminosity of 1034 cm-2s-1 with an adequate protection of magnet and detector components.

  10. QCD at collider energies

    NASA Astrophysics Data System (ADS)

    Nicolaidis, A.; Bordes, G.

    1986-05-01

    We examine available experimental distributions of transverse energy and transverse momentum, obtained at the CERN pp¯ collider, in the context of quantum chromodynamics. We consider the following. (i) The hadronic transverse energy released during W+/- production. This hadronic transverse energy is made out of two components: a soft component which we parametrize using minimum-bias events and a semihard component which we calculate from QCD. (ii) The transverse momentum of the produced W+/-. If the transverse momentum (or the transverse energy) results from a single gluon jet we use the formalism of Dokshitzer, Dyakonov, and Troyan, while if it results from multiple-gluon emission we use the formalism of Parisi and Petronzio. (iii) The relative transverse momentum of jets. While for W+/- production quarks play an essential role, jet production at moderate pT and present energies is dominated by gluon-gluon scattering and therefore we can study the Sudakov form factor of the gluon. We suggest also how through a Hankel transform of experimental data we can have direct access to the Sudakov form factors of quarks and gluons.

  11. When Black Holes Collide

    NASA Technical Reports Server (NTRS)

    Baker, John

    2010-01-01

    Among the fascinating phenomena predicted by General Relativity, Einstein's theory of gravity, black holes and gravitational waves, are particularly important in astronomy. Though once viewed as a mathematical oddity, black holes are now recognized as the central engines of many of astronomy's most energetic cataclysms. Gravitational waves, though weakly interacting with ordinary matter, may be observed with new gravitational wave telescopes, opening a new window to the universe. These observations promise a direct view of the strong gravitational dynamics involving dense, often dark objects, such as black holes. The most powerful of these events may be merger of two colliding black holes. Though dark, these mergers may briefly release more energy that all the stars in the visible universe, in gravitational waves. General relativity makes precise predictions for the gravitational-wave signatures of these events, predictions which we can now calculate with the aid of supercomputer simulations. These results provide a foundation for interpreting expect observations in the emerging field of gravitational wave astronomy.

  12. When Black Holes Collide

    NASA Technical Reports Server (NTRS)

    Baker, John

    2010-01-01

    Among the fascinating phenomena predicted by General Relativity, Einstein's theory of gravity, black holes and gravitational waves, are particularly important in astronomy. Though once viewed as a mathematical oddity, black holes are now recognized as the central engines of many of astronomy's most energetic cataclysms. Gravitational waves, though weakly interacting with ordinary matter, may be observed with new gravitational wave telescopes, opening a new window to the universe. These observations promise a direct view of the strong gravitational dynamics involving dense, often dark objects, such as black holes. The most powerful of these events may be merger of two colliding black holes. Though dark, these mergers may briefly release more energy that all the stars in the visible universe, in gravitational waves. General relativity makes precise predictions for the gravitational-wave signatures of these events, predictions which we can now calculate with the aid of supercomputer simulations. These results provide a foundation for interpreting expect observations in the emerging field of gravitational wave astronomy.

  13. The signatures of doubly charged leptons in future linear colliders

    NASA Astrophysics Data System (ADS)

    Guo, Yu-Chen; Yue, Chong-Xing; Liu, Zhi-Cheng

    2017-08-01

    We discuss the production of the doubly charged leptons in future linear electron positron colliders, such as the International Linear Collider and Compact Linear Collider. Such states are introduced in extended weak-isospin multiplets by composite models. We discuss the production cross section of {e}-γ \\to {L}--{W}+ and carry out analyses for hadronic, semi-leptonic and pure leptonic channels based on the full simulation performance of the silicon detector. The 3- and 5-sigma statistical significance exclusion curves are provided in the model parameter space. It is found that the hadronic channel could offer the most possible detectable signature.

  14. Beam Rounders for Circular Colliders

    SciTech Connect

    A. Burov; S. Nagaitsev; Ya. Derbenev

    2001-07-01

    By means of linear optics, an arbitrary uncoupled beam can be locally transformed into a round (rotation-invariant) state and then back. This provides an efficient way to round beams in the interaction region of circular colliders.

  15. Physicists dream of supersized collider

    NASA Astrophysics Data System (ADS)

    Hao, Cindy

    2015-12-01

    Particle physicists in China are hopeful that the Chinese government will allocate 1 billion yuan (about £104m) to design what would be the world's largest particle accelerator - the Circular Electron Positron Collider (CEPC).

  16. Beam rounders for circular colliders

    SciTech Connect

    A. Burov and S. Nagaitsev

    2002-12-10

    By means of linear optics, an arbitrary uncoupled beam can be locally transformed into a round (rotation-invariant) state and then back. This provides an efficient way to round beams in the interaction region of circular colliders.

  17. CERN Collider, France-Switzerland

    NASA Image and Video Library

    2013-08-23

    This image, acquired by NASA Terra spacecraft, is of the CERN Large Hadron Collider, the world largest and highest-energy particle accelerator laying beneath the French-Swiss border northwest of Geneva yellow circle.

  18. Stable massive particles at colliders

    SciTech Connect

    Fairbairn, M.; Kraan, A.C.; Milstead, D.A.; Sjostrand, T.; Skands, P.; Sloan, T.; /Lancaster U.

    2006-11-01

    We review the theoretical motivations and experimental status of searches for stable massive particles (SMPs) which could be sufficiently long-lived as to be directly detected at collider experiments. The discovery of such particles would address a number of important questions in modern physics including the origin and composition of dark matter in the universe and the unification of the fundamental forces. This review describes the techniques used in SMP-searches at collider experiments and the limits so far obtained on the production of SMPs which possess various colour, electric and magnetic charge quantum numbers. We also describe theoretical scenarios which predict SMPs, the phenomenology needed to model their production at colliders and interactions with matter. In addition, the interplay between collider searches and open questions in cosmology such as dark matter composition are addressed.

  19. [New technology for linear colliders

    SciTech Connect

    McIntyre, P.M.

    1992-08-12

    This report discusses the following topics on research of microwave amplifiers for linear colliders: Context in current microwave technology development; gated field emission for microwave cathodes; cathode fabrication and tests; microwave cathode design using field emitters; and microwave localization.

  20. Complex of a Protective Antibody with its Ebola Virus GP Peptide Epitope: Unusual Features of a Vlambdalx Light Chain

    DTIC Science & Technology

    2008-01-01

    GussIntroduction The Ebola virus causes a severe hemorrhagic fever usually involving uncontrolled viral replication, multiple organ failure, and death...day after challenge.12 The epitope has previously beenmapped to nine residues (EQHHRRTDN, amino acids 405– 413) within the Ebola Zaire GP mucin-like...corresponds to a region of the mucin-like domain of the Ebola Zaire GP. Residues P404–P414 (based on the numbering in Ebola Zaire GP) are unambiguously

  1. Positron sources for Linear Colliders

    SciTech Connect

    Gai Wei; Liu Wanming

    2009-09-02

    Positron beams have many applications and there are many different concepts for positron sources. In this paper, only positron source techniques for linear colliders are covered. In order to achieve high luminosity, a linear collider positron source should have a high beam current, high beam energy, small emittance and, for some applications, a high degree of beam polarization. There are several different schemes presently being developed around the globe. Both the differences between these schemes and their common technical challenges are discussed.

  2. Polarized muon beams for muon collider

    NASA Astrophysics Data System (ADS)

    Skrinsky, A. N.

    1996-11-01

    An option for the production of intense and highly polarized muon beams, suitable for a high-luminosity muon collider, is described briefly. It is based on a multi-channel pion-collection system, narrow-band pion-to-muon decay channels, proper muon spin gymnastics, and ionization cooling to combine all of the muon beams into a single bunch of ultimately low emittance.

  3. Muon muon collider: Feasibility study

    SciTech Connect

    1996-06-18

    A feasibility study is presented of a 2 + 2 TeV muon collider with a luminosity of L = 10{sup 35} cm{sup {minus}2} s{sup {minus}1}. The resulting design is not optimized for performance, and certainly not for cost; however, it does suffice--the authors believe--to allow them to make a credible case, that a muon collider is a serious possibility for particle physics and, therefore, worthy of R and D support so that the reality of, and interest in, a muon collider can be better assayed. The goal of this support would be to completely assess the physics potential and to evaluate the cost and development of the necessary technology. The muon collider complex consists of components which first produce copious pions, then capture the pions and the resulting muons from their decay; this is followed by an ionization cooling channel to reduce the longitudinal and transverse emittance of the muon beam. The next stage is to accelerate the muons and, finally, inject them into a collider ring which has a small beta function at the colliding point. This is the first attempt at a point design and it will require further study and optimization. Experimental work will be needed to verify the validity of diverse crucial elements in the design.

  4. When Rubble Piles Collide...

    NASA Astrophysics Data System (ADS)

    Leinhardt, Z. M.; Richardson, D. C.; Quinn, T.

    1999-01-01

    There is increasing evidence that many or most km-sized bodies in the Solar System may be rubble piles, that is, gravitationally bound aggregates of material susceptible to disruption or distortion by planetary tides (Richardson, Bottke, & Love 1998, Icarus 134, 47). If this is true, then collisions may occur in free space between rubble piles. Here we present preliminary results from a project to map the parameter space of rubble-pile collisions. The results will assist in parameterization of collision outcomes for simulations of Solar System formation and may give insight into scaling laws for catastrophic disruption. We use a direct numerical method (Richardson, Quinn, Stadel, & Lake 1998, submitted) to evolve the particle positions and velocities under the constraints of gravity and physical collisions. We test the dependence of the collision outcomes on the impact speed and impact parameter, as well as the spin and size of the colliding bodies. We use both spheroidal and ellipsoidal shapes, the former as a control and the latter as a more representative model of real bodies. Speeds are kept low so that the maximum strain on the component material does not exceed the crushing strength. This is appropriate for dynamically cool systems, such as in the primordial disk during the early stage of planet formation or possibly in the present-day classical Kuiper Belt. We compare our results to analytic estimates and to stellar system collision models. Other parameters, such as the coefficient of restitution (dissipation), bulk density, and particle resolution will be investigated systematically in future work.

  5. COLLIDE-2: Collisions Into Dust Experiment-2

    NASA Technical Reports Server (NTRS)

    Colwell, Joshua E.

    2002-01-01

    The Collisions Into Dust Experimental (COLLIDE-2) was the second flight of the COLLIDE payload. The payload performs six low-velocity impact experiments to study the collisions that are prevalent in planetary ring systems and in the early stages of planet formation. Each impact experiment is into a target of granular material, and the impacts occur at speeds between 1 and 100 cm/s in microgravity and in a vacuum. The experiments are recorded on digital videotape which is later analyzed. During the period of performance a plan was developed to address some of the technical issues that prevented the first flight of COLLIDE from being a complete success, and also to maximize the scientific return based on the science results from the first flight. The experiment was modified following a series of reviews of the design plan, and underwent extensive testing. The data from the experiment show that the primary goal of identifying transition regimes for low-velocity impacts based on cratering versus accretion was achieved. Following a brief period of storage, the experiment flew regimes for low-velocity impacts based on cratering versus accretion was achieved. as a Hitchhiker payload on the MACH-1 Hitchhiker bridge on STS-108 in December 2001. These data have been analyzed and submitted for publication. That manuscript is attached to this report. The experiment was retrieved in January 2002, and all six impact experiments functioned nominally. Preliminary results were reported at the Lunar and Planetary Science Conference.

  6. Attitudes towards obesity treatment in GP training practices: a focus group study.

    PubMed

    Jochemsen-van der Leeuw, H G A; van Dijk, N; Wieringa-de Waard, M

    2011-08-01

    Both patients and government expect the GP to treat obesity. Previous studies reported a negative attitude of GPs towards this task. Little is known about the attitude of GP trainees. To assess the attitude and other factors that influence the willingness and ability of GP trainees to provide lifestyle interventions for overweight patients. A qualitative study was performed using focus groups, consisting of first- and third-year trainees, GP trainers and teachers. Two researchers analysed the data independently. First-year trainees lack knowledge and a positive attitude. Third-year trainees, although trained in motivational interviewing techniques, lack specific knowledge and feel cheated when discussing eating habits. Trainers are despondent as they rarely observe long-lasting results. Teachers warn the trainees not to have high hopes. The trainers and trainees fear ruining the relationship with their patient, and all make a request for evidence-based multidisciplinary treatment programmes, joint responsibility and an image change in society to stop the epidemic. Trainees do not feel more competent in treating overweight patients successfully over the course of their GP specialty training and GP trainers are not convinced of the success of the treatment of overweight patients. Therefore, it could be equally important to reflect on the GP trainer as a role model as to concentrate on the education of the trainee. Both need a revived attitude and evidence-based treatment programmes, help from policy makers and an attitude change in society are desired.

  7. GP73 — EDRN Public Portal

    Cancer.gov

    The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. GP73 is a type II Golgi transmembrane protein. It processes proteins synthesized in the rough endoplasmic reticulum and assists in the transport of protein cargo through the Golgi apparatus. The expression of the GP73 gene has been observed to be upregulated in response to viral infection. Alternatively spliced transcript variants encoding the same protein have been described for this gene. Kladeny, RD. et al. 2000, found significant up-regulation of GOLPH2 expression in human hepatocyte cells infected with a recombinant adenovirus. EDRN investigator Block, TM et al. 2005, found that GP73 over-expression in serum correlate with liver cancer in woodchucks and humans. Chinnayian's lab reported that GP73 transcript was over-expressed in prostate cancer patients urine sediment (Laxman B. et al. 2008).

  8. Crystal Ball: On the Future High Energy Colliders

    SciTech Connect

    Shiltsev, Vladimir

    2015-09-20

    High energy particle colliders have been in the forefront of particle physics for more than three decades. At present the near term US, European and international strategies of the particle physics community are centered on full exploitation of the physics potential of the Large Hadron Collider (LHC) through its high-luminosity upgrade (HL-LHC). A number of next generation collider facilities have been proposed and are currently under consideration for the medium- and far-future of the accelerator-based high energy physics. In this paper we offer a uniform approach to evaluation of various accelerators based on the feasibility of their energy reach, performance reach and cost range. We briefly review such post-LHC options as linear e+e- colliders in Japan (ILC) or at CERN (CLIC), muon collider, and circular lepton or hadron colliders in China (CepC/SppC) and Europe (FCC). We conclude with a look into ultimate energy reach accelerators based on plasmas and crystals, and some perspectives for the far future of accelerator-based particle physics.

  9. Design study of beam dynamics issues for a one TeV next linear collider based upon the relativistic klystron two-beam accelerator

    SciTech Connect

    Li, H.; Houck, T.; Goffeney, N.; Henestroza, E.; Sessler, A.; Westenskow, G.; Yu, S.

    1995-06-01

    A design study has recently been conducted for exploring the feasibility of a relativistic-klystron two-beam accelerator (RK-TBA) system as a rf power source for a 1 TeV linear collider. We present, in this paper, the beam dynamics part of this study. We have achieved in our design study acceptable transverse and longitudinal beam stability properties for the resulting high efficiency and low cost RK-TBA. {copyright} 1995 {ital American Institute of Physics}.

  10. Design study of beam dynamics issues for 1 TeV next linear collider based upon the relativistic-klystron two-beam accelerator

    SciTech Connect

    Li, H.; Goffeney, N.; Henestroza, E.; Sessler, A.; Yu, S.; Houck, T.; Westenskow, G.

    1994-11-01

    A design study has recently been conducted for exploring the feasibility of a relativistic-klystron two-beam accelerator (RK-TBA) system as a rf power source for a 1 TeV linear collider. The author present, in this paper, the beam dynamics part of this study. They have achieved in their design study acceptable transverse and longitudinal beam stability properties for the resulting high efficiency and low cost RK-TBA.

  11. Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

    NASA Astrophysics Data System (ADS)

    Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

    2016-10-01

    Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4.

  12. Military GP training-the future.

    PubMed

    Herod, T P; Johnson, G A

    2013-01-01

    There is clearly a significant step from being a well-supported GP Registrar to being a fully independent GP in the NHS and this is even more apparent for a newly qualified Military GP There are many additional duties and responsibilities placed upon a Military GP that the current training curriculum and exams do not cover and which must be learnt post-CCT, whilst undertaking independent practice for the first time. Having a Military First 5 initiative for support during this time would no doubt be of some use, but having a dedicated period of training to re-militarise newly qualified Military GPs would provide an opportunity to improve and make more efficient the initial transition from training to independent practice. In the long term, incorporating as much as possible of this proposed period of post-CCT Military training into a 4th year of GP training would be the ideal. However, discussions between Surgeon General, the Defence Deanery and the RCGP would be required to define which training elements would be acceptable to be incorporated and there will no doubt be some aspects (e.g. weapons handling) that might be deemed unacceptable by the RCGP, and thus a period of post-CCT Military training may still be a key component of a longer term solution. The options for enhancing Military GP training warrant thorough exploration as they have the potential to provide significant benefit not only for future trainees but also for the military in general.

  13. Hansenula polymorpha expressed heat shock protein gp96 exerts potent T cell activation activity as an adjuvant.

    PubMed

    Li, Yang; Song, Haolei; Li, Jin; Wang, Yanzhong; Yan, Xiaoli; Zhao, Bao; Zhang, Xiaojun; Wang, Saifeng; Chen, Lizhao; Qiu, Bingsheng; Meng, Songdong

    2011-02-20

    Previous studies together with ours showed that heat shock protein gp96 as an adjuvant induces antigen specific T cell responses against cancer and infectious diseases. However, at present there is no efficient method to obtain high amount of full-length gp96 by in vitro expression. Here, we used the yeast Hansenula polymorpha as an efficient host for gp96 recombinant protein production. The transformant clones with highly expressed recombinant proteins were screened and selected by measuring the halo size which indicates enzymatic hydrolysis of starch in the medium. High-level production of gp96 (around 150mg/mL) was achieved by using high-cell density fed-batch cultivations. We showed that peptide binding of the recombinant protein has similar specificity and intrinsic binding parameters as that of the native gp96. We next examined the self-assembly properties and high-order structures of the recombinant protein. Moreover, the H. polymorpha expressed recombinant gp96 can effectively induce HBV-specific CTL response in immunized mice while Escherichia coli-expressed gp96 cannot. Our results therefore may provide bases for structure and functional studies of gp96 and thereby potentially expedite the development of gp96-based vaccines for immunotherapy of cancer or infectious diseases.

  14. Nonglobal correlations in collider physics

    SciTech Connect

    Moult, Ian; Larkoski, Andrew J.

    2016-01-13

    Despite their importance for precision QCD calculations, correlations between in- and out-of-jet regions of phase space have never directly been observed. These so-called non-global effects are present generically whenever a collider physics measurement is not explicitly dependent on radiation throughout the entire phase space. In this paper, we introduce a novel procedure based on mutual information, which allows us to isolate these non-global correlations between measurements made in different regions of phase space. We study this procedure both analytically and in Monte Carlo simulations in the context of observables measured on hadronic final states produced in e+e- collisions, though it is more widely applicable.The procedure exploits the sensitivity of soft radiation at large angles to non-global correlations, and we calculate these correlations through next-to-leading logarithmic accuracy. The bulk of these non-global correlations are found to be described in Monte Carlo simulation. They increase by the inclusion of non-perturbative effects, which we show can be incorporated in our calculation through the use of a model shape function. As a result, this procedure illuminates the source of non-global correlations and has connections more broadly to fundamental quantities in quantum field theory.

  15. Nonglobal correlations in collider physics

    DOE PAGES

    Moult, Ian; Larkoski, Andrew J.

    2016-01-13

    Despite their importance for precision QCD calculations, correlations between in- and out-of-jet regions of phase space have never directly been observed. These so-called non-global effects are present generically whenever a collider physics measurement is not explicitly dependent on radiation throughout the entire phase space. In this paper, we introduce a novel procedure based on mutual information, which allows us to isolate these non-global correlations between measurements made in different regions of phase space. We study this procedure both analytically and in Monte Carlo simulations in the context of observables measured on hadronic final states produced in e+e- collisions, though itmore » is more widely applicable.The procedure exploits the sensitivity of soft radiation at large angles to non-global correlations, and we calculate these correlations through next-to-leading logarithmic accuracy. The bulk of these non-global correlations are found to be described in Monte Carlo simulation. They increase by the inclusion of non-perturbative effects, which we show can be incorporated in our calculation through the use of a model shape function. As a result, this procedure illuminates the source of non-global correlations and has connections more broadly to fundamental quantities in quantum field theory.« less

  16. Attitudes towards health inequalities amongst GP trainers in Glasgow, and their ideas for changes in training.

    PubMed

    Blane, David N; Hesselgreaves, Hannah; McLean, Gary; Lough, Murray; Watt, Graham C M

    2013-02-01

    WHAT IS ALREADY KNOWN IN THIS AREA: Recent government policy has emphasised the important role that GPs have to play in addressing health inequalities. The RCGP curriculum asserts the importance of gaining a better understanding of health inequalities during GP training. GP training in Scotland continues to take place in disproportionately affluent areas. WHAT THIS WORK ADDS: This is the first study to look at attitudes of GP trainers towards health inequalities and to explore their ideas for changes in training that may address health inequalities. There were noticeable differences in the views of GP trainers--both in terms of the causes of health inequalities and the role of primary care in tackling inequalities--depending on whether they were based in more affluent or more deprived practices. Practice rotations were suggested by all groups as a means to give GP trainees exposure to the particular challenges of both affluent and deprived practice populations. SUGGESTIONS FOR FUTURE RESEARCH: Pilot studies of practice rotations between deprived and affluent areas would be of value. Evaluation of nMRCGP assessments (particularly the Clinical Skills Assessment, CSA) with regard to representativeness of general practice in deprived areas should be considered. Further qualitative research into the attitudes of GP trainees towards health inequalities, and GP trainers from different--less deprived--practice areas, would also be of interest. [corrected].

  17. Characterization of human colorectal cancer MDR1/P-gp Fab antibody.

    PubMed

    Zhang, Xuemei; Xiao, Gary Guishan; Gao, Ying

    2013-01-01

    In this study, the peptide sized 21 kDa covering P-gp transmembrane region was first prepared for generating a novel mouse monoclonal antibody Fab fragment with biological activity against multiple drug resistance protein P-gp21 by phage display technology. Phage-displayed antibody library prepared from mice spleen tissues was selected against the recombinant protein P-gp21 with five rounds of panning. A number of clones expressing Fab bound to P-gp21, showing neutralized activity in vitro, were isolated and screened by enzyme-linked immunosorbent assay based on its recognition properties to P-gp21 and human colorectal cancer tissue homogenate, resulting in identification of an optimal recombinant Fab clone (Number 29). Further characterization by recloning number 29 into an expression vector showed significant induction of the Fab antibody in the clone number 29 by Isopropyl β-D-1-thiogalactopyranoside (IPTG). After purified by HiTrap Protein L, the specificity of the Fab antibody to P-gp21 was also confirmed. Not only was the targeted region of this monoclonal Fab antibody identified as a 16-peptide epitope (ALKDKKELEGSGKIAT) comprising residues 883-898 within the transmembrane (TM) domain of human P-gp, but also the binding ability with it was verified. The clinical implication of our results for development of personalized therapy of colorectal cancer will be further studied.

  18. GP43 from Paracoccidioides brasiliensis inhibits macrophage functions. An evasion mechanism of the fungus.

    PubMed

    Flavia Popi, Ana Flavia; Lopes, José Daniel; Mariano, Mario

    2002-01-01

    Macrophages constitute one of the primary cellular mechanisms that impairs parasite invasion of host tissues. The phagocytic and microbicidal properties of these cells can be modulated by specific membrane receptors involved in cell-microorganism interactions. Gp43, the main antigen secreted by Paracoccidiodes brasiliensis (Pb), the causative agent of Paracoccidioidomycosis, is a high mannose glycoprotein. The role played by gp43 in the pathogenesis of the disease is not completely known. Here, we describe the influence of this molecule on the interaction between peritoneal murine macrophages and Pb. Phagocytosis of Pb, live or heat-killed, by adherent peritoneal cells from both, B10.A (susceptible) and A/Sn (resistant) mice, was evaluated. Addition of different concentrations of gp43 to the culture medium inhibited, in a dose-dependent pattern, phagocytosis of live or heat-killed Pb by peritoneal macrophages from both B10.A and A/Sn mice. Gp43 also inhibits phagocytosis of zymosan particles but did not interfere with the uptake of opsonized sheep red blood cells. It was also shown that both gp43 and heat-killed Pb have an inhibitory effect on the release of NO by zymosan stimulated macrophages. Finally, we demonstrated that gp43 inhibits the fungicidal ability of macrophages from both lineages. Based on these data, it is suggested that gp43 can be considered one of the evasion mechanisms for the installation of primary infection in susceptible hosts.

  19. Status of the MEIC ion collider ring design

    SciTech Connect

    Morozov, Vasiliy; Derbenev, Yaroslav; Harwood, Leigh; Hutton, Andrew; Lin, Fanglei; Pilat, Fulvia; Zhang, Yuhong; Cai, Yunhai; Nosochkov, Y. M.; Sullivan, Michael; Wang, M.-H.; Wienands, Uli; Gerity, James; Mann, Thomas; McIntyre, Peter; Pogue, Nathaniel; Sattarov, Akhdiyor

    2015-09-01

    We present an update on the design of the ion collider ring of the Medium-energy Electron-Ion Collider (MEIC) proposed by Jefferson Lab. The design is based on the use of super-ferric magnets. It provides the necessary momentum range of 8 to 100 GeV/c for protons and ions, matches the electron collider ring design using PEP-II components, fits readily on the JLab site, offers a straightforward path for a future full-energy upgrade by replacing the magnets with higher-field ones in the same tunnel, and is more cost effective than using presently available current-dominated super-conducting magnets. We describe complete ion collider optics including an independently-designed modular detector region.

  20. Status of the MEIC ion collider ring design

    SciTech Connect

    Morozov, V. S.; Derbenev, Ya. S.; Harwood, L.; Hutton, A.; Lin, F.; Pilat, F.; Zhang, Y.; Cai, Y.; Nosochkov, Y. M.; Sullivan, M.; Wang, M-H; Wienands, U.; Gerity, J.; Mann, T.; McIntyre, P.; Pogue, N. J.; Satttarov, A.

    2015-07-14

    We present an update on the design of the ion collider ring of the Medium-energy Electron-Ion Collider (MEIC) proposed by Jefferson Lab. The design is based on the use of super-ferric magnets. It provides the necessary momentum range of 8 to 100 GeV/c for protons and ions, matches the electron collider ring design using PEP-II components, fits readily on the JLab site, offers a straightforward path for a future full-energy upgrade by replacing the magnets with higher-field ones in the same tunnel, and is more cost effective than using presently available current-dominated superconducting magnets. We describe complete ion collider optics including an independently-designed modular detector region.

  1. Test ordering by GP trainees

    PubMed Central

    Morgan, Simon; Morgan, Andy; Kerr, Rohan; Tapley, Amanda; Magin, Parker

    2016-01-01

    Abstract Objective To assess the effectiveness of an educational intervention on test-ordering attitudes and intended practice of GP trainees, and any associations between changes in test ordering and trainee characteristics. Design Preworkshop and postworkshop survey of attitudes to test ordering, intended test-ordering practices for 3 clinical scenarios (fatigue, screening, and shoulder pain), and tolerance for uncertainty. Setting Three Australian regional general practice training providers. Participants General practice trainees (N = 167). Intervention A 2-hour workshop session and an online module. Main outcome measures Proportion of trainees who agreed with attitudinal statements before and after the workshop; proportion of trainees who would order tests, mean number of tests ordered, and number of appropriate and inappropriate tests ordered for each scenario before and after the workshop. Results Of 167 trainees, 132 (79.0%) completed both the preworkshop and postworkshop questionnaires. A total of 122 trainees attended the workshop. At baseline, 88.6% thought that tests can harm patients, 84.8% believed overtesting was a problem, 72.0% felt pressured by patients, 52.3% believed that tests would reassure patients, and 50.8% thought that they were less likely to be sued if they ordered tests. There were desirable changes in all attitudes after the workshop. Before the workshop, the mean number of tests that trainees would have ordered was 4.4, 4.8, and 1.5 for the fatigue, screening, and shoulder pain scenarios, respectively. After the workshop there were decreases in the mean number of both appropriate tests (decrease of 0.94) and inappropriate tests (decrease of 0.24) in the fatigue scenario; there was no change in the mean number of appropriate tests and a decrease in inappropriate tests (decrease of 0.76) in the screening scenario; and there was an increase in the proportion of trainees who would appropriately not order tests in the shoulder pain

  2. Will there be energy frontier colliders after LHC?

    SciTech Connect

    Shiltsev, Vladimir

    2016-09-15

    High energy particle colliders have been in the forefront of particle physics for more than three decades. At present the near term US, European and international strategies of the particle physics community are centered on full exploitation of the physics potential of the Large Hadron Collider (LHC) through its high-luminosity upgrade (HL-LHC). The future of the world-wide HEP community critically depends on the feasibility of possible post-LHC colliders. The concept of the feasibility is complex and includes at least three factors: feasibility of energy, feasibility of luminosity and feasibility of cost. Here we overview all current options for post-LHC colliders from such perspective (ILC, CLIC, Muon Collider, plasma colliders, CEPC, FCC, HE-LHC) and discuss major challenges and accelerator R&D required to demonstrate feasibility of an energy frontier accelerator facility following the LHC. We conclude by taking a look into ultimate energy reach accelerators based on plasmas and crystals, and discussion on the perspectives for the far future of the accelerator-based particle physics.

  3. Beyond the Large Hadron Collider: A First Look at Cryogenics for CERN Future Circular Colliders

    NASA Astrophysics Data System (ADS)

    Lebrun, Philippe; Tavian, Laurent

    Following the first experimental discoveries at the Large Hadron Collider (LHC) and the recent update of the European strategy in particle physics, CERN has undertaken an international study of possible future circular colliders beyond the LHC. The study, conducted with the collaborative participation of interested institutes world-wide, considers several options for very high energy hadron-hadron, electron-positron and hadron-electron colliders to be installed in a quasi-circular underground tunnel in the Geneva basin, with a circumference of 80 km to 100 km. All these machines would make intensive use of advanced superconducting devices, i.e. high-field bending and focusing magnets and/or accelerating RF cavities, thus requiring large helium cryogenic systems operating at 4.5 K or below. Based on preliminary sets of parameters and layouts for the particle colliders under study, we discuss the main challenges of their cryogenic systems and present first estimates of the cryogenic refrigeration capacities required, with emphasis on the qualitative and quantitative steps to be accomplished with respect to the present state-of-the-art.

  4. Neutrino Factory and Muon Collider Fellow

    SciTech Connect

    Hanson, Gail G.; Snopak, Pavel; Bao, Yu

    2015-03-20

    Muons are fundamental particles like electrons but much more massive. Muon accelerators can provide physics opportunities similar to those of electron accelerators, but because of the larger mass muons lose less energy to radiation, allowing more compact facilities with lower operating costs. The way muon beams are produced makes them too large to fit into the vacuum chamber of a cost-effective accelerator, and the short muon lifetime means that the beams must be reduced in size rather quickly, without losing too many of the muons. This reduction in size is called "cooling." Ionization cooling is a new technique that can accomplish such cooling. Intense muon beams can then be accelerated and injected into a storage ring, where they can be used to produce neutrino beams through their decays or collided with muons of the opposite charge to produce a muon collider, similar to an electron-positron collider. We report on the research carried out at the University of California, Riverside, towards producing such muon accelerators, as part of the Muon Accelerator Program based at Fermilab. Since this research was carried out in a university environment, we were able to involve both undergraduate and graduate students.

  5. Muon Collider Machine-Detector Interface

    SciTech Connect

    Mokhov, Nikolai V.; /Fermilab

    2011-08-01

    In order to realize the high physics potential of a Muon Collider (MC) a high luminosity of {mu}{sup +}{mu}{sup -}-collisions at the Interaction Point (IP) in the TeV range must be achieved ({approx}10{sup 34} cm{sup -2}s{sup -1}). To reach this goal, a number of demanding requirements on the collider optics and the IR hardware - arising from the short muon lifetime and from relatively large values of the transverse emittance and momentum spread in muon beams that can realistically be obtained with ionization cooling should be satisfied. These requirements are aggravated by limitations on the quadrupole gradients as well as by the necessity to protect superconducting magnets and collider detectors from muon decay products. The overall detector performance in this domain is strongly dependent on the background particle rates in various sub-detectors. The deleterious effects of the background and radiation environment produced by the beam in the ring are very important issues in the Interaction Region (IR), detector and Machine-Detector Interface (MDI) designs. This report is based on studies presented very recently.

  6. Searching for dark matter at colliders

    NASA Astrophysics Data System (ADS)

    Richard, Francois; Arcadi, Giorgio; Mambrini, Yann

    2015-04-01

    Dark Matter (DM) detection prospects at future colliders are reviewed under the assumption that DM particles are fermions of the Majorana or Dirac type. Although the discussion is quite general, one will keep in mind the recently proposed candidate based on an excess of energetic photons observed in the center of our Galaxy with the Fermi-LAT satellite. In the first part we will assume that DM interactions are mediated by vector bosons, or . In the case of -boson Direct Detection limits force only axial couplings with the DM. This solution can be naturally accommodated by Majorana DM but is disfavored by the GC excess. Viable scenarios can be instead found in the case of mediator. These scenarios can be tested at colliders through ISR events, . A sensitive background reduction can be achieved by using highly polarized beams. In the second part scalar particles, in particular Higgs particles, have been considered as mediators. The case of the SM Higgs mediator is excluded by limits on the invisible branching ratio of the Higgs. On the contrary particularly interesting is the case in which the DM interactions are mediated by the pseudoscalar state in two Higgs-doublet model scenarios. In this last case the main collider signature is.

  7. Gp96 enhances the immunogenicity of subunit vaccine of porcine reproductive and respiratory syndrome virus.

    PubMed

    Chen, Caiwei; Li, Jing; Bi, Yuhai; Jia, Xiaojuan; Meng, Songdong; Sun, Lei; Liu, Wenjun

    2012-08-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the pig industry worldwide. Currently available commercial vaccines provide limited protection due to delayed and weak cell-mediated immunity and neutralizing antibody production, thus the immunomodulators should be considered in order to improve the efficacy of PRRSV vaccines. Heat shock protein gp96 may be used as a modulator to enhance both innate and adaptive immune responses. In the present study, two multi-epitope subunit vaccines, named as Cp1 and Cp2, were designed based on the conserved B cell epitopes of viral proteins with the N-terminal 22-370 amino acids (aa) of porcine gp96 (Gp96N) chosen as the adjuvant. Immune responses elicited by the different combinations of Cp1/Cp2 and Gp96N were examined in mice and piglets. The results indicated that the group of Cp1/Cp2-Gp96N (CG) combination induced 3-4-fold higher titers of Cp1/Cp2-ELISA antibodies and neutralizing antibodies (NAs) in mice than the groups which received Cp1/Cp2 immunization alone or with Freund's adjuvant. Additionally, Gp96N significantly enhanced the levels of lymphocyte proliferative responses of splenocytes or peripheral blood mononuclear cells from vaccinated mice or piglets. The production of IFN-γ in mice splenocytes, TNF-α, IFN-γ, and IL-12 in sera of piglets were also remarkably increased with the treatment of Gp96N, while IL-4 was reduced by half and IL-10 was decreased to an undetectable level. These results suggest that the porcine Gp96N could effectively enhance the innate and adaptive immune responses of Cp1/Cp2 with a Th1-type bias. Therefore, the multi-epitope subunit vaccine Cp1/Cp2 co-administered with porcine Gp96N might potentially be a promising candidate vaccine for the prevention and control of PRRSV in pigs.

  8. The viral protein gp120 decreases the acetylation of neuronal tubulin: potential mechanism of neurotoxicity.

    PubMed

    Avdoshina, Valeria; Caragher, Seamus P; Wenzel, Erin D; Taraballi, Francesca; Mocchetti, Italo; Harry, Gaylia Jean

    2017-05-01

    The human immunodeficiency virus (HIV) envelope protein gp120 promotes axonal damage and neurite pruning, similar to that observed in HIV-positive subjects with neurocognitive disorders. Thus, gp120 has been used to examine molecular and cellular pathways underlying HIV-mediated neuronal dysfunction. Gp120 binds to tubulin beta III, a component of neuronal microtubules. Microtubule function, which modulates the homeostasis of neurons, is regulated by polymerization and post-translational modifications. Based on these considerations, we tested the hypothesis that gp120 induces dynamic instability of neuronal microtubules. We first observed that gp120 prevents the normal polymerization of tubulin in vitro. We then tested whether gp120 alters the post-translational modifications in tubulin by examining the ability of gp120 to change the levels of acetylated tubulin in primary rat neuronal cultures. Gp120 elicited a time-dependent decrease in tubulin acetylation that was reversed by Helix-A peptide, a compound that competitively displaces the binding of gp120 to neuronal microtubules. To determine whether post-translational modifications in tubulin also occur in vivo, we measured acetylated tubulin in the cerebral cortex of HIV transgenic rats (HIV-tg). We observed a decrease in tubulin acetylation in 5- and 9-month-old HIV-tg rats when compared to age-matched wild type. Neither changes in microglia morphology nor alterations in mRNA levels for interleukin-1β and tumor necrosis factor α were detected in 5-month-old animals. Our findings propose neuronal microtubule instability as a novel mechanism of HIV neurotoxicity, without evidence of enhanced inflammation. © 2017 International Society for Neurochemistry.

  9. Linear Colliders: Achieving High Luminosity

    NASA Astrophysics Data System (ADS)

    Dugan, Gerald

    2002-04-01

    Four styles of linear collider are under active consideration by the high energy physics community as candidates for the next machine at the energy frontier. The four concepts (CLIC, the C-band linear collider, NLC/JLC and TESLA) differ widely in technology but share similar goals for energy and luminosity. The luminosity goal is more than three orders of magntiude larger than what has been acheived at the SLC. Nevertheless, as a result of many years of world-wide accelerator R&D efforts, feasible designs now exist for machines capable of reaching this goal. This talk will review the methods proposed by each linear collider concept to attain its luminosity goal. The most challenging issues facing each concept will be outlined and compared, and the areas requiring further R&D efforts will be noted.

  10. Muon Collider Task Force Report

    SciTech Connect

    Ankenbrandt, C.; Alexahin, Y.; Balbekov, V.; Barzi, E.; Bhat, C.; Broemmelsiek, D.; Bross, A.; Burov, A.; Drozhdin, A.; Finley, D.; Geer, S.; /Fermilab /Argonne /Brookhaven /Jefferson Lab /LBL, Berkeley /MUONS Inc., Batavia /UCLA /UC, Riverside /Mississippi U.

    2007-12-01

    Muon Colliders offer a possible long term path to lepton-lepton collisions at center-of-mass energies {radical}s {ge} 1 TeV. In October 2006 the Muon Collider Task Force (MCTF) proposed a program of advanced accelerator R&D aimed at developing the Muon Collider concept. The proposed R&D program was motivated by progress on Muon Collider design in general, and in particular, by new ideas that have emerged on muon cooling channel design. The scope of the proposed MCTF R&D program includes muon collider design studies, helical cooling channel design and simulation, high temperature superconducting solenoid studies, an experimental program using beams to test cooling channel RF cavities and a 6D cooling demonstration channel. The first year of MCTF activities are summarized in this report together with a brief description of the anticipated FY08 R&D activities. In its first year the MCTF has made progress on (1) Muon Collider ring studies, (2) 6D cooling channel design and simulation studies with an emphasis on the HCC scheme, (3) beam preparations for the first HPRF cavity beam test, (4) preparations for an HCC four-coil test, (5) further development of the MANX experiment ideas and studies of the muon beam possibilities at Fermilab, (6) studies of how to integrate RF into an HCC in preparation for a component development program, and (7) HTS conductor and magnet studies to prepare for an evaluation of the prospects for of an HTS high-field solenoid build for a muon cooling channel.

  11. Recent results from hadron colliders

    SciTech Connect

    Frisch, H.J. )

    1990-12-10

    This is a summary of some of the many recent results from the CERN and Fermilab colliders, presented for an audience of nuclear, medium-energy, and elementary particle physicists. The topics are jets and QCD at very high energies, precision measurements of electroweak parameters, the remarkably heavy top quark, and new results on the detection of the large flux of B mesons produced at these machines. A summary and some comments on the bright prospects for the future of hadron colliders conclude the talk. 39 refs., 44 figs., 3 tabs.

  12. A functional interaction between gp41 and gp120 is observed for monomeric but not oligomeric, uncleaved HIV-1 Env gp140.

    PubMed

    Guttman, Miklos; Lee, Kelly K

    2013-11-01

    The envelope glycoprotein (Env) is the sole antigenic feature on the surface of HIV and the target for the humoral immune system. Soluble, uncleaved gp140 Env constructs truncated at the transmembrane domain are being investigated intensively as potential vaccine immunogens by many groups, and understanding their structural properties is essential. We used hydrogen/deuterium-exchange mass spectrometry and small-angle X-ray scattering to probe structural order in a panel of commonly used gp140 constructs and matched gp120 monomers. We observed that oligomeric forms of uncleaved gp140, generally presumed to be trimeric, contain a protease-resistant form of gp41 akin to the postfusion, helical bundle conformation and appear to lack specific interactions between gp120 and gp41. In contrast, the monomeric form of gp140 shows significant stabilization of the gp120 inner domain imparted by the gp41 region, demonstrating excellent agreement with past mutagenesis studies. Moreover, the gp140 monomers respond to CD4 binding in manner that is consistent with the initial stages of Env activation: CD4 binding induces structural ordering throughout gp120 while loosening its association with gp41. The results indicate that uncleaved gp140 oligomers do not represent an authentic prefusion form of Env, whereas gp140 monomers isolated from the same glycoprotein preparations in many ways exhibit function and internal structural order that are consistent with expectations for certain aspects of native Env. gp140 monomers may thus be a useful reagent for advancing structural and functional studies.

  13. Anti-HIV Double Variable Domain Immunoglobulins Binding Both gp41 and gp120 for Targeted Delivery of Immunoconjugates

    PubMed Central

    Craig, Ryan B.; Summa, Christopher M.; Corti, Miriam; Pincus, Seth H.

    2012-01-01

    Background Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs) that bind to both epitopes. Methods Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. Findings The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK]nA) resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS]n). In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. Conclusions DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved. PMID:23056448

  14. Muon Muon Collider: Feasibility Study

    SciTech Connect

    Gallardo, J.C.; Palmer, R.B.; Tollestrup, A.V.; Sessler, A.M.; Skrinsky, A.N.; Ankenbrandt, C.; Geer, S.; Griffin, J.; Johnstone, C.; Lebrun, P.; McInturff, A.; Mills, Frederick E.; Mokhov, N.; Moretti, A.; Neuffer, D.; Ng, K.Y.; Noble, R.; Novitski, I.; Popovic, M.; Qian, C.; Van Ginneken, A. /Fermilab /Brookhaven /Wisconsin U., Madison /Tel Aviv U. /Indiana U. /UCLA /LBL, Berkeley /SLAC /Argonne /Sobolev IM, Novosibirsk /UC, Davis /Munich, Tech. U. /Virginia U. /KEK, Tsukuba /DESY /Novosibirsk, IYF /Jefferson Lab /Mississippi U. /SUNY, Stony Brook /MIT /Columbia U. /Fairfield U. /UC, Berkeley

    2012-04-05

    A feasibility study is presented of a 2 + 2 TeV muon collider with a luminosity of L = 10{sup 35} cm{sup -2}s{sup -1}. The resulting design is not optimized for performance, and certainly not for cost; however, it does suffice - we believe - to allow us to make a credible case, that a muon collider is a serious possibility for particle physics and, therefore, worthy of R and D support so that the reality of, and interest in, a muon collider can be better assayed. The goal of this support would be to completely assess the physics potential and to evaluate the cost and development of the necessary technology. The muon collider complex consists of components which first produce copious pions, then capture the pions and the resulting muons from their decay; this is followed by an ionization cooling channel to reduce the longitudinal and transverse emittance of the muon beam. The next stage is to accelerate the muons and, finally, inject them into a collider ring wich has a small beta function at the colliding point. This is the first attempt at a point design and it will require further study and optimization. Experimental work will be needed to verify the validity of diverse crucial elements in the design. Muons because of their large mass compared to an electron, do not produce significant synchrotron radiation. As a result there is negligible beamstrahlung and high energy collisions are not limited by this phenomena. In addition, muons can be accelerated in circular devices which will be considerably smaller than two full-energy linacs as required in an e{sup +} - e{sup -} collider. A hadron collider would require a CM energy 5 to 10 times higher than 4 TeV to have an equivalent energy reach. Since the accelerator size is limited by the strength of bending magnets, the hadron collider for the same physics reach would have to be much larger than the muon collider. In addition, muon collisions should be cleaner than hadron collisions. There are many detailed particle

  15. Blended learning in CME: the perception of GP trainers.

    PubMed

    Te Pas, E; Meinema, J G; Visser, M R M; van Dijk, N

    2016-05-01

    Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical Education (CME) course in evidence-based medicine (EBM). This study reports on our experience and investigated the factors influencing the perception on usefulness and logistics of blended learning for learners in CME. In total, 170 GP trainers participated in the intervention. We used questionnaires, observations during the four face-to-face meetings and evaluations in the e-course over one year. Additionally we organised focus groups to gain insight in some of the outcomes of the questionnaires and interpretations of the observations. The GP trainers found the design and the educational method (e-course in combination with meetings) attractive, instructive and complementary. Factors influencing their learning were (1) educational design, (2) educational method, (3) topic of the intervention, (4) time (planning), (5) time (intervention), (6) learning style, (7) technical issues, (8) preconditions and (9) level of difficulty. A close link between daily practice and the educational intervention was considered an important precondition for the success of the intervention in this group of learners. GP trainers were positive about blended learning: they found e-learning a useful way to gain knowledge and the meetings a pleasant way of transferring the knowledge into practice. Although some preconditions should be taken into consideration during its development and implementation, they would participate in similarly designed learning in the future.

  16. Evaluating the effects of GP remuneration: problems and prospects.

    PubMed

    Scott, A; Hall, J

    1995-03-01

    General practice reform is occurring in a number of countries. Little is known, however, of the effects of remunerating general practitioners on the costs and outcomes of care. Valuable lessons can be learned for the scope and design of future research, however, from the existing literature on the effects of general practioner (GP) remuneration. The objectives of this paper are to highlight some of the problems and pitfalls that should be avoided in any further research on the effects of GP remuneration and to identify the main issues for future research. Eighteen studies of the effects of GP remuneration have been reviewed, with a focus on the methods used. Eight studies addressed the effect of changes in the level of remuneration, three evaluated the effect of special payments and bonuses and seven assessed the effects of different remuneration systems. Although there are often practical constraints on the choice of study design, crude 'before and after' analyses and the use of aggregate data should be avoided in favour of prospective evaluations using consultation-based data. The studies reviewed did not evaluate the effects of remuneration on patient welfare and were characterised by the omission of major confounding variables and an inability to generalise to other settings. These issues present a considerable challenge to researchers, GPs and policy makers.

  17. Muon Colliders: The Next Frontier

    ScienceCinema

    Tourun, Yagmur [Illinois Institute of Technology, Chicago, Illinois, United States

    2016-07-12

    Muon Colliders provide a path to the energy frontier in particle physics but have been regarded to be "at least 20 years away" for 20 years. I will review recent progress in design studies and hardware R&D and show that a Muon Collider can be established as a real option for the post-LHC era if the current vigorous R&D effort revitalized by the Muon Collider Task Force at Fermilab can be supported to its conclusion. All critical technologies are being addressed and no show-stoppers have emerged. Detector backgrounds have been studied in detail and appear to be manageable and the physics can be done with existing detector technology. A muon facility can be built through a staged scenario starting from a low-energy muon source with unprecedented intensity for exquisite reach for rare processes, followed by a Neutrino Factory with ultrapure neutrino beams with unparalleled sensitivity for disentangling neutrino mixing, leading to an energy frontier Muon Collider with excellent energy resolution.

  18. B physics at hadron colliders

    SciTech Connect

    Butler, J.N.; /Fermilab

    2005-09-01

    This paper discusses the physics opportunity and challenges for doing high precision B physics experiments at hadron colliders. It describes how these challenges have been addressed by the two currently operating experiments, CDF and D0, and how they are addressed by three experiments, ATLAS, CMS, and LHCb, at the LHC.

  19. The very large hadron collider

    SciTech Connect

    1998-09-01

    This paper reviews the purposes to be served by a very large hadron collider and the organization and coordination of efforts to bring it about. There is some discussion of magnet requirements and R&D and the suitability of the Fermilab site.

  20. Physics at high energy photon photon colliders

    SciTech Connect

    Chanowitz, M.S.

    1994-06-01

    I review the physic prospects for high energy photon photon colliders, emphasizing results presented at the LBL Gamma Gamma Collider Workshop. Advantages and difficulties are reported for studies of QCD, the electroweak gauge sector, supersymmetry, and electroweak symmetry breaking.

  1. Screening HIV-1 fusion inhibitors based on capillary electrophoresis head-end microreactor targeting to the core structure of gp41.

    PubMed

    Liu, Lihong; Xu, Xiaoying; Liu, Yanhui; Zhang, Xuanxuan; Li, Lin; Jia, Zhimin

    2016-02-20

    In this paper, we design a microreactor based on electrophoretically mediated microanalysis (EMMA) with capillary electrophoresis (CE) for screening HIV-1 inhibitors that bind to the N-terminal heptad repeat (NHR, N36) region. Initially, a test sample plug is loaded into a capillary filled with buffer solution followed by N36 peptide solution, and the two solutions simultaneously mix by diffusion. Then, voltage is applied, and the sample molecules pass through the N36 peptide zone. The active compounds combine with N36, leading to a loss in the peak height of the active compound. More than 100 traditional Chinese medicine extracts (TCME) were screened, and an extract of Pheretima aspergillum (E. Perrier) (L5) was identified as having potent inhibitory activity. The results showed that L5 could significantly inhibit the HIV-1JR-FL pseudotyped virus infection; the 50% effective concentration (EC50) of L5 was approximately 32.1±1.2μg/mL, and the 50% cytotoxicity concentration (CC50) value of L5 was 146.9±4.4μg/mL, suggesting that L5 had low in vitro cytotoxicity on U87-CD4-CCR5 cells. The new method is simple and rapid, is free of antibodies, and does not require tedious processes.

  2. Cardiovascular risk factors and motivation for a healthy life-style in a German community--results of the GP-based Oestringen study.

    PubMed

    Wiesemann, Armin; Ludt, Sabine; Szecsenyi, Joachim; Scheuermann, Wolfgang; Scheidt, Reginald

    2004-10-01

    This paper explores the motivation of patients towards a healthy life-style in a small community with a special general practice and community-based health education program in order to identify reasons for different motivations and barriers and to improve preventive measures and outcome. The last of six standardised health surveys carried out over 9 years in the five general practices was therefore combined with a questionnaire to explore the attitudes of a sample of patients from these practices (N = 1044) and all attendees of 11 health education courses (N = 153). In addition to the cardiovascular risk factors, data were collected on sociodemographic factors and motivations for health promotion. The results show that, over time, the risk factors of hypertension (P < 0.001) and smoking (P < 0.005) had decreased. Health-promoting activities were not associated with cardiovascular risk factors; the motivations "duty" and "staying young" correlated with gender (P < 0.05). Patients with good health and white collar professions were more active. About 20% specified specific barriers to health-related activities. As expected, the participants of an educational program were more highly motivated by "fun", "fitness" and "meaningfulness". This group was mainly female. Future preventive measures should take into account that motivation for health promotion depends more on psychosocial factors than on risk factors; frequent obstacles should be noticed in the community.

  3. From Neutrino Factory to Muon Collider

    SciTech Connect

    Geer, S.; /Fermilab

    2010-01-01

    Both Muon Colliders and Neutrino Factories require a muon source capable of producing and capturing {Omicron}(10{sup 21}) muons/year. This paper reviews the similarities and differences between Neutrino Factory and Muon Collider accelerator complexes, the ongoing R&D needed for a Muon Collider that goes beyond Neutrino Factory R&D, and some thoughts about how a Neutrino Factory on the CERN site might eventually be upgraded to a Muon Collider.

  4. Membrane binding properties of EBV gp110 C-terminal domain; evidences for structural transition in the membrane environment

    SciTech Connect

    Park, Sung Jean; Seo, Min-Duk; Lee, Suk Kyeong; Lee, Bong Jin

    2008-09-30

    Gp110 of Epstein-Barr virus (EBV) mainly localizes on nuclear/ER membranes and plays a role in the assembly of EBV nucleocapsid. The C-terminal tail domain (gp110 CTD) is essential for the function of gp110 and the nuclear/ER membranes localization of gp110 is ruled by its C-terminal unique nuclear localization signal (NLS), consecutive four arginines. In the present study, the structural properties of gp110 CTD in membrane mimics were investigated using CD, size-exclusion chromatography, and NMR, to elucidate the effect of membrane environment on the structural transition and to compare the structural feature of the protein in the solution state with that of the membrane-bound form. CD and NMR analysis showed that gp110 CTD in a buffer solution appears to adopt a stable folding intermediate which lacks compactness, and a highly helical structure is formed only in membrane environments. The helical content of gp110 CTD was significantly affected by the negative charge as well as the size of membrane mimics. Based on the elution profiles of the size-exclusion chromatography, we found that gp110 CTD intrinsically forms a trimer, revealing that a trimerization region may exist in the C-terminal domain of gp110 like the ectodomain of gp110. The mutation of NLS (RRRR) to RTTR does not affect the overall structure of gp110 CTD in membrane mimics, while the helical propensity in a buffer solution was slightly different between the wild-type and the mutant proteins. This result suggests that not only the helicity induced in membrane environment but also the local structure around NLS may be related to trafficking to the nuclear membrane. More detailed structural difference between the wild-type and the mutant in membrane environment was examined using synthetic two peptides including the wild-type NLS and the mutant NLS.

  5. Molecular Cloning and Expression of a Gene Encoding Cryptosporidium parvum Glycoproteins gp40 and gp15

    PubMed Central

    Cevallos, Ana Maria; Zhang, Xiaoping; Waldor, Matthew K.; Jaison, Smitha; Zhou, Xiaoyin; Tzipori, Saul; Neutra, Marian R.; Ward, Honorine D.

    2000-01-01

    Cryptosporidium parvum is a significant cause of diarrheal disease worldwide. The specific molecules that mediate C. parvum-host cell interactions and the molecular mechanisms involved in the pathogenesis of cryptosporidiosis are unknown. In this study we have shown that gp40, a mucin-like glycoprotein, is localized to the surface and apical region of invasive stages of the parasite and is shed from its surface. gp40-specific antibodies neutralize infection in vitro, and native gp40 binds specifically to host cells, implicating this glycoprotein in C. parvum attachment to and invasion of host cells. We have cloned and sequenced a gene designated Cpgp40/15 that encodes gp40 as well as gp15, an antigenically distinct, surface glycoprotein also implicated in C. parvum-host cell interactions. Analysis of the deduced amino acid sequence of the 981-bp Cpgp40/15 revealed the presence of an N-terminal signal peptide, a polyserine domain, multiple predicted O-glycosylation sites, a single potential N-glycosylation site, and a hydrophobic region at the C terminus, a finding consistent with what is required for the addition of a GPI anchor. There is a single copy of Cpgp40/15 in the C. parvum genome, and this gene does not contain introns. Our data indicate that the two Cpgp40/15-encoded proteins, gp40 and gp15, are products of proteolytic cleavage of a 49-kDa precursor protein which is expressed in intracellular stages of the parasite. The surface localization of gp40 and gp15 and their involvement in the host-parasite interaction suggest that either or both of these glycoproteins may serve as effective targets for specific preventive or therapeutic measures for cryptosporidiosis. PMID:10858228

  6. Agar gel immunodiffusion analysis using baculovirus-expressed recombinant bovine leukemia virus envelope glycoprotein (gp51/gp30T-)

    PubMed Central

    Lim, Seong In; Jeong, Wooseog; Tark, Dong Seob; Yang, Dong Kun

    2009-01-01

    Bovine leukemia virus (BLV) envelope glycoprotein (gp51/gp30T-), consisting of BLV gp51 and BLV gp30 that lacked its C-terminal transmembrane domain, was expressed in insect cells under the control of the baculovirus polyhedron promoter. Recombinant BLV gp51/gp30T- secreted from insect cells was determined by immunofluorescence, enzyme-linked immunosorbent and western blot assays using a BLV-specific monoclonal antibody and BLV-positive bovine antibodies. An agar gel immunodiffusion (AGID) test using gp51/gp30T- as the antigen for the detection of BLV antibodies in serum was developed and compared to traditional AGID, which uses wild type BLV antigen derived from fetal lamb kidney cells. AGID with the recombinant BLV gp51/gp30T- was relatively more sensitive than traditional AGID. When the two methods were tested with bovine sera from the field, the recombinant BLV gp51/gp30T- and traditional antigen had a relative sensitivity of 69.8% and 67.4%, respectively, and a relative specificity of 93.3% and 92.3%. These results indicated that the recombinant BLV gp51/gp30T- is an effective alternative antigen for the diagnosis of BLV infection in cattle. PMID:19934599

  7. Mapping the interactions of the single-stranded DNA binding protein of bacteriophage T4 (gp32) with DNA lattices at single nucleotide resolution: gp32 monomer binding

    PubMed Central

    Jose, Davis; Weitzel, Steven E.; Baase, Walter A.; von Hippel, Peter H.

    2015-01-01

    Combining biophysical measurements on T4 bacteriophage replication complexes with detailed structural information can illuminate the molecular mechanisms of these ‘macromolecular machines’. Here we use the low energy circular dichroism (CD) and fluorescent properties of site-specifically introduced base analogues to map and quantify the equilibrium binding interactions of short (8 nts) ssDNA oligomers with gp32 monomers at single nucleotide resolution. We show that single gp32 molecules interact most directly and specifically near the 3′-end of these ssDNA oligomers, thus defining the polarity of gp32 binding with respect to the ssDNA lattice, and that only 2–3 nts are directly involved in this tight binding interaction. The loss of exciton coupling in the CD spectra of dimer 2-AP (2-aminopurine) probes at various positions in the ssDNA constructs, together with increases in fluorescence intensity, suggest that gp32 binding directly extends the sugar-phosphate backbone of this ssDNA oligomer, particularly at the 3′-end and facilitates base unstacking along the entire 8-mer lattice. These results provide a model (and ‘DNA map’) for the isolated gp32 binding to ssDNA targets, which serves as the nucleation step for the cooperative binding that occurs at transiently exposed ssDNA sequences within the functioning T4 DNA replication complex. PMID:26275775

  8. HIGH ENERGY PHYSICS POTENTIAL AT MUON COLLIDERS

    SciTech Connect

    PARSA,Z.

    2000-04-07

    In this paper, high energy physics possibilities and future colliders are discussed. The {mu}{sup +} {mu}{sup {minus}} collider and experiments with high intensity muon beams as the stepping phase towards building Higher Energy Muon Colliders (HEMC) are briefly reviewed and encouraged.

  9. Shedding Light on Dark Matter at Colliders

    NASA Astrophysics Data System (ADS)

    Mitsou, Vasiliki A.

    2013-12-01

    Dark matter remains one of the most puzzling mysteries in Fundamental Physics of our times. Experiments at high-energy physics colliders are expected to shed light to its nature and determine its properties. This review focuses on recent searches for dark matter signatures at the Large Hadron Collider, also discussing related prospects in future e+e- colliders.

  10. The solution structure of the circular trinucleotide cr(GpGpGp) determined by NMR and molecular mechanics calculation.

    PubMed Central

    Mooren, M M; Wijmenga, S S; van der Marel, G A; van Boom, J H; Hilbers, C W

    1994-01-01

    The 3'-5' circular trinucleotide cr(GpGpGp) was studied by means of 1D and 2D high resolution NMR techniques and molecular mechanics calculations. Analysis of the J-couplings, obtained from the 1H and 13C-NMR spectra, allowed the determination of the conformation of the sugar rings and of the 'circular' phosphate backbone. In the course of the investigations it was found that the Karplus-equation most recently parametrized for the CCOP J-coupling constants could not account for the measured J(C4'P) of 11.1 Hz and a new parametrization for both HCOP and CCOP coupling constants is therefore presented. Subsequent analysis of the coupling constants yielded 'fixed' values for the torsion angles beta and delta (with beta = 178 degrees and delta = 139 degrees). The value of the latter angle corresponds to an S-type sugar conformation. The torsion angles gamma and epsilon are involved in a rapid equilibrium in which they are converted between the gauche(+) and trans and between the trans and gauche(-) domain respectively. We show that the occurrence of epsilon in the gauche(-) domain necessitates S-type sugar conformations. Given the aforementioned values for beta, gamma, delta and epsilon the ring closure constraints for the ring, formed by the phosphate backbone can only be fulfilled if alpha and zeta adopt some special values. After energy minimization with the CHARMm force field only two combinations of alpha and zeta result in energetically favourable structures, i.e. the combination alpha (t)/zeta(g-) in case gamma is in a gauche(+) and epsilon is in a trans conformation, and the combination alpha (t)/zeta (g+) for the combination gamma (t)/epsilon (g-). The results are discussed in relation to earlier findings obtained for cd(ApAp) and cr(GpGp), the latter molecule being a regulator of the synthesis of cellulose in Acetobacter xylinum. PMID:8041628

  11. The solution structure of the circular trinucleotide cr(GpGpGp) determined by NMR and molecular mechanics calculation.

    PubMed

    Mooren, M M; Wijmenga, S S; van der Marel, G A; van Boom, J H; Hilbers, C W

    1994-07-11

    The 3'-5' circular trinucleotide cr(GpGpGp) was studied by means of 1D and 2D high resolution NMR techniques and molecular mechanics calculations. Analysis of the J-couplings, obtained from the 1H and 13C-NMR spectra, allowed the determination of the conformation of the sugar rings and of the 'circular' phosphate backbone. In the course of the investigations it was found that the Karplus-equation most recently parametrized for the CCOP J-coupling constants could not account for the measured J(C4'P) of 11.1 Hz and a new parametrization for both HCOP and CCOP coupling constants is therefore presented. Subsequent analysis of the coupling constants yielded 'fixed' values for the torsion angles beta and delta (with beta = 178 degrees and delta = 139 degrees). The value of the latter angle corresponds to an S-type sugar conformation. The torsion angles gamma and epsilon are involved in a rapid equilibrium in which they are converted between the gauche(+) and trans and between the trans and gauche(-) domain respectively. We show that the occurrence of epsilon in the gauche(-) domain necessitates S-type sugar conformations. Given the aforementioned values for beta, gamma, delta and epsilon the ring closure constraints for the ring, formed by the phosphate backbone can only be fulfilled if alpha and zeta adopt some special values. After energy minimization with the CHARMm force field only two combinations of alpha and zeta result in energetically favourable structures, i.e. the combination alpha (t)/zeta(g-) in case gamma is in a gauche(+) and epsilon is in a trans conformation, and the combination alpha (t)/zeta (g+) for the combination gamma (t)/epsilon (g-). The results are discussed in relation to earlier findings obtained for cd(ApAp) and cr(GpGp), the latter molecule being a regulator of the synthesis of cellulose in Acetobacter xylinum.

  12. Event simulation based on three-fluid hydrodynamics for collisions at energies available at the Dubna Nuclotron-based Ion Collider Facility and at the Facility for Antiproton and Ion Research in Darmstadt

    NASA Astrophysics Data System (ADS)

    Batyuk, P.; Blaschke, D.; Bleicher, M.; Ivanov, Yu. B.; Karpenko, Iu.; Merts, S.; Nahrgang, M.; Petersen, H.; Rogachevsky, O.

    2016-10-01

    We present an event generator based on the three-fluid hydrodynamics approach for the early stage of the collision, followed by a particlization at the hydrodynamic decoupling surface to join to a microscopic transport model, ultrarelativistic quantum molecular dynamics, to account for hadronic final-state interactions. We present first results for nuclear collisions of the Facility for Antiproton and Ion Research-Nuclotron-based Ion Collider Facility energy scan program (Au+Au collisions, √{sN N}=4 -11 GeV ). We address the directed flow of protons and pions as well as the proton rapidity distribution for two model equations of state, one with a first-order phase transition and the other with a crossover-type softening at high densities. The new simulation program has the unique feature that it can describe a hadron-to-quark matter transition which proceeds in the baryon stopping regime that is not accessible to previous simulation programs designed for higher energies.

  13. A systems study of an RF power source for a 1 TeV next linear collider based upon the relativistic-klystron two-beam accelerator

    SciTech Connect

    Yu, S.; Goffeney, N.; Deadrick, F.

    1994-11-01

    A systems study, including physics, engineering and costing, has been conducted to assess the feasibility of a relativistic-klystron two-beam-accelerator (RK-TBA) system as a RF power source candidate for a 1 TeV linear collider. Several key issues associated with a realizable RK-TBA system have been addressed, and corresponding schemes have been developed and examined quantitatively. A point design example has been constructed to present a concrete conceptual design which has acceptable transverse and longitudinal beam stability properties. The overall efficiency of RF production for such a power source is estimated to be 36%, and the cost of the full system is estimated to be less than 1 billion dollars.

  14. A systems study of an RF power source for a 1 TeV next linear collider based upon the relativistic-klystron two-beam accelerator

    SciTech Connect

    Yu, S.; Deadrick, F.; Goffeney, N.; Henestroza, E.; Houck, T.; Li, H.; Peters, C.; Reginato, L.; Sessler, A.; Vanecek, D.; Westenskow, G.

    1995-07-05

    A systems study, including physics, engineering, and costing, has been conducted to assess the feasibility of a relativistic-klystron two-beam-accelerator (RK-TBA) system as a RF power source candidate for a 1 TeV linear collider. Several key issues associated with a realizable RK-TBA system have been addressed, and corresponding schemes have been developed and examined quantitatively. A point design example has been constructed to present a concrete conceptual design which has acceptable transverse and longitudinal beam stability properties. The overall efficiency of RF production for such a power source is estimated to be 36%, and the cost of the full system is estimated to be less than 1 billion dollars. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  15. Stabilization of HIV-1 gp120-CD4 Receptor Complex through Targeted Interchain Disulfide Exchange*

    PubMed Central

    Cerutti, Nichole; Mendelow, Barry V.; Napier, Grant B.; Papathanasopoulos, Maria A.; Killick, Mark; Khati, Makobetsa; Stevens, Wendy; Capovilla, Alexio

    2010-01-01

    HIV-1 enters cells via interaction between the trimeric envelope (Env) glycoprotein gp120/gp41 and the host cell surface receptor molecule CD4. The requirement of CD4 for viral entry has rationalized the development of recombinant CD4-based proteins as competitive viral attachment inhibitors and immunotherapeutic agents. In this study, we describe a novel recombinant CD4 protein designed to bind gp120 through a targeted disulfide-exchange mechanism. According to structural models of the gp120-CD4 receptor complex, substitution of Ser60 on the CD4 domain 1 α-helix with Cys positions a thiol in proximity of the gp120 V1/V2 loop disulfide (Cys126–Cys196), satisfying the stereochemical and geometric conditions for redox exchange between CD4 Cys60 and gp120 Cys126, and the consequent formation of an interchain disulfide bond. In this study, we provide experimental evidence for this effect by describing the expression, purification, refolding, receptor binding and antiviral activity analysis of a recombinant two-domain CD4 variant containing the S60C mutation (2dCD4-S60C). We show that 2dCD4-S60C binds HIV-1 gp120 with a significantly higher affinity than wild-type protein under conditions that facilitate disulfide exchange and that this translates into a corresponding increase in the efficacy of CD4-mediated viral entry inhibition. We propose that targeted redox exchange between conserved gp120 disulfides and nucleophilic moieties positioned strategically on CD4 (or CD4-like scaffolds) conceptualizes a new strategy in the development of high affinity HIV-1 Env ligands, with important implications for therapy and vaccine development. More generally, this chalcogen substitution approach provides a general means of stabilizing receptor-ligand complexes where the structural and biophysical conditions for disulfide exchange are satisfied. PMID:20538591

  16. Stabilization of HIV-1 gp120-CD4 receptor complex through targeted interchain disulfide exchange.

    PubMed

    Cerutti, Nichole; Mendelow, Barry V; Napier, Grant B; Papathanasopoulos, Maria A; Killick, Mark; Khati, Makobetsa; Stevens, Wendy; Capovilla, Alexio

    2010-08-13

    HIV-1 enters cells via interaction between the trimeric envelope (Env) glycoprotein gp120/gp41 and the host cell surface receptor molecule CD4. The requirement of CD4 for viral entry has rationalized the development of recombinant CD4-based proteins as competitive viral attachment inhibitors and immunotherapeutic agents. In this study, we describe a novel recombinant CD4 protein designed to bind gp120 through a targeted disulfide-exchange mechanism. According to structural models of the gp120-CD4 receptor complex, substitution of Ser(60) on the CD4 domain 1 alpha-helix with Cys positions a thiol in proximity of the gp120 V1/V2 loop disulfide (Cys(126)-Cys(196)), satisfying the stereochemical and geometric conditions for redox exchange between CD4 Cys(60) and gp120 Cys(126), and the consequent formation of an interchain disulfide bond. In this study, we provide experimental evidence for this effect by describing the expression, purification, refolding, receptor binding and antiviral activity analysis of a recombinant two-domain CD4 variant containing the S60C mutation (2dCD4-S60C). We show that 2dCD4-S60C binds HIV-1 gp120 with a significantly higher affinity than wild-type protein under conditions that facilitate disulfide exchange and that this translates into a corresponding increase in the efficacy of CD4-mediated viral entry inhibition. We propose that targeted redox exchange between conserved gp120 disulfides and nucleophilic moieties positioned strategically on CD4 (or CD4-like scaffolds) conceptualizes a new strategy in the development of high affinity HIV-1 Env ligands, with important implications for therapy and vaccine development. More generally, this chalcogen substitution approach provides a general means of stabilizing receptor-ligand complexes where the structural and biophysical conditions for disulfide exchange are satisfied.

  17. GP concordance with advice for treatment following a multidisciplinary psychogeriatric assessment.

    PubMed

    Wolfs, Claire A G; Verhey, Frans R J; Kessels, Alfons; Winkens, Ron A G; Severens, Johan L; Dirksen, Carmen D

    2007-03-01

    To evaluate the concordance of General Practitioners (GPs) with advice for treatment after a multidisciplinary psychogeriatric assessment by the Diagnostic Observation Centre for PsychoGeriatric patients (DOC-PG). Concordance checklists, listing the recommendations from the multidisciplinary team, were sent to the GPs in order to establish GP concordance. Regression models were used to study the associations between various patient and GP characteristics and level of concordance. Furthermore, results of a questionnaire (to identify the level of satisfaction regarding the services provided by the DOC-PG) were compared with the level of GP concordance. Based on 530 recommendations, the overall GP concordance rate amounted to 71%. The most common types of advice pertained to medication, GP follow-up/advice and referral. GP concordance with advice regarding admissions was the highest, followed by advice concerning the arrangement of daycare, home care and the adaptation of medication. GP concordance was lowest for referral recommendations to other specialties and recommendations regarding psychoeducation. Concordance was higher for patients who lived alone, for patients with fewer cognitive problems, when the number of recommendations did not exceed six and in group practices. Concordance was dependent on the type of advice. Satisfaction with DOC-PG did not correlate with the level of concordance. In general, GPs showed a high level of concordance with advice from the DOC-PG. Enhancement of GP concordance can be achieved by limiting the number of recommendations, giving detailed explanations about the purpose of recommendations and educating GPs by doing. (c) 2006 John Wiley & Sons, Ltd.

  18. Factors influencing the EBM behaviour of GP trainers: a mixed method study.

    PubMed

    Te Pas, E; van Dijk, N; Bartelink, M E L; Wieringa-De Waard, M

    2013-01-01

    General practitioner (GP) trainees state that their trainers are not consistent in using evidence-based medicine (EBM) or are even dismissive of it. As trainers are important role models in the Dutch GP training system this could have a large influence on the EBM training of GP trainees. To establish the motivations and barriers of Dutch GP trainers in using EBM. A questionnaire on personal characteristics, knowledge, skills (Berlin, score 0-15) and attitude (McColl, VAS score 0-100), and statements about EBM barriers were presented to 106 GP trainers. Additionally, three focus group sessions with trainers (n = 30) were held. Knowledge and skills were less than half correct (mean 6.1, standard deviation (SD) 2.9); the overall score on attitude was 58.8 (SD 9.4). Factor analysis showed four categories of barriers: EBM competence (mean 3.5 (SD 0.8)), search activities (mean 3.5 (SD 0.8)), motivation (mean 3.8 (SD 0.7)) and time (mean 2.5 (SD 0.9)). After analysis of the focus group sessions, five categories of motivations and barriers predominated: EBM competence, attitude and behaviour, sources, time and logistics. GP trainers experience motivations in EBM; however, these motivations can also be barriers, depending on the trainer's level of knowledge and attitude.

  19. Student-centred GP ambassadors: Perceptions of experienced clinical tutors in general practice undergraduate training.

    PubMed

    Von Below, Bernhard; Haffling, Ann-Christin; Brorsson, Annika; Mattsson, Bengt; Wahlqvist, Mats

    2015-06-01

    To explore experienced general practitioner (GP) tutor perceptions of a skilled GP tutor of medical students. Interview study based on focus groups. Twenty GPs experienced in tutoring medical students at primary health care centres in two Swedish regions were interviewed. Four focus-group interviews were analysed using qualitative content analysis. Twenty GP tutors, median age 50, specifically selected according to age, gender, and location participated in two focus groups in Gothenburg and Malmö, respectively. Meaning units in the texts were extracted, coded and condensed into categories and themes. Three main themes emerged: "Professional as GP and ambassador to general practice", "Committed and student-centred educator", and "Coordinator of the learning environment". Experienced GP tutors describe their skills as a clinical tutor as complex and diversified. A strong professional identity within general practice is vital and GP tutors describe themselves as ambassadors to general practice, essential to the process of recruiting a new generation of general practitioners. Leaders of clinical education and health care planners must understand the complexity in a clinical tutor's assignment and provide adequate support, time, and resources in order to facilitate a sustainable tutorship and a good learning environment, which could also improve the necessary recruitment of future GPs.

  20. Molecular Recognition of CXCR4 by a Dual Tropic HIV-1 gp120 V3 Loop

    PubMed Central

    Tamamis, Phanourios; Floudas, Christodoulos A.

    2013-01-01

    HIV-1 cell entry is initiated by the interaction of the viral envelope glycoprotein gp120 with CD4, and chemokine coreceptors CXCR4 and CCR5. The molecular recognition of CXCR4 or CCR5 by the HIV-1 gp120 is mediated through the V3 loop, a fragment of gp120. The binding of the V3 loop to CXCR4 or CCR5 determines the cell tropism of HIV-1 and constitutes a key step before HIV-1 cell entry. Thus, elucidating the molecular recognition of CXCR4 by the V3 loop is important for understanding HIV-1 viral infectivity and tropism, and for the design of HIV-1 inhibitors. We employed a comprehensive set of computational tools, predominantly based on free energy calculations and molecular-dynamics simulations, to investigate the molecular recognition of CXCR4 by a dual tropic V3 loop. We report what is, to our knowledge, the first HIV-1 gp120 V3 loop:CXCR4 complex structure. The computationally derived structure reveals an abundance of polar and nonpolar intermolecular interactions contributing to the HIV-1 gp120:CXCR4 binding. Our results are in remarkable agreement with previous experimental findings. Therefore, this work sheds light on the functional role of HIV-1 gp120 V3 loop and CXCR4 residues associated with HIV-1 coreceptor activity. PMID:24048002

  1. Future Electron-Hadron Colliders

    SciTech Connect

    Litvinenko, V.

    2010-05-23

    Outstanding research potential of electron-hadron colliders (EHC) was clearly demonstrated by first - and the only - electron-proton collider HERA (DESY, Germany). Physics data from HERA revealed new previously unknown facets of Quantum Chromo-Dynamics (QCD). EHC is an ultimate microscope probing QCD in its natural environment, i.e. inside the hadrons. In contrast with hadrons, electrons are elementary particles with known initial state. Hence, scattering electrons from hadrons provides a clearest pass to their secrets. It turns EHC into an ultimate machine for high precision QCD studies and opens access to rich physics with a great discovery potential: solving proton spin puzzle, observing gluon saturation or physics beyond standard model. Access to this physics requires high-energy high-luminosity EHCs and a wide reach in the center-of-mass (CM) energies. This paper gives a brief overview of four proposed electron-hadron colliders: ENC at GSI (Darmstadt, Germany), ELIC/MEIC at TJNAF (Newport News, VA, USA), eRHIC at BNL (Upton, NY, USA) and LHeC at CERN (Geneva, Switzerland). Future electron-hadron colliders promise to deliver very rich physics not only in the quantity but also in the precision. They are aiming at very high luminosity two-to-four orders of magnitude beyond the luminosity demonstrated by the very successful HERA. While ENC and LHeC are on opposite side of the energy spectrum, eRHIC and ELIC are competing for becoming an electron-ion collider (EIC) in the U.S. Administrations of BNL and Jlab, in concert with US DoE office of Nuclear Physics, work on the strategy for down-selecting between eRHIC and ELIC. The ENC, EIC and LHeC QCD physics programs to a large degree are complimentary to each other and to the LHC physics. In last decade, an Electron Ion Collider (EIC) collaboration held about 25 collaboration meetings to develop physics program for EIC with CM energy {approx}100 GeV. One of these meetings was held at GSI, where ENC topic was in the

  2. Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

    SciTech Connect

    Duan, Liangwei; Du, Jiansen; Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun; Liu, Xinqi

    2016-04-15

    Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

  3. Development of Small-molecule HIV Entry Inhibitors Specifically Targeting gp120 or gp41.

    PubMed

    Lu, Lu; Yu, Fei; Cai, Lifeng; Debnath, Asim K; Jiang, Shibo

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein surface subunit gp120 and transmembrane subunit gp41 play important roles in HIV-1 entry, thus serving as key targets for the development of HIV-1 entry inhibitors. T20 peptide (enfuvirtide) is the first U.S. FDA-approved HIV entry inhibitor; however, its clinical application is limited by the lack of oral availability. Here, we have described the structure and function of the HIV-1 gp120 and gp41 subunits and reviewed advancements in the development of small-molecule HIV entry inhibitors specifically targeting these two Env glycoproteins. We then compared the advantages and disadvantages of different categories of HIV entry inhibitor candidates and further predicted the future trend of HIV entry inhibitor development.

  4. Development of Small-molecule HIV Entry Inhibitors Specifically Targeting gp120 or gp41

    PubMed Central

    Lu, Lu; Yu, Fei; Cai, Lifeng; Debnath, Asim K.; Jiang, Shibo

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein surface subunit gp120 and transmembrane subunit gp41 play important roles in HIV-1 entry, thus serving as key targets for the development of HIV-1 entry inhibitors. T20 peptide (enfuvirtide) is the first U.S. FDA-approved HIV entry inhibitor; however, its clinical application is limited by the lack of oral availability. Here, we have described the structure and function of the HIV-1 gp120 and gp41 subunits and reviewed advancements in the development of small-molecule HIV entry inhibitors specifically targeting these two Env glycoproteins. We then compared the advantages and disadvantages of different categories of HIV entry inhibitor candidates and further predicted the future trend of HIV entry inhibitor development. PMID:26324044

  5. Structure of an extracellular gp130 cytokine receptor signaling complex.

    PubMed

    Chow, D; He, X; Snow, A L; Rose-John, S; Garcia, K C

    2001-03-16

    The activation of gp130, a shared signal-transducing receptor for a family of cytokines, is initiated by recognition of ligand followed by oligomerization into a higher order signaling complex. Kaposi's sarcoma-associated herpesvirus encodes a functional homolog of human interleukin-6 (IL-6) that activates human gp130. In the 2.4 angstrom crystal structure of the extracellular signaling assembly between viral IL-6 and human gp130, two complexes are cross-linked into a tetramer through direct interactions between the immunoglobulin domain of gp130 and site III of viral IL-6, which is necessary for receptor activation. Unlike human IL-6 (which uses many hydrophilic residues), the viral cytokine largely uses hydrophobic amino acids to contact gp130, which enhances the complementarity of the viral IL-6-gp130 binding interfaces. The cross-reactivity of gp130 is apparently due to a chemical plasticity evident in the amphipathic gp130 cytokine-binding sites.

  6. COLLIDE: Collisions into Dust Experiment

    NASA Technical Reports Server (NTRS)

    Colwell, Joshua E.

    1999-01-01

    The Collisions Into Dust Experiment (COLLIDE) was completed and flew on STS-90 in April and May of 1998. After the experiment was returned to Earth, the data and experiment were analyzed. Some anomalies occurred during the flight which prevented a complete set of data from being obtained. However, the experiment did meet its criteria for scientific success and returned surprising results on the outcomes of very low energy collisions into powder. The attached publication, "Low Velocity Microgravity Impact Experiments into Simulated Regolith," describes in detail the scientific background, engineering, and scientific results of COLLIDE. Our scientific conclusions, along with a summary of the anomalies which occurred during flight, are contained in that publication. We offer it as our final report on this grant.

  7. Experimental Approaches at Linear Colliders

    SciTech Connect

    Jaros, John A

    2002-02-13

    Precision measurements have played a vital role in our understanding of elementary particle physics. Experiments performed using e{sup +}e{sup -} collisions have contributed an essential part. Recently, the precision measurements at LEP and SLC have probed the standard model at the quantum level and severely constrained the mass of the Higgs boson [1]. Coupled with the limits on the Higgs mass from direct searches [2], this enables the mass to be constrained to be in the range 115-205 GeV. Developments in accelerator R and D have matured to the point where one could contemplate construction of a linear collider with initial energy in the 500 GeV range and a credible upgrade path to {approx} 1 TeV. Now is therefore the correct time to critically evaluate the case for such a facility. The Working Group E3, Experimental Approaches at Linear Colliders, was encouraged to make this evaluation. The group was charged with examining critically the physics case for a Linear Collider (LC) of energy of order 1 TeV as well as the cases for higher energy machines, assessing the performance requirements and exploring the viability of several special options. In addition it was asked to identify the critical areas where R and D is required (the complete text of the charge can be found in the Appendix). In order to address this, the group was organized into subgroups, each of which was given a specific task. Three main groups were assigned to the TeV-class Machines, Multi-TeV Machines and Detector Issues. The central activity of our working group was the exploration of TeV class machines, since they are being considered as the next major initiative in high energy physics. We have considered the physics potential of these machines, the special options that could be added to the collider after its initial running, and addressed a number of important questions. Several physics scenarios were suggested in order to benchmark the physics reach of the linear collider and persons were

  8. Crab Cavities for Linear Colliders

    SciTech Connect

    Burt, G.; Ambattu, P.; Carter, R.; Dexter, A.; Tahir, I.; Beard, C.; Dykes, M.; Goudket, P.; Kalinin, A.; Ma, L.; McIntosh, P.; Shulte, D.; Jones, Roger M.; Bellantoni, L.; Chase, B.; Church, M.; Khabouline, T.; Latina, A.; Adolphsen, C.; Li, Z.; Seryi, Andrei; /SLAC

    2011-11-08

    Crab cavities have been proposed for a wide number of accelerators and interest in crab cavities has recently increased after the successful operation of a pair of crab cavities in KEK-B. In particular crab cavities are required for both the ILC and CLIC linear colliders for bunch alignment. Consideration of bunch structure and size constraints favour a 3.9 GHz superconducting, multi-cell cavity as the solution for ILC, whilst bunch structure and beam-loading considerations suggest an X-band copper travelling wave structure for CLIC. These two cavity solutions are very different in design but share complex design issues. Phase stabilisation, beam loading, wakefields and mode damping are fundamental issues for these crab cavities. Requirements and potential design solutions will be discussed for both colliders.

  9. Conventional power sources for colliders

    SciTech Connect

    Allen, M.A.

    1987-07-01

    At SLAC we are developing high peak-power klystrons to explore the limits of use of conventional power sources in future linear colliders. In an experimental tube we have achieved 150 MW at 1 ..mu..sec pulse width at 2856 MHz. In production tubes for SLAC Linear Collider (SLC) we routinely achieve 67 MW at 3.5 ..mu..sec pulse width and 180 pps. Over 200 of the klystrons are in routine operation in SLC. An experimental klystron at 8.568 GHz is presently under construction with a design objective of 30 MW at 1 ..mu..sec. A program is starting on the relativistic klystron whose performance will be analyzed in the exploration of the limits of klystrons at very short pulse widths.

  10. Polarized proton collider at RHIC

    NASA Astrophysics Data System (ADS)

    Alekseev, I.; Allgower, C.; Bai, M.; Batygin, Y.; Bozano, L.; Brown, K.; Bunce, G.; Cameron, P.; Courant, E.; Erin, S.; Escallier, J.; Fischer, W.; Gupta, R.; Hatanaka, K.; Huang, H.; Imai, K.; Ishihara, M.; Jain, A.; Lehrach, A.; Kanavets, V.; Katayama, T.; Kawaguchi, T.; Kelly, E.; Kurita, K.; Lee, S. Y.; Luccio, A.; MacKay, W. W.; Mahler, G.; Makdisi, Y.; Mariam, F.; McGahern, W.; Morgan, G.; Muratore, J.; Okamura, M.; Peggs, S.; Pilat, F.; Ptitsin, V.; Ratner, L.; Roser, T.; Saito, N.; Satoh, H.; Shatunov, Y.; Spinka, H.; Syphers, M.; Tepikian, S.; Tominaka, T.; Tsoupas, N.; Underwood, D.; Vasiliev, A.; Wanderer, P.; Willen, E.; Wu, H.; Yokosawa, A.; Zelenski, A. N.

    2003-03-01

    In addition to heavy ion collisions (RHIC Design Manual, Brookhaven National Laboratory), RHIC will also collide intense beams of polarized protons (I. Alekseev, et al., Design Manual Polarized Proton Collider at RHIC, Brookhaven National Laboratory, 1998 [2]), reaching transverse energies where the protons scatter as beams of polarized quarks and gluons. The study of high energy polarized protons beams has been a long term part of the program at BNL with the development of polarized beams in the Booster and AGS rings for fixed target experiments. We have extended this capability to the RHIC machine. In this paper we describe the design and methods for achieving collisions of both longitudinal and transverse polarized protons in RHIC at energies up to s=500 GeV.

  11. ep Collider experiments and physics

    SciTech Connect

    Atwood, D.; Baur, U.; Bluemlein, J.

    1992-12-31

    The physics prospects for detectors at ep colliders are examined. Colliders considered include the HERA facility at DESY, LEP I {times} LHC, and LEP II {times} LHC at CERN. Physics topics studied include machine energy and polarization, as well as detector resolution, calibration, jet identification and backgrounds from beam-gas interactions. QCD topics include measurements of the quark and gluon structure functions and parton distributions, as well as the expansion of the observable cross section into angular functions. Electroweak topics include measurements of the weak mixing angle, radiative corrections, and WW{gamma} (WWZ) couplings. Topics beyond the standard model include observation of new Z`s, indirect production of Leptoquarks, pair production of sfermions and searches for R-parity-violating SUSY particle production.

  12. Development of HIV-1 fusion inhibitors targeting gp41.

    PubMed

    Lu, K; Asyifah, M R; Shao, F; Zhang, D

    2014-06-01

    The HIV-1 envelope protein glycoprotein 41 (gp41) is crucial in the HIV-1 infection process, therefore gp41 has emerged as an attractive target for drug design against AIDS. During the past few decades, tremendous efforts have been made on developing inhibitors that can prevent the HIV-1 entry process via suppressing functional gp41. In this review, the development of HIV-1 fusion inhibitors targeting gp41 including peptide inhibitors, small molecule inhibitors, vaccines and neutralized antibodies will be discussed.

  13. Collective accelerator for electron colliders

    SciTech Connect

    Briggs, R.J.

    1985-05-13

    A recent concept for collective acceleration and focusing of a high energy electron bunch is discussed, in the context of its possible applicability to large linear colliders in the TeV range. The scheme can be considered to be a member of the general class of two-beam accelerators, where a high current, low voltage beam produces the acceleration fields for a trailing high energy bunch.

  14. A collider observable QCD axion

    DOE PAGES

    Dimopoulos, Savas; Hook, Anson; Huang, Junwu; ...

    2016-11-09

    Here, we present a model where the QCD axion is at the TeV scale and visible at a collider via its decays. Conformal dynamics and strong CP considerations account for the axion coupling strongly enough to the standard model to be produced as well as the coincidence between the weak scale and the axion mass. The model predicts additional pseudoscalar color octets whose properties are completely determined by the axion properties rendering the theory testable.

  15. Solid State Technology Meets Collider Challenge

    SciTech Connect

    Hazi, A

    2005-09-20

    Probing the frontiers of particle physics and delving into the mysteries of the universe and its beginnings require machines that can accelerate beams of fundamental particles to very high energies and then collide those beams together, producing a multitude of exotic subatomic particles. The proposed Next Linear Collider (NLC), being developed by Stanford Linear Accelerator Center (SLAC), Lawrence Livermore and Lawrence Berkeley national laboratories, and Fermi National Accelerator Laboratory (Fermilab), is such a machine. The NLC is expected to produce a variety of subatomic particles by smashing together electrons and their antimatter counterparts (positrons) at nearly the speed of light with energies in the teraelectronvolt (TeV) range. Plans are that the NLC will initially operate at 0.5 TeV and ultimately be scaled up to 1.5 TeV. (See S&TR, April 2000, pp. 12-16.) Work at the facility will complement the research to be conducted at another high-energy particle accelerator, the 14-TeV Large Hadron Collider at the European Laboratory for Particle Physics (commonly known by the acronym CERN from its former name) in Geneva, which is scheduled for completion in 2007. Achieving beam energy levels in the TeV range requires modulator systems that can convert ac line power--the same type of power one gets from the wall plug--into dc pulses. Ultimately, these pulses are transformed into radiofrequency (rf) pulses that ''kick'' the particles up to the required energy levels. Livermore scientists and engineers have designed a solid-state modulator to replace oldstyle modulators based on vacuum-tube technology. These new modulators promise to be far more efficient, reliable, and serviceable than the previous components. Livermore's Laboratory Directed Research and Development Program supported the basic research and development on the solid-state modulator technology, and SLAC supported the systems integration.

  16. Chromaticity correction for a muon collider optics

    SciTech Connect

    Alexahin, Y.; Gianfelice-Wendt, E.; Kapin, V.; /Fermilab

    2011-03-01

    Muon Collider (MC) is a promising candidate for the next energy frontier machine. However, in order to obtain peak luminosity in the 10{sup 34} cm{sup 2}s{sup -1} range the collider lattice designmust satisfy a number of stringent requirements. In particular the expected large momentum spread of the muon beam and the very small {beta}* call for a careful correction of the chromatic effects. Here we present a particular solution for the interaction region (IR) optics whose distinctive feature is a three-sextupole local chromatic correction scheme. The scheme may be applied to other future machines where chromatic effects are expected to be large. The expected large muon energy spread requires the optics to be stable over a wide range of momenta whereas the required luminosity calls for {beta}* in the mm range. To avoid luminosity degradation due to hour-glass effect, the bunch length must be comparatively small. To keep the needed RF voltage within feasible limits the momentum compaction factor must be small over the wide range of momenta. A low {beta}* means high sensitivity to alignment and field errors of the Interaction Region (IR) quadrupoles and large chromatic effects which limit the momentum range of optics stability and require strong correction sextupoles, which eventually limit the Dynamic Aperture (DA). Finally, the ring circumference should be as small as possible, luminosity being inversely proportional to the collider length. A promising solution for a 1.5 TeV center of mass energy MC with {beta}* = 1 m in both planes has been proposed. This {beta}* value has been chosen as a compromise between luminosity and feasibility based on the magnet design and energy deposition considerations. The proposed solution for the IR optics together with a new flexible momentum compaction arc cell design allows to satisfy all requirements and is relatively insensitive to the beam-beam effect.

  17. State of hadron collider physics

    SciTech Connect

    Grannis, P.D. |

    1993-12-01

    The 9th Topical Workshop on Proton-Antiproton Collider Physics in Tsukuba Japan demonstrated clearly the enormous breadth of physics accessible in hadron cowders. Although no significant chinks were reported in the armor of the Standard Model, new results presented in this meeting have expanded our knowledge of the electroweak and strong interactions and have extended the searches for non-standard phenomena significantly. Much of the new data reported came from the CDF and D0 experiments at the Fermilab cowder. Superb operation of the Tevatron during the 1992-1993 Run and significant advances on the detector fronts -- in particular, the emergence of the new D0 detector as a productive physics instrument in its first outing and the addition of the CDF silicon vertex detector -- enabled much of this advance. It is noteworthy however that physics from the CERN collider experiments UA1 and UA4 continued to make a large impact at this meeting. In addition, very interesting summary talks were given on new results from HERA, cosmic ray experiments, on super-hadron collider physics, and on e{sup +}e{sup {minus}} experiments at LEP and TRISTAN. These summaries are reported in elsewhere in this volume.

  18. String resonances at hadron colliders

    NASA Astrophysics Data System (ADS)

    Anchordoqui, Luis A.; Antoniadis, Ignatios; Dai, De-Chang; Feng, Wan-Zhe; Goldberg, Haim; Huang, Xing; Lüst, Dieter; Stojkovic, Dejan; Taylor, Tomasz R.

    2014-09-01

    We consider extensions of the standard model based on open strings ending on D-branes, with gauge bosons due to strings attached to stacks of D-branes and chiral matter due to strings stretching between intersecting D-branes. Assuming that the fundamental string mass scale Ms is in the TeV range and that the theory is weakly coupled, we discuss possible signals of string physics at the upcoming HL-LHC run (integrated luminosity =3000 fb-1) with a center-of-mass energy of √s =14 TeV and at potential future pp colliders, HE-LHC and VLHC, operating at √s =33 and 100 TeV, respectively (with the same integrated luminosity). In such D-brane constructions, the dominant contributions to full-fledged string amplitudes for all the common QCD parton subprocesses leading to dijets and γ +jet are completely independent of the details of compactification and can be evaluated in a parameter-free manner. We make use of these amplitudes evaluated near the first (n=1) and second (n=2) resonant poles to determine the discovery potential for Regge excitations of the quark, the gluon, and the color singlet living on the QCD stack. We show that for string scales as large as 7.1 TeV (6.1 TeV) lowest massive Regge excitations are open to discovery at the ≥5σ in dijet (γ +jet) HL-LHC data. We also show that for n=1 the dijet discovery potential at HE-LHC and VLHC exceedingly improves: up to 15 TeV and 41 TeV, respectively. To compute the signal-to-noise ratio for n=2 resonances, we first carry out a complete calculation of all relevant decay widths of the second massive level string states (including decays into massless particles and a massive n=1 and a massless particle), where we rely on factorization and conformal field theory techniques. Helicity wave functions of arbitrary higher spin massive bosons are also constructed. We demonstrate that for string scales Ms≲10.5 TeV (Ms≲28 TeV) detection of n =2 Regge recurrences at HE-LHC (VLHC) would become the smoking gun for D

  19. HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling Pathways

    PubMed Central

    Berth, Sarah H.; Mesnard-Hoaglin, Nichole; Wang, Bin; Kim, Hajwa; Song, Yuyu; Sapar, Maria; Morfini, Gerardo

    2016-01-01

    Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment. Significantly, we found that gp120 severely impaired both anterograde and retrograde FAT. Providing a mechanistic basis for these effects, pharmacological experiments revealed an involvement of various phosphotransferases in this toxic effect, including members of mitogen-activated protein kinase pathways (Tak-1, p38, and c-Jun N-terminal Kinase (JNK)), inhibitor of kappa-B-kinase 2 (IKK2), and PP1. Biochemical experiments and axonal outgrowth assays in cell lines and primary cultures extended these findings. Impairments in neurite outgrowth in DRG neurons by gp120 were rescued using a Tak-1 inhibitor, implicating a Tak-1 mitogen-activated protein kinase pathway in gp120 neurotoxicity. Taken together, these observations indicate that kinase-based impairments in FAT represent a novel mechanism underlying gp120 neurotoxicity consistent with the dying-back degeneration seen in DSP. Targeting gp120-based impairments in FAT with specific kinase inhibitors might provide a novel therapeutic strategy to prevent axonal degeneration in DSP. PMID:27872270

  20. VINCIA for hadron colliders

    NASA Astrophysics Data System (ADS)

    Fischer, N.; Prestel, S.; Ritzmann, M.; Skands, P.

    2016-11-01

    We present the first public implementation of antenna-based QCD initial- and final-state showers. The shower kernels are 2→ 3 antenna functions, which capture not only the collinear dynamics but also the leading soft (coherent) singularities of QCD matrix elements. We define the evolution measure to be inversely proportional to the leading poles, hence gluon emissions are evolved in a p_perp measure inversely proportional to the eikonal, while processes that only contain a single pole (e.g., g→ qbar{q}) are evolved in virtuality. Non-ordered emissions are allowed, suppressed by an additional power of 1/Q^2. Recoils and kinematics are governed by exact on-shell 2→ 3 phase-space factorisations. This first implementation is limited to massless QCD partons and colourless resonances. Tree-level matrix-element corrections are included for QCD up to O(α _s^4) (4 jets), and for Drell-Yan and Higgs production up to O(α _s^3) ( V / H + 3 jets). The resulting algorithm has been made publicly available in Vincia 2.0.

  1. VINCIA for hadron colliders

    DOE PAGES

    Fischer, Nadine; Prestel, S.; Ritzmann, M.; ...

    2016-10-28

    We present the first public implementation of antenna-based QCD initial- and final-state showers. The shower kernels are 2→3 antenna functions, which capture not only the collinear dynamics but also the leading soft (coherent) singularities of QCD matrix elements. We define the evolution measure to be inversely proportional to the leading poles, hence gluon emissions are evolved in a p⊥ measure inversely proportional to the eikonal, while processes that only contain a single pole (e.g., g → qq¯) are evolved in virtuality. Non-ordered emissions are allowed, suppressed by an additional power of 1/Q2. Recoils and kinematics are governed by exact on-shellmore » 2 → 3 phase-space factorisations. This first implementation is limited to massless QCD partons and colourless resonances. Tree-level matrix-element corrections are included for QCD up to O(α4s) (4 jets), and for Drell–Yan and Higgs production up to O(α3s) (V / H + 3 jets). Finally, the resulting algorithm has been made publicly available in Vincia 2.0.« less

  2. AgedCare+GP: description and evaluation of an in-house model of general practice in a residential aged-care facility.

    PubMed

    Pain, Tilley; Stainkey, Lesley; Chapman, Sue

    2014-01-01

    This paper describes a medical model to provide in-house GP services to residents of aged-care facilities. Access to GP services for aged-care residents is decreasing, partially due to the changing demographic of the Australian GP workforce. The model we have developed is an in-house GP (AgedCare+GP) trialled in a publicly funded residential aged-care facility (RACF). The service model was based on the GP cooperative used in our after-hours general practice (AfterHours+GP). Briefly, the service model involves rostering a core group of GPs to provide weekly sessional clinics at the RACF. Financial contributions from appropriate Medicare Benefits Schedule (MBS) items for aged-care planning (including chronic conditions) provided adequate funds to operate the clinic for RACF residents. Evaluation of the service model used the number of resident transfers to the local emergency department as the primary outcome measure. There were 37 transfers of residents in the 3 months before the commencement of the AgedCare+GP and 11 transfers over a 3-month period at the end of the first year of operation; a reduction of almost 70%. This project demonstrates that AgedCare+GP is a successful model for GP service provision to RACF residents, and it also reduces the number of emergency department transfers.

  3. Meeting local complex health needs by building the capacity of general practice: the University of Queensland GP super clinic model.

    PubMed

    Dart, Jared M; Jackson, Claire L; Chenery, Helen J; Shaw, Paul N; Wilkinson, David

    2010-07-19

    The GP Super Clinics Program is a highly topical and controversial initiative with varying levels of support within the policy, consumer and health care communities. Here, we describe the GP super clinic initiative of the University of Queensland (UQ), and how it aims to enhance primary-care capacity in the regions where clinics are based. The UQ GP super clinic model has considered the concerns of general practitioners, patients and other stakeholders, and addresses the needs of these groups while providing an excellent opportunity for the university to be involved in innovative service delivery, community-based education, primary-care service design and evaluation.

  4. N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus

    SciTech Connect

    Dey, Antu K.; David, Kathryn B.; Ray, Neelanjana; Ketas, Thomas J.; Klasse, Per J.; Doms, Robert W.; Moore, John P.

    2008-03-01

    The native, functional HIV-1 envelope glycoprotein (Env) complex is a trimer of two non-covalently associated subunits: the gp120 surface glycoprotein and the gp41 transmembrane glycoprotein. However, various non-functional forms of Env are present on virus particles and HIV-1-infected cells, some of which probably arise as the native complex decays. The aberrant forms include gp120-gp41 monomers and oligomers, as well as gp41 subunits from which gp120 has dissociated. The presence of non-functional Env creates binding sites for antibodies that do not recognize native Env complexes and that are, therefore, non-neutralizing. Non-native Env forms (monomers, dimers, tetramers and aggregates) can also arise when soluble gp140 proteins, lacking the cytoplasmic and transmembrane domains of gp41, are expressed for vaccine studies. We recently identified five amino acids in the gp41 N-terminal region (I535, Q543, S553, K567 and R588) that promote gp140 trimerization. We have now studied their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells. The 5 substitutions in gp41 reduce the expression of non-trimeric gp160s, without affecting trimer levels. Pseudovirions bearing the mutant Env are fully infectious with similar kinetics of Env-mediated fusion. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. Hence the gp41 substitutions do not adversely affect Env structure, supporting their use for making new Env-based vaccines. The mutant Env might also help in studies intended to correlate antibody binding to virus neutralization. Of note is that the 5 residues are much more frequent, individually or collectively, in viruses from subtypes other than B.

  5. The impact of a GP clinical audit on the provision of smoking cessation advice

    PubMed Central

    McKay-Brown, Lisa; Bishop, Nicole; Balmford, James; Borland, Ron; Kirby, Catherine; Piterman, Leon

    2008-01-01

    Aim To investigate whether participation in a clinical audit and education session would improve GP management of patients who smoke. Methods GPs who participated in an associated smoking cessation research program were invited to complete a three-stage clinical audit. This process included a retrospective self-audit of smoking cessation management practices over the 6 months prior to commencing the study, attending a 2.5 hour education session about GP management of smoking cessation, and completion of a second retrospective self-audit 6 months later. Twenty-eight GPs completed the full audit and education process, providing information about their smoking cessation management with 1114 patients. The main outcome measure was changes in GP management of smoking cessation with patients across the audit period, as measured by the clinical audit tool. Results The majority of GPs (57%) indicated that as a result of the audit process they had altered their approach to the management of patients who smoke. Quantitative analyses confirmed significant increases in various forms of evidence-based smoking cessation management practices to assist patients to quit, or maintain quitting across the audit period. However comparative analyses of patient data challenged these findings, suggesting that the clinical audit process had less impact on GP practice than suggested in GP's self-reported audit data. Conclusion This study provides some support for the combined use of self-auditing, feedback and education to improve GP management of smoking cessation. However further research is warranted to examine GP- and patient-based reports of outcomes from clinical audit and other educational interventions. PMID:18973708

  6. Complex of a Protective Antibody with its Ebola Virus GP Peptide Epitope: Unusual Features of a V lambda x Light Chain

    DTIC Science & Technology

    2007-10-01

    GussIntroduction The Ebola virus causes a severe hemorrhagic fever usually involving uncontrolled viral replication, multiple organ failure, and death...administered one day after challenge.12 The epitope has previously beenmapped to nine residues (EQHHRRTDN, amino acids 405– 413) within the Ebola Zaire GP...VEQHHRRTDND) corresponds to a region of the mucin-like domain of the Ebola Zaire GP. Residues P404–P414 (based on the numbering in Ebola Zaire GP) are

  7. GpIIb/IIIa+ subpopulation of rat megakaryocyte progenitor cells exhibits high responsiveness to human thrombopoietin.

    PubMed

    Kato, T; Horie, K; Hagiwara, T; Maeda, E; Tsumura, H; Ohashi, H; Miyazaki, H

    1996-08-01

    The recently cloned factor thrombopoietin (TPO) has been shown to exhibit megakaryocyte colony-stimulating activity in vitro. In this investigation, to further evaluate the action of TPO on megakaryocyte progenitor cells (colony-forming units-megakaryocyte [CFU-MK]), GpIIb/IIIa+ and GpIIb/IIIa- populations of CFU-MK were prepared from rat bone marrow cells based on their reactivity with P55 antibody, a monoclonal antibody against rat GpIIb/IIIa, and their responsiveness to recombinant human TPO (rhTPO) and recombinant rat interleukin-3 (rrIL-3) was examined using a megakaryocyte colony-forming assay (Meg-CSA). rhTPO supported only megakaryocyte colony growth from both fractions in a dose-dependent fashion. The mean colony size observed with the GpIIb/IIIa+ population was smaller than that seen with the GpIIb/IIIa- population. With the optimal concentration of either rhTPO or rrIL-3, similar numbers of megakaryocyte colonies were formed from the GpIIb/IIIa+ population previously shown to be highly enriched for CFU-MK. In contrast, the maximum number of megakaryocyte colonies from the GpIIb/IIIa- population stimulated by rhTPO was only 24.2% of that achieved with rrIL-3. Morphologic analysis of rhTPO-promoted megakaryocyte colonies from the GpIIb/IIIa+ population showed that the average colony size was smaller but that the mean diameter of individual megakaryocytes was larger than in megakaryocyte colonies promoted with rrIL-3. rhTPO plus rrIL-3, each at suboptimal concentrations, had an additive effect on proliferation of CFU-MK in the GpIIb/IIIa+ fraction, whereas rhTPO plus murine IL-6 or murine granulocyte-macrophage colony-stimulating factor (mG-M-CSF) modestly but significantly reduced megakaryocyte colony growth. These results indicate that TPO preferentially acts on GpIIb/IIIa+ late CFU-MK with lower proliferative capacity and interacts with some other cytokines in CFU-MK development.

  8. Massive Stars in Colliding Wind Systems: the GLAST Perspective

    SciTech Connect

    Reimer, Anita; Reimer, Olaf; /Stanford U., HEPL /KIPAC, Menlo Park

    2011-11-29

    Colliding winds of massive stars in binary systems are considered as candidate sites of high-energy non-thermal photon emission. They are already among the suggested counterparts for a few individual unidentified EGRET sources, but may constitute a detectable source population for the GLAST observatory. The present work investigates such population study of massive colliding wind systems at high-energy gamma-rays. Based on the recent detailed model (Reimer et al. 2006) for non-thermal photon production in prime candidate systems, we unveil the expected characteristics of this source class in the observables accessible at LAT energies. Combining the broadband emission model with the presently cataloged distribution of such systems and their individual parameters allows us to conclude on the expected maximum number of LAT-detections among massive stars in colliding wind binary systems.

  9. Update on the MEIC electron collider ring design

    SciTech Connect

    Lin, Fangei; Derbenev, Yaroslav S.; Harwood, Leigh; Hutton, Andrew; Morozov, Vasiliy; Pilat, Fulvia; Zhang, Yuhong; Cai, Y.; Nosochkov, Y. M.; Sullivan, Michael; Wang, M.-H; Wienands, Uli

    2015-09-01

    The electron collider ring of the Medium-energy Electron-Ion Collider (MEIC) at Jefferson Lab is designed to accumulate and store a high-current polarized electron beam for collisions with an ion beam. We consider a design of the electron collider ring based on reusing PEP-II components, such as magnets, power supplies, vacuum system, etc. This has the potential to significantly reduce the cost and engineering effort needed to bring the project to fruition. This paper reports on an electron ring optics design considering the balance of PEP-II hardware parameters (such as dipole sagitta, magnet field strengths and acceptable synchrotron radiation power) and electron beam quality in terms of equilibrium emittances.

  10. Update on the MEIC electron collider ring design

    SciTech Connect

    Lin, F.; Derbenev, Ya. S.; Harwood, L.; Hutton, A.; Morozov, V. S.; Pilat, F.; Zhang, Y.; Cai, Y.; Nosochkov, Y. M.; Sullivan, M.; Wang, M-H; Wienands, U.

    2015-07-14

    The electron collider ring of the Medium-energy Electron-Ion Collider (MEIC) at Jefferson Lab is designed to accumulate and store a high-current polarized electron beam for collisions with an ion beam. We consider a design of the electron collider ring based on reusing PEPII components, such as magnets, power supplies, vacuum system, etc. This has the potential to significantly reduce the cost and engineering effort needed to bring the project to fruition. This paper reports on an electron ring optics design considering the balance of PEP-II hardware parameters (such as dipole sagitta, magnet field strengths and acceptable synchrotron radiation power) and electron beam quality in terms of equilibrium emittances.

  11. Symmetric Achromatic Low-Beta Collider Interaction Region Design Concept

    SciTech Connect

    Morozov, Vasiliy S.; Derbenev, Yaroslav S.; Lin, Fanglei; Johnson, Rolland P.

    2013-01-01

    We present a new symmetry-based concept for an achromatic low-beta collider interaction region design. A specially-designed symmetric Chromaticity Compensation Block (CCB) induces an angle spread in the passing beam such that it cancels the chromatic kick of the final focusing quadrupoles. Two such CCB?s placed symmetrically around an interaction point allow simultaneous compensation of the 1st-order chromaticities and chromatic beam smear at the IP without inducing significant 2nd-order aberrations. We first develop an analytic description of this approach and explicitly formulate 2nd-order aberration compensation conditions at the interaction point. The concept is next applied to develop an interaction region design for the ion collider ring of an electron-ion collider. We numerically evaluate performance of the design in terms of momentum acceptance and dynamic aperture. The advantages of the new concept are illustrated by comparing it to the conventional distributed-sextupole chromaticity compensation scheme.

  12. GP Section selects Best Student Paper

    NASA Astrophysics Data System (ADS)

    The AGU Geomagnetism and Paleomagnetism (GP) Section has announced its selection of a paper entitled “Multicomponent Magnetization of the Upper Silurian-Lower Devonian Ringerike Sandstone, Adjacent Dikes, and Permian Lavas, Oslo, Norway” as the best GP student paper presented at the 1986 AGU Spring Meeting. The primary author, Dartmouth College Ph.D. candidate David Douglass, was assisted on the paper by a colleague from Lamont-Doherty Geological Observatory. Douglass received his B.S. in geology from the University of California, Los Angeles, in 1980, and in 1984, he received his M.S. in earth sciences at Dartmouth. His current studies examine the paleomagnetism, structure, and sedimentation of several North Atlantic old red sandstone basins.

  13. The Multi-Purpose Detector (MPD) of the collider experiment

    NASA Astrophysics Data System (ADS)

    Golovatyuk, V.; Kekelidze, V.; Kolesnikov, V.; Rogachevsky, O.; Sorin, A.

    2016-08-01

    The project NICA (Nuclotron-based Ion Collider fAcility) is aimed to study dense baryonic matter in heavy-ion collisions in the energy range up to √{s_{NN}} = 11 GeV with average luminosity of L = 1027 cm-2s-1 (for 197Au79). The experimental program at the NICA collider will be performed with the Multi-Purpose Detector (MPD). We report on the main physics objectives of the NICA heavy-ion program and present the main detector components.

  14. Nb3Sn dipoles for the lower energy muon collider

    NASA Astrophysics Data System (ADS)

    Gupta, R.; Green, M.; Scanlan, R.

    1998-04-01

    The dipoles in the muon collider operate in an enviornment where a large amount of radiation-induced heat is deposited on the superconducting coils. The heating is maximum at the coil midplane. A racetrack coil based NB3Sn dipole for the lower energy muon collider is being developed which minimizes this problem. A conceptual design of this 14 tesla dipole will be presented which would have a large gap at the coil midplane. To elimate radiation-induced heating at the ends, the conductors blocks closer to midplane will have the turns returned on the same side of the aperture but away from the magnet center.

  15. Hyperion 5113/GP Infrasound Sensor Evaluation.

    SciTech Connect

    Merchant, Bion J.

    2015-08-01

    Sandia National Laboratories has tested and evaluated an infrasound sensor, the 5113/GP manufactured by Hyperion. These infrasound sensors measure pressure output by a methodology developed by the University of Mississippi. The purpose of the infrasound sensor evaluation was to determine a measured sensitivity, transfer function, power, self-noise, dynamic range, and seismic sensitivity. These sensors are being evaluated prior to deployment by the U.S. Air Force.

  16. GP-B error modeling and analysis

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The analysis and modeling for the Gravity Probe B (GP-B) experiment is reported. The finite-wordlength induced errors in Kalman filtering computation were refined. Errors in the crude result were corrected, improved derivation steps are taken, and better justifications are given. The errors associated with the suppression of the 1-noise were analyzed by rolling the spacecraft and then performing a derolling operation by computation.

  17. Cooling of electronics in collider experiments

    SciTech Connect

    Richard P. Stanek et al.

    2003-11-07

    Proper cooling of detector electronics is critical to the successful operation of high-energy physics experiments. Collider experiments offer unique challenges based on their physical layouts and hermetic design. Cooling systems can be categorized by the type of detector with which they are associated, their primary mode of heat transfer, the choice of active cooling fluid, their heat removal capacity and the minimum temperature required. One of the more critical detector subsystems to require cooling is the silicon vertex detector, either pixel or strip sensors. A general design philosophy is presented along with a review of the important steps to include in the design process. Factors affecting the detector and cooling system design are categorized. A brief review of some existing and proposed cooling systems for silicon detectors is presented to help set the scale for the range of system designs. Fermilab operates two collider experiments, CDF & D0, both of which have silicon systems embedded in their detectors. A review of the existing silicon cooling system designs and operating experience is presented along with a list of lessons learned.

  18. GP Workbench Manual: Technical Manual, User's Guide, and Software Guide

    USGS Publications Warehouse

    Oden, Charles P.; Moulton, Craig W.

    2006-01-01

    GP Workbench is an open-source general-purpose geophysical data processing software package written primarily for ground penetrating radar (GPR) data. It also includes support for several USGS prototype electromagnetic instruments such as the VETEM and ALLTEM. The two main programs in the package are GP Workbench and GP Wave Utilities. GP Workbench has routines for filtering, gridding, and migrating GPR data; as well as an inversion routine for characterizing UXO (unexploded ordinance) using ALLTEM data. GP Workbench provides two-dimensional (section view) and three-dimensional (plan view or time slice view) processing for GPR data. GP Workbench can produce high-quality graphics for reports when Surfer 8 or higher (Golden Software) is installed. GP Wave Utilities provides a wide range of processing algorithms for single waveforms, such as filtering, correlation, deconvolution, and calculating GPR waveforms. GP Wave Utilities is used primarily for calibrating radar systems and processing individual traces. Both programs also contain research features related to the calibration of GPR systems and calculating subsurface waveforms. The software is written to run on the Windows operating systems. GP Workbench can import GPR data file formats used by major commercial instrument manufacturers including Sensors and Software, GSSI, and Mala. The GP Workbench native file format is SU (Seismic Unix), and subsequently, files generated by GP Workbench can be read by Seismic Unix as well as many other data processing packages.

  19. Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity.

    PubMed

    Drummer, Heidi E; Hill, Melissa K; Maerz, Anne L; Wood, Stephanie; Ramsland, Paul A; Mak, Johnson; Poumbourios, Pantelis

    2013-01-01

    The HIV-1 gp120-gp41 complex, which mediates viral fusion and cellular entry, undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody (NAb). Understanding how conserved protein determinants retain functionality in the context of such evolution is important for their evaluation and exploitation as potential drug and/or vaccine targets. In this study, we examined how the conserved gp120-gp41 association site, formed by the N- and C-terminal segments of gp120 and the disulfide-bonded region (DSR) of gp41, adapts to glycan changes that are linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D) with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. We reasoned that the locations of suppressors point to structural elements that are functionally linked to the gp120-gp41 association site. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn¹³⁶ in V1 (T138N mutation) in conjunction with the L494I substitution in C5 within the association site. In culture 2, replication was restored with deletion of the N¹³⁹INN sequence, which ablates the overlapping Asn¹⁴¹-Asn¹⁴²-Ser-Ser potential N-linked glycosylation sequons in V1, in conjunction with D601N in the DSR. The 136 and 142 glycan mutations appeared to exert their suppressive effects by altering the dependence of gp120-gp41 interactions on the DSR residues, Leu⁵⁹³, Trp⁵⁹⁶ and Lys⁶⁰¹. The 136 and/or 142 glycan mutations increased the sensitivity of HIV-1 pseudovirions to the glycan-dependent NAbs 2G12 and PG16, and also pooled IgG obtained from HIV-1-infected individuals. Thus adjacent V1 glycans allosterically modulate the distal gp120-gp41 association site. We propose that this represents a mechanism for functional adaptation of the gp120-gp41 association site to an evolving glycan shield in a

  20. Binary Encoded-Prototype Tree for Probabilistic Model Building GP

    NASA Astrophysics Data System (ADS)

    Yanase, Toshihiko; Hasegawa, Yoshihiko; Iba, Hitoshi

    In recent years, program evolution algorithms based on the estimation of distribution algorithm (EDA) have been proposed to improve search ability of genetic programming (GP) and to overcome GP-hard problems. One such method is the probabilistic prototype tree (PPT) based algorithm. The PPT based method explores the optimal tree structure by using the full tree whose number of child nodes is maximum among possible trees. This algorithm, however, suffers from problems arising from function nodes having different number of child nodes. These function nodes cause intron nodes, which do not affect the fitness function. Moreover, the function nodes having many child nodes increase the search space and the number of samples necessary for properly constructing the probabilistic model. In order to solve this problem, we propose binary encoding for PPT. In this article, we convert each function node to a subtree of binary nodes where the converted tree is correct in grammar. Our method reduces ineffectual search space, and the binary encoded tree is able to express the same tree structures as the original method. The effectiveness of the proposed method is demonstrated through the use of two computational experiments.

  1. CB2 Receptor Agonists Protect Human Dopaminergic Neurons against Damage from HIV-1 gp120

    PubMed Central

    Hu, Shuxian; Sheng, Wen S.; Rock, R. Bryan

    2013-01-01

    Despite the therapeutic impact of anti-retroviral therapy, HIV-1-associated neurocognitive disorder (HAND) remains a serious threat to AIDS patients, and there currently remains no specific therapy for the neurological manifestations of HIV-1. Recent work suggests that the nigrostriatal dopaminergic area is a critical brain region for the neuronal dysfunction and death seen in HAND and that human dopaminergic neurons have a particular sensitivity to gp120-induced damage, manifested as reduced function (decreased dopamine uptake), morphological changes, and reduced viability. Synthetic cannabinoids inhibit HIV-1 expression in human microglia, suppress production of inflammatory mediators in human astrocytes, and there is substantial literature demonstrating the neuroprotective properties of cannabinoids in other neuropathogenic processes. Based on these data, experiments were designed to test the hypothesis that synthetic cannabinoids will protect dopaminergic neurons against the toxic effects of the HIV-1 protein gp120. Using a human mesencephalic neuronal/glial culture model, which contains dopaminergic neurons, microglia, and astrocytes, we were able to show that the CB1/CB2 agonist WIN55,212-2 blunts gp120-induced neuronal damage as measured by dopamine transporter function, apoptosis and lipid peroxidation; these actions were mediated principally by the CB2 receptor. Adding supplementary human microglia to our cultures enhances gp120-induced damage; WIN55,212-2 is able to alleviate this enhanced damage. Additionally, WIN55,212-2 inhibits gp120-induced superoxide production by purified human microglial cells, inhibits migration of human microglia towards supernatants generated from gp120-stimulated human mesencephalic neuronal/glial cultures and reduces chemokine and cytokine production from the human mesencephalic neuronal/glial cultures. These data suggest that synthetic cannabinoids are capable of protecting human dopaminergic neurons from gp120 in a variety

  2. Cultural competency training of GP Registrars-exploring the views of GP Supervisors.

    PubMed

    Watt, Kelly; Abbott, Penny; Reath, Jenny

    2015-10-06

    An equitable multicultural society requires General Practitioners (GPs) to be proficient in providing health care to patients from diverse backgrounds. This requires a certain set of attitudes, knowledge and skills known as cultural competence. While training in cultural competence is an important part of the Australian GP Registrar training curriculum, it is unclear who provides this training apart from in Aboriginal and Torres Strait Islander training posts. The majority of Australian GP Registrar training takes place in a workplace setting facilitated by the GP Supervisor. In view of the central role of GP Supervisors, their views on culturally competent practice, and their role in its development in Registrars, are important to ascertain. We conducted 14 semi-structured interviews with GP Supervisors. These were audiotaped, transcribed verbatim and thematically analyzed using an iterative approach. The Supervisors interviewed frequently viewed cultural competence as adequately covered by using patient-centered approaches. The Supervisor role in promoting cultural competence of Registrars was affirmed, though training was noted to occur opportunistically and focused largely on patient-centered care rather than health disparities. Formal training for both Registrars and Supervisors may be beneficial not only to develop a deeper understanding of cultural competence and its relevance to practice but also to promote more consistency in training from Supervisors in the area, particularly with respect to self-reflection, non-conscious bias and utilizing appropriate cultural knowledge without stereotyping and assumption-making.

  3. Using GP trainees as role players as a teaching/training tool for established GP trainers.

    PubMed

    Emerson, Kim; Moore, Penny; Edwards, Jill

    2017-02-16

    This work aimed to evaluate the effectiveness of using GP trainees in place of professional actors, to role-play trainees with 'difficulties' or various challenging characteristics, as an educational tool for skills development of experienced GP trainers. The context was a residential experienced GP trainers' course and the role players were local ST3 GP trainees. Professional actors have been used for this purpose for many years in medical education at all levels, particularly in teaching communication and consultation skills in the Thames Valley area of the UK. We wanted to trial and evaluate whether using GP trainees themselves, with their own more authentic 'hinterland' of experience, (but no acting training) would be as, or more, effective than using actors. The exercise was successful and showed, through post-course feedback (immediate written feedback and later on-line questionnaire), that the use of trainees was considered by the delegates to be an effective, adaptable and realistic training tool, and more so than using professional actors. The trainees also reported educational benefit from the experience.

  4. Colliding with a crunching bubble

    SciTech Connect

    Freivogel, Ben; Freivogel, Ben; Horowitz, Gary T.; Shenker, Stephen

    2007-03-26

    In the context of eternal inflation we discuss the fate of Lambda = 0 bubbles when they collide with Lambda< 0 crunching bubbles. When the Lambda = 0 bubble is supersymmetric, it is not completely destroyed by collisions. If the domain wall separating the bubbles has higher tension than the BPS bound, it is expelled from the Lambda = 0 bubble and does not alter its long time behavior. If the domain wall saturates the BPS bound, then it stays inside the Lambda = 0 bubble and removes a finite fraction of future infinity. In this case, the crunch singularity is hidden behind the horizon of a stable hyperbolic black hole.

  5. LHC: The Large Hadron Collider

    ScienceCinema

    Lincoln, Don

    2016-07-12

    The Large Hadron Collider (or LHC) is the world’s most powerful particle accelerator. In 2012, scientists used data taken by it to discover the Higgs boson, before pausing operations for upgrades and improvements. In the spring of 2015, the LHC will return to operations with 163% the energy it had before and with three times as many collisions per second. It’s essentially a new and improved version of itself. In this video, Fermilab’s Dr. Don Lincoln explains both some of the absolutely amazing scientific and engineering properties of this modern scientific wonder.

  6. Detector Background at Muon Colliders

    SciTech Connect

    Mokhov, N.V.; Striganov, S.I.; /Fermilab

    2011-09-01

    Physics goals of a Muon Collider (MC) can only be reached with appropriate design of the ring, interaction region (IR), high-field superconducting magnets, machine-detector interface (MDI) and detector. Results of the most recent realistic simulation studies are presented for a 1.5-TeV MC. It is shown that appropriately designed IR and MDI with sophisticated shielding in the detector have a potential to substantially suppress the background rates in the MC detector. The main characteristics of backgrounds are studied.

  7. Tevatron instrumentation: boosting collider performance

    SciTech Connect

    Shiltsev, Vladimir; Jansson, Andreas; Moore, Ronald; /Fermilab

    2006-05-01

    The Tevatron in Collider Run II (2001-present) is operating with six times more bunches, many times higher beam intensities and luminosities than in Run I (1992-1995). Beam diagnostics were crucial for the machine start-up and the never-ending luminosity upgrade campaign. We present the overall picture of the Tevatron diagnostics development for Run II, outline machine needs for new instrumentation, present several notable examples that led to Tevatron performance improvements, and discuss the lessons for the next big machines--LHC and ILC.

  8. Stability of colliding ion beams

    SciTech Connect

    Foote, E.A.; Kulsrud, R.M.

    1980-11-01

    We determine conditions for stability of two identical colliding ion beams in the presence of neutralizing electrons, but no background ions. Such a situation is envisioned for the Counterstreaming Ion Torus. The ion beams are taken to be Maxwellian in their frames of reference. The approximation of electrostatic and electromagnetic modes is made. The stability of the electrostatic modes depends on the relation between the ion electron temperature ratio and the relative beam velocities. The stability of the electromagnetic mode depends on the relation between the ion plasma ..beta.. and the relative beam velocities.

  9. Colliding-beam-accelerator lattice

    SciTech Connect

    Claus, J.; Cornacchia, M.; Courant, E.D.; Parzen, G.

    1983-01-01

    We describe the lattice of the Colliding Beam Accelerator, a 400 x 400 GeV pp facility proposed for construction at Brookhaven National Laboratory. The structure adopted is very versatile, in part in consequence of its desirable behavior as function of momentum deviation and as function of the betatron tunes. Each of the six insertions can be arranged to meet specific requirements at the crossing points as illustrated by a discussion of the tuneable low-beta insertions. The luminosity in these low-beta insertions (2 x 10/sup 33/ cm/sup -2/ sec/sup -1/) would be an order of magnitude larger than the standard insertions.

  10. Muon Colliders and Neutrino Factories

    SciTech Connect

    Kaplan, Daniel M.

    2015-05-29

    Muon colliders and neutrino factories are attractive options for future facilities aimed at achieving the highest lepton-antilepton collision energies and precision measurements of Higgs boson and neutrino mixing matrix parameters. The facility performance and cost depend on how well a beam of muons can be cooled. Recent progress in muon cooling design studies and prototype tests nourishes the hope that such facilities could be built starting in the coming decade. The status of the key technologies and their various demonstration experiments is summarized. Prospects "post-P5" are also discussed.

  11. LHC: The Large Hadron Collider

    SciTech Connect

    Lincoln, Don

    2015-03-04

    The Large Hadron Collider (or LHC) is the world’s most powerful particle accelerator. In 2012, scientists used data taken by it to discover the Higgs boson, before pausing operations for upgrades and improvements. In the spring of 2015, the LHC will return to operations with 163% the energy it had before and with three times as many collisions per second. It’s essentially a new and improved version of itself. In this video, Fermilab’s Dr. Don Lincoln explains both some of the absolutely amazing scientific and engineering properties of this modern scientific wonder.

  12. A model for computing at the SSC (Superconducting Super Collider)

    SciTech Connect

    Baden, D. . Dept. of Physics); Grossman, R. . Lab. for Advanced Computing)

    1990-06-01

    High energy physics experiments at the Superconducting Super Collider (SSC) will show a substantial increase in complexity and cost over existing forefront experiments, and computing needs may no longer be met via simple extrapolations from the previous experiments. We propose a model for computing at the SSC based on technologies common in private industry involving both hardware and software. 11 refs., 1 fig.

  13. Kaluza-Klein Physics at Muon Colliders

    SciTech Connect

    Rizzo, Thomas G.

    1999-11-04

    We discuss the physics of Kaluza-Klein excitations of the Standard Model gauge bosons that can be explored by a high energy muon collider in the era after the LHC and TeV Linear Collider. We demonstrate that the muon collider is a necessary ingredient in the unraveling the properties of such states and, perhaps, proving their existence. The possibility of observing the resonances associated with the excited KK graviton states of the Randall-Sundrum model is also discussed.

  14. International Workshop on Linear Colliders 2010

    SciTech Connect

    2010-10-25

    IWLC2010 International Workshop on Linear Colliders 2010ECFA-CLIC-ILC joint meeting: Monday 18 October - Friday 22 October 2010Venue: CERN and CICG (International Conference Centre Geneva, Switzerland) This year, the International Workshop on Linear Colliders organized by the European Committee for Future Accelerators (ECFA) will study the physics, detectors and accelerator complex of a linear collider covering both CLIC and ILC options.Contact Workshop Secretariat  IWLC2010 is hosted by CERN

  15. Effects of chronic alcohol drinking on receptor-binding, internalization, and degradation of human immunodeficiency virus 1 envelope protein gp120 in hepatocytes.

    PubMed

    Singh, Ashok K; Jiang, Yin; Gupta, Shveta

    2007-12-01

    Although alcohol drinking increases susceptibility to human immunodeficiency virus (HIV) infection, possible mechanisms underlying the effects of alcohol are not yet known. Since the HIV envelope protein gp120 plays a key role in progression of HIV infection, the aim of the present study was to evaluate the toxicity and degradation of gp120 in hepatocytes isolated from liver of alcohol-preferring rats drinking either 15% ethanol in water or pure water for 70 days. The hypothesis was that alcohol drinking augmented the toxicity, but suppressed degradation of gp120. Hepatocytes from water-drinking rats (C-cells) or ethanol-drinking rats (Et-cells) were treated with laptacystin, anti-CD4 antibodies, CCR5 antagonist, or mannose, followed by [(125)I]gp120 or native gp120. At predetermined intervals, control (C) and ethanol exposed (Et) cells were analyzed for toxicity and degradation of gp120. In C-cells, [(125)I]gp120 binding and internalization peaked within 5-45 min and remained elevated for up to 10h and then decreased gradually. In Et-cells, [(125)I]gp120 binding peaked comparably to C-cells, but the binding remained to the peak level throughout the experimental period. C-cells exhibited the lysosomal/ubiquitin-mediated degradation of intracellular gp120, resulting in released gp120 fragments into the incubation medium that suppressed gp120-CD4 binding, improved cell viability, and inhibited gp120-induced apoptosis. Ethanol drinking suppressed gp120 degradation in and release of gp120 fragments from hepatocytes. The incubation medium of Et-cells did not suppress gp120-CD4 binding or the gp120-mediated apoptosis in hepatocytes. Thus, chronic alcohol drinking augmented the adverse effects of gp120 possibly by suppressing its degradation in hepatocytes. The present observation also suggests that a number of CCR5 or ubiquitin-based therapeutic drugs may not be effective in suppressing HIV infection in alcohol-drinking subjects.

  16. SLAC-Linac-Collider (SLC) Project

    SciTech Connect

    Wiedemann, H.

    1981-02-01

    The proposed SLAC Linear Collider Project (SLC) and its features are described in this paper. In times of ever increasing costs for energy the electron storage ring principle is about to reach its practical limit. A new class of colliding beam beam facilities, the Linear Colliders, are getting more and more attractive and affordable at very high center-of-mass energies. The SLC is designed to be a poineer of this new class of colliding beam facilities and at the same time will serve as a valuable tool to explore the high energy physics at the level of 100 GeV in the center-of-mass system.

  17. Accelerator aspects of photon colliders at TESLA

    NASA Astrophysics Data System (ADS)

    Walker, Nicholas J.

    2001-10-01

    The TESLA linear collider is being primarily designed as a 500- 800 GeV centre of mass e +e - linear collider. However, a second interaction region is being incorporated into the design with a crossing angle of 32 mrad, which is suitable for use as a γγ collider. In this paper we will review those aspects of the current machine design which are critical to the operation of TESLA as a photon collider, paying particular attention to the preservation of small horizontal emittances, and—in the absence of beamstrahlung—limits on reduced horizontal beam cross-section at the interaction point.

  18. Recognition of similar epitopes on varicella-zoster virus gpI and gpIV by monoclonal antibodies.

    PubMed Central

    Vafai, A; Wroblewska, Z; Mahalingam, R; Cabirac, G; Wellish, M; Cisco, M; Gilden, D

    1988-01-01

    Two monoclonal antibodies, MAb43.2 and MAb79.0, prepared against varicella-zoster virus (VZV) proteins were selected to analyze VZV gpIV and gpI, respectively. MAb43.2 reacted only with cytoplasmic antigens, whereas MAb79.0 recognized both cytoplasmic and membrane antigens in VZV-infected cells. Immunoprecipitation of in vitro translation products with MAb43.2 revealed only proteins encoded by the gpIV gene, whereas MAb79.0 precipitated proteins encoded by the gpIV and gpI genes. Pulse-chase analysis followed by immunoprecipitation of VZV-infected cells indicated reactivity of MAb43.2 with three phosphorylated precursor species of gpIV and reactivity of MAb79.0 with the precursor and mature forms of gpI and gpIV. These results indicated that (i) MAb43.2 and MAb79.0 recognize different epitopes on VZV gpIV, (ii) glycosylation of gpIV ablates recognition by MAb43.2, and (iii) gpIV is phosphorylated. To map the binding site of MAb79.0 on gpI, the pGEM transcription vector, containing the coding region of the gpI gene, was linearized, and three truncated gpI DNA fragments were generated. RNA was transcribed from each truncated fragment by using SP6 RNA polymerase, translated in vitro in a rabbit reticulocyte lysate, and immunoprecipitated with MAb79.0 and human sera. The results revealed the existence of an antibody-binding site within 14 amino acid residues located between residues 109 to 123 on the predicted amino acid sequences of gpI. From the predicted amino acid sequences, 14 residues on gpI (residues 107 to 121) displayed a degree of similarity (36%) to two regions (residues 55 to 69 and 245 to 259) of gp IV. Such similarities may account for the binding of MAb79.0 to both VZV gpI and gpIV. Images PMID:2455814

  19. Results from p p colliders

    SciTech Connect

    Huth, J.

    1991-08-01

    Recent results {bar p}p colliders are presented. From elastic scattering experiments at the Tevatron, an average value of {sigma}{sub tot} = 72.1{plus minus}2 mb is reported, along with a new measurement of {rho} = 0.13 {plus minus} 0.7. New measurements of jet direct photon and high p{sub t} W and Z production are compared to more precise, higher order predictions from perturbative QCD. Recently available data on the W mass and width give combined values for M{sub W} = 80.14{plus minus}0.27 GeV/c{sup 2}, and {Gamma}(W) =2. 14 {plus minus} 0.08 GeV. From electroweak radiative corrections and M{sub W}, one finds M{sub top} = 130{plus minus}40 GeV/c{sup 2}, with a 95% C.L. upper limit at 210 GeV/c{sup 2}. Current limits on M{sub top} are presented, along with a review of the prospects for top discovery. From jet data there is no evidence of quark substructure down to the distance scale of 1.4 {times} 10{sup {minus}17} cm, nor is there evidence for supersymmetry or heavy gauge bosons at {bar p}p colliders, allowing lower limits on M{sub W}, > 520 GeV/c{sup 2} and M{sub Z} 412 GeV/c{sup 2}. 66 refs., 26 figs.

  20. Disentangling heavy flavor at colliders

    NASA Astrophysics Data System (ADS)

    Ilten, Philip; Rodd, Nicholas L.; Thaler, Jesse; Williams, Mike

    2017-09-01

    We propose two new analysis strategies for studying charm and beauty quarks at colliders. The first strategy is aimed at testing the kinematics of heavy-flavor quarks within an identified jet. Here, we use the SoftDrop jet-declustering algorithm to identify two subjets within a large-radius jet, using subjet flavor tagging to test the heavy-quark splitting functions of QCD. For subjets containing a J /ψ or ϒ , this declustering technique can also help probe the mechanism for quarkonium production. The second strategy is aimed at isolating heavy-flavor production from gluon splitting. Here, we introduce a new FlavorCone algorithm, which smoothly interpolates from well-separated heavy-quark jets to the gluon-splitting regime where jets overlap. Because of its excellent ability to identify charm and beauty hadrons, the LHCb detector is ideally suited to pursue these strategies, though similar measurements should also be possible at ATLAS and CMS. Together, these SoftDrop and FlavorCone studies should clarify a number of aspects of heavy-flavor physics at colliders, and provide crucial information needed to improve heavy-flavor modeling in parton-shower generators.

  1. New technology for linear colliders

    SciTech Connect

    McIntyre, P.M.

    1991-08-01

    The purpose of this contract is to develop and evaluate new technology for future e{sup +}e{sup {minus}} linac colliders. TeV linac colliders will require major improvements in the performance of microwave power tubes: >100 mW/m peak power, {approximately}20 GHz frequency, and high frequency. For the past three years we have been developing gigatron, a new design concept for microwave power tubes. It incorporates three key innovations: a gated field-emitter cathode which produces a fully modulated electron beam directly into the vacuum; a ribbon beam geometry which eliminates space charge and phase dispersion, and a traveling wave coupler which provides optimum output coupling even over a wide ribbon beam. During the past year we have built prototypes of two cathode designs: a stripline edge-emitter array and a porous silicon dioxide cathode. A highlight of our results is the development and testing of the porous SiO{sub 2} cathode. It delivers exceptional performance as a modulated electron source in general and for gigatron in particular. Its high emitter density and low work function accommodate higher tube gain, simpler cathode coupling, and higher peak power than any other technology. The protection of the active emitting surface by {approximately}2 {mu}m of porous SiO{sub 2} should provide for rugged operation in a tube environment.

  2. Very large hadron collider (VLHC)

    SciTech Connect

    1998-09-01

    A VLHC informal study group started to come together at Fermilab in the fall of 1995 and at the 1996 Snowmass Study the parameters of this machine took form. The VLHC as now conceived would be a 100 TeV hadron collider. It would use the Fermilab Main Injector (now nearing completion) to inject protons at 150 GeV into a new 3 TeV Booster and then into a superconducting pp collider ring producing 100 TeV c.m. interactions. A luminosity of {approximately}10{sup 34} cm{sup -2}s{sup -1} is planned. Our plans were presented to the Subpanel on the Planning for the Future of US High- Energy Physics (the successor to the Drell committee) and in February 1998 their report stated ``The Subpanel recommends an expanded program of R&D on cost reduction strategies, enabling technologies, and accelerator physics issues for a VLHC. These efforts should be coordinated across laboratory and university groups with the aim of identifying design concepts for an economically and technically viable facility`` The coordination has been started with the inclusion of physicists from Brookhaven National Laboratory (BNL), Lawrence Berkeley National Laboratory (LBNL), and Cornell University. Clearly, this collaboration must expanded internationally as well as nationally. The phrase ``economically and technically viable facility`` presents the real challenge.

  3. Hadron colliders (SSC/LHC)

    SciTech Connect

    Chao, A.W.; Palmer, R.B. |; Evans, L.; Gareyte, J.; Siemann, R.H.

    1992-12-31

    The nominal SSC and LHC designs should operate conservatively at luminosities up to 10{sup 33} cm{sup {minus}2} s{sup {minus}1}. This luminosity is dictated by the event rates that can be handled by the detectors. However, this limit is event dependent (e.g. it does not take much of a detector to detect the event pp {yields} elephant; all one needs is extremely high luminosity). As such, it is useful to explore the possibility of going beyond the 10{sup 33} cm{sup {minus}2} s{sup {minus}1} level. Such exploration will also improve the accelerator physics understanding of pp collider designs. If the detector limitations are removed, the first accelerator limits occur when the luminosity is at the level of 10{sup 34} cm{sup {minus}2}s{sup {minus}1}. These accelerator limits will first be reviewed. The authors will then continue on to explore even higher luminosity as the ultimate limit of pp colliders. Accelerator technologies needed to achieve this ultimate luminosity as well as the R and D needed to reach it are discussed.

  4. Structural basis for HIV-1 gp120 recognition by a germ-line version of a broadly neutralizing antibody

    PubMed Central

    Scharf, Louise; West, Anthony P.; Gao, Han; Lee, Terri; Scheid, Johannes F.; Nussenzweig, Michel C.; Bjorkman, Pamela J.; Diskin, Ron

    2013-01-01

    Efforts to design an effective antibody-based vaccine against HIV-1 would benefit from understanding how germ-line B-cell receptors (BCRs) recognize the HIV-1 gp120/gp41 envelope spike. Potent VRC01-like (PVL) HIV-1 antibodies derived from the VH1-2*02 germ-line allele target the conserved CD4 binding site on gp120. A bottleneck for design of immunogens capable of eliciting PVL antibodies is that VH1-2*02 germ-line BCR interactions with gp120 are uncharacterized. Here, we report the structure of a VH1-2*02 germ-line antibody alone and a germ-line heavy-chain/mature light-chain chimeric antibody complexed with HIV-1 gp120. VH1-2*02 residues make extensive contacts with the gp120 outer domain, including all PVL signature and CD4 mimicry interactions, but not critical CDRH3 contacts with the gp120 inner domain and bridging sheet that are responsible for the improved potency of NIH45-46 over closely related clonal variants, such as VRC01. Our results provide insight into initial recognition of HIV-1 by VH1-2*02 germ-line BCRs and may facilitate the design of immunogens tailored to engage and stimulate broad and potent CD4 binding site antibodies. PMID:23524883

  5. Polymorphisms in the platelet-specific collagen receptor GP6 are associated with risk of nonfatal myocardial infarction in Caucasians

    PubMed Central

    Shaffer, JR; Kammerer, CM; Dorn, J; Ferrell, RE; Iacoviello, L; Trevisan, M; Donahue, RP

    2010-01-01

    Background and Aims Glycoprotein 6 (GP6) is a platelet-specific collagen receptor implicated in the thrombotic pathway to acute myocardial infarction (AMI), but a possible genetic relationship between GP6 and AMI is poorly understood. We tested for the genetic association between AMI and single nucleotide polymorphisms (SNPs) in 24 loci, including GP6. Methods and Results We conducted a case-control study of AMI and GP6 in a community-based population (n=652 cases, 625 controls). We also examined men and women separately and stratified the latter by use of hormone replacement therapy (HRT). Among both sexes, the strongest association was for a protective missense polymorphism (rs1163662) in the GP6 gene (OR=0.70; Bonferroni-adjusted p<0.05). SNPs in GP6 were also strongly associated with AMI among women who reported ever taking HRT, but not among women who never took HRT. Haplotype analyses were consistent with the single-SNP findings. Conclusions In this sample of white non-Hispanic men and women, several SNPs in GP6 were significantly related to risk of AMI. Development of pharmacologic therapy directed towards platelet activity and thrombosis may reduce the incidence of AMI among at-risk groups. PMID:20227257

  6. Physics considerations for laser-plasma linear colliders

    SciTech Connect

    Schroeder, Carl; Esarey, Eric; Geddes, Cameron; Benedetti, Carlo; Leemans, Wim

    2010-06-11

    Physics considerations for a next-generation linear collider based on laser-plasma accelerators are discussed. The ultra-high accelerating gradient of a laser-plasma accelerator and short laser coupling distance between accelerator stages allows for a compact linac. Two regimes of laser-plasma acceleration are discussed. The highly nonlinear regime has the advantages of higher accelerating fields and uniform focusing forces, whereas the quasi-linear regime has the advantage of symmetric accelerating properties for electrons and positrons. Scaling of various accelerator and collider parameters with respect to plasma density and laser wavelength are derived. Reduction of beamstrahlung effects implies the use of ultra-short bunches of moderate charge. The total linac length scales inversely with the square root of the plasma density, whereas the total power scales proportional to the square root of the density. A 1 TeV center-of-mass collider based on stages using a plasma density of 10{sup 17} cm{sup -3} requires tens of J of laser energy per stage (using 1 {micro}m wavelength lasers) with tens of kHz repetition rate. Coulomb scattering and synchrotron radiation are examined and found not to significantly degrade beam quality. A photon collider based on laser-plasma accelerated beams is also considered. The requirements for the scattering laser energy are comparable to those of a single laser-plasma accelerator stage.

  7. Ebola Virus GP Gene Polyadenylation Versus RNA Editing.

    PubMed

    Volchkova, Valentina A; Vorac, Jaroslav; Repiquet-Paire, Laurie; Lawrence, Philip; Volchkov, Viktor E

    2015-10-01

    Synthesis of Ebola virus (EBOV) surface glycoprotein (GP) is dependent on transcriptional RNA editing. Northern blot analysis of EBOV-infected cells using GP-gene-specific probes reveals that, in addition to full-length GP messenger RNAs (mRNAs), a shorter RNA is also synthesized, representing >40% of the total amount of GP mRNA. Sequence analysis demonstrates that this RNA is a truncated version of the full-length GP mRNA that is polyadenylated at the editing site and thus lacks a stop codon. An absence of detectable levels of protein synthesis in cellulo is consistent with the existence of tight regulation of the translation of such mRNA. However, nonstop GP mRNA was shown to be only slightly less stable than the same mRNA containing a stop codon, against the general belief in nonstop decay mechanisms aimed at detecting and destroying mRNAs lacking a stop codon. In conclusion, we demonstrate that the editing site indeed serves as a cryptic transcription termination/polyadenylation site, which rarely also functions to edit GP mRNA for expression of surface GP. This new data suggest that the downregulation of surface GP expression is even more dramatic than previously thought, reinforcing the importance of the GP gene editing site for EBOV replication and pathogenicity.

  8. Immunization with a soluble CD4-gp120 complex preferentially induces neutralizing anti-human immunodeficiency virus type 1 antibodies directed to conformation-dependent epitopes of gp120.

    PubMed

    Kang, C Y; Hariharan, K; Nara, P L; Sodroski, J; Moore, J P

    1994-09-01

    Preservation of the conformation of recombinant gp120 in an adjuvant, enabling it to elicit conformation-dependent, epitope-specific, broadly neutralizing antibodies, may be critical for the development of any gp120-based human immunodeficiency virus type 1 (HIV-1) vaccine. It was hypothesized that recombinant gp120 complexed with recombinant CD4 could stabilize the conformation-dependent neutralizing epitopes and effectively deliver them to the immune system. Therefore, a soluble CD4-gp120 complex in Syntex adjuvant formulation was tested with mice for its ability to induce neutralizing anti-gp120 antibody responses. Seventeen monoclonal antibodies (MAbs) were generated and characterized. Immunochemical studies, neutralization assays, and mapping studies with gp120 mutants indicated that the 17 MAbs fell into three groups. Four of them were directed to what is probably a conformational epitope involving the C1 domain and did not possess virus-neutralizing activities. Another four MAbs bound to V3 peptide 302-321 and exhibited cross-reactive gp120 binding and relatively weak virus-neutralizing activities. These MAbs were very sensitive to amino acid substitutions, not only in the V3 regions but also in the base of the V1/V2 loop, implying a conformational constraint on the epitope. The last group of nine MAbs recognized conformation-dependent epitopes near the CD4 binding site of gp120 and inhibited the gp120-soluble CD4 interaction. Four of these nine MAbs showed broadly neutralizing activities against multiple laboratory-adapted strains of HIV-1, three of them neutralized only HIVIIIB, and the two lower-affinity MAbs did not neutralize any strain tested. Collectively, the results from this study indicate that immunization with the CD4-gp120 complex can elicit antibodies to conformationally sensitive gp120 epitopes, with some of the antibodies having broadly neutralizing activities. We suggest that immunization with CD4-gp120 complexes may be worth evaluating

  9. Characterization of Immune Responses Induced by Ebola Virus Glycoprotein (GP) and Truncated GP Isoform DNA Vaccines and Protection Against Lethal Ebola Virus Challenge in Mice.

    PubMed

    Li, Wenfang; Ye, Ling; Carrion, Ricardo; Mohan, Gopi S; Nunneley, Jerritt; Staples, Hilary; Ticer, Anysha; Patterson, Jean L; Compans, Richard W; Yang, Chinglai

    2015-10-01

    In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed "antigenic subversion." To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge. Similar levels of anti-GP antibodies were induced by 2 immunizations with sGP and GP DNA vaccines. However, 2 immunizations with GP but not sGP DNA vaccine fully protected mice from lethal challenge. Boosting with sGP or GP DNA vaccine in mice that had been primed by GP or sGP DNA vaccine augmented the levels of anti-GP antibody responses and further improved protective efficacy against Ebola virus infection. These results show that both the quality and the levels of anti-GP antibody responses affect the efficacy of protection against Ebola virus infection.

  10. Characterization of Immune Responses Induced by Ebola Virus Glycoprotein (GP) and Truncated GP Isoform DNA Vaccines and Protection Against Lethal Ebola Virus Challenge in Mice

    PubMed Central

    Li, Wenfang; Ye, Ling; Carrion, Ricardo; Mohan, Gopi S.; Nunneley, Jerritt; Staples, Hilary; Ticer, Anysha; Patterson, Jean L.; Compans, Richard W.; Yang, Chinglai

    2015-01-01

    In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed “antigenic subversion.” To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge. Similar levels of anti-GP antibodies were induced by 2 immunizations with sGP and GP DNA vaccines. However, 2 immunizations with GP but not sGP DNA vaccine fully protected mice from lethal challenge. Boosting with sGP or GP DNA vaccine in mice that had been primed by GP or sGP DNA vaccine augmented the levels of anti-GP antibody responses and further improved protective efficacy against Ebola virus infection. These results show that both the quality and the levels of anti-GP antibody responses affect the efficacy of protection against Ebola virus infection. PMID:25877553

  11. Determinants of the choice of GP practice registration in England: evidence from a discrete choice experiment.

    PubMed

    Lagarde, Mylene; Erens, Bob; Mays, Nicholas

    2015-04-01

    There have been growing concerns that general practitioner (GP) services in England, which are based on registration with a single practice located near the patient's home, are not sufficiently convenient for patients. To inform the decision as to whether to change registration rules allowing patients to register 'out-of-area' and to estimate the demand for this wider choice, we undertook a discrete choice experiment with 1706 respondents. Latent class models were used to analyse preferences for GP practice registration comparing preferences for neighbourhood and non-neighbourhood practices. We find that there is some appetite for registering outside the neighbourhood, but this preference is not uniformly shared across the population. Specifically individuals who are less mobile (e.g. older people and those with caring responsibilities), or satisfied with their local practice are less likely to be interested in registering at a practice outside their neighbourhood. Overall, people feel most strongly about obtaining an appointment with a GP as quickly as possible. Respondents regarded weekend opening as less important than other factors, and particularly less important than extended practice opening hours from Monday to Friday. Assuming a constant demand for GP services, a policy encouraging GP practices to extend their opening hours during the week is likely to decrease the average patient waiting time for an appointment and is likely to be preferred by patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Role of a Putative gp41 Dimerization Domain in Human Immunodeficiency Virus Type 1 Membrane Fusion

    SciTech Connect

    Liu, J.; Deng, Y; Li, Q; Dey, A; Moore, J; Lu, M

    2010-01-01

    The entry of human immunodeficiency virus type 1 (HIV-1) into a target cell entails a series of conformational changes in the gp41 transmembrane glycoprotein that mediates the fusion of the viral and target cell membranes. A trimer-of-hairpins structure formed by the association of two heptad repeat (HR) regions of the gp41 ectodomain has been implicated in a late step of the fusion pathway. Earlier native and intermediate states of the protein are postulated to mediate the antiviral activity of the fusion inhibitor enfuvirtide and of broadly neutralizing monoclonal antibodies (NAbs), but the details of these structures remain unknown. Here, we report the identification and crystal structure of a dimerization domain in the C-terminal ectodomain of gp41 (residues 630 to 683, or C54). Two C54 monomers associate to form an asymmetric, antiparallel coiled coil with two distinct C-terminal {alpha}-helical overhangs. This dimer structure is conferred largely by interactions within a central core that corresponds to the sequence of enfuvirtide. The mutagenic alteration of the dimer interface severely impairs the infectivity of Env-pseudotyped viruses. Moreover, the C54 structure binds tightly to both the 2F5 and 4E10 NAbs and likely represents a potential intermediate conformation of gp41. These results should enhance our understanding of the molecular basis of the gp41 fusogenic structural transitions and thereby guide rational, structure-based efforts to design new fusion inhibitors and vaccine candidates intended to induce broadly neutralizing antibodies.

  13. Introducing peer observation of teaching to GP teachers: a questionnaire study.

    PubMed

    Adshead, Lesley; White, Patrick T; Stephenson, Anne

    2006-03-01

    In medical education programmes which rely on clinical teachers spread across diverse sites, the application of peer observation of teaching offers the potential of both supporting teachers and maintaining quality. This paper reports on a questionnaire survey carried out with general practitioner (GP) teachers of medical undergraduate students from King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals. The aim of the study was to determine GP teachers' views on a proposed programme of peer observation of their teaching. The majority of GP teachers identified benefits of the proposed scheme with 69% saying it would help improve the education of future doctors. However, despite seeing the benefits, less than half wished to take part in the programme. Two thirds cited time and paperwork as major disincentives to taking part and 62% said that they felt it would make them feel under scrutiny. No associations were found between measures of workload and willingness to take part. This suggests that a fundamental fear of scrutiny and criticism may be the main hurdle to be overcome in implementing the scheme. Imposing peer observation on GP teachers in the form proposed could create suspicion and distance between the university department and practice-based GP teachers and may even result in a loss of teachers. The introduction of peer observation is more likely to be successful if GPs' apprehensions are addressed. Using peer observation to strengthen the process of quality assurance may undermine its role in the support and development of clinical teachers.

  14. Computing and data handling requirements for SSC (Superconducting Super Collider) and LHC (Large Hadron Collider) experiments

    SciTech Connect

    Lankford, A.J.

    1990-05-01

    A number of issues for computing and data handling in the online in environment at future high-luminosity, high-energy colliders, such as the Superconducting Super Collider (SSC) and Large Hadron Collider (LHC), are outlined. Requirements for trigger processing, data acquisition, and online processing are discussed. Some aspects of possible solutions are sketched. 6 refs., 3 figs.

  15. Development work for a superconducting linear collider

    NASA Technical Reports Server (NTRS)

    Matheisen, Axel

    1995-01-01

    For future linear e(+)e(-) colliders in the TeV range several alternatives are under discussion. The TESLA approach is based on the advantages of superconductivity. High Q values of the accelerator structures give high efficiency for converting RF power into beam power. A low resonance frequency for the RF structures can be chosen to obtain a large number of electrons (positrons) per bunch. For a given luminosity the beam dimensions can be chosen conservatively which leads to relaxed beam emittance and tolerances at the final focus. Each individual superconducting accelerator component (resonator cavity) of this linear collider has to deliver an energy gain of 25 MeV/m to the beam. Today s.c. resonators are in use at CEBAF/USA, at DESY/Germany, Darmstadt/Germany KEK/Japan and CERN/Geneva. They show acceleration gradients between 5 MV/m and 10 MV/m. Encouraging experiments at CEA Saclay and Cornell University showed acceleration gradients of 20 MV/m and 25 MV/m in single and multicell structures. In an activity centered at DESY in Hamburg/Germany the TESLA collaboration is constructing a 500 MeV superconducting accelerator test facility (TTF) to demonstrate that a linear collider based on this technique can be built in a cost effective manner and that the necessary acceleration gradients of more than 15 MeV/m can be reached reproducibly. The test facility built at DESY covers an area of 3.000 m2 and is divided into 3 major activity areas: (1) The testlinac, where the performance ofthe modular components with an electron beam passing the 40 m long acceleration section can be demonstrated. (2) The test area, where all individual resonators are tested before installation into a module. (3) The preparation and assembly area, where assembly of cavities and modules take place. We report here on the design work to reach a reduction of costs compared to actual existing superconducting accelerator structures and on the facility set up to reach high acceleration gradients in

  16. Development work for a superconducting linear collider

    NASA Astrophysics Data System (ADS)

    Matheisen, Axel

    1995-04-01

    For future linear e(+)e(-) colliders in the TeV range several alternatives are under discussion. The TESLA approach is based on the advantages of superconductivity. High Q values of the accelerator structures give high efficiency for converting RF power into beam power. A low resonance frequency for the RF structures can be chosen to obtain a large number of electrons (positrons) per bunch. For a given luminosity the beam dimensions can be chosen conservatively which leads to relaxed beam emittance and tolerances at the final focus. Each individual superconducting accelerator component (resonator cavity) of this linear collider has to deliver an energy gain of 25 MeV/m to the beam. Today s.c. resonators are in use at CEBAF/USA, at DESY/Germany, Darmstadt/Germany KEK/Japan and CERN/Geneva. They show acceleration gradients between 5 MV/m and 10 MV/m. Encouraging experiments at CEA Saclay and Cornell University showed acceleration gradients of 20 MV/m and 25 MV/m in single and multicell structures. In an activity centered at DESY in Hamburg/Germany the TESLA collaboration is constructing a 500 MeV superconducting accelerator test facility (TTF) to demonstrate that a linear collider based on this technique can be built in a cost effective manner and that the necessary acceleration gradients of more than 15 MeV/m can be reached reproducibly. The test facility built at DESY covers an area of 3.000 m2 and is divided into 3 major activity areas: (1) The testlinac, where the performance ofthe modular components with an electron beam passing the 40 m long acceleration section can be demonstrated. (2) The test area, where all individual resonators are tested before installation into a module. (3) The preparation and assembly area, where assembly of cavities and modules take place. We report here on the design work to reach a reduction of costs compared to actual existing superconducting accelerator structures and on the facility set up to reach high acceleration gradients in

  17. Peripheral Nerve Regeneration and NGF-Dependent Neurite Outgrowth of Adult Sensory Neurons Converge on STAT3 Phosphorylation Downstream of Neuropoietic Cytokine Receptor gp130

    PubMed Central

    Quarta, Serena; Baeumer, Bastian E.; Scherbakov, Nadja; Andratsch, Manfred; Rose-John, Stefan; Dechant, Georg; Bandtlow, Christine E.

    2014-01-01

    After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130−/− mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130−/− compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130−/− mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons. PMID:25253866

  18. Peripheral nerve regeneration and NGF-dependent neurite outgrowth of adult sensory neurons converge on STAT3 phosphorylation downstream of neuropoietic cytokine receptor gp130.

    PubMed

    Quarta, Serena; Baeumer, Bastian E; Scherbakov, Nadja; Andratsch, Manfred; Rose-John, Stefan; Dechant, Georg; Bandtlow, Christine E; Kress, Michaela

    2014-09-24

    After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130(-/-) mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130(-/-) compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130(-/-) mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons. Copyright © 2014 the authors 0270-6474/14/3413222-12$15.00/0.

  19. Distinct effects of Broncho-Vaxom (OM-85 BV) on gp130 binding cytokines

    PubMed Central

    Roth, M; Block, L

    2000-01-01

    BACKGROUND—Broncho-Vaxom (OM-85 BV) is known to support respiratory tract resistance to bacterial infections. In vivo and in vitro studies in animals and humans have shown that the action of the drug is based on the modulation of the host immune response, and it has been found to upregulate interferon γ (IFN-γ) and interleukin (IL)-2, IL-6, and IL-8. These immunomodulatory effects of the compound may explain its stimulation on T helper cells and natural killer cells. Following earlier findings that OM-85 BV induces the synthesis of IL-6, a study was undertaken to investigate its possible effect on other gp130 binding cytokines including IL-11, IL-12, leukaemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neutrophil factor (CNTF). Its modulation of the corresponding receptors of the above mentioned cytokines and of the signal transducer gp130 in human pulmonary fibroblasts and peripheral blood lymphocytes was also studied.
METHODS—Transcription of cytokines was assessed by Northern blot analysis. Secretion of cytokines was analysed using commercially available enzyme linked immunosorbent assay kits. Cytokine receptors and gp130 proteins were determined by Western blot analysis.
RESULTS—OM-85 BV increased the expression of IL-11 in human lung fibroblasts, but not in lymphocytes, in a dose and time dependent manner by maximal fivefold within 20 hours. The compound inhibited serum induced IL-12 expression in peripheral blood lymphocytes but did not induce OSM, LIF, or CNTF at any concentration. In lung fibroblasts the expression of the IL-6 receptor was enhanced fourfold at a concentration of 10 µg/ml OM-85 BV while that of the IL-11 receptor was not altered. In peripheral blood lymphocytes LIF receptor α expression was downregulated in the presence of 10 µg/ml OM-85 BV. At a concentration of 10 µg/ml OM-85 BV enhanced gp130 gene transcription fivefold and increased gp130 protein accumulation in cell membranes by 2.5times

  20. Verification of 'learning credits' by GP appraisers.

    PubMed

    Murie, Jill; Wakeling, Judy

    2011-11-01

    The RCGP CPD Learning Credits system aims to enable GPs to demonstrate knowledge and skills relevant to their daily practice. Credits are self-assessed and will form part of the 'evidence' necessary for successful revalidation. At an appraisal, GP appraisers verify the credits in terms of the time spent on the CPD activity and its impact on the GP's practice. The purpose of this study was to examine the extent to which GPs (as appraisees) are able to self-assess their own learning and, as appraisers, verify credits in a standardised way. All 17 GP appraisers in NHS Lanarkshire were invited to participate in a study, which triangulated three sources of evidence on credits: self-rating, peer-assessment and workshop discussion. The resultant data were analysed on an Excel spreadsheet. Outcomes included self-assessed credit value, peer-assessed mean score (range) and free text. Of the 17 appraisers, 15 completed the paperwork and 13 attended the workshop. GPs' self-assessed learning credits were equivalent to peer-assessed score in 5/15 cases, but considered overestimates in 4/15 and underestimates in 6/15 cases. The most extreme variance was for an oncology module, where the variance ranged from 28% to 200% of the self-assessed score. GPs have a variable understanding of how to award themselves learning credits and of how to judge the credits of potential appraisees. Without adequate resources for appraisal training, validated instruments, calibration and reliability, verification of the learning credit system will be flawed by its subjective and arbitrary nature.

  1. First GP student paper award given

    NASA Astrophysics Data System (ADS)

    The GP Section has initiated an award to be given to the best student paper delivered at each of the two national meetings. The first award was given to David Douglass (Department of Earth Sciences, Dartmouth College, Hanover, N.H.) for a paper entitled “Multicomponent Magnetization of the Upper Silurian—Lower Devonian Ringerike Sandstone,” which he coauthored with D.V. Kent (Lamont-Doherty Geological Observatory, Palisades, N.Y.) and presented at the 1986 AGU Spring Meeting in Baltimore, Md. A similar award will be given after the upcoming AGU Fall Meeting in San Francisco, Calif.

  2. Polarization Effects at a Muon Collider

    SciTech Connect

    Parsa, Z.

    1998-11-01

    For Muon Colliders, Polarization will be a useful tool if high polarization is achievable with little luminosity loss. Formulation and effects of beam polarization and luminosity including polarization effects in Higgs resonance studies are discussed for improving precision measurements and Higgs resonance ''discovery'' capability e.g. at the First Muon Collider (FMC).

  3. Possible limits of plasma linear colliders

    NASA Astrophysics Data System (ADS)

    Zimmermann, F.

    2017-07-01

    Plasma linear colliders have been proposed as next or next-next generation energy-frontier machines for high-energy physics. I investigate possible fundamental limits on energy and luminosity of such type of colliders, considering acceleration, multiple scattering off plasma ions, intrabeam scattering, bremsstrahlung, and betatron radiation. The question of energy efficiency is also addressed.

  4. Research and Development of Future Muon Collider

    SciTech Connect

    Yonehara, K.; /Fermilab

    2012-05-01

    Muon collider is a considerable candidate of the next generation high-energy lepton collider machine. A novel accelerator technology must be developed to overcome several intrinsic issues of muon acceleration. Recent research and development of critical beam elements for a muon accelerator, especially muon beam phase space ionization cooling channel, are reviewed in this paper.

  5. Colorectal cancer management - the role of the GP.

    PubMed

    Hanks, Heather; Veitch, Craig; Harris, Mark

    2008-04-01

    Colorectal cancer (CRC) contributes significantly to the morbidity and mortality of Australians. The introduction of the National Bowel Cancer Screening Program has focussed attention on the role of the general practitioner in CRC screening. However, their increasing role across the management spectrum of CRC remains poorly researched. This article examines the published literature on the existing and potential roles of the GP in the detection and management of CRC. Evidence about the existing and potential role of the GP was found through a literature search on Medline, PubMed, epidemiological evidence and recent guidelines. The role of the GP in CRC management varies. Some GPs play many roles such as advocate, facilitator, supporter, educator and counsellor. The role of the GP is influenced by GP-specialist communication, practice location, and patient and GP factors. There is a potential to increase this role, especially in providing psychosocial support and counselling for both the patient and their family.

  6. Collider searches for extra dimensions

    SciTech Connect

    Landsberg, Greg; /Brown U.

    2004-12-01

    Searches for extra spatial dimensions remain among the most popular new directions in our quest for physics beyond the Standard Model. High-energy collider experiments of the current decade should be able to find an ultimate answer to the question of their existence in a variety of models. Until the start of the LHC in a few years, the Tevatron will remain the key player in this quest. In this paper, we review the most recent results from the Tevatron on searches for large, TeV{sup -1}-size, and Randall-Sundrum extra spatial dimensions, which have reached a new level of sensitivity and currently probe the parameter space beyond the existing constraints. While no evidence for the existence of extra dimensions has been found so far, an exciting discovery might be just steps away.

  7. Instability of colliding metastable strings

    NASA Astrophysics Data System (ADS)

    Hiramatsu, Takashi; Eto, Minoru; Kamada, Kohei; Kobayashi, Tatsuo; Ookouchi, Yutaka

    2014-01-01

    The breaking of U(1) R symmetry plays a crucial role in modeling the breaking of supersymmetry (SUSY). In the models that possess both SUSY preserving and SUSY breaking vacua, tube-like cosmic strings called R-tubes, whose surfaces are constituted by domain walls interpolating a false and a true vacuum with some winding numbers, can exist. Their (in)stability can strongly constrain SUSY breaking models theirselves. In the present study, we investigate the dynamical (in)stability of two colliding metastable tube-like strings by field-theoretic simulations. From them, we find that the strings become unstable, depending on the relative collision angle and speed of two strings, and the false vacuum is eventually filled out by the true vacuum owing to rapid expansion of the strings or unstable bubbles created as remnants of the collision.

  8. Mutual colliding impact fast ignition

    SciTech Connect

    Winterberg, Friedwardt

    2014-09-15

    It is proposed to apply the well established colliding beam technology of high energy physics to the fast hot spot ignition of a highly compressed DT (deuterium-tritium) target igniting a larger D (deuterium) burn, by accelerating a small amount of solid deuterium, and likewise a small amount of tritium, making a head-on collision in the center of the target, projecting them through conical ducts situated at the opposite side of the target and converging in its center. In their head-on collision, the relative collision velocity is 5/3 times larger compared to the collision velocity of a stationary target. The two pieces have for this reason to be accelerated to a smaller velocity than would otherwise be needed to reach upon impact the same temperature. Since the velocity distribution of the two head-on colliding projectiles is with its two velocity peaks non-Maxwellian, the maximum cross section velocity product turns out to be substantially larger than the maximum if averaged over a Maxwellian. The D and T projectiles would have to be accelerated with two sabots driven by powerful particle or laser beams, permitting a rather large acceleration length. With the substantially larger cross section-velocity product by virtue of the non-Maxwellian velocity distribution, a further advantage is that the head-on collision produces a large magnetic field by the thermomagnetic Nernst effect, enhancing propagating burn. With this concept, the ignition of the neutron-less hydrogen-boron (HB{sup 11}) reaction might even be possible in a heterogeneous assembly of the hydrogen and the boron to reduce the bremsstrahlung-losses, resembling the heterogeneous assembly in a graphite-natural uranium reactor, there to reduce the neutron losses.

  9. Mutual colliding impact fast ignition

    NASA Astrophysics Data System (ADS)

    Winterberg, Friedwardt

    2014-09-01

    It is proposed to apply the well established colliding beam technology of high energy physics to the fast hot spot ignition of a highly compressed DT (deuterium-tritium) target igniting a larger D (deuterium) burn, by accelerating a small amount of solid deuterium, and likewise a small amount of tritium, making a head-on collision in the center of the target, projecting them through conical ducts situated at the opposite side of the target and converging in its center. In their head-on collision, the relative collision velocity is 5/3 times larger compared to the collision velocity of a stationary target. The two pieces have for this reason to be accelerated to a smaller velocity than would otherwise be needed to reach upon impact the same temperature. Since the velocity distribution of the two head-on colliding projectiles is with its two velocity peaks non-Maxwellian, the maximum cross section velocity product turns out to be substantially larger than the maximum if averaged over a Maxwellian. The D and T projectiles would have to be accelerated with two sabots driven by powerful particle or laser beams, permitting a rather large acceleration length. With the substantially larger cross section-velocity product by virtue of the non-Maxwellian velocity distribution, a further advantage is that the head-on collision produces a large magnetic field by the thermomagnetic Nernst effect, enhancing propagating burn. With this concept, the ignition of the neutron-less hydrogen-boron (HB11) reaction might even be possible in a heterogeneous assembly of the hydrogen and the boron to reduce the bremsstrahlung-losses, resembling the heterogeneous assembly in a graphite-natural uranium reactor, there to reduce the neutron losses.

  10. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

    SciTech Connect

    Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark

    2015-10-15

    The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml-1. The median IC50 of neutralized viruses was 0.033 μg ml-1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

  11. GP130 activation induces myeloma and collaborates with MYC

    PubMed Central

    Dechow, Tobias; Steidle, Sabine; Götze, Katharina S.; Rudelius, Martina; Behnke, Kerstin; Pechloff, Konstanze; Kratzat, Susanne; Bullinger, Lars; Fend, Falko; Soberon, Valeria; Mitova, Nadya; Li, Zhoulei; Thaler, Markus; Bauer, Jan; Pietschmann, Elke; Albers, Corinna; Grundler, Rebekka; Schmidt-Supprian, Marc; Ruland, Jürgen; Peschel, Christian; Duyster, Justus; Rose-John, Stefan; Bassermann, Florian; Keller, Ulrich

    2014-01-01

    Multiple myeloma (MM) is a plasma cell neoplasm that results from clonal expansion of an Ig-secreting terminally differentiated B cell. Advanced MM is characterized by tissue damage that involves bone, kidney, and other organs and is typically associated with recurrent genetic abnormalities. IL-6 signaling via the IL-6 signal transducer GP130 has been implicated as an important driver of MM pathogenesis. Here, we demonstrated that ectopic expression of constitutively active GP130 (L-GP130) in a murine retroviral transduction-transplantation model induces rapid MM development of high penetrance. L-GP130–expressing mice recapitulated all of the characteristics of human disease, including monoclonal gammopathy, BM infiltration with lytic bone lesions, and protein deposition in the kidney. Moreover, the disease was easily transplantable and allowed different therapeutic options to be evaluated in vitro and in vivo. Using this model, we determined that GP130 signaling collaborated with MYC to induce MM and was responsible and sufficient for directing the plasma cell phenotype. Accordingly, we identified Myc aberrations in the L-GP130 MM model. Evaluation of human MM samples revealed recurrent activation of STAT3, a downstream target of GP130 signaling. Together, our results indicate that deregulated GP130 activity contributes to MM pathogenesis and that pathways downstream of GP130 activity have potential as therapeutic targets in MM. PMID:25384216

  12. Pharmaceutical promotion and GP prescription behaviour.

    PubMed

    Windmeijer, Frank; de Laat, Eric; Douven, Rudy; Mot, Esther

    2006-01-01

    The aim of this paper is to empirically analyse the responses by general practitioners to promotional activities for ethical drugs by pharmaceutical companies. Promotion can be beneficial as a means of providing information, but it can also be harmful in the sense that it lowers price sensitivity of doctors and it merely is a means of maintaining market share, even when cheaper, therapeutically equivalent drugs are available. A model is estimated that includes interactions of promotion expenditures and prices and that explicitly exploits the panel structure of the data, allowing for drug specific effects and dynamic adjustments, or habit persistence. The data used are aggregate monthly GP prescriptions per drug together with monthly outlays on drug promotion for the period 1994-1999 for 11 therapeutic markets, covering more than half of the total prescription drug market in the Netherlands. Identification of price effects is aided by the introduction of the Pharmaceutical Prices Act, which established that Dutch drugs prices became a weighted average of the prices in surrounding countries after June 1996. We conclude that GP drug price sensitivity is small, but adversely affected by promotion. Ltd. Copyright (c) 2005 John Wiley & Sons, Ltd.

  13. The Relativistic Heavy Ion Collider control system

    SciTech Connect

    Clifford, T.S.; Barton, D.S.; Oerter, B.R.

    1997-12-01

    The Relativistic Heavy Ion Collider control system has been used in the commissioning of the AGS to RHIC transfer line and in the first RHIC sextant test. Much of the controls infrastructure for networks and links has been installed throughout the collider. All of the controls hardware modules needed to be built for early RHIC operations have been designed and tested. Many of these VME modules are already being used in normal AGS operations. Over 150 VME based front end computers and device controllers will be installed by the Summer of 1998 in order to be ready for Fall of 1998. A few features are being added to the front end computer core software. The bulk of the Accelerator Device Objects (ADOs) which are instantiated in the FECs, have been written and tested in the early commissioning. A configuration database has been designed. Generic control and display of ADO parameters via a spreadsheet like program on the console level computers was provided early on in the control system development. User interface tools that were developed for the AGS control system have been used in RHIC applications. Some of the basic operations programs, like alarm display and save/restore, that are used in the AGS operations have been or will be expanded to support RHIC operations. A model for application programs which involves a console level manager servicing ADOs have been verified with a few RHIC applications. More applications need to be written for the Fall of 1998 commissioning effort. A sequencer for automatic control of the fill is being written with the expectation that it will be useful in early commissioning.

  14. Uncoupling GP1 and GP2 Expression in the Lassa Virus Glycoprotein Complex: Implications for GPI Ectodomain Shedding

    DTIC Science & Technology

    2008-12-23

    may reveal novel and important roles for -DPGA in anthrax pathogenesis . 15. SUBJECT TERMS Lassa virus , glycoprotein expression, GP1, GP2, ectodomain...www.virologyj.com/content/5/1/161is glycoprotein ectodomain shedding. This phenomenon has been widely reported and characterized in Ebola virus (EBOV...relation was established between high levels of the sGP and pathogenesis via efficient blocking of the activity of virus -neutralizing circulating

  15. How Do Gut Feelings Feature in Tutorial Dialogues on Diagnostic Reasoning in GP Traineeship?

    ERIC Educational Resources Information Center

    Stolper, C. F.; Van de Wiel, M. W. J.; Hendriks, R. H. M.; Van Royen, P.; Van Bokhoven, M. A.; Van der Weijden, T.; Dinant, G. J.

    2015-01-01

    Diagnostic reasoning is considered to be based on the interaction between analytical and non-analytical cognitive processes. Gut feelings, a specific form of non-analytical reasoning, play a substantial role in diagnostic reasoning by general practitioners (GPs) and may activate analytical reasoning. In GP traineeships in the Netherlands, trainees…

  16. How Do Gut Feelings Feature in Tutorial Dialogues on Diagnostic Reasoning in GP Traineeship?

    ERIC Educational Resources Information Center

    Stolper, C. F.; Van de Wiel, M. W. J.; Hendriks, R. H. M.; Van Royen, P.; Van Bokhoven, M. A.; Van der Weijden, T.; Dinant, G. J.

    2015-01-01

    Diagnostic reasoning is considered to be based on the interaction between analytical and non-analytical cognitive processes. Gut feelings, a specific form of non-analytical reasoning, play a substantial role in diagnostic reasoning by general practitioners (GPs) and may activate analytical reasoning. In GP traineeships in the Netherlands, trainees…

  17. Structural Characterization of HIV gp41 with the Membrane-proximal External Region

    SciTech Connect

    Shi, W.; Bohon, J; Han, D; Habte, H; Qin, Y; Cho, M; Chance, M

    2010-01-01

    Human immunodeficiency virus, type 1 (HIV-1) envelope glycoprotein (gp120/gp41) plays a critical role in virus infection and pathogenesis. Three of the six monoclonal antibodies considered to have broadly neutralizing activities (2F5, 4E10, and Z13e1) bind to the membrane-proximal external region (MPER) of gp41. This makes the MPER a desirable template for developing immunogens that can elicit antibodies with properties similar to these monoclonal antibodies, with a long term goal of developing antigens that could serve as novel HIV vaccines. In order to provide a structural basis for rational antigen design, an MPER construct, HR1-54Q, was generated for x-ray crystallographic and x-ray footprinting studies to provide both high resolution atomic coordinates and verification of the solution state of the antigen, respectively. The crystal structure of HR1-54Q reveals a trimeric, coiled-coil six-helical bundle, which probably represents a postfusion form of gp41. The MPER portion extends from HR2 in continuation of a slightly bent long helix and is relatively flexible. The structures observed for the 2F5 and 4E10 epitopes agree well with existing structural data, and enzyme-linked immunosorbent assays indicate that the antigen binds well to antibodies that recognize the above epitopes. Hydroxyl radical-mediated protein footprinting of the antigen in solution reveals specifically protected and accessible regions consistent with the predictions based on the trimeric structure from the crystallographic data. Overall, the HR1-54Q antigen, as characterized by crystallography and footprinting, represents a postfusion, trimeric form of HIV gp41, and its structure provides a rational basis for gp41 antigen design suitable for HIV vaccine development.

  18. Computational study of bindings of olive leaf extract (OLE) to HIV-1 fusion protein gp41.

    PubMed

    Bao, J; Zhang, D W; Zhang, J Z H; Huang, P Lee; Huang, P Lin; Lee-Huang, S

    2007-06-12

    Recent experimental study found that OLE (olive leaf extract) has anti-HIV activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L., Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang, P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872-878, 879-884]. As part of a joint experimental and theoretical effort, we report here computational study to help identify and characterize the binding complexes of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein gp41. A number of possible binding modes are found by docking oleuropein and its metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic pocket on gp41. Detailed OLE-gp41 binding interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in our predicted OLE/gp41 complexes are identified and hydroxytyrosol is identified to be the main moiety for binding to gp41. This computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of OLE-based gp41 inhibitors.

  19. Design and performance of the Stanford Linear Collider Control System

    SciTech Connect

    Melen, R.E.

    1984-10-01

    The success of the Stanford Linear Collider (SLC) will be dependent upon the implementation of a very large advanced computer-based instrumentation and control system. This paper describes the architectural design of this system as well as a critique of its performance. This critique is based on experience obtained from its use in the control and monitoring of 1/3 of the SLAC linac and in support of an expensive experimental machine physics experimental program. 11 references, 3 figures.

  20. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1.

    PubMed Central

    Moore, J P; Cao, Y; Ho, D D; Koup, R A

    1994-01-01

    We have studied the development of the antibody response to the surface glycoprotein gp120 of human immunodeficiency virus type 1 in three individuals who presented with primary human immunodeficiency virus type 1 infection syndrome. Serum anti-gp120 antibodies were first detected 4 to 23 days after presentation, after p24 antigen and infectious-virus titers in the peripheral blood had declined manyfold from their highest values. Whether anti-gp120 antibodies present at undetectable levels are involved in clearance of viremia remains unresolved. Among the earliest detectable anti-gp120 antibodies were those to conformationally sensitive epitopes; these antibodies were able to block the binding of gp120 monomers to soluble CD4 or to a human monoclonal antibody to a discontinuous epitope overlapping the CD4-binding site. Some of these antibodies were type specific to a degree, in that they were more effective at blocking ligand binding to autologous gp120 than to heterologous gp120. However, the appearance of these antibodies did not correlate with that of antibodies able to neutralize the autologous virus in vitro by a peripheral blood mononuclear cell-based assay. Antibodies to the V3 loop were detected at about the same time as, or slightly later than, those to the CD4-binding site. There was a weak correlation between the presence of antibodies to the V3 loop and autologous virus-neutralizing activity in two of three individuals studied. However, serum from the third individual contained V3 antibodies but lacked the ability to neutralize the autologous virus in vitro, even immediately after seroconversion. Thus, no simple, universal correlate of autologous virus-neutralizing activity in a peripheral blood mononuclear cell-based assay is apparent from in vitro assays that rely on detecting antibody interactions with monomeric gp120 or fragments thereof. PMID:8035514

  1. Optimizing integrated luminosity of future hadron colliders

    NASA Astrophysics Data System (ADS)

    Benedikt, Michael; Schulte, Daniel; Zimmermann, Frank

    2015-10-01

    The integrated luminosity, a key figure of merit for any particle-physics collider, is closely linked to the peak luminosity and to the beam lifetime. The instantaneous peak luminosity of a collider is constrained by a number of boundary conditions, such as the available beam current, the maximum beam-beam tune shift with acceptable beam stability and reasonable luminosity lifetime (i.e., the empirical "beam-beam limit"), or the event pileup in the physics detectors. The beam lifetime at high-luminosity hadron colliders is largely determined by particle burn off in the collisions. In future highest-energy circular colliders synchrotron radiation provides a natural damping mechanism, which can be exploited for maximizing the integrated luminosity. In this article, we derive analytical expressions describing the optimized integrated luminosity, the corresponding optimum store length, and the time evolution of relevant beam parameters, without or with radiation damping, while respecting a fixed maximum value for the total beam-beam tune shift or for the event pileup in the detector. Our results are illustrated by examples for the proton-proton luminosity of the existing Large Hadron Collider (LHC) at its design parameters, of the High-Luminosity Large Hadron Collider (HL-LHC), and of the Future Circular Collider (FCC-hh).

  2. One-Loop Helicity Amplitudes for tt Production at Hadron Colliders

    SciTech Connect

    Badger, Simon; Sattler, Ralf; Yundin, Valery

    2011-04-01

    We present compact analytic expressions for all one-loop helicity amplitudes contributing to tt production at hadron colliders. Using recently developed generalized unitarity methods and a traditional Feynman based approach we produce a fast and flexible implementation.

  3. Transcriptomic and Metabolomic Analysis Revealed Multifaceted Effects of Phage Protein Gp70.1 on Pseudomonas aeruginosa

    PubMed Central

    Zhao, Xia; Chen, Canhuang; Jiang, Xingyu; Shen, Wei; Huang, Guangtao; Le, Shuai; Lu, Shuguang; Zou, Lingyun; Ni, Qingshan; Li, Ming; Zhao, Yan; Wang, Jing; Rao, Xiancai; Hu, Fuquan; Tan, Yinling

    2016-01-01

    The impact of phage infection on the host cell is severe. In order to take over the cellular machinery, some phage proteins were produced to shut off the host biosynthesis early in the phage infection. The discovery and identification of these phage-derived inhibitors have a significant prospect of application in antibacterial treatment. This work presented a phage protein, gp70.1, with non-specific inhibitory effects on Pseudomonas aeruginosa and Escherichia coli. Gp70.1 was encoded by early gene – orf 70.1 from P. aeruginosa phage PaP3. The P. aeruginosa with a plasmid encoding gp70.1 showed with delayed growth and had the appearance of a small colony. The combination of multifaceted analysis including microarray-based transcriptomic analysis, RT-qPCR, nuclear magnetic resonance (NMR) spectroscopy-based metabolomics and phenotype experiments were performed to investigate the effects of gp70.1 on P. aeruginosa. A total of 178 genes of P. aeruginosa mainly involved in extracellular function and metabolism were differentially expressed in the presence of gp70.1 at three examined time points. Furthermore, our results indicated that gp70.1 had an extensive impact on the extracellular phenotype of P. aeruginosa, such as motility, pyocyanin, extracellular protease, polysaccharide, and cellulase. For the metabolism of P. aeruginosa, the main effect of gp70.1 was the reduction of amino acid consumption. Finally, the RNA polymerase sigma factor RpoS was identified as a potential cellular target of gp70.1. Gp70.1 was the first bacterial inhibitor identified from Pseudomonas aeruginosa phage PaP3. It was also the first phage protein that interacted with the global regulator RpoS of bacteria. Our results indicated the potential value of gp70.1 in antibacterial applications. This study preliminarily revealed the biological function of gp70.1 and provided a reference for the study of other phage genes sharing similarities with orf70.1. PMID:27725812

  4. International Workshop on Linear Colliders 2010

    ScienceCinema

    None

    2016-07-12

    IWLC2010 International Workshop on Linear Colliders 2010ECFA-CLIC-ILC joint meeting: Monday 18 October - Friday 22 October 2010Venue: CERN and CICG (International Conference Centre Geneva, Switzerland) This year, the International Workshop on Linear Colliders organized by the European Committee for Future Accelerators (ECFA) will study the physics, detectors and accelerator complex of a linear collider covering both CLIC and ILC options.Contact Workshop Secretariat  IWLC2010 is hosted by CERN

  5. Linear Colliders: Achieving High Beam Power

    NASA Astrophysics Data System (ADS)

    Adolphsen, Chris

    2002-04-01

    For the next generation linear colliders, the luminosity will be approximately proportional to the average power of the colliding beams. Thus it is the goal of the accelerator systems of these machines to transfer wall plug power, which will be limited to a few hundred megawatts to be practical, to beam power in an efficient and low cost manner. Just as important, the beam acceleration must not degrade the small beam emittances that are necessary for high luminosity. In this paper, we examine the linac designs of the leading linear collider proposals (CLIC, JLC, NLC and TESLA) in these respects and review their R&D status.

  6. Beamstrahlung spectra in next generation linear colliders

    SciTech Connect

    Barklow, T.; Chen, P. ); Kozanecki, W. )

    1992-04-01

    For the next generation of linear colliders, the energy loss due to beamstrahlung during the collision of the e{sup +}e{sup {minus}} beams is expected to substantially influence the effective center-of-mass energy distribution of the colliding particles. In this paper, we first derive analytical formulae for the electron and photon energy spectra under multiple beamstrahlung processes, and for the e{sup +}e{sup {minus}} and {gamma}{gamma} differential luminosities. We then apply our formulation to various classes of 500 GeV e{sup +}e{sup {minus}} linear collider designs currently under study.

  7. International Workshop on Linear Colliders 2010

    ScienceCinema

    None

    2016-07-12

    IWLC2010 International Workshop on Linear Colliders 2010ECFA-CLIC-ILC joint meeting: Monday 18 October - Friday 22 October 2010Venue: CERN and CICG (International Conference Centre Geneva, Switzerland) This year, the International Workshop on Linear Colliders organized by the European Committee for Future Accelerators (ECFA) will study the physics, detectors and accelerator complex of a linear collider covering both CLIC and ILC options.Contact Workshop Secretariat  IWLC2010 is hosted by CERN

  8. SLAC linear collider conceptual design report

    SciTech Connect

    Not Available

    1980-06-01

    The linear collider system is described in detail, including the transport system, the collider lattice, final focusing system, positron production, beam damping and compression, high current electron source, instrumentation and control, and the beam luminosity. The experimental facilities and the experimental uses are discussed along with the construction schedule and estimated costs. Appendices include a discussion of space charge effects in the linear accelerator, emittance growth in the collider, the final focus system, beam-beam instabilities and pinch effects, and detector backgrounds. (GHT)

  9. Compensatable muon collider calorimeter with manageable backgrounds

    SciTech Connect

    Raja, Rajendran

    2015-02-17

    A method and system for reducing background noise in a particle collider, comprises identifying an interaction point among a plurality of particles within a particle collider associated with a detector element, defining a trigger start time for each of the pixels as the time taken for light to travel from the interaction point to the pixel and a trigger stop time as a selected time after the trigger start time, and collecting only detections that occur between the start trigger time and the stop trigger time in order to thereafter compensate the result from the particle collider to reduce unwanted background detection.

  10. Differential glycosylation of envelope gp120 is associated with differential recognition of HIV-1 by virus-specific antibodies and cell infection

    PubMed Central

    2014-01-01

    associated glycans (PG9, PG16), and an epitope including V3-base-, N332 oligomannose-, and surrounding glycans-containing epitope (PGT 121). Moreover, the different gp120 glycoforms variably inhibited HIV-1 infection of reporter cells. Conclusion Our data support the hypothesis that the glycosylation machinery of different cells shapes gp120 glycosylation and, consequently, impacts envelope recognition by specific antibodies as well as the interaction of HIV-1 gp120 with cellular receptors. These findings underscore the importance of selection of appropriately glycosylated HIV-1 envelope as a vaccine antigen. PMID:25120578

  11. The Gp78 ubiquitin ligase: probing endoplasmic reticulum complexity.

    PubMed

    St Pierre, Pascal; Nabi, Ivan R

    2012-02-01

    The endoplasmic reticulum (ER) has been classically divided, based on electron microscopy analysis, into parallel ribosome-studded rough ER sheets and a tubular smooth ER network. Recent studies have identified molecular constituents of the ER, the reticulons and DP1, that drive ER tubule formation and whose expression determines expression of ER sheets and tubules and thereby rough and smooth ER. However, segregation of the ER into only two domains remains simplistic and multiple functionally distinct ER domains necessarily exist. In this review, we will discuss the sub-organization of the ER in different domains focusing on the localization and role of the gp78 ubiquitin ligase in the mitochondria-associated smooth ER and on the evidence for a quality control ERAD domain.

  12. 76 FR 4890 - Northwest Pipeline GP; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-27

    ... Energy Regulatory Commission Northwest Pipeline GP; Notice of Application January 20, 2011. Take notice that on January 11, 2011, Northwest Pipeline GP (Northwest), 295 Chipeta Way, Salt Lake City, Utah... Project consists of: Abandonment in place of approximately 15 miles of 16-inch diameter pipeline...

  13. Residues in the gp41 Ectodomain Regulate HIV-1 Envelope Glycoprotein Conformational Transitions Induced by gp120-Directed Inhibitors.

    PubMed

    Pacheco, Beatriz; Alsahafi, Nirmin; Debbeche, Olfa; Prévost, Jérémie; Ding, Shilei; Chapleau, Jean-Philippe; Herschhorn, Alon; Madani, Navid; Princiotto, Amy; Melillo, Bruno; Gu, Christopher; Zeng, Xin; Mao, Youdong; Smith, Amos B; Sodroski, Joseph; Finzi, Andrés

    2017-03-01

    Interactions between the gp120 and gp41 subunits of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer maintain the metastable unliganded form of the viral spike. Binding of gp120 to the receptor, CD4, changes the Env conformation to promote gp120 interaction with the second receptor, CCR5 or CXCR4. CD4 binding also induces the transformation of Env into the prehairpin intermediate, in which the gp41 heptad repeat 1 (HR1) coiled coil is assembled at the trimer axis. In nature, HIV-1 Envs must balance the requirements to maintain the noncovalent association of gp120 with gp41 and to evade the host antibody response with the need to respond to CD4 binding. Here we show that the gp41 HR1 region contributes to gp120 association with the unliganded Env trimer. Changes in particular amino acid residues in the gp41 HR1 region decreased the efficiency with which Env moved from the unliganded state. Thus, these gp41 changes decreased the sensitivity of HIV-1 to cold inactivation and ligands that require Env conformational changes to bind efficiently. Conversely, these gp41 changes increased HIV-1 sensitivity to small-molecule entry inhibitors that block Env conformational changes induced by CD4. Changes in particular gp41 HR1 amino acid residues can apparently affect the relative stability of the unliganded state and CD4-induced conformations. Thus, the gp41 HR1 region contributes to the association with gp120 and regulates Env transitions from the unliganded state to downstream conformations.IMPORTANCE The development of an efficient vaccine able to prevent HIV infection is a worldwide priority. Knowledge of the envelope glycoprotein structure and the conformational changes that occur after receptor engagement will help researchers to develop an immunogen able to elicit antibodies that block HIV-1 transmission. Here we identify residues in the HIV-1 transmembrane envelope glycoprotein that stabilize the unliganded state by modulating the

  14. Inhibition of PbGP43 Expression May Suggest that gp43 is a Virulence Factor in Paracoccidioides brasiliensis

    PubMed Central

    Torres, Isaura; Hernandez, Orville; Tamayo, Diana; Muñoz, Jose F.; Leitão, Natanael P.; García, Ana M.; Restrepo, Angela

    2013-01-01

    Glycoprotein gp43 is an immunodominant diagnostic antigen for paracoccidioidomycosis caused by Paracoccidioides brasiliensis. It is abundantly secreted in isolates such as Pb339. It is structurally related to beta-1,3-exoglucanases, however inactive. Its function in fungal biology is unknown, but it elicits humoral, innate and protective cellular immune responses; it binds to extracellular matrix-associated proteins. In this study we applied an antisense RNA (aRNA) technology and Agrobacterium tumefaciens-mediated transformation to generate mitotically stable PbGP43 mutants (PbGP43 aRNA) derived from wild type Pb339 to study its role in P. brasiliensis biology and during infection. Control PbEV was transformed with empty vector. Growth curve, cell vitality and morphology of PbGP43 aRNA mutants were indistinguishable from those of controls. PbGP43 expression was reduced 80–85% in mutants 1 and 2, as determined by real time PCR, correlating with a massive decrease in gp43 expression. This was shown by immunoblotting of culture supernatants revealed with anti-gp43 mouse monoclonal and rabbit polyclonal antibodies, and also by affinity-ligand assays of extracellular molecules with laminin and fibronectin. In vitro, there was significantly increased TNF-α production and reduced yeast recovery when PbGP43 aRNA1 was exposed to IFN-γ-stimulated macrophages, suggesting reduced binding/uptake and/or increased killing. In vivo, fungal burden in lungs of BALB/c mice infected with silenced mutant was negligible and associated with decreased lung ΙΛ−10 and IL-6. Therefore, our results correlated low gp43 expression with lower pathogenicity in mice, but that will be definitely proven when PbGP43 knockouts become available. This is the first study of gp43 using genetically modified P. brasiliensis. PMID:23874627

  15. N-butyldeoxynojirimycin-mediated inhibition of human immunodeficiency virus entry correlates with impaired gp120 shedding and gp41 exposure.

    PubMed Central

    Fischer, P B; Karlsson, G B; Dwek, R A; Platt, F M

    1996-01-01

    The alpha-glucosidase inhibitor N-butyldeoxynojirimycin (NB-DNJ) is an inhibitor of human immunodeficiency virus (HIV) replication and HIV-induced syncytium formation in vitro. Although an NB-DNJ-mediated change in viral envelope N-glycan composition inhibits HIV entry at the level of post-CD4 binding, the exact mechanism of inhibition remains to be established. In this study we have examined the effects of NB-DNJ on virion envelope composition and CD4-induced gp120 shedding and gp41 exposure. Virion composition analysis revealed an NB-DNJ-mediated reduction of 15% in overall virion envelope glycoprotein content and a reduction of 26% in the proteolytic maturation of virion gp160. Taken together, these two effects resulted in a reduction of approximately 40% in virion gp120 content. CD4-induced shedding of gp120 from the surfaces of envelope-transfected Cos cells was undetectable when gp120 was expressed in the presence of NB-DNJ. Similarly, the shedding of virion-associated gp120 was reduced 7.4-fold. CD4-induced exposure of cryptic gp41 epitopes on the surfaces of HIV-expressing ACH-2 cells was also greatly impaired, and the exposure of virion-associated gp41 epitopes was reduced 4.0-fold. Finally, CD4-induced increases in the binding of antibodies to the V3 loop of ACH-2-cell-expressed envelope glycoproteins were reduced 25-fold when the glycoproteins were expressed in the presence of NB-DNJ. These results suggest that the NB-DNJ-mediated retention of glycosylated N-glycans inhibits HIV entry by a combined effect of a reduction in virion gp120 content and a qualitative defect within the remaining gp120, preventing it from undergoing conformational changes after CD4 binding. PMID:8794362

  16. The Relativistic Heavy Ion Collider

    NASA Astrophysics Data System (ADS)

    Fischer, Wolfram

    The Relativistic Heavy Ion Collider (RHIC), shown in Fig. 1, was build to study the interactions of quarks and gluons at high energies [Harrison, Ludlam and Ozaki (2003)]. The theory of Quantum Chromodynamics (QCD) describes these interactions. One of the main goals for the RHIC experiments was the creation and study of the Quark-Gluon Plasma (QGP), which was expected to be formed after the collision of heavy ions at a temperature of approximately 2 trillion kelvin (or equivalently an energy of 150 MeV). The QGP is the substance which existed only a few microseconds after the Big Bang. The QGP was anticipated to be weakly interacting like a gas but turned out to be strongly interacting and more like a liquid. Among its unusual properties is its extremely low viscosity [Auerbach and Schlomo (2009)], which makes the QGP the substance closest to a perfect liquid known to date. The QGP is opaque to moderate energy quarks and gluons leading to a phenomenon called jet quenching, where of a jet and its recoil jet only one is observable and the other suppressed after traversing and interacting with the QGP [Jacak and Müller (2012)]...

  17. Maverick dark matter at colliders

    NASA Astrophysics Data System (ADS)

    Beltrán, Maria; Hooper, Dan; Kolb, Edward W.; Krusberg, Zosia A. C.; Tait, Tim M. P.

    2010-09-01

    Assuming that dark matter is a weakly interacting massive particle (WIMP) species X produced in the early Universe as a cold thermal relic, we study the collider signal of pp or pbar{p} rightarrow bar{X}X + jets and its distinguishability from standard-model background processes associated with jets and missing energy. We assume that the WIMP is the sole particle related to dark matter within reach of the LHC — a “maverick” particle — and that it couples to quarks through a higher dimensional contact interaction. We simulate the WIMP final-state signal Xbar{X} + jets and dominant standard-model (SM) background processes and find that the dark-matter production process results in higher energies for the colored final state partons than do the standard-model background processes. As a consequence, the detectable signature of maverick dark matter is an excess over standard-model expectations of events consisting of large missing transverse energy, together with large leading jet transverse momentum and scalar sum of the transverse momenta of the jets. Existing Tevatron data and forthcoming LHC data can constrain (or discover!) maverick dark matter.

  18. Hourglass effects for asymmetric colliders

    SciTech Connect

    Furman, M.A.

    1991-05-01

    We give the expressions for the geometrical reduction factor of the luminosity and the geometrical beam-beam aggravating factor'' for the general asymmetric case, for tri-gaussian bunches colliding head on. With these formulas we attempt a (limited) analytic understanding of the multiparticle tracking simulations carried out for the proposed SLAC/LBL/LLNL B factory when parasitic crossings are ignored. We conclude the following: (a) the geometrical reduction in luminosity is {approximately}6% relative to the zero-bunch-length (nominal) value; (b) only the vertical beam-beam parameter of the LER is significantly altered by the hourglass effect: the geometrical enhancement of the central positron's vertical beam-beam parameter is {approximately}10% relative to the nominal value, and (c) the positrons at the head or tail of the bunch have vertical beam-beam parameters much larger than nominal. We discuss the electromagnetic disruption effect only qualitatively. This effect probably compensates (or overcompensates) the geometrical reduction of the luminosity, and it is possibly detrimental for the beam-beam parameters. 7 refs., 3 figs.

  19. A Tevatron collider beauty factory

    NASA Astrophysics Data System (ADS)

    This document which is labeled a final report consists of several different items. The first is a proposal for a detector to be developed for beauty physics. The detector is proposed for the Fermilab Tevatron and would be designed to measure mixing reactions, rare decay modes, and even CP violation in hadron collider beauty production. The general outline of the work proposed is given, and an estimate of the time to actually design the detector is presented, along with proposed changes to the Tevatron to accommodate the system. A preliminary report on an experiment to verify a reported observation of a 17 keV neutrino in tritium decay is presented. The present results in the decay spectra actually showing a depression below expected levels, which is not consistent with a massive neutrino. Additional interest has been shown in finishing an electrostatic beta spectrometer which was started several years previously. The instrument uses hemispherical electrostatic electric fields to retard electrons emitted in tritium decay allowing measurement of integral spectra. The design goal has a 5 eV energy resolution, which may be achievable. A new PhD student is pursuing this experiment. Also the report contains a proposal for additional work in the field of non-perturbative quantum field theory by the theoretical group at OU. The work which is proposed will be applied to electroweak and strong interactions, as well as to quantum gravitational phenomena.

  20. Proton-antiproton collider physics

    SciTech Connect

    Shochet, M.J.

    1995-07-01

    The 9th {anti p}p Workshop was held in Tsukuba, Japan in October, 1993. A number of important issues remained after that meeting: Does QCD adequately describe the large cross section observed by CDF for {gamma} production below 30 GeV? Do the CDF and D0 b-production cross sections agree? Will the Tevatron live up to its billing as a world-class b-physics facility? How small will the uncertainty in the W mass be? Is there anything beyond the Minimal Standard Model? And finally, where is the top quark? Presentations at this workshop addressed all of these issues. Most of them are now resolved, but new questions have arisen. This summary focuses on the experimental results presented at the meeting by CDF and D0 physicists. Reviews of LEP and HERA results, future plans for hadron colliders and their experiments, as well as important theoretical presentations are summarized elsewhere in this volume. Section 1 reviews physics beyond the Minimal Standard Model. Issues in b and c physics are addressed in section 3. Section 4 focuses on the top quark. Electroweak physics is reviewed in section 5, followed by QCD studies in section 6. Conclusions are drawn in section 7.

  1. Preliminary design for a 20 TeV Collider in a deep tunnel at Fermilab

    SciTech Connect

    Not Available

    1985-01-12

    The Reference Design Study for a 20 TeV Collider demonstrated the technical and cost feasibility of a 20 TeV superconducting collider facility. Based on magnets of 3T, 5T, and 6.5T the Main Ring of the Collider would have a circumference of 164 km, 113 km, or 90 km. There would be six collision regions, of which four would be developed intially. The 5T and 6.5T rings would have twelve major refrigeration stations, while the 3T design would have 24 major refrigeration stations.

  2. Written reflection in assessment and appraisal: GP and GP trainee views.

    PubMed

    Curtis, Pamela; Taylor, Gordon; Riley, Ruth; Pelly, Tom; Harris, Michael

    2017-05-01

    In the UK, evidence of written reflection is part of licensing and revalidation for general practitioners (GPs). However, there is little evidence of specific benefits compared to other forms of reflective practice. To seek GPs' and general practice (GP) trainees' views on the role of written reflection in learning and assessment. An online survey of 1005 GPs and GP trainees (GPTs) in the UK. An anonymous questionnaire containing 38 attitudinal items was administered. Descriptive statistics were used to analyse Likert scale responses, thematic analysis for free-text responses. In total 544 GPs and 461 GPTs completed the survey, with 842 (83.8%) agreeing they find verbal reflection with a colleague more useful than written reflection. Three quarters disagreed that written reflection is a way of identifying poorly performing GPs. Over 70% of respondents stated that summative, written reflection is a time-consuming, box-ticking exercise which distracts from other learning. They question its validity as part of assessment and state that its use may contribute to current difficulties with recruitment and retention to GP. For many GPs, written reflection is an onerous process rather than beneficial to their learning, indicating its continued use in assessment needs to be critically examined.

  3. High pulse power rf sources for linear colliders

    SciTech Connect

    Wilson, P.B.

    1983-09-01

    RF sources with high peak power output and relatively short pulse lengths will be required for future high gradient e/sup +/e/sup -/ linear colliders. The required peak power and pulse length depend on the operating frequency, energy gradient and geometry of the collider linac structure. The frequency and gradient are in turn constrained by various parameters which depend on the beam-beam collision dynamics, and on the total ac wall-plug power that has been committed to the linac rf system. Various rf sources which might meet these requirements are reviewed. Existing source types (e.g., klystrons, gyrotrons) and sources which show future promise based on experimental prototypes are first considered. Finally, several proposals for high peak power rf sources based on unconventional concepts are discussed. These are an FEL source (two beam accelerator), rf energy storage cavities with switching, and a photocathode device which produces an rf current by direct emission modulation of the cathode.

  4. Decoupling schemes for the SSC Collider

    SciTech Connect

    Cai, Y.; Bourianoff, G.; Cole, B.; Meinke, R.; Peterson, J.; Pilat, F.; Stampke, S.; Syphers, M.; Talman, R.

    1993-05-01

    A decoupling system is designed for the SSC Collider. This system can accommodate three decoupling schemes by using 44 skew quadrupoles in the different configurations. Several decoupling schemes are studied and compared in this paper.

  5. Final focus systems for linear colliders

    SciTech Connect

    Erickson, R.A.

    1987-11-01

    The final focus system of a linear collider must perform two primary functions, it must focus the two opposing beams so that their transverse dimensions at the interaction point are small enough to yield acceptable luminosity, and it must steer the beams together to maintain collisions. In addition, the final focus system must transport the outgoing beams to a location where they can be recycled or safely dumped. Elementary optical considerations for linear collider final focus systems are discussed, followed by chromatic aberrations. The design of the final focus system of the SLAC Linear Collider (SLC) is described. Tuning and diagnostics and steering to collision are discussed. Most of the examples illustrating the concepts covered are drawn from the SLC, but the principles and conclusions are said to be generally applicable to other linear collider designs as well. 26 refs., 17 figs. (LEW)

  6. Photon Collider Physics with Real Photon Beams

    SciTech Connect

    Gronberg, J; Asztalos, S

    2005-11-03

    Photon-photon interactions have been an important probe into fundamental particle physics. Until recently, the only way to produce photon-photon collisions was parasitically in the collision of charged particles. Recent advances in short-pulse laser technology have made it possible to consider producing high intensity, tightly focused beams of real photons through Compton scattering. A linear e{sup +}e{sup -} collider could thus be transformed into a photon-photon collider with the addition of high power lasers. In this paper they show that it is possible to make a competitive photon-photon collider experiment using the currently mothballed Stanford Linear Collider. This would produce photon-photon collisions in the GeV energy range which would allow the discovery and study of exotic heavy mesons with spin states of zero and two.

  7. Measurement of the inclusive jet cross section at the Fermilab Tevatron p pmacr collider using a cone-based jet algorithm

    NASA Astrophysics Data System (ADS)

    Aaltonen, T.; Adelman, J.; Akimoto, T.; Albrow, M. G.; Álvarez González, B.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Apresyan, A.; Arisawa, T.; Artikov, A.; Ashmanskas, W.; Attal, A.; Aurisano, A.; Azfar, F.; Azzurri, P.; Badgett, W.; Barbaro-Galtieri, A.; Barnes, V. E.; Barnett, B. A.; Bartsch, V.; Bauer, G.; Beauchemin, P.-H.; Bedeschi, F.; Bednar, P.; Beecher, D.; Behari, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Beringer, J.; Bhatti, A.; Binkley, M.; Bisello, D.; Bizjak, I.; Blair, R. E.; Blocker, C.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Boisvert, V.; Bolla, G.; Bortoletto, D.; Boudreau, J.; Boveia, A.; Brau, B.; Bridgeman, A.; Brigliadori, L.; Bromberg, C.; Brubaker, E.; Budagov, J.; Budd, H. S.; Budd, S.; Burkett, K.; Busetto, G.; Bussey, P.; Buzatu, A.; Byrum, K. L.; Cabrera, S.; Calancha, C.; Campanelli, M.; Campbell, M.; Canelli, F.; Canepa, A.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Carron, S.; Casal, B.; Casarsa, M.; Castro, A.; Catastini, P.; Cauz, D.; Cavaliere, V.; Cavalli-Sforza, M.; Cerri, A.; Cerrito, L.; Chang, S. H.; Chen, Y. C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Chlebana, F.; Cho, K.; Chokheli, D.; Chou, J. P.; Choudalakis, G.; Chuang, S. H.; Chung, K.; Chung, W. H.; Chung, Y. S.; Ciobanu, C. I.; Ciocci, M. A.; Clark, A.; Clark, D.; Compostella, G.; Convery, M. E.; Conway, J.; Copic, K.; Cordelli, M.; Cortiana, G.; Cox, D. J.; Crescioli, F.; Cuenca Almenar, C.; Cuevas, J.; Culbertson, R.; Cully, J. C.; Dagenhart, D.; Datta, M.; Davies, T.; de Barbaro, P.; de Cecco, S.; Deisher, A.; de Lorenzo, G.; Dell'Orso, M.; Deluca, C.; Demortier, L.; Deng, J.; Deninno, M.; Derwent, P. F.; di Giovanni, G. P.; Dionisi, C.; di Ruzza, B.; Dittmann, J. R.; D'Onofrio, M.; Donati, S.; Dong, P.; Donini, J.; Dorigo, T.; Dube, S.; Efron, J.; Elagin, A.; Erbacher, R.; Errede, D.; Errede, S.; Eusebi, R.; Fang, H. C.; Farrington, S.; Fedorko, W. T.; Feild, R. G.; Feindt, M.; Fernandez, J. P.; Ferrazza, C.; Field, R.; Flanagan, G.; Forrest, R.; Franklin, M.; Freeman, J. C.; Furic, I.; Gallinaro, M.; Galyardt, J.; Garberson, F.; Garcia, J. E.; Garfinkel, A. F.; Genser, K.; Gerberich, H.; Gerdes, D.; Gessler, A.; Giagu, S.; Giakoumopoulou, V.; Giannetti, P.; Gibson, K.; Gimmell, J. L.; Ginsburg, C. M.; Giokaris, N.; Giordani, M.; Giromini, P.; Giunta, M.; Giurgiu, G.; Glagolev, V.; Glenzinski, D.; Gold, M.; Goldschmidt, N.; Golossanov, A.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; González, O.; Gorelov, I.; Goshaw, A. T.; Goulianos, K.; Gresele, A.; Grinstein, S.; Grosso-Pilcher, C.; Group, R. C.; Grundler, U.; Guimaraes da Costa, J.; Gunay-Unalan, Z.; Haber, C.; Hahn, K.; Hahn, S. R.; Halkiadakis, E.; Han, B.-Y.; Han, J. Y.; Handler, R.; Happacher, F.; Hara, K.; Hare, D.; Hare, M.; Harper, S.; Harr, R. F.; Harris, R. M.; Hartz, M.; Hatakeyama, K.; Hauser, J.; Hays, C.; Heck, M.; Heijboer, A.; Heinemann, B.; Heinrich, J.; Henderson, C.; Herndon, M.; Heuser, J.; Hewamanage, S.; Hidas, D.; Hill, C. S.; Hirschbuehl, D.; Hocker, A.; Hou, S.; Houlden, M.; Hsu, S.-C.; Huffman, B. T.; Hughes, R. E.; Husemann, U.; Huston, J.; Incandela, J.; Introzzi, G.; Iori, M.; Ivanov, A.; James, E.; Jayatilaka, B.; Jeon, E. J.; Jha, M. K.; Jindariani, S.; Johnson, W.; Jones, M.; Joo, K. K.; Jun, S. Y.; Jung, J. E.; Junk, T. R.; Kamon, T.; Kar, D.; Karchin, P. E.; Kato, Y.; Kephart, R.; Keung, J.; Khotilovich, V.; Kilminster, B.; Kim, D. H.; Kim, H. S.; Kim, J. E.; Kim, M. J.; Kim, S. B.; Kim, S. H.; Kim, Y. K.; Kimura, N.; Kirsch, L.; Klimenko, S.; Knuteson, B.; Ko, B. R.; Koay, S. A.; Kondo, K.; Kong, D. J.; Konigsberg, J.; Korytov, A.; Kotwal, A. V.; Kreps, M.; Kroll, J.; Krop, D.; Krumnack, N.; Kruse, M.; Krutelyov, V.; Kubo, T.; Kuhr, T.; Kulkarni, N. P.; Kurata, M.; Kusakabe, Y.; Kwang, S.; Laasanen, A. T.; Lami, S.; Lammel, S.; Lancaster, M.; Lander, R. L.; Lannon, K.; Lath, A.; Latino, G.; Lazzizzera, I.; Lecompte, T.; Lee, E.; Lee, S. W.; Leone, S.; Lewis, J. D.; Lin, C. S.; Linacre, J.; Lindgren, M.; Lipeles, E.; Lister, A.; Litvintsev, D. O.; Liu, C.; Liu, T.; Lockyer, N. S.; Loginov, A.; Loreti, M.; Lovas, L.; Lu, R.-S.; Lucchesi, D.; Lueck, J.; Luci, C.; Lujan, P.; Lukens, P.; Lungu, G.; Lyons, L.; Lys, J.; Lysak, R.; Lytken, E.; Mack, P.; MacQueen, D.; Madrak, R.; Maeshima, K.; Makhoul, K.; Maki, T.; Maksimovic, P.; Malde, S.; Malik, S.; Manca, G.; Manousakis-Katsikakis, A.; Margaroli, F.; Marino, C.; Marino, C. P.; Martin, A.; Martin, V.; Martínez, M.; Martínez-Ballarín, R.; Maruyama, T.; Mastrandrea, P.; Masubuchi, T.; Mattson, M. E.; Mazzanti, P.; McFarland, K. S.; McIntyre, P.; McNulty, R.; Mehta, A.; Mehtala, P.; Menzione, A.; Merkel, P.; Mesropian, C.; Miao, T.; Miladinovic, N.; Miller, R.; Mills, C.; Milnik, M.; Mitra, A.; Mitselmakher, G.; Miyake, H.; Moggi, N.; Moon, C. S.; Moore, R.; Morello, M. J.; Morlok, J.; Movilla Fernandez, P.; Mülmenstädt, J.; Mukherjee, A.; Muller, Th.; Mumford, R.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Nagano, A.; Naganoma, J.; Nakamura, K.; Nakano, I.; Napier, A.; Necula, V.; Neu, C.; Neubauer, M. S.; Nielsen, J.; Nodulman, L.; Norman, M.; Norniella, O.; Nurse, E.; Oakes, L.; Oh, S. H.; Oh, Y. D.; Oksuzian, I.; Okusawa, T.; Orava, R.; Osterberg, K.; Pagan Griso, S.; Pagliarone, C.; Palencia, E.; Papadimitriou, V.; Papaikonomou, A.; Paramonov, A. A.; Parks, B.; Pashapour, S.; Patrick, J.; Pauletta, G.; Paulini, M.; Paus, C.; Pellett, D. E.; Penzo, A.; Phillips, T. J.; Piacentino, G.; Pianori, E.; Pinera, L.; Pitts, K.; Plager, C.; Pondrom, L.; Poukhov, O.; Pounder, N.; Prakoshyn, F.; Pronko, A.; Proudfoot, J.; Ptohos, F.; Pueschel, E.; Punzi, G.; Pursley, J.; Rademacker, J.; Rahaman, A.; Ramakrishnan, V.; Ranjan, N.; Redondo, I.; Reisert, B.; Rekovic, V.; Renton, P.; Rescigno, M.; Richter, S.; Rimondi, F.; Ristori, L.; Robson, A.; Rodrigo, T.; Rodriguez, T.; Rogers, E.; Rolli, S.; Roser, R.; Rossi, M.; Rossin, R.; Roy, P.; Ruiz, A.; Russ, J.; Rusu, V.; Saarikko, H.; Safonov, A.; Sakumoto, W. K.; Saltó, O.; Santi, L.; Sarkar, S.; Sartori, L.; Sato, K.; Savoy-Navarro, A.; Scheidle, T.; Schlabach, P.; Schmidt, A.; Schmidt, E. E.; Schmidt, M. A.; Schmidt, M. P.; Schmitt, M.; Schwarz, T.; Scodellaro, L.; Scott, A. L.; Scribano, A.; Scuri, F.; Sedov, A.; Seidel, S.; Seiya, Y.; Semenov, A.; Sexton-Kennedy, L.; Sfyrla, A.; Shalhout, S. Z.; Shears, T.; Shepard, P. F.; Sherman, D.; Shimojima, M.; Shiraishi, S.; Shochet, M.; Shon, Y.; Shreyber, I.; Sidoti, A.; Sinervo, P.; Sisakyan, A.; Slaughter, A. J.; Slaunwhite, J.; Sliwa, K.; Smith, J. R.; Snider, F. D.; Snihur, R.; Soha, A.; Somalwar, S.; Sorin, V.; Spalding, J.; Spreitzer, T.; Squillacioti, P.; Stanitzki, M.; St. Denis, R.; Stelzer, B.; Stelzer-Chilton, O.; Stentz, D.; Strologas, J.; Stuart, D.; Suh, J. S.; Sukhanov, A.; Suslov, I.; Suzuki, T.; Taffard, A.; Takashima, R.; Takeuchi, Y.; Tanaka, R.; Tecchio, M.; Teng, P. K.; Terashi, K.; Thom, J.; Thompson, A. S.; Thompson, G. A.; Thomson, E.; Tipton, P.; Tiwari, V.; Tkaczyk, S.; Toback, D.; Tokar, S.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Tourneur, S.; Tu, Y.; Turini, N.; Ukegawa, F.; Vallecorsa, S.; van Remortel, N.; Varganov, A.; Vataga, E.; Vázquez, F.; Velev, G.; Vellidis, C.; Veszpremi, V.; Vidal, M.; Vidal, R.; Vila, I.; Vilar, R.; Vine, T.; Vogel, M.; Volobouev, I.; Volpi, G.; Würthwein, F.; Wagner, P.; Wagner, R. G.; Wagner, R. L.; Wagner-Kuhr, J.; Wagner, W.; Wakisaka, T.; Wallny, R.; Wang, S. M.; Warburton, A.; Waters, D.; Weinberger, M.; Wester, W. C., III; Whitehouse, B.; Whiteson, D.; Wicklund, A. B.; Wicklund, E.; Williams, G.; Williams, H. H.; Wilson, P.; Winer, B. L.; Wittich, P.; Wolbers, S.; Wolfe, C.; Wright, T.; Wu, X.; Wynne, S. M.; Yagil, A.; Yamamoto, K.; Yamaoka, J.; Yang, U. K.; Yang, Y. C.; Yao, W. M.; Yeh, G. P.; Yoh, J.; Yorita, K.; Yoshida, T.; Yu, G. B.; Yu, I.; Yu, S. S.; Yun, J. C.; Zanello, L.; Zanetti, A.; Zaw, I.; Zhang, X.; Zheng, Y.; Zucchelli, S.

    2008-09-01

    We present a measurement of the inclusive jet cross section in p pmacr collisions at s=1.96TeV based on data collected by the CDF II detector with an integrated luminosity of 1.13fb-1. The measurement was made using the cone-based midpoint jet clustering algorithm in the rapidity region of |y|<2.1. The results are consistent with next-to-leading-order perturbative QCD predictions based on recent parton distribution functions (PDFs), and are expected to provide increased precision in PDFs at high parton momentum fraction x. The results are also compared to the recent inclusive jet cross section measurement using the kT jet clustering algorithm, and we find that the ratio of the cross sections measured with the two algorithms is in agreement with theoretical expectations over a large range of jet transverse momentum and rapidity.

  8. GP2-expressing cells in the conjunctiva and tear ducts of mice: identification of a novel type of cells in the squamous stratified epithelium.

    PubMed

    Kimura, Shunsuke; Kishimoto, Ayuko; Mutoh, Mami; Takahashi-Iwanaga, Hiromi; Iwanaga, Toshihiko

    2015-01-01

    GP2 is a membrane-associated secretory protein originally identified in zymogen granules of pancreatic acinar cells. Recently, this glycoprotein has attracted attention as a marker substance of M cells of Peyer's patches and for its involvement in the selective uptake of pathological bacteria via M cells. When we stained the conjunctiva and tear ducts of mice using a GP2 antibody, all goblet cells in the squamous stratified epithelium of the conjunctiva were intensely immunolabeled, while goblet cells in the intestine and airway were devoid of the immunoreactivity, indicating that the conjunctiva contains a special type of goblet cell. Further immunostaining for GP-2 labeled dispersed cells of peculiar shapes within the stratified squamous epithelium in the lacrimal canaliculi, lacrimal sac, and nasolacrimal duct. The GP2-immunoreactive cells in the tear duct projected arched or branched processes toward the basement membrane. Electron-microscopically, immunogold particles for GP2 outlined the basolateral plasma membrane of both the conjuntival goblet cells and the peculiarly shaped cells in the tear duct. Intracellularly, GP2 products of the goblet cells were localized around secretory granules in the apical cytoplasm and those of the tear duct cells inside the vesicles. The luminal contents close to apical plasma membrane were heavily labeled with immunogold particles, suggesting an exocytosis-based targeting of GP2 to the plasma membrane and its release into the lumen. The possible function of GP2 in tear ducts is discussed in relation to a defense system against invasive microoranisms and antigens.

  9. Identification by Mass Spectrometry and Immune Response Analysis of Guinea Pig Cytomegalovirus (GPCMV) Pentameric Complex Proteins GP129, 131 and 133

    PubMed Central

    Gnanandarajah, Josephine S.; Gillis, Peter A.; Hernandez-Alvarado, Nelmary; Higgins, LeeAnn; Markowski, Todd W.; Sung, Heungsup; Lumley, Sheila; Schleiss, Mark R.

    2014-01-01

    Development of a vaccine against congenital infection with human cytomegalovirus (HCMV) is a major public health priority. A potential vaccine target receiving considerable recent attention is the pentameric complex (PC) of HCMV proteins consisting of gL, gH, UL128, UL130, and UL131, since some antibodies against these target proteins are capable of potently neutralizing virus at epithelial and endothelial cell surfaces. Recently, homologous proteins have been described for guinea pig cytomegalovirus (GPCMV), consisting of gH, gL, and the GPCMV proteins GP129, GP131, and GP133. To investigate these proteins as potential vaccine targets, expression of GP129-GP133 transcripts was confirmed by reverse-transcriptase PCR. Mass spectrometry combined with western blot assays demonstrated the presence of GP129, GP131, and GP133 proteins in virus particles. Recombinant proteins corresponding to these PC proteins were generated in baculovirus, and as GST fusion proteins. Recombinant proteins were noted to be immunoreactive with convalescent sera from infected animals, suggesting that these proteins are recognized in the humoral immune response to GPCMV infection. These analyses support the study of PC-based recombinant vaccines in the GPCMV congenital infection model. PMID:24531333

  10. Mapping the interactions of the single-stranded DNA binding protein of bacteriophage T4 (gp32) with DNA lattices at single nucleotide resolution: polynucleotide binding and cooperativity

    PubMed Central

    Jose, Davis; Weitzel, Steven E.; Baase, Walter A.; Michael, Miya M.; von Hippel, Peter H.

    2015-01-01

    We here use our site-specific base analog mapping approach to study the interactions and binding equilibria of cooperatively-bound clusters of the single-stranded DNA binding protein (gp32) of the T4 DNA replication complex with longer ssDNA (and dsDNA) lattices. We show that in cooperatively bound clusters the binding free energy appears to be equi-partitioned between the gp32 monomers of the cluster, so that all bind to the ssDNA lattice with comparable affinity, but also that the outer domains of the gp32 monomers at the ends of the cluster can fluctuate on and off the lattice and that the clusters of gp32 monomers can slide along the ssDNA. We also show that at very low binding densities gp32 monomers bind to the ssDNA lattice at random, but that cooperatively bound gp32 clusters bind preferentially at the 5′-end of the ssDNA lattice. We use these results and the gp32 monomer-binding results of the companion paper to propose a detailed model for how gp32 might bind to and interact with ssDNA lattices in its various binding modes, and also consider how these clusters might interact with other components of the T4 DNA replication complex. PMID:26275774

  11. The crystal structure of HIV CRF07 B'/C gp41 reveals a hyper-mutant site in the middle of HR2 heptad repeat.

    PubMed

    Du, Jiansen; Xue, Hailing; Ma, Jing; Liu, Fang; Zhou, Jianhua; Shao, Yiming; Qiao, Wentao; Liu, Xinqi

    2013-11-01

    HIV CRF07 B'/C is a strain circulating mainly in northwest region of China. The gp41 region of CRF07 is derived from a clade C virus. In order to compare the difference of CRF07 gp41 with that of typical clade B virus, we solved the crystal structure of the core region of CRF07 gp41. Compared with clade B gp41, CRF07 gp41 evolved more basic and hydrophilic residues on its helix bundle surface. Based on sequence alignment, a hyper-mutant cluster located in the middle of HR2 heptads repeat was identified. The mutational study of these residues revealed that this site is important in HIV mediated cell-cell fusion and plays critical roles in conformational changes during viral invasion.

  12. Accelerator Considerations of Large Circular Colliders

    NASA Astrophysics Data System (ADS)

    Chao, Alex

    As we consider the tremendous physics reaches of the big future circular electron-positron and proton-proton colliders, it might be advisable to keep a close track of what accelerator challenges they face. Good progresses are being made, and yet it is reported here that substantial investments in funding, manpower, as well as a long sustained time to the R&D efforts will be required in preparation to realize these dream colliders.

  13. Accelerator considerations of large circular colliders

    NASA Astrophysics Data System (ADS)

    Chao, Alex

    2016-07-01

    As we consider the tremendous physics reaches of the big future circular electron-positron and proton-proton colliders, it might be advisable to keep a close track of what accelerator challenges they face. Good progresses are being made, and yet it is reported here that substantial investments in funding, manpower, as well as a long sustained time to the R&D efforts will be required in preparation to realize these dream colliders.

  14. Physics goals of the next linear collider

    SciTech Connect

    Kuhlman, S.; Marciano, W.J.; Gunion, J. F.; NLC ZDR Design Group; NLC Physics Working Group

    1996-05-01

    We present the prospects for the next generation of high-energy physics experiments with electron-positron colliding beams. This report summarizes the current status of the design and technological basis of a linear collider of center of mass energy 500 GeV-1.5 TeV, and the opportunities for high-energy physics experiments that this machine is expected to open. 132 refs., 54 figs., 14 tabs.

  15. MUON COLLIDERS - IONIZATION COOLING AND SOLENOIDS.

    SciTech Connect

    PARSA,Z.

    1999-03-29

    For a muon collider, to obtain the needed luminosity, the phase space volume must be greatly reduced within the muon life time. The ionization cooling is the preferred method used to compress the phase space and reduce the emittance to obtain high luminosity muon beams. Alternating solenoid lattices has been proposed for muon colliders, where the emittance are huge. We present an overview, discuss formalism, transfer maps for solenoid magnets and beam dynamics.

  16. RF pulse compression for future linear colliders

    SciTech Connect

    Wilson, P.B.

    1995-05-01

    Future (nonsuperconducting) linear colliders will require very high values of peak rf power per meter of accelerating structure. The role of rf pulse compression in producing this power is examined within the context of overall rf system design for three future colliders at energies of 1.0--1.5 TeV, 5 TeV and 25 TeV. In order keep the average AC input power and the length of the accelerator within reasonable limits, a collider in the 1.0--1.5 TeV energy range will probably be built at an x-band rf frequency, and will require a peak power on the order of 150--200 MW per meter of accelerating structure. A 5 TeV collider at 34 GHz with a reasonable length (35 km) and AC input power (225 MW) would require about 550 MW per meter of structure. Two-beam accelerators can achieve peak powers of this order by applying dc pulse compression techniques (induction linac modules) to produce the drive beam. Klystron-driven colliders achieve high peak power by a combination of dc pulse compression (modulators) and rf pulse compression, with about the same overall rf system efficiency (30--40%) as a two-beam collider. A high gain (6.8) three-stage binary pulse compression system with high efficiency (80%) is described, which (compared to a SLED-11 system) can be used to reduce the klystron peak power by about a factor of two, or alternately, to cut the number of klystrons in half for a 1.0--1.5 TeV x-band collider. For a 5 TeV klystron-driven collider, a high gain, high efficiency rf pulse compression system is essential.

  17. Final focus designs for crab waist colliders

    NASA Astrophysics Data System (ADS)

    Bogomyagkov, A.; Levichev, E.; Piminov, P.

    2016-12-01

    The crab waist collision scheme promises significant luminosity gain. The successful upgrade of the DA Φ NE collider proved the principle of crab waist collision and increased luminosity 3 times. Therefore, several new projects try to implement the scheme. The paper reviews interaction region designs with the crab waist collision scheme for already existent collider DA Φ NE and SuperKEKB, presently undergoing commissioning, for the projects of SuperB in Italy, CTau in Novosibirsk and FCC-ee at CERN.

  18. Photon Linear Collider Gamma-Gamma Summary

    SciTech Connect

    Gronberg, J

    2012-02-27

    High energy photon - photon collisions can be achieved by adding high average power short-pulse lasers to the Linear Collider, enabling an expanded physics program for the facility. The technology required to realize a photon linear collider continues to mature. Compton back-scattering technology is being developed around the world for low energy light source applications and high average power lasers are being developed for Inertial Confinement Fusion.

  19. Nuclear collisions at the Future Circular Collider

    NASA Astrophysics Data System (ADS)

    Armesto, N.; Dainese, A.; d'Enterria, D.; Masciocchi, S.; Roland, C.; Salgado, C. A.; van Leeuwen, M.; Wiedemann, U. A.

    2016-12-01

    The Future Circular Collider is a new proposed collider at CERN with centre-of-mass energies around 100 TeV in the pp mode. Ongoing studies aim at assessing its physics potential and technical feasibility. Here we focus on updates in physics opportunities accessible in pA and AA collisions not covered in previous Quark Matter contributions, including Quark-Gluon Plasma and gluon saturation studies, novel hard probes of QCD matter, and photon-induced collisions.

  20. The Relativistic Heavy Ion Collider, Rhic

    NASA Astrophysics Data System (ADS)

    Foelsche, H.; Hahn, H.; Harrison, M.; Ozaki, S.; Rhoades-Brown, M. J.

    1993-03-01

    The scope of the first relativistic energy heavy ion collider, RHIC, is discussed. Particular attention is paid to those novel features of a heavy ion collider that are distinct from the more usual proton machines. These features are derived from the experimental requirements of operation with a variety of ion species over a wide energy range as well as the increased demands on available ion sources and injector complexes. Storage of heavy ion beams for many hours is severely impacted by intrabeam scattering.

  1. When worlds collide - Mac to MS-DOS. [Data transfer to and from Apple Macintosh computers and MS-DOS based personal computers

    SciTech Connect

    Busbey, A.B.

    1989-04-01

    A number of methods and products, both hardware and software, to allow data exchange between Apple Macintosh computers and MS-DOS based systems. These included serial null modem connections, MS-DOS hardware and/or software emulation, MS-DOS disk-reading hardware and networking.

  2. Physics at the Fermilab Tevatron Proton-Antiproton Collider

    SciTech Connect

    Geer, S.

    1994-08-01

    These lectures discuss a selection of QCD and Electroweak results from the CDF and D0 experiments at the Fermilab Tevatron Proton-Antiproton Collider. Results are presently based on data samples of about 20 pb{sup {minus}1} at a center-of-mass energy of 1.8 TeV. Results discussed include jet production, direct photon production, W mass and width measurements, the triboson coupling, and most exciting of all, evidence for top quark production.

  3. INTRA-BEAM SCATTERING SCALING FOR VERY LARGE HADRON COLLIDERS.

    SciTech Connect

    WEI,J.; PARZEN,G.

    2001-06-18

    For Very Large Hadron Colliders (VLHC), flat hadron beams [2] with their vertical emittance much smaller than their horizontal emittance are proposed to maximize the design luminosity. Emittance growth caused by intra-beam scattering (IBS) is a concern on the realization of such flat-beam conditions. Based on existing IBS formalism on beams of Gaussian distribution, we analytically derive [6] the IBS growth rate and determine the IBS limit on the aspect ratio for a flat beam.

  4. Discriminating Supersymmetry and Black Holes at the Large Hadron Collider

    NASA Astrophysics Data System (ADS)

    Roy, Arunava; Cavaglia, Marco

    2008-04-01

    We assess the distinguishability between supersymmetry and black hole events at the Large Hadron Collider. Black hole events are simulated with the CATFISH black hole generator. Supersymmetry simulations use a combination of PYTHIA and ISAJET. Our study, based on event shape variables, visible and missing momenta, and analysis of dilepton events, shows that supersymmetry and black hole events at the LHC can be easily discriminated.

  5. Critical review and hydrologic application of threshold detection methods for the generalized Pareto (GP) distribution

    NASA Astrophysics Data System (ADS)

    Mamalakis, Antonios; Langousis, Andreas; Deidda, Roberto

    2016-04-01

    Estimation of extreme rainfall from data constitutes one of the most important issues in statistical hydrology, as it is associated with the design of hydraulic structures and flood water management. To that extent, based on asymptotic arguments from Extreme Excess (EE) theory, several studies have focused on developing new, or improving existing methods to fit a generalized Pareto (GP) distribution model to rainfall excesses above a properly selected threshold u. The latter is generally determined using various approaches, such as non-parametric methods that are intended to locate the changing point between extreme and non-extreme regions of the data, graphical methods where one studies the dependence of GP distribution parameters (or related metrics) on the threshold level u, and Goodness of Fit (GoF) metrics that, for a certain level of significance, locate the lowest threshold u that a GP distribution model is applicable. In this work, we review representative methods for GP threshold detection, discuss fundamental differences in their theoretical bases, and apply them to 1714 daily rainfall records from the NOAA-NCDC open-access database, with more than 110 years of data. We find that non-parametric methods that are intended to locate the changing point between extreme and non-extreme regions of the data are generally not reliable, while methods that are based on asymptotic properties of the upper distribution tail lead to unrealistically high threshold and shape parameter estimates. The latter is justified by theoretical arguments, and it is especially the case in rainfall applications, where the shape parameter of the GP distribution is low; i.e. on the order of 0.1 ÷ 0.2. Better performance is demonstrated by graphical methods and GoF metrics that rely on pre-asymptotic properties of the GP distribution. For daily rainfall, we find that GP threshold estimates range between 2÷12 mm/d with a mean value of 6.5 mm/d, while the existence of quantization in the

  6. Cellular uptake of gold nanoparticles bearing HIV gp120 oligomannosides.

    PubMed

    Arnáiz, Blanca; Martínez-Ávila, Olga; Falcon-Perez, Juan M; Penadés, Soledad

    2012-04-18

    Dendritic cells are the most potent of the professional antigen-presenting cells which display a pivotal role in the generation and regulation of adaptive immune responses against HIV-1. The migratory nature of dendritic cells is subverted by HIV-1 to gain access to lymph nodes where viral replication occurs. Dendritic cells express several calcium-dependent C-type lectin receptors including dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), which constitute a major receptor for HIV-1. DC-SIGN recognizes N-linked high-mannose glycan clusters on HIV gp120 through multivalent and Ca(2+)-dependent protein-carbohydrate interactions. Therefore, mimicking the cluster presentation of oligomannosides from the virus surface is a strategic approach for carbohydrate-based microbicides. We have shown that gold nanoparticles (mannoGNPs) displaying multiple copies of structural motifs (di-, tri-, tetra-, penta-, or heptaoligomanosides) of the N-linked high-mannose glycan of viral gp120 are efficient inhibitors of DC-SIGN-mediated trans-infection of human T cells. We have now prepared the corresponding fluorescent-labeled glyconanoparticles (FITC-mannoGNPs) and studied their uptake by DC-SIGN expressing Burkitt lymphoma cells (Raji DC-SIGN cell line) and monocyte-derived immature dendritic cells (iDCs) by flow cytometry and confocal laser scanning microscopy. We demonstrate that the 1.8 nm oligomannoside coated nanoparticles are endocytosed following both DC-SIGN-dependent and -independent pathways and part of them colocalize with DC-SIGN in early endosomes. The blocking and sequestration of DC-SIGN receptors by mannoGNPs could explain their ability to inhibit HIV-1 trans-infection of human T cells in vitro.

  7. Feasibility of Production of Moly-99 via 1-neutron Exchange Reaction 98 Mo +100 Mo -->299Mo in Strong-Focusing Auto Collider (``EXYDER'') of natural Molybdenum nuclei based on T and He-3 production data from d +d weak focusing Auto-Collider MIGMA IV

    NASA Astrophysics Data System (ADS)

    Hester, Tim; Maglich, Bogdan; Calsec Collaboration

    2015-10-01

    Copious T and 3He production from D(d, p) T and D(d, n) 3He reactions in 725 KeV colliding beams was observed in weak-focusing Self-Collider1-4 radius 15 cm, in B = 3.12 T, stabilized5 non-linearly by electron cloud oscillations with confinement time ~ 23 s. BARC's simulations7 predict that by switching to Strong Focusing Self Collider proposed by Blewett6, 10 deuterons 0.75 MeV each, will generate 1 3He + 1T +1p + 1n at a total input energy cost of 10.72 MeV. Economic value of T and 3He is 65 and 120 MeV/atom respectively. While energy balance is negative, we project economic gain 205 MeV/10.72 MeV ~ 20 i.e. 3He production/sale will fund cost of T. Assuming the luminosity achieved in MIGMA IV, we replace D beam injection with a high energy beam of 14 times ionized natural Mo ions and look for the 1-neutron reactions of the type 98Mo+100Mo -->299Mo, where 99Mo14+ will be EM channeled into a mass spectrometer and collected at one loci/ radius, while all other masses/radii rejected. Physics and engineering parameters required to produce at least 1 g of 99Mo per day, at an electricity cost of 100K, will be presented. 2- and 3-neutron exchange reactions will be considered, too.

  8. Determining the Structure of an Unliganded and Fully Glycosylated SIV gp120 Envelope Glycoprotein

    SciTech Connect

    Chen, Bing; Vogan, Erik M.; Gong, Haiyun; Skehel, John J.; Wiley, Don C.; Harrison, Stephen C.

    2010-07-13

    HIV/SIV envelope glycoproteins mediate the first steps in viral infection. They are trimers of a membrane-anchored polypeptide chain, cleaved into two fragments known as gp120 and gp41. The structure of HIV gp120 bound with receptor (CD4) has been known for some time. We have now determined the structure of a fully glycosylated SIV gp120 envelope glycoprotein in an unliganded conformation by X-ray crystallography at 4.0 {angstrom} resolution. We describe here our experimental and computational approaches, which may be relevant to other resolution-limited crystallographic problems. Key issues were attention to details of beam geometry mandated by small, weakly diffracting crystals, and choice of strategies for phase improvement, starting with two isomorphous derivatives and including multicrystal averaging. We validated the structure by analyzing composite omit maps, averaged among three distinct crystal lattices, and by calculating model-based, SeMet anomalous difference maps. There are at least four ordered sugars on many of the thirteen oligosaccharides.

  9. Vibration Stabilization of a Mechanical Model of a X-Band Linear Collider Final Focus Magnet

    SciTech Connect

    Frisch, Josef; Chang, Allison; Decker, Valentin; Doyle, Eric; Eriksson, Leif; Hendrickson, Linda; Himel, Thomas; Markiewicz, Thomas; Partridge, Richard; Seryi, Andrei; /SLAC

    2006-09-28

    The small beam sizes at the interaction point of a X-band linear collider require mechanical stabilization of the final focus magnets at the nanometer level. While passive systems provide adequate performance at many potential sites, active mechanical stabilization is useful if the natural or cultural ground vibration is higher than expected. A mechanical model of a room temperature linear collider final focus magnet has been constructed and actively stabilized with an accelerometer based system.

  10. A Laser-Driven Linear Collider: Sample Machine Parameters and Configuration

    SciTech Connect

    Colby, E.R.; England, R.J.; Noble, R.J.; /SLAC

    2011-05-20

    We present a design concept for an e{sup +}e{sup -} linear collider based on laser-driven dielectric accelerator structures, and discuss technical issues that must be addressed to realize such a concept. With a pulse structure that is quasi-CW, dielectric laser accelerators potentially offer reduced beamstrahlung and pair production, reduced event pileup, and much cleaner environment for high energy physics and. For multi-TeV colliders, these advantages become significant.

  11. [Active participation in research and teaching during post-graduate GP training: perspectives of future general practitioners].

    PubMed

    Haumann, Hannah; Flum, Elisabeth; Joos, Stefanie

    2016-12-01

    Academic institutions of general practice at German medical faculties have grown during the past years. This leads to an increase in the need of qualified young researchers and teachers in general practice (GP). Little is known about the interest in research and teaching skills and their training among general practice trainees and young GPs. This cross-sectional survey among GP trainees and young GPs examined 1. if there is an interest in the training in research and teaching skills during post-graduate GP training, 2. which fostering and hindering factors have an effect on this interest and 3. which roles are attributed to academic institutions of general practice. A web-based cross-sectional study was performed among members of "Verbundweiterbildung(plus"), a network of GP trainees, as well as "Junge Allgemeinmedizin Deutschland", the German network of young GPs. Descriptive analysis was conducted. 148 GP trainees and young GPs participated in the study, 76% (n=109) of them were GP trainees. There was interest in a position in research and teaching during post-graduate GP training among 55% (n=78). Factors associated with the interest in a position in research and teaching during post-graduate GP training were (MV 5-point Likert scale ± SD): compatibility of clinical work and research/teaching and of family and career (4.4±0.8; 4.7±0.6 respectively). The roles of academic institutions of general practice were attributed to training of medical students (4.6±0.6), post-graduate GP training (4.5±0.7) and research (4.5±0.7). GP trainees assessed the importance of training in research and teaching skills during post-graduate GP training and of the compatibility of family and career differently from young GPs (3.7±1.0 vs. 4.1±0.8 p=0.027; 4.8±0.5 vs. 4.3±0.9, p=0.016). Those interested in a position in research and teaching during post-graduate GP training showed a stronger interest in specific training in research skills (3.7±1.1 vs. 2.8±1.1, p<0.001), a

  12. Generation of ultrashort electron bunches by colliding laser pulses.

    PubMed

    Schroeder, C B; Lee, P B; Wurtele, J S; Esarey, E; Leemans, W P

    1999-05-01

    A proposed laser-plasma-based relativistic electron source [E. Esarey et al., Phys. Rev. Lett. 79, 2682 (1997)] using laser-triggered injection of electrons is investigated. The source generates ultrashort electron bunches by dephasing and trapping background plasma electrons undergoing fluid oscillations in an excited plasma wake. The plasma electrons are dephased by colliding two counterpropagating laser pulses which generate a slow phase velocity beat wave. Laser pulse intensity thresholds for trapping and the optimal wake phase for injection are calculated. Numerical simulations of test particles, with prescribed plasma and laser fields, are used to verify analytic predictions and to study the longitudinal and transverse dynamics of the trapped plasma electrons. Simulations indicate that the colliding laser pulse injection scheme has the capability to produce relativistic femtosecond electron bunches with fractional energy spread of order a few percent and normalized transverse emittance less than 1 mm mrad using 1 TW injection laser pulses.

  13. Non-collider searches for stable massive particles

    NASA Astrophysics Data System (ADS)

    Burdin, S.; Fairbairn, M.; Mermod, P.; Milstead, D.; Pinfold, J.; Sloan, T.; Taylor, W.

    2015-06-01

    The theoretical motivation for exotic stable massive particles (SMPs) and the results of SMP searches at non-collider facilities are reviewed. SMPs are defined such that they would be sufficiently long-lived so as to still exist in the cosmos either as Big Bang relics or secondary collision products, and sufficiently massive such that they are typically beyond the reach of any conceivable accelerator-based experiment. The discovery of SMPs would address a number of important questions in modern physics, such as the origin and composition of dark matter and the unification of the fundamental forces. This review outlines the scenarios predicting SMPs and the techniques used at non-collider experiments to look for SMPs in cosmic rays and bound in matter. The limits so far obtained on the fluxes and matter densities of SMPs which possess various detection-relevant properties such as electric and magnetic charge are given.

  14. Governance of the International Linear Collider Project

    SciTech Connect

    Foster, B.; Barish, B.; Delahaye, J.P.; Dosselli, U.; Elsen, E.; Harrison, M.; Mnich, J.; Paterson, J.M.; Richard, F.; Stapnes, S.; Suzuki, A.; Wormser, G.; Yamada, S.; /KEK, Tsukuba

    2012-05-31

    Governance models for the International Linear Collider Project are examined in the light of experience from similar international projects around the world. Recommendations for one path which could be followed to realize the ILC successfully are outlined. The International Linear Collider (ILC) is a unique endeavour in particle physics; fully international from the outset, it has no 'host laboratory' to provide infrastructure and support. The realization of this project therefore presents unique challenges, in scientific, technical and political arenas. This document outlines the main questions that need to be answered if the ILC is to become a reality. It describes the methodology used to harness the wisdom displayed and lessons learned from current and previous large international projects. From this basis, it suggests both general principles and outlines a specific model to realize the ILC. It recognizes that there is no unique model for such a laboratory and that there are often several solutions to a particular problem. Nevertheless it proposes concrete solutions that the authors believe are currently the best choices in order to stimulate discussion and catalyze proposals as to how to bring the ILC project to fruition. The ILC Laboratory would be set up by international treaty and be governed by a strong Council to whom a Director General and an associated Directorate would report. Council would empower the Director General to give strong management to the project. It would take its decisions in a timely manner, giving appropriate weight to the financial contributions of the member states. The ILC Laboratory would be set up for a fixed term, capable of extension by agreement of all the partners. The construction of the machine would be based on a Work Breakdown Structure and value engineering and would have a common cash fund sufficiently large to allow the management flexibility to optimize the project's construction. Appropriate contingency, clearly

  15. Status of the Future Circular Collider Study

    NASA Astrophysics Data System (ADS)

    Benedikt, Michael

    2016-03-01

    Following the 2013 update of the European Strategy for Particle Physics, the international Future Circular Collider (FCC) Study has been launched by CERN as host institute, to design an energy frontier hadron collider (FCC-hh) in a new 80-100 km tunnel with a centre-of-mass energy of about 100 TeV, an order of magnitude beyond the LHC's, as a long-term goal. The FCC study also includes the design of a 90-350 GeV high-luminosity lepton collider (FCC-ee) installed in the same tunnel, serving as Higgs, top and Z factory, as a potential intermediate step, as well as an electron-proton collider option (FCC-he). The physics cases for such machines will be assessed and concepts for experiments will be developed in time for the next update of the European Strategy for Particle Physics by the end of 2018. The presentation will summarize the status of machine designs and parameters and discuss the essential technical components to be developed in the frame of the FCC study. Key elements are superconducting accelerator-dipole magnets with a field of 16 T for the hadron collider and high-power, high-efficiency RF systems for the lepton collider. In addition the unprecedented beam power presents special challenges for the hadron collider for all aspects of beam handling and machine protection. First conclusions of geological investigations and implementation studies will be presented. The status of the FCC collaboration and the further planning for the study will be outlined.

  16. [Virtual screening of small molecular HIV-1 entry inhibitor NC-2 targeting gp120 and its action mechanism].

    PubMed

    Duan, Heng; Wang, Yuqin; Song, Deshou; Chen, Zhipeng; Qiu, Jiayin; Lu, Lu; Jiang, Shibo; Liu, Shuwen; Tan, Suiyi

    2013-06-01

    To screen the HIV-1 entry inhibitors targeting HIV-1 gp120 from the IBS natural product database by virtual screening based on the binding mode of the neutralizing antibody VRC01 with HIV-1 gp120 and investigate the anti-viral activities of the inhibitors and their action mechanisms. The binding interaction of the candidate molecules binding gp120 and changes of the binding free energy were analyzed by MM-PBSA calculation. The anti-HIV-1 activities of the tested compounds were detected by HIV-1 pseudotyped virus, laboratory-adapted HIV-1 and a cell-cell fusion assay. The cytotoxicity of the studied molecules was examined by XTT colorimetric assay. The mechanisms of the anti-viral activities of the candidate molecules were analyzed using enzyme-linked immunosorbent assay. A total of 19 molecules with distinct reduction of the binding free energy after binding with gp120 were screened from 40000 molecules. Among them, NC-2 showed anti-HIV-1 activities against HIV-1 pseudotyped virus and laboratory-adapted HIV-1, and was capable of blocking HIV-1 envelope-mediated cell-cell fusion. The IC50 of NC-2 for inhibiting HIV-1IIIB and pseudotyped HIV-1JRFL infection were 1.95∓0.44 µmol/L and 10.58∓0.13 µmol/L, respectively. The results of ELISA suggested that NC-2 could inhibit the binding of HIV-1 gp120 to CD4 without blocking the formation of gp41 six-helix bundle in vitro. This computer-based virtual screening method can be used to screen HIV-1 entry inhibitors targeting gp120. Using this virtual screening approach combined with anti-viral activity screening, we obtained a potent HIV-1 entry inhibitor NC-2 with novel structure.

  17. PROSPECTS FOR COLLIDERS AND COLLIDER PHYSICS TO THE 1 PEV ENERGY SCALE

    SciTech Connect

    KING,B.J.

    2000-05-05

    A review is given of the prospects for future colliders and collider physics at the energy frontier. A proof-of-plausibility scenario is presented for maximizing the authors progress in elementary particle physics by extending the energy reach of hadron and lepton colliders as quickly and economically as might be technically and financially feasible. The scenario comprises 5 colliders beyond the LHC--one each of e{sup +}e{sup {minus}} and hadron colliders and three {mu}{sup +}{mu}{sup {minus}} colliders--and is able to hold to the historical rate of progress in the log-energy reach of hadron and lepton colliders, reaching the 1 PeV constituent mass scale by the early 2040's. The technical and fiscal requirements for the feasibility of the scenario are assessed and relevant long-term R and D projects are identified. Considerations of both cost and logistics seem to strongly favor housing most or all of the colliders in the scenario in a new world high energy physics laboratory.

  18. Access to difficult airway equipment and training for rural GP-anaesthetists in Australia: results of a 2012 survey.

    PubMed

    Leeuwenburg, Tim J

    2012-01-01

    In rural Australia, general practitioners (GPs) form the frontline for provision of medical services. Besides responsibilities for primary care via private practice, rural doctors often provide emergency and inpatient services for rural hospitals. The aim of this study was to determine access to difficult airway equipment and training among the GP-anaesthetist cadre in rural Australia. an online survey regarding availability of difficult airway equipment, access to ongoing training and inviting comments on rural anaesthesia in general. a questionnaire was distributed to rural doctors in January 2012 via membership databases of the Rural Doctors Association of Australia and state-based Rural Doctor Workforce Agencies. 293 participants identified as a GP-anaesthetist working in rural Australia (65% response rate). Of these 83% were male, 17% female with the percentage of respondents from each state concordant with the distributions indicated by the 2010 Rural Health Workforce National Minimum Dataset. closed-ended questions were quantified and open-ended questions analysed to determine issues relevant to GP-anaesthetists. Only 53% of GP-anaesthetists reported access to a difficult airway trolley or box in their facility. Lack of availability of certain airway equipment was reported among GP-anaesthetists, with very few having access to advanced intubation aids such as videolaryngoscopes or fibreoptic devices (flexible fibrescopes and/or malleable fibreoptic stylets). Open-ended questions suggested that GP-anaesthetists desired such aids to manage difficult airways. Only 79% had access to surgical airway or paediatric airway equipment. Of the respondents, 58% reported involvement in prehospital medicine but only 12% had received training in this challenging environment. A formal arrangement for prehospital responses existed for only 7% of respondents. Despite the existence of well-publicised algorithms for difficult airway management and the need for specific

  19. Role of a Putative gp41 Dimerization Domain in Human Immunodeficiency Virus Type 1 Membrane Fusion▿

    PubMed Central

    Liu, Jie; Deng, Yiqun; Li, Qunnu; Dey, Antu K.; Moore, John P.; Lu, Min

    2010-01-01

    The entry of human immunodeficiency virus type 1 (HIV-1) into a target cell entails a series of conformational changes in the gp41 transmembrane glycoprotein that mediates the fusion of the viral and target cell membranes. A trimer-of-hairpins structure formed by the association of two heptad repeat (HR) regions of the gp41 ectodomain has been implicated in a late step of the fusion pathway. Earlier native and intermediate states of the protein are postulated to mediate the antiviral activity of the fusion inhibitor enfuvirtide and of broadly neutralizing monoclonal antibodies (NAbs), but the details of these structures remain unknown. Here, we report the identification and crystal structure of a dimerization domain in the C-terminal ectodomain of gp41 (residues 630 to 683, or C54). Two C54 monomers associate to form an asymmetric, antiparallel coiled coil with two distinct C-terminal α-helical overhangs. This dimer structure is conferred largely by interactions within a central core that corresponds to the sequence of enfuvirtide. The mutagenic alteration of the dimer interface severely impairs the infectivity of Env-pseudotyped viruses. Moreover, the C54 structure binds tightly to both the 2F5 and 4E10 NAbs and likely represents a potential intermediate conformation of gp41. These results should enhance our understanding of the molecular basis of the gp41 fusogenic structural transitions and thereby guide rational, structure-based efforts to design new fusion inhibitors and vaccine candidates intended to induce broadly neutralizing antibodies. PMID:19846514

  20. Striking HIV-1 Entry by Targeting HIV-1 gp41. But, Where Should We Target?

    PubMed Central

    Teixeira, Cátia; Barbault, Florent; Couesnon, Thierry; Gomes, José R. B.; Gomes, Paula; Maurel, François

    2016-01-01

    HIV-1 gp41 facilitates the viral fusion through a conformational switch involving the association of three C-terminal helices along the conserved hydrophobic grooves of three N-terminal helices coiled-coil. The control of these structural rearrangements is thought to be central to HIV-1 entry and, therefore, different strategies of intervention are being developed. Herewith, we describe a procedure to simulate the folding of an HIV-1 gp41 simplified model. This procedure is based on the construction of plausible conformational pathways, which describe protein transition between non-fusogenic and fusogenic conformations. The calculation of the paths started with 100 molecular dynamics simulations of the non-fusogenic conformation, which were found to converge to different intermediate states. Those presenting defined criteria were selected for separate targeted molecular dynamics simulations, subjected to a force constant imposing a movement towards the gp41 fusogenic conformation. Despite significant diversity, a preferred sequence of events emerged when the simulations were analyzed in terms of the formation, breakage and evolution of the contacts. We pointed out 29 residues as the most relevant for the movement of gp41; also, 2696 possible interactions were reduced to only 48 major interactions, which reveals the efficiency of the method. The analysis of the evolution of the main interactions lead to the detection of four main behaviors for those contacts: stable, increasing, decreasing and repulsive interactions. Altogether, these results suggest a specific small cavity of the HIV-1 gp41 hydrophobic groove as the preferred target to small molecules. PMID:26785380

  1. Matched comparison of GP and consultant rating of electronic discharge summaries.

    PubMed

    Stainkey, Lesley; Pain, Tilley; McNichol, Margaret; Hack, John; Roberts, Lynden

    2010-01-01

    Queensland Health is implementing a state-wide system to electronically generate and distribute discharge summaries. Previously, general practitioners (GPs) have indicated that the quality of the discharge summary does not support clinical handover. While the electronic system will address some issues (e.g. legibility and timeliness), the quality of the discharge summary content is predominantly independent of method of generation. As discharge summaries are usually generated by interns, we proposed that improvement in the quality of the summary may be achieved through education. This project aimed to compare the perceptions of hospital-based consultant educators and recipient GPs regarding discharge summary content and quality. The discharge summary and audit tool were sent to the recipient GP (n=134) and a hospital consultant (n=14) for satisfaction rating, using a 5- point Likert scale for questions relating to diagnosis, the listing of clinical management, medication, pathology, investigations, and recommendations to GP. Sampling was performed by selecting up to 10 discharge summaries completed by each first-year intern (n=36) in 2009, during the second, third and fourth rotations at the Townsville Hospital until a total of 403 was reached. Matched responses were compared using the Kappa statistic. The response rate was 93% (n=375) and 63% (n=254) for consultants and GPs respectively. Results from this study demonstrated that GPs were more satisfied with discharge summaries than were consultants. An anomaly occurred in three questions where, despite the majority of GPs rating satisfied or very satisfied, a small but proportionally greater number of GPs were very dissatisfied when compared with consultants. Poor or fair agreement between GPs and consultants was demonstrated in medications, pathology results, investigations and recommendations to GP, with GPs rating higher satisfaction in all questions. Lower consultant satisfaction ratings compared with GP

  2. Equity and equality in the use of GP services for elderly people: the Spanish case.

    PubMed

    Crespo-Cebada, Eva; Urbanos-Garrido, Rosa M

    2012-02-01

    To present new evidence both on the horizontal inequity in the delivery of primary health care and on the factors driving inequalities in the use of GP services for Spanish population aged 50 years and over. Cross-sectional study based on the Spanish sample of the Survey of Health, Aging and Retirement in Europe (SHARE) for 2006-07. We use the index proposed by Wagstaff and van Doorslaer (HI(WV)) to compute health care inequity. The concentration index measuring income related inequality in health care use is decomposed into the contribution of each determinant. Our results show the presence of pro-poor inequality in both the access and the frequency of use for GP services, which is mainly explained by unequal distribution of need factors. The contribution of non-need factors to income related inequality is quite higher for the conditional number of GP visits (48.13%) than for the probability of positive use (17.55%). We have also found significant pro-poor inequity in the probability of access to a GP and in the conditional number of visits for elderly people. The relevance of social determinants of health is confirmed, and hence the need for wide-scoped public policies to reduce health inequalities. At equal levels of need, rich and poor elderly people are not treated equally. As much as appropriateness of care provided is unknown, we cannot conclude that inequity in GP services really favours the lower income individuals in terms of health gains. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Striking HIV-1 Entry by Targeting HIV-1 gp41. But, Where Should We Target?

    PubMed

    Teixeira, Cátia; Barbault, Florent; Couesnon, Thierry; Gomes, José R B; Gomes, Paula; Maurel, François

    2016-01-01

    HIV-1 gp41 facilitates the viral fusion through a conformational switch involving the association of three C-terminal helices along the conserved hydrophobic grooves of three N-terminal helices coiled-coil. The control of these structural rearrangements is thought to be central to HIV-1 entry and, therefore, different strategies of intervention are being developed. Herewith, we describe a procedure to simulate the folding of an HIV-1 gp41 simplified model. This procedure is based on the construction of plausible conformational pathways, which describe protein transition between non-fusogenic and fusogenic conformations. The calculation of the paths started with 100 molecular dynamics simulations of the non-fusogenic conformation, which were found to converge to different intermediate states. Those presenting defined criteria were selected for separate targeted molecular dynamics simulations, subjected to a force constant imposing a movement towards the gp41 fusogenic conformation. Despite significant diversity, a preferred sequence of events emerged when the simulations were analyzed in terms of the formation, breakage and evolution of the contacts. We pointed out 29 residues as the most relevant for the movement of gp41; also, 2696 possible interactions were reduced to only 48 major interactions, which reveals the efficiency of the method. The analysis of the evolution of the main interactions lead to the detection of four main behaviors for those contacts: stable, increasing, decreasing and repulsive interactions. Altogether, these results suggest a specific small cavity of the HIV-1 gp41 hydrophobic groove as the preferred target to small molecules.

  4. Association of IL6ST (gp130) Polymorphism with Functional Outcome Following Spontaneous Intracerebral Hemorrhage.

    PubMed

    El Husseini, Nada; Hoffman, Benjamin M; Bennett, Ellen R; Li, Yen-Wei; Williamson Taylor, Rachel A; Hailey, Claire E; Richardson, Kara; Li, Yi-Ju; Laskowitz, Daniel T; James, Michael L

    2017-09-27

    Genes associated with the inflammatory response and cytostructural integrity may influence recovery following a brain injury. To examine this in the setting of spontaneous intracerebral hemorrhage (ICH), selected single nucleotide polymorphisms (SNPs) were assessed for associations with patient outcome. A cohort of 54 patients with supratentorial ICH were enrolled. Based on known involvement with neuroinflammation and cytostructural integrity, 10 preselected SNPs from 6 candidate genes were tested for associations with 6-month functional outcome (modified Rankin Scale [mRS] ≥ 3), mortality, and in-hospital deterioration (Glasgow Coma Scale decrease by >2 within 7 days of admission) following ICH. Fisher's exact test and logistic regression with adjustment for race and ICH score were performed. SNP rs10940495 (gp130 G/A) within the gp130 gene was the only SNP significantly associated with lower odds of an unfavorable 6-month functional outcome (odds ratio = .16 for mRS ≥ 3; 95% confidence interval, .03-.87, P = .03). Compared with major allele (A) homozygotes, minor allele (G) carriers in the IL6 signal transducer gene (gp130) locus were 84% less likely to have a poor outcome (mRS ≥ 3) at 6 months following spontaneous ICH. The SNP rs10940495 (gp130 G/A) and SNP rs3219119 (PARP-1 A/T) were associated with 6-month mortality (P = .02 and .04, respectively) only on univariate analysis. None of the SNPs examined were associated with in-hospital deterioration. In this exploratory study, SNP rs10940495 in the gp130 locus was associated with functional outcome at 6 months following spontaneous ICH. These findings, which should be validated through a larger study, suggest that inflammation plays an important role in mediating outcomes after ICH. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. GP surgeons: what are they? An audit of GP surgeons in South Australia.

    PubMed

    Abbot, Ben; Laurence, Caroline O; Elliott, Taryn

    2014-01-01

    In many parts of Australia where there is no access to local specialist services, procedural services are provided by local GPs. Within the range of procedural skills offered, a small group of GPs is able to provide surgery. Unlike other procedural areas, there remains no defined training or assessment pathway for GP surgeons. Support from specialist colleagues is variable and continuing education arbitrary. The result is a somewhat ill-defined group that is poorly understood by credentialing bodies, government, medical defence organisations and training colleges. This study aims to describe the scope of practice, initial training and ongoing support and education for GP surgeons currently practising in South Australia. Seventeen semistructured interviews were undertaken with self-identified GP surgeons (74% response rate). Areas explored included demographics, scope of practice, initial training and ongoing support and education. Content and thematic analysis was used to identify common responses and themes. The amount of initial training varied among participants, with a mean duration of training of 20 months. Initial assessment of competency for the majority of participants was assessment by a supervisor (10/17). The most common procedures undertaken were caesarean sections (94% of participants) and grafts and flaps (94%). The most common continuing professional development was clinical attachments (27%) and assisting visiting specialists or colleagues (17%). This study demonstrates a wide variation in training, scope of practice and continuing education for GPs performing surgery, highlighting the effects of a self-regulated system. There is a trend towards an increased level of training; however, engagement in continuing education remains low. Further work is needed to define this group, to enable successful planning of future training and education to support this group in rural areas.

  6. Design studies of high-luminoisty ring-ring- eletron-ion collider at CEBAF.

    SciTech Connect

    Bogacz, A.; Brindza, P.; Bruell, A.; Cardman, L.; Delayen, J.; Ostroumov, P.; Derbenev, Y.; Ent, R.; Evtushenko, P.; Grames, J.; Hutton, A.; Krafft, G.; Li, R.; Merminga, L.; Musson, J.; Poelker, M.; Thomas, A.; Wojteshowski, B.; Yunn, B.; Zhang, Y.; Fischer, W.; Montag, C.; Dudnikov, V.; Belov, A.; Derenchuk, V.; Physics; Jefferson Lab.; BNL; BTG; INR; IUCF

    2007-08-01

    Experimental studies of fundamental structure of nucleons require an electron-ion collider of a center-of-mass energy up to 90 GeV at luminosity up to 10{sup 35} cm{sup -2}s{sup -1} with both beams polarized. A CEBAF-based collider of 9 GeV electrons/positrons and 225 GeV ions is envisioned to meet this science need and as a next step for CEBAF after the planned 12 GeV energy upgrade of the fixed target program. A ring-ring scheme of this collider developed recently takes advantage of the existing polarized electron CW beam from the CEBAF and a green-field design of an ion complex with electron cooling. We present a conceptual design and report design studies of this high-luminosity collider.

  7. Durable cytotoxic immune responses against gp120 elicited by recombinant SV40 vectors encoding HIV-1 gp120 +/- IL-15.

    PubMed

    McKee, Hayley J; T'sao, Patricia Y; Vera, Maria; Fortes, Puri; Strayer, David S

    2004-08-23

    BACKGROUND: A vaccine that elicits durable, powerful anti-HIV immunity remains an elusive goal. In these studies we tested whether multiple treatments with viral vector-delivered HIV envelope antigen (gp120), with and without IL-15, could help to approach that goal. For this purpose, we used recombinant Tag-deleted SV40-derived vectors (rSV40s), since they do not elicit neutralizing antibody responses, and so can be given multiply without loss of transduction efficiency. METHODS: SV(gp120) carried the coding sequences for HIV-1NL4-3 Env, and SV(mIL-15) carried the cDNA for mouse IL-15. Singly, and in combination, these two vectors were given monthly to BALB/cJ mice. Cytotoxic immunity and cytotoxic memory were tested in direct cytotoxicity assays using unselected effector cells. Antibody vs. gp120 was measured in a binding assay. In both cases, targets were P815 cells that were stably transfected with gp120. RESULTS: Multiple injections of SV(gp120) elicited powerful anti-gp120 cytolytic activity (>70% specific lysis) by unselected spleen cells. Cells from multiply-immunized mice that were rested 1 year after their last injections still showed >60% gp120-specific lysis. Anti-gp120 antibody was first detected after 2 monthly injections of SV(gp120) and remained elevated thereafter. Adding SV(mIL-15) to the immunization regimen dramatically accelerated the development of memory cytolytic responses, with >/= 50% specific lysis seen 1 month after two treatments. IL-15 did not alter the development of antibody responses. CONCLUSIONS: Thus, rSV40s encoding antigens and immunostimulatory cytokines may be useful tools for priming and/or boosting immune responses against HIV.

  8. What is a good general practitioner (GP)? The development and evaluation of a multi-source feedback instrument for GP appraisal.

    PubMed

    Shepherd, Annabel; Lough, Murray

    2010-05-01

    Although multi-source feedback (MSF) has been used in primary healthcare, the development of an MSF instrument specific to this setting in the UK has not been previously described. The aims of this study were to develop and evaluate an MSF instrument for GPs in Scotland taking part in appraisal. The members of ten primary healthcare teams in the west of Scotland were asked to provide comments in answer to the question, 'What is a good GP?'. The data were reduced and coded by two researchers and questions were devised. Following content validity testing the MSF process was evaluated with volunteers using face-to-face interviews and a postal survey. Thirty-seven statements covering the six domains of communication skills, professional values, clinical care, working with colleagues, personality issues and duties and responsibilities were accepted as relevant by ten primary healthcare teams using a standard of 80 percent agreement. The evaluation found the MSF process to be feasible and acceptable and participants provided some evidence of educational impact. An MSF instrument for GPs has been developed based on the concept of 'the good GP' as described by the primary healthcare team. The evaluation of the resultant MSF process illustrates the potential of MSF, when delivered in the supportive environment of GP appraisal, to provide feedback which has the possibility of improving working relationships between GPs and their colleagues.

  9. Fourth Annual Large Hadron Collider Physics

    NASA Astrophysics Data System (ADS)

    The fourth annual Large Hadron Collider Physics (LHCP2016) conference will be held in Lund, Sweden, in the period of June 13-18, 2016. The conference is hosted by Lund University. The LHCP conference series has emerged in 2013 as a successful result of fusion of two international conferences, Physics at Large Hadron Collider Conference and Hadron Collider Physics Symposium. The program will be devoted to a detailed review of the latest experimental and theoretical results on collider physics, particularly the first results of the LHC Run II, and discussions on further research directions within the high energy particle physics community, both in theory and experiment. The main goal of the conference is to provide intense and lively discussions between experimenters and theorists in such research areas as the Standard Model Physics and Beyond, the Higgs Boson, Supersymmetry, Heavy Quark Physics and Heavy Ion Physics as well as to share a recent progress in the high luminosity upgrades and future colliders developments. Chairpersons: Gregorio Bernardi (LPNHE-Paris CNRS/IN2P3), Guenakh Mitselmakher (University of Florida (US)), Leif Lönnblad (Lund University (SE)), Torsten Akesson (Lund University (SE)) Editorial Board Johan Bijnens (Lund University) Andreas Hoecker (CERN) Jim Olsen (Princeton University)

  10. Muon Collider Overview: Progress and Future Plans

    SciTech Connect

    Gallardo, J.; Palmer, R.; Sessler, A.; Tollestrup, A.

    1998-06-01

    Besides continued work on the parameters of a 3-4 and 0.5 TeV center of mass (COM) collider, many studies are now concentrating on a machine near 100 GeV (COM) that could be a factory for the s-channel production of Higgs particles. We mention the research on the various com- ponents in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z tar- get and proceeding through the phase rotation and decay ({pi}{yields}{mu}{nu}{mu}) channel, muon cooling, acceleration storage in a collider ring and the collider detector. We also men- tion theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This note is a summary of a report[l] updating the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Workshop Snowmass'96.[2

  11. PAH determination based on a rapid and novel gas purge-microsyringe extraction (GP-MSE) technique in road dust of Shanghai, China: Characterization, source apportionment, and health risk assessment.

    PubMed

    Zheng, Xin; Yang, Yi; Liu, Min; Yu, Yingpeng; Zhou, John L; Li, Donghao

    2016-07-01

    A novel cleanup technique termed as gas purge-microsyringe extraction (GP-MSE) was evaluated and applied for polycyclic aromatic hydrocarbon (PAH) determination in road dust samples. A total of 68 road dust samples covering almost the entire Shanghai area were analyzed for 16 priority PAHs using gas chromatography-mass spectrometry. The results indicate that the total PAH concentrations over the investigated sites ranged from 1.04μg/g to 134.02μg/g dw with an average of 13.84μg/g. High-molecular-weight compounds (4-6 rings PAHs) were significantly dominant in the total mass of PAHs, and accounted for 77.85% to 93.62%. Diagnostic ratio analysis showed that the road dust PAHs were mainly from the mixture of petroleum and biomass/coal combustions. Principal component analysis in conjunction with multiple linear regression indicated that the two major origins of road dust PAHs were vehicular emissions and biomass/fossil fuel combustions, which contributed 66.7% and 18.8% to the total road dust PAH burden, respectively. The concentration of benzo[a]pyrene equivalent (BaPeq) varied from 0.16μg/g to 24.47μg/g. The six highly carcinogenic PAH species (benz(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, benzo(k)fluoranthene, dibenz(a,h)anthracene, and indeno(1,2,3-cd)pyrene) accounted for 98.57% of the total BaPeq concentration. Thus, the toxicity of PAHs in road dust was highly associated with high-molecular-weight compounds.

  12. A High Field Magnet Design for A Future Hadron Collider

    SciTech Connect

    Gupta, R.; Chow, K.; Dietderich, D.; Gourlay, S.; Millos, G.; McInturff, A.; Scanlan, R.

    1998-09-01

    US high energy physics community is exploring the possibilities of building a Very Large Hadron Collider (VLHC) after the completion of LHC. This paper presents a high field magnet design option based on Nb{sub 3}Sn technology. A preliminary magnetic and mechanical design of a 14-16 T, 2-in-1 dipole based on the 'common coil design' approach is presented. The computer code ROXIE has been upgraded to perform the field quality optimization of magnets based on the racetrack coil geometry. A magnet R&D program to investigate the issues related to high field magnet designs is also outlined.

  13. Characterization of the inhibitory effect of an extract of Prunella vulgaris on Ebola virus glycoprotein (GP)-mediated virus entry and infection.

    PubMed

    Zhang, Xu; Ao, Zhujun; Bello, Alexander; Ran, Xiaozhuo; Liu, Shuiping; Wigle, Jeffrey; Kobinger, Gary; Yao, Xiaojian

    2016-03-01

    Currently, no approved antiviral therapeutic is available for treatment or prevention of Ebola virus (EBOV) infection. In this study, we characterized an EBOV-glycoprotein (GP) pseudotyped HIV-1-based vector system in different cell cultures, including human umbilical vein endothelial cells (HUVECs) and human macrophages, for the screening of anti-EBOV-GP agent(s). Based on this system, we demonstrated that an aqueous extract (CHPV) from the Chinese herb Prunella vulgaris displayed a potent inhibitory effect on EBOV-GP pseudotyped virus (EBOV-GP-V)-mediated infection in various cell lines, including HUVEC and macrophage. In addition, our results indicated that CHPV was able to block an eGFP-expressing Zaire ebola virus (eGFP-ZEBOV) infection in VeroE6 cells. The anti-EBOV activity of CHPV was exhibited in a dose-dependent manner. At a 12.5 μg/ml concentration, the CHPV showed a greater than 80% inhibition of EBOV-GP-V and eGFP-EBOV infections. Likewise, our studies suggested that the inhibitory effect of CHPV occurred by binding directly to EBOV-GP-Vs and blocking the early viral events. Interestingly, our results have shown that CHPV was able to enhance the anti-EBOV activity of the monoclonal antibody MAb 2G4 against EBOV-GP. Overall, this study provides evidence that CHPV has anti-EBOV activity and may be developed as a novel antiviral approach against EBOV infection.

  14. Forced homo- and heterodimerization of all gp130-type receptor complexes leads to constitutive ligand-independent signaling and cytokine-independent growth.

    PubMed

    Suthaus, Jan; Tillmann, Anna; Lorenzen, Inken; Bulanova, Elena; Rose-John, Stefan; Scheller, Jürgen

    2010-08-01

    Naturally ligand independent constitutively active gp130 variants were described to be responsible for inflammatory hepatocellular adenomas. Recently, we genetically engineered a ligand-independent constitutively active gp130 variant based on homodimerization of Jun leucine zippers. Because also heterodimeric complexes within the gp130 family may have tumorigenic potential, we seek to generate ligand-independent constitutively active heterodimers for all known gp130-receptor complexes based on IL-15/IL-15R alpha-sushi fusion proteins. Ligand-independent heterodimerization of gp130 with WSX-1, LIFR, and OSMR and of OSMR with GPL led to constitutive, ligand-independent STAT1 and/or STAT3 and ERK1/2 phosphorylation. Moreover, these receptor combinations induced transcription of the STAT3 target genes c-myc and Pim-1 and factor-independent growth of stably transduced Ba/F3-gp130 cells. Here, we establish the IL-15/IL-15R alpha-sushi system as a new system to mimic constitutive and ligand-independent activation of homo- and heterodimeric receptor complexes, which might be applicable to other heterodimeric receptor families. A mutated IL-15 protein, which was still able to bind the IL-15R alpha-sushi domain, but not to beta- and gamma-receptor chains, in combination with the 2A peptide technology may be used to translate our in vitro data into the in vivo situation to assess the tumorigenic potential of gp130-heterodimeric receptor complexes.

  15. Forced Homo- and Heterodimerization of All gp130-Type Receptor Complexes Leads to Constitutive Ligand-independent Signaling and Cytokine-independent Growth

    PubMed Central

    Suthaus, Jan; Tillmann, Anna; Lorenzen, Inken; Bulanova, Elena; Rose-John, Stefan

    2010-01-01

    Naturally ligand independent constitutively active gp130 variants were described to be responsible for inflammatory hepatocellular adenomas. Recently, we genetically engineered a ligand-independent constitutively active gp130 variant based on homodimerization of Jun leucine zippers. Because also heterodimeric complexes within the gp130 family may have tumorigenic potential, we seek to generate ligand-independent constitutively active heterodimers for all known gp130-receptor complexes based on IL-15/IL-15Rα-sushi fusion proteins. Ligand-independent heterodimerization of gp130 with WSX-1, LIFR, and OSMR and of OSMR with GPL led to constitutive, ligand-independent STAT1 and/or STAT3 and ERK1/2 phosphorylation. Moreover, these receptor combinations induced transcription of the STAT3 target genes c-myc and Pim-1 and factor-independent growth of stably transduced Ba/F3-gp130 cells. Here, we establish the IL-15/IL-15Rα-sushi system as a new system to mimic constitutive and ligand-independent activation of homo- and heterodimeric receptor complexes, which might be applicable to other heterodimeric receptor families. A mutated IL-15 protein, which was still able to bind the IL-15Rα-sushi domain, but not to β- and γ-receptor chains, in combination with the 2A peptide technology may be used to translate our in vitro data into the in vivo situation to assess the tumorigenic potential of gp130-heterodimeric receptor complexes. PMID:20554759

  16. Supersymmetric Higgs mediated lepton flavor violation at a photon collider

    NASA Astrophysics Data System (ADS)

    Cannoni, M.; Panella, O.

    2009-03-01

    We study a new signature of lepton flavor violation (LFV) at the photon collider within supersymmetric theories. We consider the minimal supersymmetric standard model within a large tan⁡β scenario with all superpartner masses in the O(TeV) while the heavy Higgs bosons masses lie below the TeV and develop sizable loop induced LFV couplings to the leptons. We consider a photon collider based on an e+e- linear collider with s=800GeV with the parameters of the TESLA proposal and show that, with the expected integrated γγ luminosity Lγγ=200-500fb-1, the “μτ fusion” mechanism is the dominant channel for the process γγ→μτb bmacr providing detailed analytical and numerical studies of the signal and backgrounds. We impose on the parameter space present direct and indirect constraints from B physics and rare LFV τ decays and find that the LFV signal can be probed for masses of the heavy neutral Higgs bosons A, H from 300 GeV up to the kinematical limit ≃600GeV for 30≤tan⁡β≤60.

  17. Soft x-ray laser interferometry of colliding plasmas

    NASA Astrophysics Data System (ADS)

    Purvis, Mike; Dunn, James; Shlyaptsev, V. N.

    2005-10-01

    We report results of an experiment designed to study the evolution of dense colliding plasmas created by irradiating a semi-cylindrical target geometry. The measurements were conducted using a 46.9 nm wavelength capillary discharge laser probe and a robust high throughput Mach-Zehnder interferometer based on diffraction gratings. The colliding plasmas were created irradiating a Cu target with a 800 nm wavelength laser pulse of 120 ps duration and ˜ 1J energy. The plasmas are seen to expand off the target surface and collide in a focal region creating a concentrated plasma with densities reaching 1 x 10^20 cm-3. Plasmas with various degrees of collisionality can be studied by tailoring the irradiation conditions and selecting the target material. Results obtained using an Al target are compared with those of the Cu plasmas and model simulations. Work sponsored by the NNSA-SSAA program through DOE Grant # DE-FG03-02NA00062 and U.S. DOE by the U. of California LLNL through the ILSA, contract No. W-7405-Eng-48.

  18. Caterpillar, Inc. — Converter GP-Catalytic Technology (CGP) system

    EPA Pesticide Factsheets

    This EPA memo approves Caterpillar Inc. request for Caterpillar Converter GP-Catalytic Technology (CGP) system for certain wheeled hydraulic excavators in reducing emissions and will be posted on the National Clean Diesel Verified Technologies List.

  19. Recombinant expression, purification, and biophysical characterization of the transmembrane and membrane proximal domains of HIV-1 gp41.

    PubMed

    Gong, Zhen; Kessans, Sarah A; Song, Lusheng; Dörner, Katerina; Lee, Ho-Hsien; Meador, Lydia R; LaBaer, Joshua; Hogue, Brenda G; Mor, Tsafrir S; Fromme, Petra

    2014-11-01

    The transmembrane subunit (gp41) of the envelope glycoprotein of HIV-1 associates noncovalently with the surface subunit (gp120) and together they play essential roles in viral mucosal transmission and infection of target cells. The membrane proximal region (MPR) of gp41 is highly conserved and contains epitopes of broadly neutralizing antibodies. The transmembrane (TM) domain of gp41 not only anchors the envelope glycoprotein complex in the viral membrane but also dynamically affects the interactions of the MPR with the membrane. While high-resolution X-ray structures of some segments of the MPR were solved in the past, they represent the post-fusion forms. Structural information on the TM domain of gp41 is scant and at low resolution. Here we describe the design, expression and purification of a protein construct that includes MPR and the transmembrane domain of gp41 (MPR-TMTEV-6His), which reacts with the broadly neutralizing antibodies 2F5 and 4E10 and thereby may represent an immunologically relevant conformation mimicking a prehairpin intermediate of gp41. The expression level of MPR-TMTEV-6His was improved by fusion to the C-terminus of Mistic protein, yielding ∼ 1 mg of pure protein per liter. The isolated MPR-TMTEV-6His protein was biophysically characterized and is a monodisperse candidate for crystallization. This work will enable further investigation into the structure of MPR-TMTEV-6His, which will be important for the structure-based design of a mucosal vaccine against HIV-1.

  20. Binding of HIV-1 gp120 to the nicotinic receptor.

    PubMed

    Bracci, L; Lozzi, L; Rustici, M; Neri, P

    1992-10-19

    We previously described a significant sequence homology between HIV-1 gp120 and the functional sites responsible for the specific binding of snake curare-mimetic neurotoxins and rabies virus glycoprotein to the nicotinic acetylcholine receptor. Here we report findings about the existence of a mechanism of functional molecular mimicry which could enable the binding of HIV-1 gp120 to nicotinic acetylcholine receptors in muscle cells and neurons.

  1. HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates.

    PubMed

    García-Arriaza, Juan; Perdiguero, Beatriz; Heeney, Jonathan L; Seaman, Michael S; Montefiori, David C; Yates, Nicole L; Tomaras, Georgia D; Ferrari, Guido; Foulds, Kathryn E; Roederer, Mario; Self, Steven G; Borate, Bhavesh; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, Jim; Barnett, Susan W; Burke, Brian; Cristillo, Anthony D; Weiss, Deborah E; Lee, Carter; Kibler, Karen V; Jacobs, Bertram L; Wagner, Ralf; Ding, Song; Pantaleo, Giuseppe; Esteban, Mariano

    2017-05-01

    protection. Here we developed novel replicating poxvirus NYVAC-based HIV/AIDS vaccine candidates expressing clade C HIV-1 antigens, with one of them lacking the vaccinia virus B19 protein, an inhibitor of the type I interferon response. Immunization of nonhuman primates with these novel NYVAC-C-KC vectors and the protein component gp120 elicited high levels of T cell and humoral immune responses, with the vector containing a deletion in B19R inducing a trend toward a higher magnitude of CD4(+) and CD8(+) T cell responses and neutralization of some HIV-1 strains. These poxvirus vectors could be considered HIV/AIDS vaccine candidates based on their activation of potential immune correlates of protection.

  2. The Large Hadron Collider: Redefining High Energy

    SciTech Connect

    Demers, Sarah

    2007-06-19

    Particle physicists have a description of the forces of nature known as the Standard Model that has successfully withstood decades of testing at laboratories around the world. Though the Standard Model is powerful, it is not complete. Important details like the masses of particles are not explained well, and realities as fundamental as gravity, dark matter, and dark energy are left out altogether. I will discuss gaps in the model and why there is hope that some puzzles will be solved by probing high energies with the Large Hadron Collider. Beginning next year, this machine will accelerate protons to record energies, hurling them around a 27 kilometer ring before colliding them 40 million times per second. Detectors the size of five-story buildings will record the debris of these collisions. The new energy frontier made accessible by the Large Hadron Collider will allow thousands of physicists to explore nature's fundamental forces and particles from a fantastic vantage point.

  3. SUPERCONDUCTING SOLENOIDS FOR THE MUON COLLIDER

    SciTech Connect

    GREEN,M.A.; EYSSA,Y.; KENNY,S.; MILLER,J.R.; PRESTEMON,S.; WEGGEL,R.J.

    2000-06-12

    The muon collider is a new idea for lepton colliders. The ultimate energy of an electron ring is limited by synchrotron radiation. Muons, which have a rest mass that is 200 times that of an electron can be stored at much higher energies before synchrotron radiation limits ring performance. The problem with muons is their short life time (2.1 {micro}s at rest). In order to operate a muon storage ring large numbers of muon must be collected, cooled and accelerated before they decay to an electron and two neutrinos. As the authors see it now, high field superconducting solenoids are an integral part of a muon collider muon production and cooling systems. This report describes the design parameters for superconducting and hybrid solenoids that are used for pion production and collection, RF phase rotations of the pions as they decay into muons and the muon cooling (reduction of the muon emittance) before acceleration.

  4. Seismic studies for Fermilab future collider projects

    SciTech Connect

    Lauh, J.; Shiltsev, V.

    1997-11-01

    Ground motion can cause significant beam emittance growth and orbit oscillations in large hadron colliders due to a vibration of numerous focusing magnets. Larger accelerator ring circumference leads to smaller revolution frequency and, e.g. for the Fermilab Very Large Hadron Collider(VLHC) 50-150 Hz vibrations are of particular interest as they are resonant with the beam betatron frequency. Seismic measurements at an existing large accelerator under operation can help to estimate the vibrations generated by the technical systems in future machines. Comparison of noisy and quiet microseismic conditions might be useful for proper choice of technical solutions for future colliders. This article presents results of wide-band seismic measurements at the Fermilab site, namely, in the tunnel of the Tevatron and on the surface nearby, and in two deep tunnels in the Illinois dolomite which is though to be a possible geological environment of the future accelerators.

  5. Final muon cooling for a muon collider

    NASA Astrophysics Data System (ADS)

    Acosta Castillo, John Gabriel

    To explore the new energy frontier, a new generation of particle accelerators is needed. Muon colliders are a promising alternative if muon cooling can be made to work. Muons are 200 times heavier than electrons, so they produce less synchrotron radiation, and they behave like point particles. However, they have a short lifetime of 2.2 mus and the beam is more difficult to cool than an electron beam. The Muon Accelerator Program (MAP) was created to develop concepts and technologies required by a muon collider. An important effort has been made in the program to design and optimize a muon beam cooling system. The goal is to achieve the small beam emittance required by a muon collider. This work explores a final ionization cooling system using magnetic quadrupole lattices with a low enough beta* region to cool the beam to the required limit with available low Z absorbers.

  6. Collider and detector protection at beam accidents

    SciTech Connect

    I. L. Rakhno; N. V. Mokhov; A. I. Drozhdin

    2003-12-10

    Dealing with beam loss due to abort kicker prefire is considered for hadron colliders. The prefires occurred at Tevatron (Fermilab) during Run I and Run II are analyzed and a protection system implemented is described. The effect of accidental beam loss in the Large Hadron Collider (LHC) at CERN on machine and detector components is studied via realistic Monte Carlo calculations. The simulations show that beam loss at an unsynchronized beam abort would result in severe heating of conventional and superconducting magnets and possible damage to the collider detector elements. A proposed set of collimators would reduce energy deposition effects to acceptable levels. Special attention is paid to reducing peak temperature rise within the septum magnet and minimizing quench region length downstream of the LHC beam abort straight section.

  7. The Tevatron Hadron Collider: A short history

    SciTech Connect

    Tollestrup, A.V.

    1994-11-01

    The subject of this presentation was intended to cover the history of hadron colliders. However this broad topic is probably better left to historians. I will cover a much smaller portion of this subject and specialize my subject to the history of the Tevatron. As we will see, the Tevatron project is tightly entwined with the progress in collider technology. It occupies a unique place among accelerators in that it was the first to make use of superconducting magnets and indeed the basic design now forms a template for all machines using this technology. It was spawned in an incredibly productive era when new ideas were being generated almost monthly and it has matured into our highest energy collider complete with two large detectors that provide the major facility in the US for probing high Pt physics for the coming decade.

  8. An intervention modelling experiment to change GPs' intentions to implement evidence-based practice: using theory-based interventions to promote GP management of upper respiratory tract infection without prescribing antibiotics #2

    PubMed Central

    Hrisos, Susan; Eccles, Martin; Johnston, Marie; Francis, Jill; Kaner, Eileen FS; Steen, Nick; Grimshaw, Jeremy

    2008-01-01

    Background Psychological theories of behaviour may provide a framework to guide the design of interventions to change professional behaviour. Behaviour change interventions, designed using psychological theory and targeting important motivational beliefs, were experimentally evaluated for effects on the behavioural intention and simulated behaviour of GPs in the management of uncomplicated upper respiratory tract infection (URTI). Methods The design was a 2 × 2 factorial randomised controlled trial. A postal questionnaire was developed based on three theories of human behaviour: Theory of Planned Behaviour; Social Cognitive Theory and Operant Learning Theory. The beliefs and attitudes of GPs regarding the management of URTI without antibiotics and rates of prescribing on eight patient scenarios were measured at baseline and post-intervention. Two theory-based interventions, a "graded task" with "action planning" and a "persuasive communication", were incorporated into the post-intervention questionnaire. Trial groups were compared using co-variate analyses. Results Post-intervention questionnaires were returned for 340/397 (86%) GPs who responded to the baseline survey. Each intervention had a significant effect on its targeted behavioural belief: compared to those not receiving the intervention GPs completing Intervention 1 reported stronger self-efficacy scores (Beta = 1.41, 95% CI: 0.64 to 2.25) and GPs completing Intervention 2 had more positive anticipated consequences scores (Beta = 0.98, 95% CI = 0.46 to 1.98). Intervention 2 had a significant effect on intention (Beta = 0.90, 95% CI = 0.41 to 1.38) and simulated behaviour (Beta = 0.47, 95% CI = 0.19 to 0.74). Conclusion GPs' intended management of URTI was significantly influenced by their confidence in their ability to manage URTI without antibiotics and the consequences they anticipated as a result of doing so. Two targeted behaviour change interventions differentially affected these beliefs. One

  9. HSP72 and gp96 in gastroenterological cancers.

    PubMed

    Wang, Xiaoping; Wang, Qiaoxia; Lin, Huanping; Li, Sanzhong; Sun, Lijun; Yang, Yixin

    2013-02-18

    Heat shock protein 72 (HSP72) and glycoprotein 96 (gp96) are highly expressed in cancer tissues. Recent studies indicate the possible roles of HSP72 and gp96 in the development and progression of gastrointestinal carcinomas but detailed mechanisms are still ambiguous. Human esophageal cancer, gastric cancer, colon cancer and liver cancer are common gastrointestinal malignant carcinomas in the world. The studies indicated that there existed a significant correlation between the expression of HSP72, gp96 and the development and progression of digestive carcinomas. HSP72 and gp96 expression were significantly associated with the presence of tumor infiltration, lymph node and remote metastasis. Interestingly, studies have found that HSP72 chaperoned alpha-fetoprotein (AFP), HBx in hepatocellular carcinoma, and CD44 in colonic carcinomas. The further researches demonstrated that HSP72-AFP or gp96-AFP recombined vaccine could elicit specific anti-tumor immunity. The high-level expression of HSP72 and gp96 may be not only used as diagnostic or prognostic markers for gastrointestinal carcinomas but also as better immunotherapeutic vaccines in the cancers.

  10. Estrogenic protection against gp120 neurotoxicity: role of microglia.

    PubMed

    Zemlyak, Ilona; Brooke, Sheila; Sapolsky, Robert

    2005-06-07

    HIV infection of the nervous system can cause neurotoxicity, and the glycoprotein gp120 of HIV seems to play a key role in this. gp120 is neurotoxic through a multi-cellular pathway, stimulating microglia to release excitotoxins, cytokines and reactive oxygen species, which then damage neurons. We have previously shown that estrogen decreases the neurotoxicity of gp120 in mixed neuronal/glial cultures. In this study, we determine whether estrogen a) decreases the collective neurotoxicity of the factors released by gp120-treated microglia, and/or b) enhances the ability of neurons to survive such factors. To do so, we established microglial cultures, mixed neuronal/glial hippocampal cultures, and neuron-enriched cultures, independently manipulating gp120 and estrogen exposure in each type of culture, and inducing neurotoxicity in neuron-containing cultures by introducing conditioned media from gp120-treated microglial cultures. We observe that estrogen can exert some small protective effects at the level of bolstering neuronal resistance, but that the bulk of its protective effects arise at the level of decreasing the neurotoxicity of factors released by microglia.

  11. Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover.

    PubMed

    Orr, Mona W; Donaldson, Gregory P; Severin, Geoffrey B; Wang, Jingxin; Sintim, Herman O; Waters, Christopher M; Lee, Vincent T

    2015-09-08

    The bacterial second messenger cyclic di-GMP (c-di-GMP) controls biofilm formation and other phenotypes relevant to pathogenesis. Cyclic-di-GMP is synthesized by diguanylate cyclases (DGCs). Phosphodiesterases (PDE-As) end signaling by linearizing c-di-GMP to 5'-phosphoguanylyl-(3',5')-guanosine (pGpG), which is then hydrolyzed to two GMP molecules by yet unidentified enzymes termed PDE-Bs. We show that pGpG inhibits a PDE-A from Pseudomonas aeruginosa. In a dual DGC and PDE-A reaction, excess pGpG extends the half-life of c-di-GMP, indicating that removal of pGpG is critical for c-di-GMP homeostasis. Thus, we sought to identify the PDE-B enzyme(s) responsible for pGpG degradation. A differential radial capillary action of ligand assay-based screen for pGpG binding proteins identified oligoribonuclease (Orn), an exoribonuclease that hydrolyzes two- to five-nucleotide-long RNAs. Purified Orn rapidly converts pGpG into GMP. To determine whether Orn is the primary enzyme responsible for degrading pGpG, we assayed cell lysates of WT and ∆orn strains of P. aeruginosa PA14 for pGpG stability. The lysates from ∆orn showed 25-fold decrease in pGpG hydrolysis. Complementation with WT, but not active site mutants, restored hydrolysis. Accumulation of pGpG in the ∆orn strain could inhibit PDE-As, increasing c-di-GMP concentration. In support, we observed increased transcription from the c-di-GMP-regulated pel promoter. Additionally, the c-di-GMP-governed auto-aggregation and biofilm phenotypes were elevated in the ∆orn strain in a pel-dependent manner. Finally, we directly detect elevated pGpG and c-di-GMP in the ∆orn strain. Thus, we identified that Orn serves as the primary PDE-B enzyme that removes pGpG, which is necessary to complete the final step in the c-di-GMP degradation pathway.

  12. Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover

    PubMed Central

    Orr, Mona W.; Donaldson, Gregory P.; Severin, Geoffrey B.; Wang, Jingxin; Sintim, Herman O.; Waters, Christopher M.; Lee, Vincent T.

    2015-01-01

    The bacterial second messenger cyclic di-GMP (c-di-GMP) controls biofilm formation and other phenotypes relevant to pathogenesis. Cyclic-di-GMP is synthesized by diguanylate cyclases (DGCs). Phosphodiesterases (PDE-As) end signaling by linearizing c-di-GMP to 5ʹ-phosphoguanylyl-(3ʹ,5ʹ)-guanosine (pGpG), which is then hydrolyzed to two GMP molecules by yet unidentified enzymes termed PDE-Bs. We show that pGpG inhibits a PDE-A from Pseudomonas aeruginosa. In a dual DGC and PDE-A reaction, excess pGpG extends the half-life of c-di-GMP, indicating that removal of pGpG is critical for c-di-GMP homeostasis. Thus, we sought to identify the PDE-B enzyme(s) responsible for pGpG degradation. A differential radial capillary action of ligand assay-based screen for pGpG binding proteins identified oligoribonuclease (Orn), an exoribonuclease that hydrolyzes two- to five-nucleotide-long RNAs. Purified Orn rapidly converts pGpG into GMP. To determine whether Orn is the primary enzyme responsible for degrading pGpG, we assayed cell lysates of WT and ∆orn strains of P. aeruginosa PA14 for pGpG stability. The lysates from ∆orn showed 25-fold decrease in pGpG hydrolysis. Complementation with WT, but not active site mutants, restored hydrolysis. Accumulation of pGpG in the ∆orn strain could inhibit PDE-As, increasing c-di-GMP concentration. In support, we observed increased transcription from the c-di-GMP–regulated pel promoter. Additionally, the c-di-GMP–governed auto-aggregation and biofilm phenotypes were elevated in the ∆orn strain in a pel-dependent manner. Finally, we directly detect elevated pGpG and c-di-GMP in the ∆orn strain. Thus, we identified that Orn serves as the primary PDE-B enzyme that removes pGpG, which is necessary to complete the final step in the c-di-GMP degradation pathway. PMID:26305945

  13. International linear collider reference design report

    SciTech Connect

    Aarons, G.

    2007-06-22

    The International Linear Collider will give physicists a new cosmic doorway to explore energy regimes beyond the reach of today's accelerators. A proposed electron-positron collider, the ILC will complement the Large Hadron Collider, a proton-proton collider at the European Center for Nuclear Research (CERN) in Geneva, Switzerland, together unlocking some of the deepest mysteries in the universe. With LHC discoveries pointing the way, the ILC -- a true precision machine -- will provide the missing pieces of the puzzle. Consisting of two linear accelerators that face each other, the ILC will hurl some 10 billion electrons and their anti-particles, positrons, toward each other at nearly the speed of light. Superconducting accelerator cavities operating at temperatures near absolute zero give the particles more and more energy until they smash in a blazing crossfire at the centre of the machine. Stretching approximately 35 kilometres in length, the beams collide 14,000 times every second at extremely high energies -- 500 billion-electron-volts (GeV). Each spectacular collision creates an array of new particles that could answer some of the most fundamental questions of all time. The current baseline design allows for an upgrade to a 50-kilometre, 1 trillion-electron-volt (TeV) machine during the second stage of the project. This reference design provides the first detailed technical snapshot of the proposed future electron-positron collider, defining in detail the technical parameters and components that make up each section of the 31-kilometer long accelerator. The report will guide the development of the worldwide R&D program, motivate international industrial studies and serve as the basis for the final engineering design needed to make an official project proposal later this decade.

  14. Photon collider beam simulation with CAIN

    NASA Astrophysics Data System (ADS)

    Zarnecki, Aleksander Filip

    2007-11-01

    The CAIN simulation program was used to study the outgoing beam profile for the photon collider at ILC. The main aim of the analysis was to verify the feasibility of the photon linear collider running with 20 mrad electron beam crossing angle. The main problem is the distorted electron beam, which has to be removed from the interaction region. It is shown that with a new design of the final dipole, it should be possible to avoid large energy losses at the face of the magnet.

  15. Top quark studies at hadron colliders

    SciTech Connect

    Sinervo, P.K.

    1997-01-01

    The techniques used to study top quarks at hadron colliders are presented. The analyses that discovered the top quark are described, with emphasis on the techniques used to tag b quark jets in candidate events. The most recent measurements of top quark properties by the CDF and DO Collaborations are reviewed, including the top quark cross section, mass, branching fractions, and production properties. Future top quark studies at hadron colliders are discussed, and predictions for event yields and uncertainties in the measurements of top quark properties are presented.

  16. Physics Beyond the Standard Model at Colliders

    NASA Astrophysics Data System (ADS)

    Matchev, Konstantin

    These lectures introduce the modern machinery used in searches and studies of new physics Beyond the Standard Model (BSM) at colliders. The first lecture provides an overview of the main simulation tools used in high energy physics, including automated parton-level calculators, general purpose event generators, detector simulators, etc. The second lecture is a brief introduction to low energy supersymmetry (SUSY) as a representative BSM paradigm. The third lecture discusses the main collider signatures of SUSY and methods for measuring the masses of new particles in events with missing energy.

  17. Slepton Pair Production at Hadron Colliders

    NASA Astrophysics Data System (ADS)

    Fuks, B.

    2007-04-01

    In R-parity conserving supersymmetric models, sleptons are produced in pairs at hadron colliders. We show that measurements of the longitudinal single-spin asymmetry at possible polarization upgrades of existing colliders allow for a direct extraction of the slepton mixing angle. A calculation of the transverse-momentum spectrum shows the importance of resummed contributions at next-to-leading logarithmic accuracy in the small and intermediate transverse-momentum regions and little dependence on unphysical scales and non-perturbative contributions.

  18. Suppressing Electron Cloud in Future Linear Colliders

    SciTech Connect

    Pivi, M; Kirby, R.E.; Raubenheimer, T.O.; Le Pimpec, F.; /PSI, Villigen

    2005-05-27

    Any accelerator circulating positively charged beams can suffer from a build-up of an electron cloud (EC) in the beam pipe. The cloud develops through ionization of residual gases, synchrotron radiation and secondary electron emission and, when severe, can cause instability, emittance blow-up or loss of the circulating beam. The electron cloud is potentially a luminosity limiting effect for both the Large Hadron Collider (LHC) and the International Linear Collider (ILC). For the ILC positron damping ring, the development of the electron cloud must be suppressed. This paper discusses the state-of-the-art of the ongoing SLAC and international R&D program to study potential remedies.

  19. SUSY CP phases and asymmetries at colliders

    NASA Astrophysics Data System (ADS)

    Kittel, Olaf

    2009-06-01

    In the Minimal Supersymmetric Standard Model, physical phases of complex parameters lead to CP violation. We show how triple products of particle momenta or spins can be used to construct asymmetries, that allow us to probe these CP phases. To give specific examples, we discuss the production of neutralinos at the International Linear Collider (ILC). For the Large Hadron Collider (LHC), we discuss CP asymmetries in squark decays, and in the tri-lepton signal. We find that the CP asymmetries can be as large as 60%.

  20. Beam instrumentation for the Tevatron Collider

    SciTech Connect

    Moore, Ronald S.; Jansson, Andreas; Shiltsev, Vladimir; /Fermilab

    2009-10-01

    The Tevatron in Collider Run II (2001-present) is operating with six times more bunches and many times higher beam intensities and luminosities than in Run I (1992-1995). Beam diagnostics were crucial for the machine start-up and the never-ending luminosity upgrade campaign. We present the overall picture of the Tevatron diagnostics development for Run II, outline machine needs for new instrumentation, present several notable examples that led to Tevatron performance improvements, and discuss the lessons for future colliders.

  1. Collider physics for the late 1980's

    SciTech Connect

    Hinchliffe, I.

    1987-02-27

    Topics in the Standard Model of strong and electroweak interactions and how these topics are relevant for the high energy colliders are discussed. Radiative corrections in the Glashow-Weinberg-Salam model are discussed, stressing how these corrections may be measured at LEP and the SLC. CP violation is discussed, followed by a discussion of the Higgs boson and the searches which can be carried out for it. Some features of quantum chromodynamics are discussed which are relevant to hadron colliders. Some of the problems which the Standard Model does not solve are discussed. 115 refs., 53 figs. (LEW)

  2. A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice

    SciTech Connect

    Qi, Zhi; Pan, Chungen; Lu, Hong; Shui, Yuan; Li, Lin; Li, Xiaojuan; Xu, Xueqing; Liu, Shuwen; Jiang, Shibo

    2010-07-30

    Research highlights: {yields} One recombinant mimetics of gp41 prehairpin fusion intermediate (PFI) consisting of gp41 N46 sequence, foldon and IgG Fc, designated N46FdFc, was expressed. {yields} N46FdFc-induced antibodies in mice that neutralized HIV-1 infection, inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. {yields} These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines. -- Abstract: HIV-1 gp41 prehairpin fusion intermediate (PFI) composed of three N-terminal heptad repeats (NHR) plays a crucial role in viral fusion and entry and represents an attractive target for anti-HIV therapeutics (e.g., enfuvirtide) and vaccines. In present study, we constructed and expressed two recombinant gp41 PFI mimetics, designated N46Fd and N46FdFc. N46Fd consists of N46 (residues 536-581) in gp41 NHR and foldon (Fd), a trimerization motif. N46FdFc is composed of N46Fd fused with human IgG Fc fragment as an immunoenhancer. We immunized mice with N46 peptide, N46Fd and N46FdFc, respectively, and found that only N46FdFc elicited neutralizing antibody response in mice against infection by HIV-1 strains IIIB (clade B, X4), 92US657 (clade B, R5), and 94UG103 (clade A, X4R5). Anti-N46FdFc antibodies inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines.

  3. Recent SuperB Design Choices Improve Next-Generation e e___ B-Factory Collider

    SciTech Connect

    Wittmer, W.; Bertsche, K.; Chao, A.; Novokhatski, A.; Nosochkov, Y.; Seeman, J.; Sullivan, M.K.; Wienands, U.; Bogomyagkov, A.V.; Levichev, E.; Nikitin, S.; Piminov, P.; Shatilov, D.; Sinyatkin, S.; Vobly, P.; Okunev, I.N.; Bolzon, B.; Brunetti, L.; Jeremie, A.; Biagini, M.E.; Boni, R.; /Frascati /INFN, Pisa /Pisa U. /INFN, Genoa /Genoa U. /CERN /Orsay, LAL /Saclay

    2011-08-19

    The SuperB international team continues to optimize the design of an electron-positron collider, which will allow the enhanced study of the origins of flavor physics. The project combines the best features of a linear collider (high single-collision luminosity) and a storage-ring collider (high repetition rate), bringing together all accelerator physics aspects to make a very high luminosity of 10{sup 36} cm{sup -2} sec{sup -1}. This asymmetric-energy collider with a polarized electron beam will produce hundreds of millions of B-mesons at the {Upsilon}(4S) resonance. The present design is based on extremely low emittance beams colliding at a large Piwinski angle to allow very low {beta}*{sub y} without the need for ultra short bunches. Use of crab-waist sextupoles will enhance the luminosity, suppressing dangerous resonances and allowing for a higher beam-beam parameter. The project has flexible beam parameters, improved dynamic aperture, and spin-rotators in the Low Energy Ring for longitudinal polarization of the electron beam at the Interaction Point. Optimized for best colliding-beam performance, the facility may also provide high-brightness photon beams for synchrotron radiation applications.

  4. Cbl-b inhibits P-gp transporter function by preventing its translocation into caveolae in multiple drug-resistant gastric and breast cancers.

    PubMed

    Zhang, Ye; Qu, Xiujuan; Teng, Yuee; Li, Zhi; Xu, Ling; Liu, Jing; Ma, Yanju; Fan, Yibo; Li, Ce; Liu, Shizhou; Wang, Zhenning; Hu, Xuejun; Zhang, Jingdong; Liu, Yunpeng

    2015-03-30

    The transport function of P-glycoprotein (P-gp) requires its efficient localization to caveolae, a subset of lipid rafts, and disruption of caveolae suppresses P-gp transport function. However, the regulatory molecules involved in the translocation of P-gp into caveolae remain unknown. In the present study, we showed that c-Src dependent Caveolin-1 phosphorylation promoted the translocation of P-gp into caveolae, resulting in multidrug resistance in adriamycin resistant gastric cancer SGC7901/Adr and breast cancer MCF-7/Adr cells. In a negative feedback loop, the translocation of Cbl-b from the nucleus to the cytoplasm prevented the localization of P-gp to caveolae resulting in the reversal of MDR through the ubiquitination and degradation of c-Src. Clinical data showed a significant positive relationship between Cbl-b expression and survival in P-gp positive breast cancer patients who received anthracycline-based chemotherapy. Our findings identified a new regulatory mechanism of P-gp transport function in multiple drug-resistant gastric and breast cancers.

  5. Antibody repertoire against HIV-1 gp120 triggered in nude and normal mice by GM-CSF/gp120 immunization.

    PubMed

    del Real, G; Llorente, M; Lucas, P; Kremer, L; Torán, J L; Martínez-A, C

    1999-08-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) facilitates the induction of primary immune responses by activating and recruiting antigen-presenting cells (APC), which efficiently present antigen determinants to Th cells. We have derived a functional GM-CSF/gp120 chimeric protein that, following immunization in soluble, adjuvant-independent form in normal mice, triggers highly specific, high affinity anti-gp120 antibodies. In contrast, nude mice respond with mutated, polyreactive, low affinity antibodies that mature further and increase in affinity in T cell-reconstituted nude mice. Anti-gp120 antibody production in nude mice is mediated principally by GM-CSF/gp120-triggered IL-4 production, since neutralizing anti-IL-4 abrogates the in vivo response. The anti-gp120 antibody response in normal, nude and T cell-reconstituted nude mice is encoded at a remarkably high frequency by the VH81X and VH7183 genes, a family used notably during fetal life and, when expressed at the adult stage, associated with autoimmune disease. We conclude that HIV gp120 binds and selects a subpopulation of developing B cells expressing a set of VH genes associated with immunodeficiency and autoimmunity.

  6. The cholesterol-binding motif of the HIV-1 glycoprotein gp41 regulates lateral sorting and oligomerization.

    PubMed

    Schwarzer, Roland; Levental, Ilya; Gramatica, Andrea; Scolari, Silvia; Buschmann, Volker; Veit, Michael; Herrmann, Andreas

    2014-10-01

    Enveloped viruses often use membrane lipid rafts to assemble and bud, augment infection and spread efficiently. However, the molecular bases and functional consequences of the partitioning of viral glycoproteins into microdomains remain intriguing questions in virus biology. Here, we measured Foerster resonance energy transfer by fluorescence lifetime imaging microscopy (FLIM-FRET) to study the role of distinct membrane proximal regions of the human immunodeficiency virus glycoprotein gp41 for lipid raft partitioning in living Chinese hamster ovary cells (CHO-K1). Gp41 was labelled with a fluorescent protein at the exoplasmic face of the membrane, preventing any interference of the fluorophore with the proposed role of the transmembrane and cytoplasmic domains in lateral organization of gp41. Raft localization was deduced from interaction with an established raft marker, a fluorescently tagged glycophosphatidylinositol anchor and the cholesterol recognition amino acid consensus (CRAC) was identified as the crucial lateral sorting determinant in CHO-K1 cells. Interestingly, the raft association of gp41 indicates a substantial cell-to-cell heterogeneity of the plasma membrane microdomains. In complementary fluorescence polarization microscopy, a distinct CRAC requirement was found for the oligomerization of the gp41 variants. Our data provide further insight into the molecular basis and biological implications of the cholesterol dependent lateral sorting of viral glycoproteins for virus assembly at cellular membranes.

  7. A novel enzyme-linked immunosorbent assay for screening HIV-1 fusion inhibitors targeting HIV-1 Gp41 core structure.

    PubMed

    Pang, Wei; Wang, Rui-Rui; Gao, Yue-Dong; Yang, Liu-Meng; Sun, Yi; Huang, Jing-Fei; Tien, Po; Zheng, Yong-Tang

    2011-02-01

    The gp41 subunit of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein mediates the fusion of viral and host cell membranes. As the HIV-1 enters the host cells, the 2 helical regions, HR1 and HR2, in the ectodomain of gp41 can form a 6-helix bundle, which brings the viral and target cell membranes to close proximity and serves as an attractive target for developing HIV-1 fusion inhibitors. Now, there are several cell- and molecule-based assays to identify potential HIV-1 fusion inhibitors targeting gp41. However, these assays cannot be used universally because they are time-consuming, inconvenient, and expensive. In the present study, the authors expressed and purified GST-HR121 and C43-30a proteins that were derived from the HIV-1 gp41 ectodomain region. GST-HR121 has a function similar to the HR1 peptide of gp41, whereas C43-30a is an HR2-derived peptide that added 50 amino acid residues (aa) in the N-terminal of C43. Further research found they could interact with each other, and a potential HIV-1 fusion inhibitor could inhibit this interaction. On the basis of this fact, a novel, rapid, and economic enzyme-linked immunosorbent assay was established, which can be developed for high-throughput screening of HIV-1 fusion inhibitors.

  8. Enkephalin, neurotensin, and substance P immunoreactivite neurones of the rat GP following 6-hydroxydopamine lesion of the substantia nigra.

    PubMed

    Martorana, A; Fusco, F R; D'Angelo, V; Sancesario, G; Bernardi, G

    2003-10-01

    The ascending dopaminergic tract influences the activity of GP neurones in normal conditions. Its lesion may lead to an up-regulation of activity in this nucleus that is contrary to what would be expected based on the current model of the basal ganglia function. In this study we investigated the occurrence of enkephalin, neurotensin, and substance P immunoreactivity of the rat globus pallidus (GP) following lesion of the nigrostriatal pathway induced by the injection of the toxin 6-hydroxydopamine into the substantia nigra. Since 60-65% of GP neurones are immunopositive for parvalbumin, the immunoreactivity for peptides was evaluated, considering the different content in parvalbumin of pallidal neurones types, at early and chronic phases of denervation. Our results showed that a lesion of the nigrostriatal pathway induced the expression of enkephalin, neurotensin, and substance P immunoreactivity in numerous pallidal cell bodies. Each subgroup of neurones showed a different pattern of distribution. These modifications equally involved the two main subclasses of neurones. However parvalbumin-negative neurones were modified to a larger extent than the parvalbumin-positive ones. These data indicate that nigrostriatal lesion induces in a wide and unexpected peptide synthesis at least in three different subgroups of GP neurones. These modifications might be useful to further histochemically characterise neurones of the GP.

  9. gp78 functions downstream of Hrd1 to promote degradation of misfolded proteins of the endoplasmic reticulum

    PubMed Central

    Zhang, Ting; Xu, Yue; Liu, Yanfen; Ye, Yihong

    2015-01-01

    Eukaryotic cells eliminate misfolded proteins from the endoplasmic reticulum (ER) via a conserved process termed ER-associated degradation (ERAD). Central regulators of the ERAD system are membrane-bound ubiquitin ligases, which are thought to channel misfolded proteins through the ER membrane during retrotranslocation. Hrd1 and gp78 are mammalian ubiquitin ligases homologous to Hrd1p, an ubiquitin ligase essential for ERAD in Saccharomyces cerevisiae. However, the functional relevance of these proteins to Hrd1p is unclear. In this paper, we characterize the gp78-containing ubiquitin ligase complex and define its functional interplay with Hrd1 using biochemical and recently developed CRISPR-based genetic tools. Our data show that transient inactivation of the gp78 complex by short hairpin RNA–mediated gene silencing causes significant stabilization of both luminal and membrane ERAD substrates, but unlike Hrd1, which plays an essential role in retrotranslocation and ubiquitination of these ERAD substrates, knockdown of gp78 does not affect either of these processes. Instead, gp78 appears to act downstream of Hrd1 to promote ERAD via cooperation with the BAG6 chaperone complex. We conclude that the Hrd1 complex forms an essential retrotranslocation module that is evolutionarily conserved, but the mammalian ERAD system uses additional ubiquitin ligases to assist Hrd1 during retrotranslocation. PMID:26424800

  10. Secondary structure of gp160 and gp120 envelope glycoproteins of human immunodeficiency virus type 1: a Fourier transform infrared spectroscopic study.

    PubMed Central

    Decroly, E; Cornet, B; Martin, I; Ruysschaert, J M; Vandenbranden, M

    1993-01-01

    The secondary structure of the precursor (gp160) of the envelope protein of human immunodeficiency virus type 1 (BH10) and its receptor-binding subunit (gp120) was studied by Fourier-transformed attenuated total reflection spectroscopy. A higher alpha-helix/beta-sheet ratio in the gp120 subunit than in the precursor indicates a structural heterogeneity between the two subunits (gp120 and gp41), in agreement with classical secondary-structure predictions. The secondary structure of gp41 was estimated and compared with existing models. The high alpha-helical content in gp41 and the dominant beta-sheet content in gp120 resemble the distribution in influenza virus hemagglutinin subunits. PMID:8497064

  11. Secondary structure of gp160 and gp120 envelope glycoproteins of human immunodeficiency virus type 1: a Fourier transform infrared spectroscopic study.

    PubMed

    Decroly, E; Cornet, B; Martin, I; Ruysschaert, J M; Vandenbranden, M

    1993-06-01

    The secondary structure of the precursor (gp160) of the envelope protein of human immunodeficiency virus type 1 (BH10) and its receptor-binding subunit (gp120) was studied by Fourier-transformed attenuated total reflection spectroscopy. A higher alpha-helix/beta-sheet ratio in the gp120 subunit than in the precursor indicates a structural heterogeneity between the two subunits (gp120 and gp41), in agreement with classical secondary-structure predictions. The secondary structure of gp41 was estimated and compared with existing models. The high alpha-helical content in gp41 and the dominant beta-sheet content in gp120 resemble the distribution in influenza virus hemagglutinin subunits.

  12. Cross-talk among gp130 cytokines in adipocytes.

    PubMed

    Zvonic, Sanjin; Baugh, James E; Arbour-Reily, Patricia; Mynatt, Randall L; Stephens, Jacqueline M

    2005-10-07

    The interleukin-6 (IL-6) family of cytokines is a family of structurally and functionally related proteins, including IL-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1). These proteins are also known as gp130 cytokines because they all share gp130 as a common transducer protein within their functional receptor complexes. Several of these cytokines (LIF, OSM, CNTF, and CT-1) also utilize the LIF receptor (LIFR) as a component of their receptor complex. We have shown that all of these cytokines are capable of activating both the JAK/STAT and p42/44 mitogen-activated protein kinase signaling pathways in 3T3-L1 adipocytes. By performing a variety of preincubation studies and examining the ability of these cytokines to activate STATs, ERKs, and induce transcription of SOCS-3 mRNA, we have also examined the ability of gp130 cytokines to modulate the action of their family members. Our results indicate that a subset of gp130 cytokines, in particular CT-1, LIF, and OSM, has the ability to impair subsequent signaling activity initiated by gp130 cytokines. However, IL-6 and CNTF do not exhibit this cross-talk ability. Moreover, our results indicate that the cross-talk among gp130 cytokines is mediated by the ability of these cytokines to induce ligand-dependent degradation of the LIFR, in a proteasome-independent manner, which coincides with decreased levels of LIFR at the plasma membrane. In summary, our results demonstrate that an inhibitory cross-talk among specific gp130 cytokines in 3T3-L1 adipocytes occurs as a result of specific degradation of LIFR via a lysosome-mediated pathway.

  13. Exploring resilience in rural GP registrars--implications for training.

    PubMed

    Walters, Lucie; Laurence, Caroline O; Dollard, Joanne; Elliott, Taryn; Eley, Diann S

    2015-07-02

    Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care providers. This study sought to explore GP registrars' perceptions of their resilience and strategies they used to maintain resilience in rural general practice. In this qualitative interpretive research, semi-structured interviews were recorded, transcribed and analysed using an inductive approach. Initial coding resulted in a coding framework which was refined using constant comparison and negative case analysis. Authors developed consensus around the final conceptual model. Eighteen GP registrars from: Australian College of Rural and Remote Medicine Independent Pathway, and three GP regional training programs with rural training posts. Six main themes emerged from the data. Firstly, rural GP registrars described four dichotomous tensions they faced: clinical caution versus clinical courage; flexibility versus persistence; reflective practice versus task-focused practice; and personal connections versus professional commitment. Further themes included: personal skills for balance which facilitated resilience including optimistic attitude, self-reflection and metacognition; and finally GP registrars recognised the role of their supervisors in supporting and stretching them to enhance their clinical resilience. Resilience is maintained as on a wobble board by balancing professional tensions within acceptable limits. These limits are unique to each individual, and may be expanded through personal growth and professional development as part of rural general practice training.

  14. Difficult Decisions: The Superconducting Super Collider.

    ERIC Educational Resources Information Center

    Newton, David E.; Slesnick, Irwin L.

    1990-01-01

    The fundamental principles of the superconducting super collider are presented. Arguments for the construction of this apparatus and policy issues surrounding its construction are discussed. Charts of the fundamental atomic particles and forces and the history of particle accelerators are provided. An activity for discussing this controversial…

  15. Difficult Decisions: The Superconducting Super Collider.

    ERIC Educational Resources Information Center

    Newton, David E.; Slesnick, Irwin L.

    1990-01-01

    The fundamental principles of the superconducting super collider are presented. Arguments for the construction of this apparatus and policy issues surrounding its construction are discussed. Charts of the fundamental atomic particles and forces and the history of particle accelerators are provided. An activity for discussing this controversial…

  16. Black Holes and the Large Hadron Collider

    ERIC Educational Resources Information Center

    Roy, Arunava

    2011-01-01

    The European Center for Nuclear Research or CERN's Large Hadron Collider (LHC) has caught our attention partly due to the film "Angels and Demons." In the movie, an antimatter bomb attack on the Vatican is foiled by the protagonist. Perhaps just as controversial is the formation of mini black holes (BHs). Recently, the American Physical Society…

  17. QCD parton model at collider energies

    SciTech Connect

    Ellis, R.K.

    1984-09-01

    Using the example of vector boson production, the application of the QCD improved parton model at collider energies is reviewed. The reliability of the extrapolation to SSC energies is assessed. Predictions at ..sqrt..S = 0.54 TeV are compared with data. 21 references.

  18. From the LHC to Future Colliders

    SciTech Connect

    De Roeck, A.; Ellis, J.; Grojean, C.; Heinemeyer, S.; Jakobs, K.; Weiglein, G.; Azuelos, G.; Dawson, S.; Gripaios, B.; Han, T.; Hewett, J.; Lancaster, M.; Mariotti, C.; Moortgat, F.; Moortgat-Pick, G.; Polesello, G.; Riemann, S.; Assamagan, K.; Bechtle, P.; Carena, M.; Chachamis, G.; /more authors..

    2010-06-11

    Discoveries at the LHC will soon set the physics agenda for future colliders. This report of a CERN Theory Institute includes the summaries of Working Groups that reviewed the physics goals and prospects of LHC running with 10 to 300 fb{sup -1} of integrated luminosity, of the proposed sLHC luminosity upgrade, of the ILC, of CLIC, of the LHeC and of a muon collider. The four Working Groups considered possible scenarios for the first 10 fb{sup -1} of data at the LHC in which (i) a state with properties that are compatible with a Higgs boson is discovered, (ii) no such state is discovered either because the Higgs properties are such that it is difficult to detect or because no Higgs boson exists, (iii) a missing-energy signal beyond the Standard Model is discovered as in some supersymmetric models, and (iv) some other exotic signature of new physics is discovered. In the contexts of these scenarios, theWorking Groups reviewed the capabilities of the future colliders to study in more detail whatever new physics may be discovered by the LHC. Their reports provide the particle physics community with some tools for reviewing the scientific priorities for future colliders after the LHC produces its first harvest of new physics from multi-TeV collisions.

  19. Physics Case for the International Linear Collider

    SciTech Connect

    Fujii, Keisuke; Grojean, Christophe; Peskin, Michael E.; Barklow, Tim; Gao, Yuanning; Kanemura, Shinya; Kim, Hyungdo; List, Jenny; Nojiri, Mihoko; Perelstein, Maxim; Poeschl, Roman; Reuter, Juergen; Simon, Frank; Tanabe, Tomohiko; Yu, Jaehoon; Wells, James D.; Murayama, Hitoshi; Yamamoto, Hitoshi; /Tohoku U.

    2015-06-23

    We summarize the physics case for the International Linear Collider (ILC). We review the key motivations for the ILC presented in the literature, updating the projected measurement uncertainties for the ILC experiments in accord with the expected schedule of operation of the accelerator and the results of the most recent simulation studies.

  20. Future Accelerators, Muon Colliders, and Neutrino Factories

    SciTech Connect

    Richard A Carrigan, Jr.

    2001-12-19

    Particle physics is driven by five great topics. Neutrino oscillations and masses are now at the fore. The standard model with extensions to supersymmetry and a Higgs to generate mass explains much of the field. The origins of CP violation are not understood. The possibility of extra dimensions has raised tantalizing new questions. A fifth topic lurking in the background is the possibility of something totally different. Many of the questions raised by these topics require powerful new accelerators. It is not an overstatement to say that for some of the issues, the accelerator is almost the experiment. Indeed some of the questions require machines beyond our present capability. As this volume attests, there are parts of the particle physics program that have been significantly advanced without the use of accelerators such as the subject of neutrino oscillations and many aspects of the particle-cosmology interface. At this stage in the development of physics, both approaches are needed and important. This chapter first reviews the status of the great accelerator facilities now in operation or coming on within the decade. Next, midrange possibilities are discussed including linear colliders with the adjunct possibility of gamma-gamma colliders, muon colliders, with precursor neutrino factories, and very large hadron colliders. Finally visionary possibilities are considered including plasma and laser accelerators.

  1. Beam-beam issues in asymmetric colliders

    SciTech Connect

    Furman, M.A.

    1992-07-01

    We discuss generic beam-beam issues for proposed asymmetric e{sup +}- e{sup -} colliders. We illustrate the issues by choosing, as examples, the proposals by Cornell University (CESR-B), KEK, and SLAC/LBL/LLNL (PEP-II).

  2. Precision electroweak physics at future collider experiments

    SciTech Connect

    Baur, U.; Demarteau, M.

    1996-11-01

    We present an overview of the present status and prospects for progress in electroweak measurements at future collider experiments leading to precision tests of the Standard Model of Electroweak Interactions. Special attention is paid to the measurement of the {ital W} mass, the effective weak mixing angle, and the determination of the top quark mass. Their constraints on the Higgs boson mass are discussed.

  3. Proton-proton colliding beam facility ISABELLE

    SciTech Connect

    Hahn, H

    1980-01-01

    This paper attempts to present the status of the ISABELLE construction project, which has the objective of building a 400 + 400 GeV proton colliding beam facility. The major technical features of the superconducting accelerators with their projected performance are described. Progress made so far, difficulties encountered, and the program until completion in 1986 is briefly reviewed.

  4. Beam dynamics issues for linear colliders

    SciTech Connect

    Ruth, R.D.

    1987-09-01

    In this paper we discuss various beam dynamics issues for linear colliders. The emphasis is to explore beam dynamics effects which lead to an effective dilution of the emittance of the beam and thus to a loss of luminosity. These considerations lead to various tolerances which are evaluated for a particular parameter set.

  5. Black Holes and the Large Hadron Collider

    ERIC Educational Resources Information Center

    Roy, Arunava

    2011-01-01

    The European Center for Nuclear Research or CERN's Large Hadron Collider (LHC) has caught our attention partly due to the film "Angels and Demons." In the movie, an antimatter bomb attack on the Vatican is foiled by the protagonist. Perhaps just as controversial is the formation of mini black holes (BHs). Recently, the American Physical Society…

  6. The status of the Stanford Linear Collider

    SciTech Connect

    Stiening, R.

    1987-03-01

    The Stanford Linear Collider is described, and the status of commissioning of the major SLC systems is given, including the electron source and 1.2 GeV linac, storage rings, 50 GeV linac, and positron source. Beam transport between the linac and final focus, and the final focus optical system are described. (LEW)

  7. Constitutively Active Mutant gp130 Receptor Protein from Inflammatory Hepatocellular Adenoma Is Inhibited by an Anti-gp130 Antibody That Specifically Neutralizes Interleukin 11 Signaling*

    PubMed Central

    Sommer, Jan; Effenberger, Timo; Volpi, Elena; Waetzig, Georg H.; Bernhardt, Marten; Suthaus, Jan; Garbers, Christoph; Rose-John, Stefan; Floss, Doreen M.; Scheller, Jürgen

    2012-01-01

    Ligand-independent constitutively active gp130 mutants were described to be responsible for the development of inflammatory hepatocellular adenomas (IHCAs). These variants had gain-of-function somatic mutations within the extracellular domain 2 (D2) of the gp130 receptor chain. Cytokine-dependent Ba/F3 cells were transduced with the constitutively active variant of gp130 featuring a deletion in the domain 2 from Tyr-186 to Tyr-190 (gp130ΔYY). These cells showed constitutive phosphorylation of signal transducer and activator of transcription-3 (STAT3) and cytokine-independent proliferation. Deletion of the Ig-like domain 1 (D1) of gp130, but not anti-gp130 mAbs directed against D1, abolished constitutive activation of gp130ΔYY, highlighting that this domain is involved in ligand-independent activation of gp130ΔYY. Moreover, soluble variants of gp130 were not able to inhibit the constitutive activation of gp130ΔYY. However, the inhibition of constitutive activation of gp130ΔYY was achieved by the anti-gp130 mAb B-P4, which specifically inhibits gp130 signaling by IL-11 but not by other IL-6 type cytokines. IL-11 but not IL-6 levels were found previously to be up-regulated in IHCAs, suggesting that mutations in gp130 are leading to IL-11-like signaling. The mAb B-P4 might be a valuable tool to inhibit the constitutive activation of naturally occurring gp130 mutants in IHCAs and rare cases of gp130-associated hepatocellular carcinoma. PMID:22523320

  8. Linear Collider Physics Resource Book Snowmass 2001

    SciTech Connect

    Ronan , M.T.

    2001-06-01

    The American particle physics community can look forward to a well-conceived and vital program of experimentation for the next ten years, using both colliders and fixed target beams to study a wide variety of pressing questions. Beyond 2010, these programs will be reaching the end of their expected lives. The CERN LHC will provide an experimental program of the first importance. But beyond the LHC, the American community needs a coherent plan. The Snowmass 2001 Workshop and the deliberations of the HEPAP subpanel offer a rare opportunity to engage the full community in planning our future for the next decade or more. A major accelerator project requires a decade from the beginning of an engineering design to the receipt of the first data. So it is now time to decide whether to begin a new accelerator project that will operate in the years soon after 2010. We believe that the world high-energy physics community needs such a project. With the great promise of discovery in physics at the next energy scale, and with the opportunity for the uncovering of profound insights, we cannot allow our field to contract to a single experimental program at a single laboratory in the world. We believe that an e{sup +}e{sup -} linear collider is an excellent choice for the next major project in high-energy physics. Applying experimental techniques very different from those used at hadron colliders, an e{sup +}e{sup -} linear collider will allow us to build on the discoveries made at the Tevatron and the LHC, and to add a level of precision and clarity that will be necessary to understand the physics of the next energy scale. It is not necessary to anticipate specific results from the hadron collider programs to argue for constructing an e{sup +}e{sup -} linear collider; in any scenario that is now discussed, physics will benefit from the new information that e{sup +}e{sup -} experiments can provide. This last point merits further emphasis. If a new accelerator could be designed and

  9. Evaluation of chitosan-GP hydrogel biocompatibility in osteochondral defects: an experimental approach

    PubMed Central

    2014-01-01

    Background Articular cartilage, because of its avascular nature, has little capacity for spontaneous healing, and tissue engineering approaches, employing different biomaterials and cells, are under development. Among the investigated biomaterials are the chitosan-based hydrogels. Although thoroughly studied in other mammalian species, studies are scarce in equines. So, the aim of the present study was to investigate the biocompatibility of chitosan-GP in horse joints submitted to high mechanical loads. Results An osteochondral defect was created by arthroscopy in the medial surface of lateral trochlea of talus of left or right leg, randomly selected, from six healthy geldings. The defect was filled up with chitosan-GP. The contralateral joint received an identical defect with no implant. The chondral fragment removed to produce the defect was collected, processed and used as the “Initial” sample (normal cartilage) for histology, immunohistochemistry, and metabolic labelling of PGs. After 180 days, the repair tissues were collected, and also analyzed. At the end of the experiment (180 days after lesion), the total number of cells per field in repair tissues was equal to control, and macrophages and polymorphonuclear cells were not detected, suggesting that no significant inflammation was present. These cells were able to synthesize type II collagen and proteoglycans (PGs). Nevertheless, the cell population in these tissues, both in presence of chitosan-GP and in untreated controls, were heterogeneous, with a lower proportion of type II collagen-positives cells and some with a fibroblastic aspect. Moreover, the PGs synthesized in repair tissues formed in presence or absence of chitosan-GP were similar to those of normal cartilage. However, the chitosan-GP treated tissue had an disorganized appearance, and blood vessels were present. Conclusions Implanted chitosan-GP did not evoke an important inflammatory reaction, and permitted cell growth. These cells were

  10. An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques.

    PubMed

    Schwartz, Jennifer A; Prado, Ilia; Misamore, Johnathan; Weiss, Deborah; Francis, Jesse; Pal, Ranajit; Huaman, Maria; Cristillo, Anthony; Lewis, George K; Gallo, Robert C; DeVico, Anthony L; Fouts, Timothy R

    2016-07-01

    are unlikely to elicit autoimmune antibody responses, supporting the advancement of gp120-CD4 complex-based antigens, such as FLSC, into clinical testing.

  11. An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques

    PubMed Central

    Schwartz, Jennifer A.; Prado, Ilia; Misamore, Johnathan; Weiss, Deborah; Francis, Jesse; Pal, Ranajit; Huaman, Maria; Cristillo, Anthony; Lewis, George K.; Gallo, Robert C.; DeVico, Anthony L.

    2016-01-01

    are unlikely to elicit autoimmune antibody responses, supporting the advancement of gp120-CD4 complex-based antigens, such as FLSC, into clinical testing. PMID:27193040

  12. Council tax valuation bands and contacts with a GP out-of-hours service

    PubMed Central

    Beale, Norman; Taylor, Gordon; Gwynne, Mark; Peart, Carole

    2006-01-01

    UK GPs are no longer responsible for the organisation of out-of-hours care for their patients, but resources remains capitation-based. This cross-sectional study tests whether council tax valuation bands can predict the demand for such services. All out-of-hours contacts made by patients in North Wiltshire over 4 months were classified by council tax band; frequencies compared with official population statistics. Council tax band predicts out-of-hours GP workload irrespective of age and sex: the more modest the home, the higher the GP contact rate. It may prove more difficult to sustain out-of-hours services in deprived parts of the UK. PMID:16611518

  13. Towards a Future Linear Collider and The Linear Collider Studies at CERN

    ScienceCinema

    None

    2016-07-12

    During the week 18-22 October, more than 400 physicists will meet at CERN and in the CICG (International Conference Centre Geneva) to review the global progress towards a future linear collider. The 2010 International Workshop on Linear Colliders will study the physics, detectors and accelerator complex of a linear collider covering both the CLIC and ILC options. Among the topics presented and discussed will be the progress towards the CLIC Conceptual Design Report in 2011, the ILC Technical Design Report in 2012, physics and detector studies linked to these reports, and an increasing numbers of common working group activities. The seminar will give an overview of these topics and also CERN’s linear collider studies, focusing on current activities and initial plans for the period 2011-16. n.b: The Council Chamber is also reserved for this colloquium with a live transmission from the Main Auditorium.

  14. Space-charge limitations in a collider

    SciTech Connect

    Fedotov, A.; Heimerle, M.

    2010-08-03

    Design of several projects which envision hadron colliders operating at low energies such as NICA at JINR [1] and Electron-Nucleon Collider at FAIR [2] is under way. In Brookhaven National Laboratory (BNL), a new physics program requires operation of Relativistic Heavy Ion Collider (RHIC) with heavy ions at low energies at g=2.7-10 [3]. In a collider, maximum achievable luminosity is typically limited by beam-beam effects. For heavy ions significant luminosity degradation, driving bunch length and transverse emittance growth, comes from Intrabeam Scattering (IBS). At these low energies, IBS growth can be effectively counteracted, for example, with cooling techniques. If IBS were the only limitation, one could achieve small hadron beam emittance and bunch length with the help of cooling, resulting in a dramatic luminosity increase. However, as a result of low energies, direct space-charge force from the beam itself is expected to become the dominant limitation. Also, the interplay of both beambeam and space-charge effects may impose an additional limitation on achievable maximum luminosity. Thus, understanding at what values of space-charge tune shift one can operate in the presence of beam-beam effects in a collider is of great interest for all of the above projects. Operation of RHIC for Low-Energy physics program started in 2010 which allowed us to have a look at combined impact of beam-beam and space-charge effects on beam lifetime experimentally. Here we briefly discuss expected limitation due to these effects with reference to recent RHIC experience.

  15. High-brightness injectors for hadron colliders

    SciTech Connect

    Wangler, T.P.

    1990-01-01

    The counterrotating beams in collider rings consist of trains of beam bunches with N{sub B} particles per bunch, spaced a distance S{sub B} apart. When the bunches collide, the interaction rate is determined by the luminosity, which is defined as the interaction rate per unit cross section. For head-on collisions between cylindrical Gaussian beams moving at speed {beta}c, the luminosity is given by L = N{sub B}{sup 2}{beta}c/4{pi}{sigma}{sup 2}S{sub B}, where {sigma} is the rms beam size projected onto a transverse plane (the two transverse planes are assumed identical) at the interaction point. This beam size depends on the rms emittance of the beam and the focusing strength, which is a measure of the 2-D phase-space area in each transverse plane, and is defined in terms of the second moments of the beam distribution. Our convention is to use the rms normalized emittance, without factors of 4 or 6 that are sometimes used. The quantity {tilde {beta}} is the Courant-Synder betatron amplitude function at the interaction point, a characteristic of the focusing lattice and {gamma} is the relativistic Lorentz factor. Achieving high luminosity at a given energy, and at practical values of {tilde {beta}} and S{sub B}, requires a large value for the ratio N{sub B}{sup 2}/{var epsilon}{sub n}, which implies high intensity and small emittance. Thus, specification of the luminosity sets the requirements for beam intensity and emittance, and establishes the requirements on the performance of the injector to the collider ring. In general, for fixed N{sub B}, the luminosity can be increased if {var epsilon}{sub n} can be reduced. The minimum emittance of the collider is limited by the performance of the injector; consequently the design of the injector is of great importance for the ultimate performance of the collider.

  16. Classification as clustering: a Pareto cooperative-competitive GP approach.

    PubMed

    McIntyre, Andrew R; Heywood, Malcolm I

    2011-01-01

    Intuitively population based algorithms such as genetic programming provide a natural environment for supporting solutions that learn to decompose the overall task between multiple individuals, or a team. This work presents a framework for evolving teams without recourse to prespecifying the number of cooperating individuals. To do so, each individual evolves a mapping to a distribution of outcomes that, following clustering, establishes the parameterization of a (Gaussian) local membership function. This gives individuals the opportunity to represent subsets of tasks, where the overall task is that of classification under the supervised learning domain. Thus, rather than each team member representing an entire class, individuals are free to identify unique subsets of the overall classification task. The framework is supported by techniques from evolutionary multiobjective optimization (EMO) and Pareto competitive coevolution. EMO establishes the basis for encouraging individuals to provide accurate yet nonoverlaping behaviors; whereas competitive coevolution provides the mechanism for scaling to potentially large unbalanced datasets. Benchmarking is performed against recent examples of nonlinear SVM classifiers over 12 UCI datasets with between 150 and 200,000 training instances. Solutions from the proposed coevolutionary multiobjective GP framework appear to provide a good balance between classification performance and model complexity, especially as the dataset instance count increases.

  17. Guanine-06 methylation reduces the reactivity of d(GpG) towards platinum complexes.

    PubMed

    Struik, A F; Zuiderwijk, C T; van Boom, J H; Elding, L I; Reedijk, J

    1991-12-01

    6-methylated guanine dinucleotides were used to study the influence of hydrogen bonding on the specific binding of the antitumor drug cDDP, cis-PtCl2(NH3)2, to DNA. In this interaction, the guanine-06 site appears to be important in explaining the preference for a pGpG-N7(1),N7(2) chelate, which results from H-bridge formation with the ammine ligand of cDDP. Guanine-06 methylated dinucleotides and the nonmodified dinucleotides were reacted with [Pt(dien)Cl]+, cis-PtCl2(NH3)2, and cis-[Pt(NH3)2(H2O)2]2+ and the reaction products were characterized by 1H NMR using pH titrations. Methylation at guanine-06 clearly reduces the preference for the guanine. In competition experiments monitored by NMR and experiments using UV spectrophotometry a decreasing reactivity towards [Pt(dien)(H2O)]2+ and cis-[Pt(NH3)2(H2O)2]2+ was found, in the order of d(GpG) greater than d(GomepG) greater than d(GpGome) greater than d(GomepGome). The difference in reactivity between 5' guanine methylation and 3' guanine methylation is ascribed to differences in the H-bond formation with the backbone phosphate. The resulting reduced stacking of the bases in both modified dinucleotides, compared to the bases in d(GpG), results in a preference for the 3' guanine over 5'.

  18. Biochemical characterization of nuclear pore complex protein gp210 oligomers.

    PubMed

    Favreau, C; Bastos, R; Cartaud, J; Courvalin, J C; Mustonen, P

    2001-07-01

    The membrane-spanning glycoprotein gp210 is a major component of the nuclear pore complex. This nucleoporin contains a large cisternal N-terminal domain, a short C-terminal cytoplasmic tail, and a single transmembrane segment. We show here that dimers of native gp210 can be isolated from cell extracts by immunoprecipitation, and from purified rat liver nuclear envelopes by velocity sedimentation and gel filtration. Cross-linking of proteins in isolated membranes prior to solubilization dramatically increases the proportion of dimers. The dimers are SDS-resistant, as previously observed for some integral membrane proteins of cis-Golgi and plasma membrane proteins, including glycophorin A. Larger oligomers of gp210 can also be obtained by gel filtration and denaturing electrophoresis, but unlike the dimers are dissociated by reduction and heating in the presence of SDS. We propose that gp210 is organized into the pore membrane as a large array of gp210 dimers that may constitute a luminal submembranous protein skeleton.

  19. Liposome-Mediated Cellular Delivery of Active gp91phox

    PubMed Central

    Marques, Bruno; Liguori, Lavinia; Paclet, Marie-Hélène; Villegas-Mendéz, Ana; Rothe, Romy; Morel, Françoise; Lenormand, Jean-Luc

    2007-01-01

    Background Gp91phox is a transmembrane protein and the catalytic core of the NADPH oxidase complex of neutrophils. Lack of this protein causes chronic granulomatous disease (CGD), a rare genetic disorder characterized by severe and recurrent infections due to the incapacity of phagocytes to kill microorganisms. Methodology Here we optimize a prokaryotic cell-free expression system to produce integral mammalian membrane proteins. Conclusions Using this system, we over-express truncated forms of the gp91phox protein under soluble form in the presence of detergents or lipids resulting in active proteins with a “native-like” conformation. All the proteins exhibit diaphorase activity in the presence of cytosolic factors (p67phox, p47phox, p40phox and Rac) and arachidonic acid. We also produce proteoliposomes containing gp91phox protein and demonstrate that these proteins exhibit activities similar to their cellular counterpart. The proteoliposomes induce rapid cellular delivery and relocation of recombinant gp91phox proteins to the plasma membrane. Our data support the concept of cell-free expression technology for producing recombinant proteoliposomes and their use for functional and structural studies or protein therapy by complementing deficient cells in gp91phox protein. PMID:17848987

  20. SLAC electron-positron colliders: present and future

    SciTech Connect

    Richter, B.

    1986-09-01

    Stanford University's colliding beam program is outlined, including the SPEAR and PEP colliders and the SLAC linear collider. The accelerator developments to be pursued on these facilities are discussed, as well as advanced accelerator research and development. The items covered in the advanced accelerator research include beamstrahlung, stability requirements, breakdown limits, and power sources. (LEW)