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. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. [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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  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. 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

  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. 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.

  12. 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

  13. 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.

  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. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. (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.

  5. 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

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

    DTIC Science & Technology

    2008-12-23

    BioMed CentralVirology Journal ssOpen AcceResearch Uncoupling GP1 and GP2 expression in the Lassa virus glycoprotein complex: implications for GP1...contributors Abstract Background: Sera from convalescent Lassa fever patients often contains antibodies to Lassa virus (LASV) glycoprotein 1 (GP1...uncoupled Lassa virus (LASV) glycoprotein 1 (GP1) and glycoprotein 2 (GP2) were established. Soluble GP1 was generated using either the native

  7. 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.

  8. 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

  9. 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.

  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

    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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Lattice design for the future ERL-based electron hadron colliders eRHIC and LHeC

    SciTech Connect

    Trbojevic, D.; Beebe-Wang, J.; Hao, Y.; Litvinenko, V.N.; Ptitsyn, V.; Kayran, D.; Tsoupas, N.

    2011-03-28

    We present a lattice design of a CW Electron Recovery Linacs (ERL) for future electron hadron colliders eRHIC and LHeC. In eRHIC, an six-pass ERL installed in the existing Relativistic Heavy Ion Collider (RHIC) tunnel will collide 5-30 GeV polarized electrons with RHIC's 50-250 (325) GeV polarized protons or 20-100 (130) GeV/u heavy ions. In LHeC a stand-along, 3-pass 60 GeV CW ERL will collide polarized electrons with 7 TeV protons. After collision, electron beam energy is recovered and electrons are dumped at low energy. Two superconducting linacs are located in the two straight sections in both ERLs. The multiple arcs are made of Flexible Momentum Compaction lattice (FMC) allowing adjustable momentum compaction for electrons with different energies. The multiple arcs, placed above each other, are matched to the two linac's straight sections with splitters and combiners.

  16. 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.

  17. 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.

  18. 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``.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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].

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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:

  11. 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.

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

    DTIC Science & Technology

    2008-12-23

    BioMed CentralVirology Journal ssOpen AcceResearch Uncoupling GP1 and GP2 expression in the Lassa virus glycoprotein complex: implications for GP1...contributors Abstract Background: Sera from convalescent Lassa fever patients often contains antibodies to Lassa virus (LASV) glycoprotein 1 (GP1...uncoupled Lassa virus (LASV) glycoprotein 1 (GP1) and glycoprotein 2 (GP2) were established. Soluble GP1 was generated using either the native

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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:…

  9. 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.

  10. 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)

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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).

  16. 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.

  17. 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.

  18. 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.

  19. 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].

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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).

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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

  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. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Luminosity limitations for Electron-Ion Collider

    SciTech Connect

    Valeri Lebedev

    2000-09-01

    The major limitations on reaching the maximum luminosity for an electron ion collider are discussed in application to the ring-ring and linac-ring colliders. It is shown that with intensive electron cooling the luminosity of 10{sup 33} cm{sup -2} s{sup -1} is feasible for both schemes for the center-of-mass collider energy above approximately 15 GeV. Each scheme has its own pros and cons. The ring-ring collider is better supported by the current accelerator technology while the linac-ring collider suggests unique features for spin manipulations of the electron beam. The article addresses a general approach to a choice of collider scheme and parameters leaving details for other conference publications dedicated to particular aspects of the ring-ring and linac-ring colliders.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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…

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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...

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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).

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  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. 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.

  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. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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)

  11. 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.

  12. 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.

  13. 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)]...

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  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. 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)

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 'The kids are alright' - Changes in GP consultations with children 2000-15.

    PubMed

    Bayram, Clare; Harrison, Christopher; Charles, Janice; Britt, Helena

    2015-12-01

    The ageing of Australia's population has led to a focus on the health resources required for older patients, and there has been concern that this might be at the expense of children's healthcare. Over the past few decades the number of children in Australia has increased, but has steadily declined as a proportion of the population. This has paralleled an increase in the absolute number of general practitioner (GP) encounters with children aged <15 years, but a decline in the percentage of GP workload from 14.3% in 2000-01 to 11.2% in 2013-14. There are disparities in the use of general practice services by age, with children making up a greater proportion of the population (19.3%) than of GP visits (13.0%), while people aged 65 years and older accounted for 13.0% of the population and 26.5% of visits in 2006. It is unclear whether the decline in the proportion of GP workload accounted for by children reflects a change in the way children use these general practice services, or a redistribution based on the ageing of the patient population. Over time, there have been marked changes in the types of problems managed in children. From the 1990s to 2001, Australia's children became well vaccinated and decreasingly likely to have 'traditional' childhood illnesses (notably infections). More recently, there has been significant growth in the management of child mental health problems in general practice, although mental health problems account for a small proportion of childhood problems managed. We examined children's use of general practice services and the problems managed in 2000-03 and 2012-15 to determine whether their service use has been influenced by the demands associated with the management of older Australians, and whether trends in problems managed identified in early studies have continued.

  20. The Ambiguous Effect of GP Competition: The Case of Hospital Admissions.

    PubMed

    Islam, M Kamrul; Kjerstad, Egil

    2016-10-14

    In the theoretical literature on general practitioner (GP) behaviour, one prediction is that intensified competition induces GPs to provide more services resulting in fewer hospital admissions. This potential substitution effect has drawn political attention in countries looking for measures to reduce the growth in demand for hospital care. However, intensified competition may induce GPs to secure hospital admissions a signal to attract new patients and to keep the already enlisted ones satisfied, resulting in higher admission rates at hospitals. Using both static and dynamic panel data models, we aim to enhance the understanding of whether such relations are causal. Results based on ordinary least square (OLS) models indicate that aggregate inpatient admissions are negatively associated with intensified competition both in the full sample and for the sub-sample patients aged 45 to 69, while outpatient admissions are positively associated. Fixed-effect estimations do not confirm these results though. However, estimations of dynamic models show significant negative (positive) effects of GP competition on aggregate inpatient (outpatient) admissions in the full sample and negative effects on aggregate inpatient admissions and emergency admissions for the sub-sample. Thus, intensified GP competition may reduce inpatient hospital admissions by inducing GPs to provide more services, whereas, the alternative hypothesis seems valid for outpatient admissions. © 2016 The Authors. Health Economics Published by John Wiley & Sons, Ltd.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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%.

  6. 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)

  7. 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.

  8. Patient influences on satisfaction and loyalty for GP services.

    PubMed

    Rundle-Thiele, Sharyn; Russell-Bennett, Rebekah

    2010-04-01

    Little is known about the influence that patients themselves have on their loyalty to a general practitioner (GP). Consequently, a theoretical framework that draws on diverse literature is proposed to suggest that along with satisfaction, patient loyalty is an important outcome for GPs. Comprising 174 Australian patients, this study identified that knowledgeable patients reported lower levels of loyalty while older patients and patients visiting a GP more frequently reported higher levels of loyalty. The results suggest that extending patient-centered care practices to encompass all patients may be warranted in order to improve patient satisfaction and loyalty. Further, future research opportunities abound, with intervention and dyadic research methodologies recommended.

  9. Immunization with Hexon Modified Adenoviral Vectors Integrated with gp83 Epitope Provides Protection against Trypanosoma cruzi Infection

    PubMed Central

    Gu, Linlin; Krendelchtchikova, Valentina; Nde, Pius N.; Pratap, Siddharth; Lima, Maria F.; Villalta, Fernando; Matthews, Qiana L.

    2014-01-01

    Background Trypanosoma cruzi is the causative agent of Chagas disease. Chagas disease is an endemic infection that affects over 8 million people throughout Latin America and now has become a global challenge. The current pharmacological treatment of patients is unsuccessful in most cases, highly toxic, and no vaccines are available. The results of inadequate treatment could lead to heart failure resulting in death. Therefore, a vaccine that elicits neutralizing antibodies mediated by cell-mediated immune responses and protection against Chagas disease is necessary. Methodology/Principal Findings The “antigen capsid-incorporation” strategy is based upon the display of the T. cruzi epitope as an integral component of the adenovirus' capsid rather than an encoded transgene. This strategy is predicted to induce a robust humoral immune response to the presented antigen, similar to the response provoked by native Ad capsid proteins. The antigen chosen was T. cruzi gp83, a ligand that is used by T. cruzi to attach to host cells to initiate infection. The gp83 epitope, recognized by the neutralizing MAb 4A4, along with His6 were incorporated into the Ad serotype 5 (Ad5) vector to generate the vector Ad5-HVR1-gp83-18 (Ad5-gp83). This vector was evaluated by molecular and immunological analyses. Vectors were injected to elicit immune responses against gp83 in mouse models. Our findings indicate that mice immunized with the vector Ad5-gp83 and challenged with a lethal dose of T. cruzi trypomastigotes confer strong immunoprotection with significant reduction in parasitemia levels, increased survival rate and induction of neutralizing antibodies. Conclusions/Significance This data demonstrates that immunization with adenovirus containing capsid-incorporated T. cruzi antigen elicits a significant anti-gp83-specific response in two different mouse models, and protection against T. cruzi infection by eliciting neutralizing antibodies mediated by cell-mediated immune responses

  10. Characterization of Humoral Immune Responses against Capsid Protein p24 and Transmembrane Glycoprotein gp41 of Human Immunodeficiency Virus Type 1 in China.

    PubMed

    Li, Xiufen; Wu, Yue; Ren, Xuqi; Deng, Shuyun; Hu, Guifang; Yu, Shouyi; Tang, Shixing

    2016-01-01

    The objective of this study was to extend our previous research and to further characterize the humoral immune responses against HIV-1 p24, gp41 and the specific peptides carrying the immunodominant epitopes (IDEs) that react with human serum samples from HIV-1-infected individuals in China. We found that the majority (90.45%, 180/199) of the samples did not react with any of the three HIV-1 p24 peptides carrying IDEs, but did react with the recombinant full-length p24, suggesting that these samples tested in China were primarily directed against the conformational epitopes of HIV-1 p24. In contrast, 84.54% (164/194) of the samples reacted with at least one HIV-1 linear gp41 peptide, in particular the gp41-p1 peptide (amino acids 560-616). Both recently and long-term HIV-1-infected individuals displayed similar humoral immune responses against the recombinant gp41. However, samples from long-term HIV-1-infected subjects but not from recently infected subjects, showed a very strong reaction against the gp41-p1 peptide. The different response patterns observed for the two groups against the gp41 and the peptide gp41-p1 were statistically significant (P<0.01, Chi-square test). These results have direct relevance and importance for design of improved HIV-1 p24 detection assays and the gp41- based immunoassay that can be used to reliably distinguish recent and long-term HIV-1 infection.

  11. PCR detection of human papillomavirus: comparison between MY09/MY11 and GP5+/GP6+ primer systems.

    PubMed

    Qu, W; Jiang, G; Cruz, Y; Chang, C J; Ho, G Y; Klein, R S; Burk, R D

    1997-06-01

    Human papillomavirus (HPV) is an etiologic agent of cervical cancer and is the most common sexually transmitted disease in women. PCR amplification of HPV genomes is the most sensitive method for the detection of cervicovaginal HPV. We have compared the two most commonly used PCR primer sets, MY09/MY11 (MY-PCR) and GP5+/GP6+ (GP+-PCR), for the detection of HPV DNA in cervicovaginal lavage samples from 208 women. Oligonucleotide probes for 39 different HPV types were used. Both primer sets amplified a wide spectrum of HPV genotypes and detected similar overall prevalences of 45% (94 of 208) and 43% (89 of 208), respectively. The MY-PCR system detected 27 of 30 (90%) samples with multiple HPV types, whereas the GP+-PCR system detected 14 of 30 (47%) samples with multiple HPV types. Differences in the detection of HPV types 35, 53, and 61 were noted between the two primer systems. Serial dilution of plasmid templates indicated a 3-log decrease in the amplification of HPV type 35 by MY-PCR and HPV types 53 and 61 by GP+-PCR. These results indicate that although the MY-PCR and GP+-PCR identified nearly equivalent prevalences of HPV in a set of clinical samples, differences in the detection of specific types and infections with multiple types were found. Differences in the sensitivities and characteristics of the PCR systems for the detection of HPV within clinical samples should be considered when comparing data between studies and/or in designing new studies or clinical trials.

  12. Peptide Triazole Inactivators of HIV-1 Utilize a Conserved Two-Cavity Binding Site at the Junction of the Inner and Outer Domains of Env gp120

    PubMed Central

    Aneja, Rachna; Rashad, Adel A.; Li, Huiyuan; Sundaram, Ramalingam Venkat Kalyana; Duffy, Caitlin; Bailey, Lauren D.; Chaiken, Irwin

    2015-01-01

    We used coordinated mutagenesis, synthetic design, and flexible docking to investigate the structural mechanism of Env gp120 encounter by peptide triazole (PT) inactivators of HIV-1. Prior results demonstrated that the PT class of inhibitors suppresses binding at both CD4 and coreceptor sites on Env and triggers gp120 shedding, leading to cell-independent irreversible virus inactivation. Despite these enticing anti-HIV-1 phenotypes, structural understanding of the PT–gp120 binding mechanism has been incomplete. Here we found that PT engages two inhibitor ring moieties at the junction between the inner and outer domains of the gp120 protein. The results demonstrate how combined occupancy of two gp120 cavities can coordinately suppress both receptor and coreceptor binding and conformationally entrap the protein in a destabilized state. The two-cavity model has common features with small molecule gp120 inhibitor binding sites and provides a guide for further design of peptidomimetic HIV-1 inactivators based on the PT pharmacophore. PMID:25860784

  13. The crystal structure of HIV CRF07 B′/C gp41 reveals a hyper-mutant site in the middle of HR2 heptad repeat

    SciTech Connect

    Du, Jiansen; Xue, Hailing; Ma, Jing; Liu, Fang; Zhou, Jianhua; Shao, Yiming; Liu, Xinqi

    2013-11-15

    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. - Highlights: • We solved the crystal structure of HIV CRF07 gp41 core region. • A hyper-mutant cluster in the middle of HR2 heptads repeat was identified. • The hyper-mutant site is important in HIV-cell fusion. • The model will help to understand the HIV fusion process.

  14. 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.

  15. 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…

  16. 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.

  17. 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.

  18. 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.

  19. 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).

  20. 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.

  1. 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…

  2. 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.

  3. 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)

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Potable Water Treatment Facility General Permit (PWTF GP) ...

    EPA Pesticide Factsheets

    2017-04-10

    The Final PWTF GP establishes permit eligibility conditions, Notice of Intent (NOI) requirements, effluent limitations, standards, prohibitions, and best management practices for facilities that discharge to waters in the Commonwealth of Massachusetts (including both Commonwealth and Indian country lands) and the State of New Hampshire.

  9. Technology in practice – GP computer use by age.

    PubMed

    Henderson, Joan; Pollack, Allan; Gordon, Julie; Miller, Graeme

    2014-12-01

    Since 2005, more than 95% of general practitioners (GPs) have had access to computers in their clinical work. We have analysed the most recent 2 years of BEACH data (April 2012-March 2014) to determine whether GP age affects clinical computer use.

  10. GP Exercise Referral Schemes: Improving the Patient's Experience

    ERIC Educational Resources Information Center

    Wormald, Helen; Ingle, Lee

    2004-01-01

    Objective: The main objective of this study was to explore patients' perceptions of general practitioner (GP) exercise referral (ER) schemes with a view to providing a better service for future patients. Design: A qualitative focus group methodology. Setting: Meeting rooms or communal areas in leisure centres across North Yorkshire. Method: Thirty…

  11. Binding-induced Stabilization and Assembly of the Phage P22 Tail Accessory Factor gp4

    SciTech Connect

    Olia,A.; Al-Bassam, J.; Winn-Stapley, D.; Joss, L.; Casjens, S.; Cingolani, G.

    2006-01-01

    To infect and replicate, bacteriophage P22 injects its 43 kbp genome across the cell wall of Salmonella enterica serovar Typhimurium. The attachment of phage P22 to the host cell as well as the injection of the viral DNA into the host is mediated by the virion's tail complex. This 2.8 MDa molecular machine is formed by five proteins, which include the portal protein gp1, the adhesion tailspike protein gp9, and three tail accessory factors: gp4, gp10, gp26. We have isolated the tail accessory factor gp4 and characterized its structure and binding interactions with portal protein. Interestingly, gp4 exists in solution as a monomer, which displays an exceedingly low structural stability (T{sub m} 34 {sup o}C). Unfolded gp4 is prone to aggregation within a narrow range of temperatures both in vitro and in Salmonella extracts. In the virion the thermal unfolding of gp4 is prevented by the interaction with the dodecameric portal protein, which stabilizes the structure of gp4 and suppresses unfolded gp4 from irreversibly aggregating in the Salmonella milieu. The structural stabilization of gp4 is accompanied by the concomitant oligomerization of the protein to form a ring of 12 subunits bound to the lower end of the portal ring. The interaction of gp4 with portal protein is complex and likely involves the distinct binding of two non-equivalent sets of six gp4 proteins. Binding of the first set of six gp4 equivalents to dodecameric portal protein yields a gp(1){sub 12}:gp(4){sub 6} assembly intermediate, which is stably populated at 30 {sup o}C and can be resolved by native gel electrophoresis. The final product of the assembly reaction is a bi-dodecameric gp(1){sub 12}:gp(4){sub 12} complex, which appears hollow by electron microscopy, suggesting that gp4 does not physically plug the DNA entry/exit channel, but acts as a structural adaptor for the other tail accessory factors: gp10 and gp26.

  12. 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)

  13. Designing a Soluble Near Full-Length HIV-1 GP41 Trimer

    DTIC Science & Technology

    2012-11-26

    envelope; gp41 trimer; bacteriophage T4 display; prehairpin fusion intermediate. Background: The envelope glycoprotein gp41 is a key component of...protein into trimers and defined oligomers. These gp41 trimers were displayed on bacteriophage T4 capsid nanoparticles by attaching to the small...gp41 Trimers on the Bacteriophage T4 Nanoparticle—Eight hundred and seventy copies of a small outer capsid protein, Soc (9 kDa), decorate the surface

  14. Design of a 6 TeV muon collider

    SciTech Connect

    Wang, M. -H.; Nosochkov, Y.; Cai, Y.; Palmer, M.

    2015-05-19

    A design of a muon collider ring with the center of mass energy of 6 TeV is presented. The ring circumference is about 6.3 km, and the beta functions at collision point are 1 cm in both planes. The ring linear optics, the non-linear chromaticity correction scheme in the Interaction Region (IR), and the additional non-linear field orthogonal knobs are described. The IR magnet specifications are based on the maximum pole tip field of 20 T in dipoles and 15 T in quadrupoles. The results of the beam dynamics optimization for maximum dynamic aperture are presented.

  15. Design of a 6 TeV Muon Collider

    SciTech Connect

    Wang, M-H.; Nosochkov, Y.; Cai, Y.; Palmer, M.

    2015-06-01

    A design of a muon collider ring with the center of mass energy of 6 TeV is presented. The ring circumference is about 6.3 km, and the $\\beta$ functions at collision point are 1 cm in both planes. The ring linear optics, the non-linear chromaticity correction scheme in the Interaction Region (IR), and the additional non-linear field orthogonal knobs are described. The IR magnet specifications are based on the maximum pole tip field of 20 T in dipoles and 15 T in quadrupoles. The results of the beam dynamics optimization for maximum dynamic aperture are presented.

  16. The dijet invariant mass at the Tevatron Collider

    SciTech Connect

    Giannetti, P. )

    1990-05-09

    The differential cross section of the process p + pbar {yields} jet + jet + X as a function of the dijet invariant mass has been measured with the CDF detector at a center of mass energy of 1.8 TeV at the Tevatron Collider in Fermilab. The present analysis is based on the sample of events collected in the 1988/89 run, amounting to a total integrated luminosity of 4.2 pb{sup {minus}1}. A comparison to leading order QCD and quark compositeness predictions is presented as well as a study of the sensitivity of the mass spectrum to the gluon radiation. 10 refs., 6 figs.

  17. Holographic instant conformal symmetry breaking by colliding conical defects

    NASA Astrophysics Data System (ADS)

    Ageev, D. S.; Aref'eva, I. Ya.

    2016-12-01

    We study instant conformal symmetry breaking as a holographic effect of ultrarelativistic particles moving in the AdS3 space-time. We give a qualitative picture of this effect based on calculating the two-point correlation functions and the entanglement entropy of the corresponding boundary theory. We show that in the geodesic approximation, because of gravitational lensing of the geodesics, the ultrarelativistic massless defect produces a zone structure for correlators with broken conformal invariance. At the same time, the holographic entanglement entropy also exhibits a transition to nonconformal behavior. Two colliding massless defects produce a more diverse zone structure for correlators and the entanglement entropy.

  18. A Molecular Switch Abrogates Glycoprotein 100 (gp100) T-cell Receptor (TCR) Targeting of a Human Melanoma Antigen*

    PubMed Central

    Bianchi, Valentina; Bulek, Anna; Fuller, Anna; Lloyd, Angharad; Attaf, Meriem; Rizkallah, Pierre J.; Dolton, Garry; Sewell, Andrew K.; Cole, David K.

    2016-01-01

    Human CD8+ cytotoxic T lymphocytes can mediate tumor regression in melanoma through the specific recognition of HLA-restricted peptides. Because of the relatively weak affinity of most anti-cancer T-cell receptors (TCRs), there is growing emphasis on immunizing melanoma patients with altered peptide ligands in order to induce strong anti-tumor immunity capable of breaking tolerance toward these self-antigens. However, previous studies have shown that these immunogenic designer peptides are not always effective. The melanocyte differentiation protein, glycoprotein 100 (gp100), encodes a naturally processed epitope that is an attractive target for melanoma immunotherapies, in particular peptide-based vaccines. Previous studies have shown that substitutions at peptide residue Glu3 have a broad negative impact on polyclonal T-cell responses. Here, we describe the first atomic structure of a natural cognate TCR in complex with this gp100 epitope and highlight the relatively high affinity of the interaction. Alanine scan mutagenesis performed across the gp100280–288 peptide showed that Glu3 was critically important for TCR binding. Unexpectedly, structural analysis demonstrated that the Glu3 → Ala substitution resulted in a molecular switch that was transmitted to adjacent residues, abrogating TCR binding and T-cell recognition. These findings help to clarify the mechanism of T-cell recognition of gp100 during melanoma responses and could direct the development of altered peptides for vaccination. PMID:26917722

  19. Recent Results from Hera Collider

    NASA Astrophysics Data System (ADS)

    Levonian, Sergey

    2013-11-01

    HERA collaborations H1 and ZEUS are publishing final analyses based on complete e±p statistics of ~ 0.5 fb-1 per experiment and using combinations of their data sets. Here selected recent results are presented from three areas: structure of the proton, searches for new physics and investigations of QCD phenomena at low Bjorken x.

  20. HIV-1 gp120 Mannoses Induce Immunosuppressive Responses from Dendritic Cells

    PubMed Central

    Shan, Meimei; Klasse, Per Johan; Banerjee, Kaustuv; Dey, Antu K; Iyer, Sai Prasad N; Dionisio, Robert; Charles, Dustin; Campbell-Gardener, Lila; Olson, William C; Sanders, Rogier W; Moore, John P

    2007-01-01

    The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is a vaccine immunogen that can signal via several cell surface receptors. To investigate whether receptor biology could influence immune responses to gp120, we studied its interaction with human, monocyte-derived dendritic cells (MDDCs) in vitro. Gp120 from the HIV-1 strain JR-FL induced IL-10 expression in MDDCs from 62% of donors, via a mannose C-type lectin receptor(s) (MCLR). Gp120 from the strain LAI was also an IL-10 inducer, but gp120 from the strain KNH1144 was not. The mannose-binding protein cyanovirin-N, the 2G12 mAb to a mannose-dependent gp120 epitope, and MCLR-specific mAbs inhibited IL-10 expression, as did enzymatic removal of gp120 mannose moieties, whereas inhibitors of signaling via CD4, CCR5, or CXCR4 were ineffective. Gp120-stimulated IL-10 production correlated with DC-SIGN expression on the cells, and involved the ERK signaling pathway. Gp120-treated MDDCs also responded poorly to maturation stimuli by up-regulating activation markers inefficiently and stimulating allogeneic T cell proliferation only weakly. These adverse reactions to gp120 were MCLR-dependent but independent of IL-10 production. Since such mechanisms might suppress immune responses to Env-containing vaccines, demannosylation may be a way to improve the immunogenicity of gp120 or gp140 proteins. PMID:17983270

  1. Functional characterization of Autographa californica multiple nucleopolyhedrovirus gp16 (ac130)

    SciTech Connect

    Yang, Ming; Huang, Cui; Qian, Duo-Duo; Li, Lu-Lin

    2014-09-15

    To investigate the function of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) gp16, multiple gp16-knockout and repair mutants were constructed and characterized. No obvious difference in productivity of budded virus, DNA synthesis, late gene expression and morphogenesis was observed between gp16-knockout and repair viruses, but gp16 deletion resulted in six hours of lengthening in ST{sub 50} to the third instar Spodoptera exigua larvae in bioassays. GP16 was fractionated mainly in the light membrane fraction, by subcellular fractionation. A GP16-EGFP fusion protein was predominantly localized close around the nuclear membrane in infected cells, being coincident with formation of the vesicles associated with the nuclear membrane, which hosted nucleocapsids released from the nucleus. These data suggest that gp16 is not required for viral replication, but may be involved in membrane trafficking associated with the envelopment/de-envelopment of budded viruses when they cross over the nuclear membrane and pass through cytoplasm. - Highlights: • gp16 knockout and repair mutants of AcMNPV were constructed and characterized. • AcMNPV gp16 is not essential to virus replication. • Deletion of gp16 resulted in time lengthening to kill S. exigua larvae. • GP16 was localized close around the nuclear membrane of infected cells. • GP16 was fractionated in the light membrane fraction in subcellular fractionation.

  2. An energy recovery electron linac-on-ring collider

    SciTech Connect

    Merminga, L.; Krafft, G.A.; Lebedev, V.A.; Ben-Zvi, I.

    2000-09-14

    We present the design of high-luminosity electron-proton/ion colliders in which the electrons are produced by an Energy Recovering Linac (ERL). Electron-proton/ion colliders with center of mass energies between 14 GeV and 100 GeV (protons) or 63 GeV/A (ions) and luminosities at the 10{sup 33}(per nucleon) level have been proposed recently as a means for studying hadronic structure. The linac-on-ring option presents significant advantages with respect to: (1) spin manipulations (2) reduction of the synchrotron radiation load in the detectors (3) a wide range of continuous energy variability. Rf power and beam dump considerations require that the electron linac recover the beam energy. Based on extrapolations from actual measurements and calculations, energy recovery is expected to be feasible at currents of a few hundred mA and multi-GeV energies. Luminosity projections for the linac-ring scenario based on fundamental limitations are presented. The feasibility of an energy recovery electron linac-on-proton ring collider is investigated and four conceptual point designs are shown corresponding to electron to proton energies of: 3 GeV on 15 GeV, 5 GeV on 50 GeV and 10 GeV on 250 GeV, and for gold ions with 100 GeV/A. The last two designs assume that the protons or ions are stored in the existing RHIC accelerator. Accelerator physics issues relevant to proton rings and energy recovery linacs are discussed and a list of required R and D for the realization of such a design is presented.

  3. Department of Energy assessment of the Large Hadron Collider

    SciTech Connect

    1996-06-01

    This report summarizes the conclusions of the committee that assessed the cost estimate for the Large Hadron Collider (LHC). This proton-proton collider will be built at CERN, the European Laboratory for Particle Physics near Geneva, Switzerland. The committee found the accelerator-project cost estimate of 2.3 billion in 1995 Swiss francs, or about $2 billion US, to be adequate and reasonable. The planned project completion date of 2005 also appears achievable, assuming the resources are available when needed. The cost estimate was made using established European accounting procedures. In particular, the cost estimate does not include R and D, prototyping and testing, spare parts, and most of the engineering labor. Also excluded are costs for decommissioning the Large Electron-Positron collider (LEP) that now occupies the tunnel, modifications to the injector system, the experimental areas, preoperations costs, and CERN manpower. All these items are assumed by CERN to be included in the normal annual operations budget rather than the construction budget. Finally, contingency is built into the base estimate, in contrast to Department of Energy (DOE) estimates that explicitly identify contingency. The committee`s charge, given by Dr. James F. Decker, Deputy Directory of the DOE Office of Energy Research, was to understand the basis for the LHC cost estimate, identify uncertainties, and judge the overall validity of the estimate, proposed schedule, and related issues. The committee met at CERN April 22--26, 1996. The assessment was based on the October 1995 LHC Conceptual Design Report or ``Yellow Book,`` cost estimates and formal presentations made by the CERN staff, site inspection, detailed discussions with LHC technical experts, and the committee members` considerable experience.

  4. Managerialism and the British GP: the GP as manager and as managed.

    PubMed

    Warwicker, T

    1998-01-01

    The focus of the paper is on the relationship between General Practitioners (GPs) and central government. This relationship dates from the introduction of national health insurance in the UK. From the outset it had an impact on GPs' medical role, their professional status and income. The structure created in 1911 meant that GPs operated as franchisees and, notwithstanding Labour's policy objective of creating a salaried service, this role continued, effectively unchanged, after the creation of the National Health Service (NHS) in 1948. General practice was also the poor relation in contrast to hospital medicine, a feature intensified by the priorities of the NHS. These forces meant that GPs had a dual role: that of clinician and gatekeeper to specialist hospital services, a role in which they exercised substantial clinical freedom: and running a small business, a feature which was exaggerated by the absence of grant aid to improve premises prior to the Family Doctor Charter of 1965. This structural relationship has been progressively transformed by changes in the 1980s and 1990s. On the one hand the emphasis on cost control has seen central government attempting to combine a financial with a clinical gate-keeping keeping role. The crucial change in this respect is the creation of GP fundholding which, in turn, could be seen to have implications for the subordinate status of GPs within the medical profession. However, this has been combined with trends to greater measures of control over GPs. Of central importance in this respect were the changes introduced by the 1990 GP contract. The contract involved an attempt to substantially reduce clinical autonomy by building in much more detailed contractual duties with respect, for example, to health promotion activities. This was combined with the use of financial incentives to reach, for example, immunization targets. Control over clinical autonomy has also involved constraints over prescribing and the shift from Family

  5. Expression and immunological characterization of cardamom mosaic virus coat protein displaying HIV gp41 epitopes.

    PubMed

    Damodharan, Subha; Gujar, Ravindra; Pattabiraman, Sathyamurthy; Nesakumar, Manohar; Hanna, Luke Elizabeth; Vadakkuppattu, Ramanathan D; Usha, Ramakrishnan

    2013-05-01

    The coat protein of cardamom mosaic virus (CdMV), a member of the genus Macluravirus, assembles into virus-like particles when expressed in an Escherichia coli expression system. The N and C-termini of the coat protein were engineered with the Kennedy peptide and the 2F5 and 4E10 epitopes of gp41 of HIV. The chimeric proteins reacted with sera from HIV positive persons and also stimulated secretion of cytokines by peripheral blood mononuclear cells from these persons. Thus, a system based on the coat protein of CdMV can be used to display HIV-1 antigens.

  6. Collider signatures of flavorful Higgs bosons

    NASA Astrophysics Data System (ADS)

    Altmannshofer, Wolfgang; Eby, Joshua; Gori, Stefania; Lotito, Matteo; Martone, Mario; Tuckler, Douglas

    2016-12-01

    Motivated by our limited knowledge of the Higgs couplings to the first two generation fermions, we analyze the collider phenomenology of a class of two Higgs doublet models (2HDMs) with a nonstandard Yukawa sector. One Higgs doublet is mainly responsible for the masses of the weak gauge bosons and the third-generation fermions, while the second Higgs doublet provides mass for the lighter fermion generations. The characteristic collider signatures of this setup differ significantly from well-studied 2HDMs with natural flavor conservation, flavor alignment, or minimal flavor violation. New production mechanisms for the heavy scalar, pseudoscalar, and charged Higgs involving second-generation quarks can become dominant. The most interesting decay modes include H /A →c c ,t c ,μ μ ,τ μ and H±→c b ,c s ,μ ν . Searches for low-mass dimuon resonances are currently among the best probes of the heavy Higgs bosons in this setup.

  7. Slepton Flavor Physics at Linear Colliders

    NASA Astrophysics Data System (ADS)

    Dine, Michael; Grossman, Yuval; Thomas, Scott

    If low energy supersymmetry is realized in nature it is possible that a first generation linear collider will only have access to some of the superpartners with electroweak quantum numbers. Among these, sleptons can provide sensitive probes for lepton flavor violation through potentially dramatic lepton violating signals. Theoretical proposals to understand the absence of low energy quark and lepton flavor changing neutral currents are surveyed and many are found to predict observable slepton flavor violating signals at linear colliders. The observation or absence of such sflavor violation will thus provide important indirect clues to very high energy physics. Previous analyses of slepton flavor oscillations are also extended to include the effects of finite width and mass differences.

  8. Probes of Universal Extra Dimensions at Colliders

    SciTech Connect

    Rizzo, Thomas G.

    2001-06-28

    In the Universal Extra Dimensions model of Appelquist, Cheng and Dobrescu, all of the Standard Model fields are placed in the bulk and thus have Kaluza-Klein (KK) excitations. These KK states can only be pair produced at colliders due to the tree-level conservation of KK number, with the lightest of them being stable and possibly having a mass as low as {approx_equal} 350 400 GeV. After calculating the contribution to g-2 in this model we investigate the production cross sections and signatures for these particles at both hadron and lepton colliders. We demonstrate that these signatures critically depend upon whether the lightest KK states remain stable or are allowed to decay by any of a number of new physics mechanisms. These mechanisms which induce KK decays are studied in detail.

  9. Future high energy colliders symposium. Summary report

    SciTech Connect

    Parsa, Z. |

    1996-12-31

    A `Future High Energy Colliders` Symposium was held October 21-25, 1996 at the Institute for Theoretical Physics (ITP) in Santa Barbara. This was one of the 3 symposia hosted by the ITP and supported by its sponsor, the National Science Foundation, as part of a 5 month program on `New Ideas for Particle Accelerators`. The long term program and symposia were organized and coordinated by Dr. Zohreh Parsa of Brookhaven National Laboratory/ITP. The purpose of the symposium was to discuss the future direction of high energy physics by bringing together leaders from the theoretical, experimental and accelerator physics communities. Their talks provided personal perspectives on the physics objectives and the technology demands of future high energy colliders. Collectively, they formed a vision for where the field should be heading and how it might best reach its objectives.

  10. TARGETRY FOR A MU+MU- COLLIDER.

    SciTech Connect

    KIRK,H.G.

    1999-03-29

    The requirement for high luminosity in a {mu}{sup +}{mu}{sup -} collider leads one to conclude that a prodigious source of pions is needed followed by an efficient capture/decay channel. Significant targetry issues are raised by these demands. Among these are (1) the best target configuration to tolerate a high-rep rate, high-power proton beam ({approx} 10{sup 14} ppp at 15 Hz), (2) the pion spectra of the produced pions and (3) the best configuration for maximizing the quantity of captured pions. In this paper, the current thinking of the {mu}{sup +}{mu}{sup -} collider collaboration for solutions to these issues is discussed. In addition, we give a description of the R&D program designed to provide a proof-of-principle for a muon capture system capable of meeting the demands of a future high-luminosity machine.

  11. Testing electroweak baryogenesis with future colliders

    NASA Astrophysics Data System (ADS)

    Curtin, David; Meade, Patrick; Yu, Chiu-Tien

    2014-11-01

    Electroweak Baryogenesis (EWBG) is a compelling scenario for explaining the matter-antimatter asymmetry in the universe. Its connection to the electroweak phase transition makes it inherently testable. However, completely excluding this scenario can seem difficult in practice, due to the sheer number of proposed models. We investigate the possibility of postulating a "no-lose" theorem for testing EWBG in future e + e - or hadron colliders. As a first step we focus on a factorized picture of EWBG which separates the sources of a stronger phase transition from those that provide new sources of CP violation. We then construct a "nightmare scenario" that generates a strong first-order phase transition as required by EWBG, but is very difficult to test experimentally. We show that a 100 TeV hadron collider is both necessary and possibly sufficient for testing the parameter space of the nightmare scenario that is consistent with EWBG.

  12. New DIS and collider results on PDFs

    SciTech Connect

    Rizvi, E.

    2015-05-15

    The HERA ep collider experiments have measured the proton structure functions over a wide kinematic range. New data from the H1 experiment now extend the range to higher 4-momentum transfer (√(Q{sup 2})) over which a precision of ∼ 2% is achieved in the neutral current channel. A factor of two reduction in the systematic uncertainties over previous measurement is attained. The charged current structure function measurements are also significantly improved in precision. These data, when used in QCD analyses of the parton density functions (PDFs) reduce the PDF uncertainties particularly at high momentum fractions x which is relevant to low energy neutrino scattering cross sections. New data from the LHC pp collider experiments may also offer significant high x PDF improvements as the experimental uncertainties improve.

  13. Initial operation of the Tevatron collider

    SciTech Connect

    Johnson, R.

    1987-03-01

    The Tevatron is now the highest energy proton synchrotron and the only accelerator made with superconducting magnets. Operating since 1983 as a fixed-target machine at energies up to 800 GeV, it has now been modified to operate as a 900 GeV antiproton-proton collider. This paper describes the initial operation of the machine in this mode. The new features of the Fermilab complex, including the antiproton source and the Main Ring injector with its two overpasses and new rf requirements, are discussed. Beam characteristics in the Tevatron (including lifetimes, emittances, luminosity, beam-beam tune shifts, backgrounds, and low beta complications), the coordination of the steps in the accelerator chain, and the commissioning history are also discussed. Finally, some plans for the improvement of the collider are presented.

  14. Reverse Emittance Exchange for Muon Colliders

    SciTech Connect

    V. Ivanov, A. Afanasev, C.M. Ankenbrandt, R.P. Johnson, G.M. Wang, S.A. Bogacz, Y.S. Derbenev

    2009-05-01

    Muon collider luminosity depends on the number of muons in the storage ring and on the transverse size of the beams in collision. Ionization cooling as it is currently envisioned will not cool the beam sizes sufficiently well to provide adequate luminosity without large muon intensities. Six-dimensional cooling schemes will reduce the longitudinal emittance of a muon beam so that smaller high frequency RF cavities can be used for later stages of cooling and for acceleration. However, the bunch length at collision energy is then shorter than needed to match the interaction region beta function. New ideas to shrink transverse beam dimensions by lengthening each bunch will help achieve high luminosity in muon colliders. Analytic expressions for the reverse emittance exchange mechanism were derived, including a new resonant method of beam focusing.

  15. In vitro culture and structural differences in the major immunoreactive protein gp36 of geographically distant Ehrlichia canis isolates.

    PubMed

    Zweygarth, Erich; Cabezas-Cruz, Alejandro; Josemans, Antoinette I; Oosthuizen, Marinda C; Matjila, Paul T; Lis, Katarzyna; Broniszewska, Marzena; Schöl, Heidrun; Ferrolho, Joana; Grubhoffer, Libor; Passos, Lygia M F

    2014-06-01

    Ehrlichia canis, the etiologic agent of canine ehrlichiosis, is an obligate intracytoplasmic Gram-negative tick-borne bacterium belonging to the Anaplasmataceae family. E. canis is distributed worldwide and can cause serious and fatal infections in dogs. Among strains of E. canis, the 16S rRNA gene DNA sequences are highly conserved. Using this gene to genetically differentiate isolates is therefore difficult. As an alternative, the gene gp36, which encodes for a major immunoreactive protein in E. canis, has been successfully used to characterize the genetic diversity of this pathogen. The present study describes the isolation and continuous propagation of a Spanish and 2 South African isolates of E. canis in IDE8 tick cells. Subsequently, canine DH82 cell cultures were infected using initial bodies obtained from infected IDE8 cultures. It was possible to mimic the life cycle of E. canis in vitro by transferring infection from tick cells to canine cells and back again. To characterize these E. canis strains at the molecular level, the 16S rRNA and gp36 genes were amplified by PCR, sequenced, and aligned with corresponding sequences available in GenBank. All 16S rRNA sequences amplified in this study were identical to previously reported E. canis strains. Maximum likelihood analysis based on the gp36 amino acid sequences showed that the South African and Spanish strains fall into 2 well-defined phylogenetic clusters amongst other E. canis strains. The members of these 2 phylogenetic clusters shared 2 unique molecular properties in the gp36 amino acid sequences: (i) deletion of glycine 117 and (ii) the presence of an additional putative N-linked glycosylation site. We further show correlation between the putative secondary structure and the theoretical isoelectric point (pI) of the gp36 amino acid sequences. A putative role of gp36 as an adhesin in E. canis is discussed. Overall, we report the successful in vitro culture of 3 new E. canis strains which present

  16. Shed GP of Ebola Virus Triggers Immune Activation and Increased Vascular Permeability

    PubMed Central

    Escudero-Pérez, Beatriz; Volchkova, Valentina A.; Dolnik, Olga; Lawrence, Philip; Volchkov, Viktor E.

    2014-01-01

    During Ebola virus (EBOV) infection a significant amount of surface glycoprotein GP is shed from infected cells in a soluble form due to cleavage by cellular metalloprotease TACE. Shed GP and non-structural secreted glycoprotein sGP, both expressed from the same GP gene, have been detected in the blood of human patients and experimentally infected animals. In this study we demonstrate that shed GP could play a particular role during EBOV infection. In effect it binds and activates non-infected dendritic cells and macrophages inducing the secretion of pro- and anti-inflammatory cytokines (TNFα, IL1β, IL6, IL8, IL12p40, and IL1-RA, IL10). Activation of these cells by shed GP correlates with the increase in surface expression of co-stimulatory molecules CD40, CD80, CD83 and CD86. Contrary to shed GP, secreted sGP activates neither DC nor macrophages while it could bind DCs. In this study, we show that shed GP activity is likely mediated through cellular toll-like receptor 4 (TLR4) and is dependent on GP glycosylation. Treatment of cells with anti-TLR4 antibody completely abolishes shed GP-induced activation of cells. We also demonstrate that shed GP activity is negated upon addition of mannose-binding sera lectin MBL, a molecule known to interact with sugar arrays present on the surface of different microorganisms. Furthermore, we highlight the ability of shed GP to affect endothelial cell function both directly and indirectly, demonstrating the interplay between shed GP, systemic cytokine release and increased vascular permeability. In conclusion, shed GP released from virus-infected cells could activate non-infected DCs and macrophages causing the massive release of pro- and anti-inflammatory cytokines and effect vascular permeability. These activities could be at the heart of the excessive and dysregulated inflammatory host reactions to infection and thus contribute to high virus pathogenicity. PMID:25412102

  17. Really large hadron collider working group summary

    SciTech Connect

    Dugan, G.; Limon, P.; Syphers, M.

    1996-12-01

    A summary is presented of preliminary studies of three 100 TeV center-of-mass hadron colliders made with magnets of different field strengths, 1.8T, 9.5T and 12.6T. Descriptions of the machines, and some of the major and most challenging subsystems, are presented, along with parameter lists and the major issues for future study.

  18. Top physics at the Tevatron Collider

    SciTech Connect

    Margaroli, Fabrizio; /Purdue U.

    2007-10-01

    The top quark has been discovered in 1995 at the CDF and DO experiments located in the Tevatron ring at the Fermilab laboratory. After more than a decade the Tevatron collider, with its center-of-mass energy collisions of 1.96 TeV, is still the only machine capable of producing such exceptionally heavy particle. Here I present a selection of the most recent CDF and DO measurements performed analyzing {approx} 1 fb{sup -1} of integrated luminosity.

  19. Longitudinal damping in the Tevatron collider

    SciTech Connect

    Kerns, Q.A.; Jackson, G.; Kerns, C.R.; Miller, H.; Reid, J.; Siemann, R.; Wildman, D.

    1989-03-01

    This paper describes the damper design for 6 proton on 6 pbar bunches in the Tevatron collider. Signal pickup, transient phase detection, derivative networks, and phase correction via the high-level rf are covered. Each rf station is controlled by a slow feedback loop. In addition, global feedback loops control each set of four cavities, one set for protons and one set for antiprotons. Operational experience with these systems is discussed. 7 refs., 9 figs.

  20. Progress report on the SLAC Linear Collider

    SciTech Connect

    Rees, J.

    1986-06-01

    The SLAC Linear Collider project (SLC) is reported as being near completion. The performance specifications are tabulated both for the initial form and for eventual goals. Various parts of the SLC are described and the status of their construction is reported, including the front end electron gun and booster, the linac, damping ring, positron source, SLC arcs, and conventional facilities. 5 refs., 12 figs. (LEW)

  1. Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing alpha-gal epitopes.

    PubMed

    Abdel-Motal, Ussama M; Wang, Shixia; Awad, Amany; Lu, Shan; Wigglesworth, Kim; Galili, Uri

    2010-02-17

    Developing an effective HIV-1 vaccine will require strategies to enhance antigen presentation to the immune system. In a previous study we demonstrated a marked increase in immunogenicity of the highly glycosylated HIV-1 gp120 protein following enzymatic addition of alpha-gal epitopes to the carbohydrate chains. In the present study we determined whether gp120(alphagal) can also serve as an effective platform for targeting other HIV-1 proteins to APC and thus increase immunogenicity of both proteins. For this purpose we produced a recombinant fusion protein between gp120 and the HIV-1 matrix p24 protein (gp120/p24). Multiple alpha-gal epitopes were synthesized enzymatically on the gp120 portion of the fusion protein to generate a gp120(alphagal)/p24 vaccine. Immune responses to gp120(alphagal)/p24 compared to gp120/p24 vaccine lacking alpha-gal epitopes were evaluated in alpha1,3galactosyltransferase knockout (KO) mice. These mice lack alpha-gal epitopes and, therefore, are capable of producing the anti-Gal antibody. T cell responses to p24, as assessed by ELISPOT and by CD8+ T cells intracellular staining assays for IFNgamma, was on average 12- and 10-fold higher, respectively, in gp120(alphagal)/p24 immunized mice than in mice immunized with gp120/p24. In addition, cellular and humoral immune responses against gp120 were higher by 10-30-fold in mice immunized with gp120(alphagal)/p24 than in gp120/p24 immunized mice. Our data suggest that the alpha-gal epitopes on the gp120 portion of the fusion protein can significantly augment the immunogenicity of gp120, as well as that of the fused viral protein which lacks alpha-gal epitopes. This strategy of anti-Gal mediated targeting to APC may be used for production of effective HIV-1 vaccines comprised of various viral proteins fused to gp120.

  2. Tryptophan dendrimers that inhibit HIV replication, prevent virus entry and bind to the HIV envelope glycoproteins gp120 and gp41.

    PubMed

    Rivero-Buceta, Eva; Doyagüez, Elisa G; Colomer, Ignacio; Quesada, Ernesto; Mathys, Leen; Noppen, Sam; Liekens, Sandra; Camarasa, María-José; Pérez-Pérez, María-Jesús; Balzarini, Jan; San-Félix, Ana

    2015-12-01

    Dendrimers containing from 9 to 18 tryptophan residues at the peryphery have been efficiently synthesized and tested against HIV replication. These compounds inhibit an early step of the replicative cycle of HIV, presumably virus entry into its target cell. Our data suggest that HIV inhibition can be achieved by the preferred interaction of the compounds herein described with glycoproteins gp120 and gp41 of the HIV envelope preventing interaction between HIV and the (co)receptors present on the host cells. The results obtained so far indicate that 9 tryptophan residues on the periphery are sufficient for efficient gp120/gp41 binding and anti-HIV activity.

  3. Role of GP82 in the selective binding to gastric mucin during oral infection with Trypanosoma cruzi.

    PubMed

    Staquicini, Daniela I; Martins, Rafael M; Macedo, Silene; Sasso, Gisela R S; Atayde, Vanessa D; Juliano, Maria A; Yoshida, Nobuko

    2010-03-02

    Oral infection by Trypanosoma cruzi has been the primary cause of recent outbreaks of acute Chagas' diseases. This route of infection may involve selective binding of the metacyclic trypomastigote surface molecule gp82 to gastric mucin as a first step towards invasion of the gastric mucosal epithelium and subsequent systemic infection. Here we addressed that question by performing in vitro and in vivo experiments. A recombinant protein containing the complete gp82 sequence (J18), a construct lacking the gp82 central domain (J18*), and 20-mer synthetic peptides based on the gp82 central domain, were used for gastric mucin binding and HeLa cell invasion assays, or for in vivo experiments. Metacyclic trypomastigotes and J18 bound to gastric mucin whereas J18* failed to bind. Parasite or J18 binding to submaxillary mucin was negligible. HeLa cell invasion by metacyclic forms was not affected by gastric mucin but was inhibited in the presence of submaxillary mucin. Of peptides tested for inhibition of J18 binding to gastric mucin, the inhibitory peptide p7 markedly reduced parasite invasion of HeLa cells in the presence of gastric mucin. Peptide p7*, with the same composition as p7 but with a scrambled sequence, had no effect. Mice fed with peptide p7 before oral infection with metacyclic forms developed lower parasitemias than mice fed with peptide p7*. Our results indicate that selective binding of gp82 to gastric mucin may direct T. cruzi metacyclic trypomastigotes to stomach mucosal epithelium in oral infection.

  4. 9-D polarized proton transport in the MEIC figure-8 collider ring: first steps

    SciTech Connect

    Meot, F.; Morozov, V. S.

    2014-10-24

    Spin tracking studies in the MEIC figure-8 collider ion ring are presented, based on a very preliminary design of the lattice. They provide numerical illustrations of some of the aspects of the figure-8 concept, including spin-rotator based spin control, and lay out the path towards a complete spin tracking simulation of a figure-8 ring.

  5. 9-D polarized proton transport in the MEIC figure 8 collider ring - first steps

    SciTech Connect

    Meot, F.; Morozov, V. S.

    2015-05-03

    Spin tracking studies in the MEIC figure-8 collider ion ring are presented, based on a very preliminary design of the lattice. They provide numerical illustrations of some of the aspects of the figure-8 concept, including spin-rotator based spin control, and lay out the path towards a complete spin tracking simulation of a figure-8 ring.

  6. Structure and Dynamics of Colliding Plasma Jets

    DOE PAGES

    Li, C.; Ryutov, D.; Hu, S.; ...

    2013-12-01

    Monoenergetic-proton radiographs of laser-generated, high-Mach-number plasma jets colliding at various angles shed light on the structures and dynamics of these collisions. The observations compare favorably with results from 2D hydrodynamic simulations of multistream plasma jets, and also with results from an analytic treatment of electron flow and magnetic field advection. In collisions of two noncollinear jets, the observed flow structure is similar to the analytic model’s prediction of a characteristic feature with a narrow structure pointing in one direction and a much thicker one pointing in the opposite direction. Spontaneous magnetic fields, largely azimuthal around the colliding jets and generatedmore » by the well-known ∇Te ×∇ne Biermann battery effect near the periphery of the laser spots, are demonstrated to be “frozen in” the plasma (due to high magnetic Reynolds number RM ~5×10⁴) and advected along the jet streamlines of the electron flow. These studies provide novel insight into the interactions and dynamics of colliding plasma jets.« less

  7. Structure and Dynamics of Colliding Plasma Jets

    SciTech Connect

    Li, C.; Ryutov, D.; Hu, S.; Rosenberg, M.; Zylstra, A.; Seguin, F.; Frenje, J.; Casey, D.; Gatu Johnson, M.; Manuel, M.; Rinderknecht, H.; Petrasso, R.; Amendt, P.; Park, H.; Remington, B.; Wilks, S.; Betti, R.; Froula, D.; Knauer, J.; Meyerhofer, D.; Drake, R.; Kuranz, C.; Young, R.; Koenig, M.

    2013-12-01

    Monoenergetic-proton radiographs of laser-generated, high-Mach-number plasma jets colliding at various angles shed light on the structures and dynamics of these collisions. The observations compare favorably with results from 2D hydrodynamic simulations of multistream plasma jets, and also with results from an analytic treatment of electron flow and magnetic field advection. In collisions of two noncollinear jets, the observed flow structure is similar to the analytic model’s prediction of a characteristic feature with a narrow structure pointing in one direction and a much thicker one pointing in the opposite direction. Spontaneous magnetic fields, largely azimuthal around the colliding jets and generated by the well-known ∇Te ×∇ne Biermann battery effect near the periphery of the laser spots, are demonstrated to be “frozen in” the plasma (due to high magnetic Reynolds number RM ~5×10⁴) and advected along the jet streamlines of the electron flow. These studies provide novel insight into the interactions and dynamics of colliding plasma jets.

  8. Linear collider IR and final focus introduction

    SciTech Connect

    Irwin, J.; Burke, D.

    1991-09-01

    The Linear Collider subgroup of the Accelerator Physics working group concerned itself with all aspects of the Next Linear Collider (NLC) design from the end of the accelerating structure to and through the interaction region. Within this region are: (1) a collimation section, (2) muon protection (of the detector from the collimator), (3) final focus system, (4) interaction point physics, and (5) detector masking from synchrotron radiation and beam-beam pair production. These areas of study are indicated schematically in Fig. 1. The parameters for the Next Linear Collider are still in motion, but attention has settled on a handful of parameter sets. Energies under consideration vary from 0.5 to 1.5 TeV in the center of mass, and luminosities vary from 10{sup 33} to 10{sup 34} cm{sup {minus}2}s{sup {minus}1}. To be concrete we chose as a guide for our studies the parameter sets labeled F and G, Table 1 from Palmer. These cover large and small crossing angle cases and 0.4 m to 1.8 m of free length at the interaction point.

  9. Advanced Concepts for Electron-Ion Collider

    SciTech Connect

    Yaroslav Derbenev

    2002-08-01

    A superconducting energy recovery linac (ERL) of 5 to 10 GeV was proposed earlier as an alternative to electron storage rings to deliver polarized electron beam for electron-ion collider (EIC). To enhance the utilization efficiency of electron beam from a polarized source, it is proposed to complement the ERL by circulator ring (CR) wherein the injected electrons undergo up to 100 revolutions colliding with the ion beam. In this way, electron injector and linac operate in pulsed current (beam energy recovery) regime of a relatively low average current, while the polarization is still easily delivered and preserved. To make it also easier delivering and manipulating the proton and light ion polarization, twisted (figure 8) synchrotrons are proposed for heavy particle booster and collider ring. Same type of beam orbit can be used then for electron circulator. Electron cooling (EC) of the ion beam is considered an inevitable component of high luminosity EIC (1033/s. cm2 or above). It is recognized that EC also gives a possibility to obtain very short ion bunches, that allows much stronger final focusing. At the same time, short bunches make feasible the crab crossing (and traveling focus for ion beam) at collision points, hence, allow maximizing the collision rate. As a result, one can anticipate the luminosity increase by one or two orders of magnitude.

  10. The Relativistic Heavy Ion Collider at Brookhaven

    SciTech Connect

    Hahn, H.

    1988-01-01

    The conceptual design of a Relativistic Heavy Ion Collider (RACK) to be constructed in the existing 3.8 km tunnel at Brookhaven has been developed. The collider has been designed to provide collisions of gold ions at six intersection points with a luminosity of about 5 /times/ 10/sup 26/cm/sup /minus/2/sec/sup /minus/1/ at an energy of 100 GeV/u in each beam. Collisions with different ion species, including protons, will be possible. The collider consists of two interlaced, but otherwise separate, superconducting magnet rings. The 9.7 m long dipoles will operate at 3.5 T. Their 8 cm aperture was determined by the dimensions of gold ion beams taking into account diffusion due to intrabeam scattering. Heavy ion beams will be available from the Tandem Van de Graaff/Booster/AGS complex. The salient design features and the reasons for major design choices of the proposed machine are discussed in this paper. 24 refs., 7 figs., 2 tabs.

  11. 2001 Report on the Next Linear Collider

    SciTech Connect

    Gronnberg, J; Breidenbach; Burke, D; Corlett, J; Dombeck, T; Markiewicz, T

    2001-08-28

    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.

  12. An Electron-Ion Collider at CEBAF

    SciTech Connect

    Kees de Jager; Lia Merminga; Ya. Derbenev

    2002-10-01

    Electron-ion colliders with a center of mass energy between 15 and 100 GeV, a luminosity of at least 10{sup 33}cm{sup -1}s{sup -1}, and a polarization of both beams at or above 80% have been proposed for future studies of hadronic structure. The scheme proposed here would accelerate the electron beam using the CEBAF recirculating linac with energy recovery. If all accelerating structures presently installed in the CEBAF tunnel are replaced by ones with a {approx}20 MV/m gradient, then a single recirculation results in an electron beam energy of about 5 GeV. After colliding with protons/light ions circulating in a figure-of-eight storage ring (for flexibility of spin manipulation) at an energy of up to 100 GeV, the electrons are re-injected into the CEBAF accelerator for deceleration and energy recovery. In this report several lay-out options and their respective feasibilities will be presented and discussed, together with parameters which would provide a luminosity of up to 1 x 10{sup 35} cm{sup -2}s{sup -1}. The feasibility of combining such a collider at a center-of-mass energy [sq rt] s of up to 43 GeV with a fixed target facility of 25 GeV is also explored.

  13. 2009: A Colliding-Wind Odyssey

    NASA Astrophysics Data System (ADS)

    Fahed, R.; Moffat, A. F. J.; Zorec, J.; Eversberg, T.; Chené, A. N.; Alves, F.; Arnold, W.; Bergmann, T.; Corcoran, M. F.; Correia Viegas, N. G.; Dougherty, S. M.; Fernando, A.; Frémat, Y.; Gouveia Carreira, L. F.; Hunger, T.; Knapen, J. H.; Leadbeater, R.; Marques Dias, F.; Martayan, C.; Morel, T.; Pittard, J. M.; Pollock, A. M. T.; Rauw, G.; Reinecke, N.; Ribeiro, J.; Romeo, N.; Sánchez-Gallego, J. R.; dos Santos, E. M.; Schanne, L.; Stahl, O.; Stober, Ba.; Stober, Be.; Vollmann, K.; Williams, P. M.

    2012-12-01

    We present the results from two optical spectroscopic campaigns on colliding-wind binaries (CWB) which both occurred in 2009. The first one was on WR 140 (WC7pd + O5.5fc), the archetype of CWB, which experienced periastron passage of its highly elliptical 8-year orbit in January. The WR 140 campaign consisted of a unique and constructive collaboration between amateur and professional astronomers and took place at half a dozen locations, including Teide Observatory, Observatoire de Haute Provence, Dominion Astrophysical Observatory, Observatoire du Mont-Mégantic and at several small private observatories. The second campaign was on a selection of 5 short-period WR + O binaries not yet studied for colliding-wind effects: WR 12 (WN8h), WR 21 (WN5o + O7 V), WR 30 (WC6 + O7.5 V), WR 31 (WN4o + O8), and WR 47 (WN6o + O5). The campaign took place at Leoncito Observatory, Argentina, during 1 month. We provide updated values of most of these systems for the orbital parameters, new estimates for the WR and O star masses and new constraints on the mass-loss rates and colliding wind geometry.

  14. Developing GP monitoring systems guided by a soft systems approach.

    PubMed

    Hindle, T

    1995-11-01

    This paper describes a selected aspect of a research project concerned with 'contracts and competition' in the recently reformed National Health Service. The particular feature highlighted in this paper is the central role played by the general practitioners in the health service as principal sources of the demands made on provider units (particularly hospitals) and, hence, critical determinants of volumes and costs in contracting. A practical outcome of the research has been the development of GP monitoring systems to be used by provider units particularly in the context of marketing-led referral expectations. The approach used to highlight areas of potential GP contract management and monitoring improvements has been a development of soft systems methodology.

  15. Inhibition of HIV-1 gp41 expression with hammerhead ribozymes.

    PubMed

    Fedoruk-Wyszomirska, Agnieszka; Szymański, Maciej; Głodowicz, Paweł; Gabryelska, Marta; Wyszko, Eliza; Estrin, William J; Barciszewski, Jan

    2015-10-01

    Despite great progress in the treatment of AIDS, HIV-1 remains one of the major concerns as a human pathogen. One of the therapeutic strategies against viral infections is the application of catalytic ribonucleic acids (ribozymes) that can significantly reduce expression of a target gene by site-specific hydrolysis of its mRNA. In the present paper, we report a study on the activity of several variants of hammerhead ribozymes targeting a conserved region within mRNA encoding HIV-1 envelope glycoprotein gp41. On the basis of the data from in vitro assays and gene silencing in the cultured cells, we propose a new hammerhead ribozyme targeting the gp41-encoding sequence that can be potentially used as a therapeutic agent in AIDS treatment. Moreover, we demonstrate that the hydrolytic activity of the ribozyme in the intracellular environment cannot be inferred solely from the results of in vitro experiments.

  16. Lessons learned from an Internet GP information system.

    PubMed

    Briggs, J S; Bradley, M P

    1998-01-01

    We describe the prototype of an application that in actual use would allow GPs to find out more information about consultants at hospitals. This would aid the GP in making the decision about which consultant a patient should be referred to. The requirements of the application from the GP's perspective are described, together with some of the issues that have to be resolved before hospitals can provide the necessary information in a standard format. The application is implemented as a client--server system using standard Internet technologies such as Java and HTML. This architecture has a number of advantages but also revealed some issues concerning security and the format of data, among other things. The project showed that there is a desire for such a system and that that desire can be fulfilled at a relatively low cost.

  17. Current and Future Scientific Investigations at GP-SANS

    NASA Astrophysics Data System (ADS)

    Debeer-Schmitt, Lisa; Bailey, Katherine; Melnichenko, Yuri; He, Lilin; Littrell, Ken

    The general-purpose small-angle neutron scattering beam line, GP-SANS, in operation since 2007, is optimized for investigation of structures with dimensions from 0.5 to 200 nm. Along with high neutron flux, sample environments can easily be integrated into the beam line providing the user a versatile temperature range from 30 mK to 1600 K. In addition, there are two cryomagnets (horizontal 4.5 T and vertical 8 T), pressure cells, stop flow cell, electrochemical cell, load frames and custom-build equipment available to users allowing for significant flexibility in experimental setup. GP-SANS has supported investigation of a diverse array of intriguing scientific topics, including polymer solutions, gel and blends, colloids, micelles, , molecular self-assembly and interactions in complex fluids, microemulsions, spin textures and magnetic domains in novel materials, porosity in geological materials and phase separation, grain growth, and orientation in metallurgical alloys.

  18. HIV-1 gp120 as a therapeutic target: Navigating a moving labyrinth

    PubMed Central

    Acharya, Priyamvada; Lusvarghi, Sabrina; Bewley, Carole A.; Kwong, Peter D.

    2015-01-01

    Introduction The HIV-1 gp120 envelope (Env) glycoprotein mediates attachment of virus to human target cells that display requisite receptors, CD4 and co-receptor, generally CCR5. Despite high affinity interactions with host receptors and proof-of-principle by the drug maraviroc that interference with CCR5 provides therapeutic benefit, no licensed drug currently targets gp120. Areas covered An overview of the role of gp120 in HIV-1 entry and of sites of potential gp120 vulnerability to therapeutic inhibition is presented. Viral defenses that protect these sites and turn gp120 into a moving labyrinth are discussed together with strategies for circumventing these defenses to allow therapeutic targeting of gp120 sites of vulnerability. Expert opinion The gp120 envelope glycoprotein interacts with host proteins through multiple interfaces and has conserved structural features at these interaction sites. In spite of this, targeting gp120 for therapeutic purposes is challenging. Env mechanisms evolved to evade the humoral immune response also shield it from potential therapeutics. Nevertheless, substantial progress has been made in understanding HIV-1 gp120 structure and its interactions with host receptors, and in developing therapeutic leads that potently neutralize diverse HIV-1 strains. Synergies between advances in understanding, needs for therapeutics against novel viral targets, and characteristics of breadth and potency for a number of gp120-targetting lead molecules bodes well for gp120 as a HIV-1 therapeutic target. PMID:25724219

  19. Characterization of a trimeric MPER containing HIV-1 gp41 antigen

    SciTech Connect

    Hinz, Andreas; Schoehn, Guy; Quendler, Heribert; Hulsik, David Lutje; Stiegler, Gabi; Katinger, Hermann; Seaman, Michael S.; Montefiori, David; Weissenhorn, Winfried

    2009-08-01

    The membrane-proximal external region (MPER) of gp41 is considered as a prime target for the induction of neutralizing antibodies, since it contains the epitopes for three broadly neutralizing antibodies (2F5, 4E10 and Z13). Here we present a novel gp41 construct (HA-gp41) comprising gp41 HR2 and MPER fused to two triple-stranded coiled-coil domains at both ends. HA-gp41 is trimeric, has a high helical content in solution and forms rod-like structures as revealed by negative staining electron microscopy. Immunization of rabbits with HA-gp41 induced antibodies directed against MPER, which failed to exert significant neutralization capacity against envelopes from primary isolates. Thus trimerisation of MPER regions does not suffice to induce a potent neutralizing antibody response specific for conserved regions within gp41.

  20. JGR-Solid Earth and Planets GP editor appointed

    NASA Astrophysics Data System (ADS)

    Ken Hoffman (Physics Department, California Polytechnic State University, San Luis Obispo) has been appointed GP editor for papers submitted to the Journal of Geophysical Research—Solid Earth and Planets. His tenure will be from January 1987 to December 1988. Hoffman holds a Ph.D. in geophysics from the University of California, Berkeley, and has published extensively in the areas of rock magnetism, paleomagnetism, lunar paleointensity, and most recently, geomagnetic dipole field reversal modeling.

  1. Formation and repair kinetics of Pt-(GpG) DNA adducts in extracted circulating tumour cells and response to platinum treatment

    PubMed Central

    Nel, I; Gauler, T C; Eberhardt, W E; Nickel, A-C; Schuler, M; Thomale, J; Hoffmann, A-C

    2013-01-01

    Background: Pt-(GpG) intrastrand crosslinks are the major DNA adducts induced by platinum-based anticancer drugs. In the cell lines and mouse models, the persistence of these lesions correlates significantly with cell damage. Here we studied Pt-(GpG) DNA adducts in circulating tumour cells (CTC) treated with cisplatin in medium upfront to systemic therapy from patients with advanced non-small-cell lung cancer (NSCLC). Methods: Blood was drawn before systemic treatment and the CD45/CD15-depleted fraction of mononuclear cells was exposed to cisplatin, verified for the presence of CTC by pan-cytokeratin (pCK) staining and immunoanalysed for the level of Pt-(GpG) in DNA. Results: Immunostaining for pCK, CD45 and subsequently for Pt-(GpG) adducts in the cisplatin-exposed cells (ex vivo) at different time points depicted distinct differences for adduct persistence in CTC between responders vs non-responders. Conclusion: Pt-(GpG) adducts can be detected in CTC from NSCLC patients and assessing their kinetics may constitute a clinically feasible biomarker for response prediction and dose individualisation of platinum-based chemotherapy. This functional pre-therapeutic test might represent a more biological approach than measuring protein factors or other molecular markers. PMID:23942068

  2. The Role of gp120 Flexibility in Binding

    NASA Astrophysics Data System (ADS)

    Rader, A. J.

    2009-03-01

    Current treatment of the human immunodeficiency virus (HIV) focuses on delivering several drugs to to a few specific viral protein targets. A complementary antiviral therapy involves targeting the process of viral entry. Viral entry is a dynamic process which involves a series of conformational changes by the HIV envelope glycoproteins (gp120 and gp41). The extraordinary conformational flexibility, glycosylation and strain variability of these proteins complicate the development of an effective vaccine. We present results from the graph theoretical analysis of flexibility and rigidity using the Floppy Inclusion and Rigid Substructure Topography (FIRST) software for all known HIV-1 gp120 structures. Comparisons between structures using this mechanical stability and intrinsic flexibility is used to identify a consensus rigid region that might serve as drug targets in a pre-complex conformation. Furthermore, analysis of structures with various binding partners illustrates the differential partitioning of mechanical flexibility and strain. We relate these differences in mechanical stability to thermodynamic differences in binding and stabilizing mutations.

  3. Neutralizing Antibodies from the Sera of Human Immunodeficiency Virus Type 1-Infected Individuals Bind to Monomeric gp120 and Oligomeric gp140

    PubMed Central

    Stamatos, Nicholas M.; Mascola, John R.; Kalyanaraman, Vaniambadi S.; Louder, Mark K.; Frampton, Lynn M.; Birx, Deborah L.; VanCott, Thomas C.

    1998-01-01

    Antibodies that neutralize primary isolates of human immunodeficiency virus type 1 (HIV-1) appear during HIV-1 infection but are difficult to elicit by immunization with current vaccine products comprised of monomeric forms of HIV-1 envelope glycoprotein gp120. The limited neutralizing antibody response generated by gp120 vaccine products could be due to the absence or inaccessibility of the relevant epitopes. To determine whether neutralizing antibodies from HIV-1-infected patients bind to epitopes accessible on monomeric gp120 and/or oligomeric gp140 (ogp140), purified total immunoglobulin from the sera of two HIV-1-infected patients as well as pooled HIV immune globulin were selectively depleted of antibodies which bound to immobilized gp120 or ogp140. After passage of each immunoglobulin preparation through the respective columns, antibody titers against gp120 and ogp140 were specifically reduced at least 128-fold. The gp120- and gp140-depleted antibody fraction from each serum displayed reduced neutralization activity against three primary and two T-cell line-adapted (TCLA) HIV-1 isolates. Significant residual neutralizing activity, however, persisted in the depleted sera, indicating additional neutralizing antibody specificities. gp120- and ogp140-specific antibodies eluted from each column neutralized both primary and TCLA viruses. These data demonstrate the presence and accessibility of epitopes on both monomeric gp120 and ogp140 that are specific for antibodies that are capable of neutralizing primary isolates of HIV-1. Thus, the difficulties associated with eliciting neutralizing antibodies by using current monomeric gp120 subunit vaccines may be related less to improper protein structure and more to ineffective immunogen formulation and/or presentation. PMID:9811699

  4. Antibody to gp41 MPER alters functional properties of HIV-1 Env without complete neutralization.

    PubMed

    Kim, Arthur S; Leaman, Daniel P; Zwick, Michael B

    2014-07-01

    Human antibody 10E8 targets the conserved membrane proximal external region (MPER) of envelope glycoprotein (Env) subunit gp41 and neutralizes HIV-1 with exceptional potency. Remarkably, HIV-1 containing mutations that reportedly knockout 10E8 binding to linear MPER peptides are partially neutralized by 10E8, producing a local plateau in the dose response curve. Here, we found that virus partially neutralized by 10E8 becomes significantly less neutralization sensitive to various MPER antibodies and to soluble CD4 while becoming significantly more sensitive to antibodies and fusion inhibitors against the heptad repeats of gp41. Thus, 10E8 modulates sensitivity of Env to ligands both pre- and post-receptor engagement without complete neutralization. Partial neutralization by 10E8 was influenced at least in part by perturbing Env glycosylation. With unliganded Env, 10E8 bound with lower apparent affinity and lower subunit occupancy to MPER mutant compared to wild type trimers. However, 10E8 decreased functional stability of wild type Env while it had an opposite, stabilizing effect on MPER mutant Envs. Clade C isolates with natural MPER polymorphisms also showed partial neutralization by 10E8 with altered sensitivity to various gp41-targeted ligands. Our findings suggest a novel mechanism of virus neutralization by demonstrating how antibody binding to the base of a trimeric spike cross talks with adjacent subunits to modulate Env structure and function. The ability of an antibody to stabilize, destabilize, partially neutralize as well as alter neutralization sensitivity of a virion spike pre- and post-receptor engagement may have implications for immunotherapy and vaccine design.

  5. Estimates of Hadronic Backgrounds in Future e+e- LinearColliders

    SciTech Connect

    Ohgaki, Tomomi

    1998-05-01

    We have estimated hadronic backgrounds for an e+e- linear collider at a center- of-mass energy of 5 TeV. In order to achieve a required luminosity in TeV e+ e- colliders, the high beamstrahlung parameter {Upsilon}, such as several thousands, is caused. In the high {Upsilon} regime, the {gamma}{gamma} luminosities due to the collision of beamstrahlung photons are calculated by using the CAIN code. According to the {gamma}{gamma} luminosity distribution, we have estimated the hadronic backgrounds of {gamma}{gamma} {yields} minijets based on the parton distributions of the Drees and Grassie model by the PYTHIA 5.7 code. The Japan Linear Collider (J LC-1) detector simulator is applied for selection performances in the detector.

  6. Development of a Non-Magnetic Inertial Sensor for Vibration Stabilization in a Linear Collider

    SciTech Connect

    Frisch, Josef; Decker, Valentin; Doyle, Eric; Hendrickson, Linda; Himel, Thomas; Markiewicz, Thomas; Seryi, Andrei; Chang, Allison; Partridge, Richard; /Brown U.

    2006-09-01

    One of the options for controlling vibration of the final focus magnets in a linear collider is to use active feedback based on accelerometers. While commercial geophysics sensors have noise performance that substantially exceeds the requirements for a linear collider, they are physically large, and cannot operate in the strong magnetic field of the detector. Conventional nonmagnetic sensors have excessive noise for this application. We report on the development of a non-magnetic inertial sensor, and on a novel commercial sensor both of which have demonstrated the required noise levels for this application.

  7. On the Preference of Cold RF Technology for the International Linear Collider

    SciTech Connect

    Gamp, Alexander

    2006-01-03

    On August 20th 2004 the International Technology Recommendation Panel (ITRP) released its recommendation that the Linear Collider be based on Superconducting RF Technology. Following a request of the organizers of this conference we will summarise in this article the arguments worked out and presented by the ITRP, which led to this recommendation. The main features of both RF-technologies, the favoured L-band RF system of the superconducting version of the Linear Collider and the X-band-technology anticipated for the normal-conducting alternative will be briefly described.

  8. GPU-optimized Code for Long-term Simulations of Beam-beam Effects in Colliders

    SciTech Connect

    Roblin, Yves; Morozov, Vasiliy; Terzic, Balsa; Aturban, Mohamed A.; Ranjan, D.; Zubair, Mohammed

    2013-06-01

    We report on the development of the new code for long-term simulation of beam-beam effects in particle colliders. The underlying physical model relies on a matrix-based arbitrary-order symplectic particle tracking for beam transport and the Bassetti-Erskine approximation for beam-beam interaction. The computations are accelerated through a parallel implementation on a hybrid GPU/CPU platform. With the new code, a previously computationally prohibitive long-term simulations become tractable. We use the new code to model the proposed medium-energy electron-ion collider (MEIC) at Jefferson Lab.

  9. Survey and alignment for a 20-TeV on 20-TeV collider

    SciTech Connect

    Close, E.R.; Douglas, D.R.; Sah, R.C.

    1983-08-01

    The effects of magnet misalignments in a 20-TeV on 20-TeV anti pp collider are simulated numerically. Both short-range and long-range alignment errors are considered for an example lattice design, and closed-orbit errors are simulated. Finally, closed orbit corrections using a least-squares scheme are performed. Automatic surveying methods are attractive for a multi-TeV collider, because of the large accelerator circumference, the large number of magnets, and the small tunnel cross section. The specific example of an automatic surveying scheme based upon an Inertial Navigation System is discussed, and the most important sources of error are described.

  10. Calculation of detector backgrounds at TeV linear colliders

    SciTech Connect

    Himel, T.

    1988-11-01

    It is necessary to carefully design masks and beam lines to prevent the high energy physics detector from being inundated with background particles from a high energy linear collider. Presented here are preliminary calculations on two of the three expected backgrounds: photons from synchrotron radiation produced in the final focus quadrupoles, and electrons which lose energy due to bremsstrahlung and are then bent into a mask or quadrupole by the field of the opposite beam. The former can be controlled with proper masking. The latter may pose a problem, so further calculations are needed. Work was also done on the third expected source of background: electrons in the tail of the beam which hit masks where showers are made whose products enter the detector. This work was very preliminary and is not included in this write-up. All the calculations here are based on the 1 TeV center-of-mass linear collider design of R. Palmer and the final focus design of K. Oide which can be found in these proceedings. Extrapolations to other accelerator designs should be straightforward.

  11. The International Linear Collider Technical Design Report - Volume 2: Physics

    SciTech Connect

    Baer, Howard; Barklow, Tim; Fujii, Keisuke; Gao, Yuanning; Hoang, Andre; Kanemura, Shinya; List, Jenny; Logan, Heather E.; Nomerotski, Andrei; Perelstein, Maxim; Peskin, Michael E.; Pöschl, Roman; Reuter, Jürgen; Riemann, Sabine; Savoy-Navarro, Aurore; Tait, Tim P.; Yu, Jaehoon

    2013-06-26

    The International Linear Collider Technical Design Report (TDR) describes in four volumes the physics case and the design of a 500 GeV centre-of-mass energy linear electron-positron collider based on superconducting radio-frequency technology using Niobium cavities as the accelerating structures. The accelerator can be extended to 1 TeV and also run as a Higgs factory at around 250 GeV and on the Z0 pole. A comprehensive value estimate of the accelerator is give, together with associated uncertainties. It is shown that no significant technical issues remain to be solved. Once a site is selected and the necessary site-dependent engineering is carried out, construction can begin immediately. The TDR also gives baseline documentation for two high-performance detectors that can share the ILC luminosity by being moved into and out of the beam line in a "push-pull" configuration. These detectors, ILD and SiD, are described in detail. They form the basis for a world-class experimental programme that promises to increase significantly our understanding of the fundamental processes that govern the evolution of the Universe.

  12. The International Linear Collider Technical Design Report - Volume 4: Detectors

    SciTech Connect

    Behnke, Ties

    2013-06-26

    The International Linear Collider Technical Design Report (TDR) describes in four volumes the physics case and the design of a 500 GeV centre-of-mass energy linear electron-positron collider based on superconducting radio-frequency technology using Niobium cavities as the accelerating structures. The accelerator can be extended to 1 TeV and also run as a Higgs factory at around 250 GeV and on the Z0 pole. A comprehensive value estimate of the accelerator is give, together with associated uncertainties. It is shown that no significant technical issues remain to be solved. Once a site is selected and the necessary site-dependent engineering is carried out, construction can begin immediately. The TDR also gives baseline documentation for two high-performance detectors that can share the ILC luminosity by being moved into and out of the beam line in a "push-pull" configuration. These detectors, ILD and SiD, are described in detail. They form the basis for a world-class experimental programme that promises to increase significantly our understanding of the fundamental processes that govern the evolution of the Universe.

  13. Global Numerical Modeling of the Muon Collider Target

    NASA Astrophysics Data System (ADS)

    Roman, Samulyak; Glimm, James

    2000-11-01

    The problem of free surface instabilities is the major concern in the study of the Muon Collider target. The target is in the form of a mercury jet interacting with high energy proton beams in the presence of a strong magnetic field. Strong pressure waves caused by the target - proton beam interaction lead to strong disturbances of the jet surface and to the jet breakup into droplets. The global numerical simulation of the Muon Collider target was done by using FronTier, a compressible fluid dynamics code. FronTier is capable to work with free surfaces and, in particular, to model the propagation of free jets. The code is based on the method of front tracking, a numerical technique for solving systems of conservation laws in which the evolution of discontinuities is determined through the solution of the associated Riemann problem. To model the behavior of the real material (mercury) under the influence of proton beams a SESAME type tabulated equation of state for mercury was created in a wide temperature - density domain which includes the fluid state of mercury, the vapor state and the state above the critical point. The numerical simulation of the target evolution driven by strong pressure waves is important for the optimal target design.

  14. eRHIC - Future Electron-Ion Collider at BNL

    SciTech Connect

    Ptitsyn, V.

    2006-07-11

    The work on the detailed design of electron-ion collider, eRHIC, on the basis of existing RHIC machine is underway. eRHIC aims to be an instrument for the exploration of important QCD aspects using collisions of polarized electrons and positrons on ions and polarized protons in the center of mass energy range of 30-100 GeV, with a luminosity of 1032-1034 cm-2s-1 for c-p and 1030-1032 cm-2s-1 for c-Au collisions. An electron accelerator, which delivers about 0.5A polarized electron beam current in the electron energy range of 5 to 10 GeV, would be constructed at BNL, near the existing RHIC complex and would intersect an ion ring in at least one of the available ion ring interaction regions. One design option considers the circular electron machine based on the accelerator technology similar to that of storage rings at the e+-e- B-factories. Another pursued design option employs an energy recovery linac for electron acceleration. This option paves way to higher luminosities but meets challenges of developments of high current electron polarized source and high beam power ERL technologies. To maximize the collider luminosity certain upgrades are considered for RHIC ion rings.

  15. Highly Polarized Ion Sources for Electron Ion Colliders (EIC)

    SciTech Connect

    V.G. Dudnikov, R.P. Johnson, Y.S. Derbenev, Y. Zhang

    2010-03-01

    The operation of the RHIC facility at BNL and the Electron Ion Colliders (EIC) under development at Jefferson Laboratory and BNL need high brightness ion beams with the highest polarization. Charge exchange injection into a storage ring or synchrotron and Siberian snakes have the potential to handle the needed polarized beam currents, but first the ion sources must create beams with the highest possible polarization to maximize collider productivity, which is proportional to a high power of the polarization. We are developing one universal H-/D- ion source design which will synthesize the most advanced developments in the field of polarized ion sources to provide high current, high brightness, ion beams with greater than 90% polarization, good lifetime, high reliability, and good power efficiency. The new source will be an advanced version of an atomic beam polarized ion source (ABPIS) with resonant charge exchange ionization by negative ions. An integrated ABPIS design will be prepared based on new materials and an optimized magnetic focusing system. Polarized atomic and ion beam formation, extraction, and transport for the new source will be computer simulated.

  16. Superconducting Magnet Technology for Future High Energy Proton Colliders

    NASA Astrophysics Data System (ADS)

    Gourlay, Stephen

    2017-01-01

    Interest in high field dipoles has been given a boost by new proposals to build a high-energy proton-proton collider to follow the LHC and programs around the world are taking on the task to answer the need. Studies aiming toward future high-energy proton-proton colliders at the 100 TeV scale are now being organized. The LHC and current cost models are based on technology close to four decades old and point to a broad optimum of operation using dipoles with fields between 5 and 12T when site constraints, either geographical or political, are not a factor. Site geography constraints that limit the ring circumference can drive the required dipole field up to 20T, which is more than a factor of two beyond state-of-the-art. After a brief review of current progress, the talk will describe the challenges facing future development and present a roadmap for moving high field accelerator magnet technology forward. This work was supported by the Director, Office of Science, High Energy Physics, US Department of Energy, under contract No. DE-AC02-05CH11231.

  17. Mini-P-gp and P-gp Co-Expression in Brown Trout Erythrocytes: A Prospective Blood Biomarker of Aquatic Pollution

    PubMed Central

    Valton, Emeline; Amblard, Christian; Desmolles, François; Combourieu, Bruno; Penault-Llorca, Frédérique; Bamdad, Mahchid

    2015-01-01

    In aquatic organisms, such as fish, blood is continually exposed to aquatic contaminants. Multidrug Resistance (MDR) proteins are ubiquitous detoxification membrane pumps, which recognize various xenobiotics. Moreover, their expression is induced by a large class of drugs and pollutants. We have highlighted the co-expression of a mini P-gp of 75 kDa and a P-gp of 140 kDa in the primary culture of brown trout erythrocytes and in the erythrocytes of wild brown trout collected from three rivers in the Auvergne region of France. In vitro experiments showed that benzo[a]pyrene, a highly toxic pollutant model, induced the co-expression of mini-P-gp and P-gp in trout erythrocytes in a dose-dependent manner and relay type response. Similarly, in the erythrocytes of wild brown trout collected from rivers contaminated by a mixture of PAH and other multi-residues of pesticides, mini-P-gp and P-gp were able to modulate their expression, according to the nature of the pollutants. The differential and complementary responses of mini-P-gp and P-gp in trout erythrocytes suggest the existence in blood cells of a real protective network against xenobiotics/drugs. This property could be exploited to develop a blood biomarker of river pollution. PMID:26854141

  18. Structural Basis for Species Selectivity in the HIV-1 gp120-CD4 Interaction: Restoring Affinity to gp120 in Murine CD4 Mimetic Peptides

    PubMed Central

    Kassler, Kristin; Meier, Julia; Eichler, Jutta; Sticht, Heinrich

    2011-01-01

    The first step of HIV-1 infection involves interaction between the viral glycoprotein gp120 and the human cellular receptor CD4. Inhibition of the gp120-CD4 interaction represents an attractive strategy to block HIV-1 infection. In an attempt to explore the known lack of affinity of murine CD4 to gp120, we have investigated peptides presenting the putative gp120-binding site of murine CD4 (mCD4). Molecular modeling indicates that mCD4 protein cannot bind gp120 due to steric clashes, while the larger conformational flexibility of mCD4 peptides allows an interaction. This finding is confirmed by experimental binding assays, which also evidenced specificity of the peptide-gp120 interaction. Molecular dynamics simulations indicate that the mCD4-peptide stably interacts with gp120 via an intermolecular β-sheet, while an important salt-bridge formed by a C-terminal lysine is lost. Fixation of the C-terminus by introducing a disulfide bridge between the N- and C-termini of the peptide significantly enhanced the affinity to gp120. PMID:22312332

  19. Genetic analysis and natural polymorphisms in HIV-1 gp41 isolates from Maputo City, Mozambique.

    PubMed

    Ismael, Nália; Bila, Dulce; Mariani, Diana; Vubil, Adolfo; Mabunda, Nedio; Abreu, Celina; Jani, Ilesh; Tanuri, Amilcar

    2014-06-01

    Enfuvirtide was the first fusion inhibitor approved by the Food and Drug Administration (FDA) in 2003 for HIV-1 infection in treatment-experienced patient. It is the first approved antiviral agent to attack the HIV life cycle in its early stages. For HIV fusion to occur, the HR1 and HR2 domains in the gp41 region need to interact. Enfuvirtide is a synthetic peptide that corresponds to 36 amino acids of the HR2, which competitively binds to HR1 inhibiting the interaction with the HR2 domain thus preventing fusogenic conformation and inhibiting viral entry into host cells. Resistance to enfuvirtide is conferred by mutations occurring in the HR1 region involving residues 36-45. Mozambique, a sub-Saharan country, with an HIV prevalence of 11.5%, provides first line and second line antiretroviral therapy (ART)-based treatment. In poor resource settings such as Mozambique the lack of adequate infrastructures, the high costs of viral load tests, and the availability of salvage treatment have hindered the intended objective of monitoring HIV treatment, suggesting an important concern regarding the development of drug resistance. The general aim of this study was to evaluate naturally occurring polymorphisms and resistance-associated mutations in the gp41 region of HIV-1 isolates from Mozambique. The study included 78 patients naive to ARV treatment and 28 patients failing first line regimen recruited from Centro de Saúde Alto-Maé situated in Maputo. The gp41 gene from 103 patients was sequenced and resistance-associated mutations for enfuvirtide were screened. Subtype analysis revealed that 96% of the sequences were classified as subtype C, 2% as subtype G, 1% as subtype A1, and the other 1% as a mosaic form composed of A1/C. No enfuvirtide resistance-associated mutations in HR1 of gp41 were detected. The major polymorphisms in the HR1 were N42S, L54M, A67T, and V72I. This study suggests that this new class of antiviral drug may be effective as a salvage therapy in

  20. Models for the Binary Complex of Bacteriophage T4 Gp59 Helicase Loading Protein. GP32 Single-Stranded DNA-Binding Protein and Ternary Complex with Pseudo-Y Junction DNA

    SciTech Connect

    Hinerman, Jennifer M.; Dignam, J. David; Mueser, Timothy C.

    2012-04-05

    The bacteriophage T4 gp59 helicase assembly protein (gp59) is required for loading of gp41 replicative helicase onto DNA protected by gp32 single-stranded DNA-binding protein. The gp59 protein recognizes branched DNA structures found at replication and recombination sites. Binding of gp32 protein (full-length and deletion constructs) to gp59 protein measured by isothermal titration calorimetry demonstrates that the gp32 protein C-terminal A-domain is essential for protein-protein interaction in the absence of DNA. Sedimentation velocity experiments with gp59 protein and gp32ΔB protein (an N-terminal B-domain deletion) show that these proteins are monomers but form a 1:1 complex with a dissociation constant comparable with that determined by isothermal titration calorimetry. Small angle x-ray scattering (SAXS) studies indicate that the gp59 protein is a prolate monomer, consistent with the crystal structure and hydrodynamic properties determined from sedimentation velocity experiments. SAXS experiments also demonstrate that gp32ΔB protein is a prolate monomer with an elongated A-domain protruding from the core. Moreover, fitting structures of gp59 protein and the gp32 core into the SAXS-derived molecular envelope supports a model for the gp59 protein-gp32ΔB protein complex. Our earlier work demonstrated that gp59 protein attracts full-length gp32 protein to pseudo-Y junctions. A model of the gp59 protein-DNA complex, modified to accommodate new SAXS data for the binary complex together with mutational analysis of gp59 protein, is presented in the accompanying article (Dolezal, D., Jones, C. E., Lai, X., Brister, J. R., Mueser, T. C., Nossal, N. G., and Hinton, D. M. (2012) J. Biol. Chem. 287, 18596–18607).

  1. The dark penguin shines light at colliders

    NASA Astrophysics Data System (ADS)

    Primulando, Reinard; Salvioni, Ennio; Tsai, Yuhsin

    2015-07-01

    Collider experiments are one of the most promising ways to constrain Dark Matter (DM) interactions. For several types of DM-Standard Model couplings, a meaningful interpretation of the results requires to go beyond effective field theory, considering simplified models with light mediators. This is especially important in the case of loop-mediated interactions. In this paper we perform the first simplified model study of the magnetic dipole interacting DM, by including the one-loop momentum-dependent form factors that mediate the coupling — given by the Dark Penguin — in collider processes. We compute bounds from the monojet, monophoton, and diphoton searches at the 8 and 14 TeV LHC, and compare the results to those of direct and indirect detection experiments. Future searches at the 100 TeV hadron collider and at the ILC are also addressed. We find that the optimal search strategy requires loose cuts on the missing transverse energy, to capture the enhancement of the form factors near the threshold for on-shell production of the mediators. We consider both minimal models and models where an additional state beyond the DM is accessible. In the latter case, under the assumption of anarchic flavor structure in the dark sector, the LHC monophoton and diphoton searches will be able to set much stronger bounds than in the minimal scenario. A determination of the mass of the heavier dark fermion might be feasible using the M T2 variable. In addition, if the Dark Penguin flavor structure is almost aligned with that of the DM mass, a displaced signal from the decay of the heavier dark fermion into the DM and photon can be observed. This allows us to set constraints on the mixings and couplings of the model from an existing search for non-pointing photons.

  2. Electron Cloud Effect in the Linear Colliders

    SciTech Connect

    Pivi, M

    2004-09-13

    Beam induced multipacting, driven by the electric field of successive positively charged bunches, may arise from a resonant motion of electrons, generated by secondary emission, bouncing back and forth between opposite walls of the vacuum chamber. The electron-cloud effect (ECE) has been observed or is expected at many storage rings [1]. In the beam pipe of the Damping Ring (DR) of a linear collider, an electron cloud is produced initially by ionization of the residual gas and photoelectrons from the synchrotron radiation. The cloud is then sustained by secondary electron emission. This electron cloud can reach equilibrium after the passage of only a few bunches. The electron-cloud effect may be responsible for collective effects as fast coupled-bunch and single-bunch instability, emittance blow-up or incoherent tune shift when the bunch current exceeds a certain threshold, accompanied by a large number of electrons in the vacuum chamber. The ECE was identified as one of the most important R&D topics in the International Linear Collider Report [2]. Systematic studies on the possible electron-cloud effect have been initiated at SLAC for the GLC/NLC and TESLA linear colliders, with particular attention to the effect in the positron main damping ring (MDR) and the positron Low Emittance Transport which includes the bunch compressor system (BCS), the main linac, and the beam delivery system (BDS). We present recent computer simulation results for the main features of the electron cloud generation in both machine designs. Thus, single and coupled-bunch instability thresholds are estimated for the GLC/NLC design.

  3. Pseudorabies virus glycoproteins gII and gp50 are essential for virus penetration.

    PubMed Central

    Rauh, I; Mettenleiter, T C

    1991-01-01

    Pseudorabies virus (PrV) glycoproteins gII and gp50 are major constituents of the viral envelope and targets of neutralizing monoclonal antibodies. Both are homologs of essential glycoproteins found in herpes simplex virus, gB (gII) and gD (gp50). We recently isolated a gII-negative PrV deletion mutant on complementing cell lines and established the essential character of gII for PrV replication (I. Rauh, F. Weiland, F. Fehler, G. Keil, and T.C. Mettenleiter, J. Virol. 65: 621-631, 1991). In this report, we describe the isolation of a gp50-negative PrV mutant after constructing cell lines that constitutively express gp50 and phenotypically complement the gp50 defect. Analysis of the gp50- mutant proved that gp50 is essential for PrV replication. Further studies showed that both gII and gp50 are required for viral penetration into target cells. The penetration defect in the gII and gp50 deletion mutants could be overcome by experimental polyethylene glycol-induced membrane fusion. Surprisingly, whereas gII proved to be essential for both penetration and cell-cell spread of the virus, gp50 was required only for penetration and appeared dispensable for direct cell-cell spread. Images PMID:1654444

  4. Molecular and Physicochemical Factors Governing Solubility of the HIV gp41 Ectodomain.

    PubMed

    Manssour-Triedo, Fadia; Crespillo, Sara; Morel, Bertrand; Casares, Salvador; Mateo, Pedro L; Notka, Frank; Roger, Marie G; Mouz, Nicolas; El-Habib, Raphaelle; Conejero-Lara, Francisco

    2016-08-23

    The HIV gp41 ectodomain (e-gp41) is an attractive target for the development of vaccines and drugs against HIV because of its crucial role in viral fusion to the host cell. However, because of the high insolubility of e-gp41, most biophysical and structural analyses have relied on the production of truncated versions removing the loop region of gp41 or the utilization of nonphysiological solubilizing conditions. The loop region of gp41 is also known as principal immunodominant domain (PID) because of its high immunogenicity, and it is essential for gp41-mediated HIV fusion. In this study we identify the aggregation-prone regions of the amino acid sequence of the PID and engineer a highly soluble mutant that preserves the trimeric structure of the wild-type e-gp41 under physiological pH. Furthermore, using a reverse mutagenesis approach, we analyze the role of mutated amino acids upon the physicochemical factors that govern solubility of e-gp41. On this basis, we propose a molecular model for e-gp41 self-association, which can guide the production of soluble e-gp41 mutants for future biophysical analyses and biotechnological applications.

  5. The Large Hadron Collider and Grid computing.

    PubMed

    Geddes, Neil

    2012-02-28

    We present a brief history of the beginnings, development and achievements of the worldwide Large Hadron Collider Computing Grid (wLCG). The wLCG is a huge international endeavour, which is itself embedded within, and directly influences, a much broader computing and information technology landscape. It is often impossible to identify true cause and effect, and they may appear very different from the different perspectives (e.g. information technology industry or academic researcher). This account is no different. It represents a personal view of the developments over the last two decades and is therefore inevitably biased towards those things in which the author has been personally involved.

  6. Relativistic klystron research for linear colliders

    SciTech Connect

    Allen, M.A.; Callin, R.S.; Deruyter, H.; Eppley, K.R.; Fant, K.S.; Fowkes, W.R.; Herrmannsfeldt, W.B.; Higo, T.; Hoag, H.A.; Koontz, R.F.

    1988-09-01

    Relativistic klystrons are being developed as a power source for high gradient accelerator applications which include large linear electron-positron colliders, compact accelerators, and FEL sources. We have attained 200 MW peak power at 11.4 GHz from a relativistic klystron, and 140 MV/m longitudinal gradient in a short 11.4 GHz accelerator section. We report here on the design of our relativistic klystrons, the results of our experiments so far, and some of our plans for the near future. 5 refs., 9 figs., 1 tab.

  7. Black Holes and the Large Hadron Collider

    NASA Astrophysics Data System (ADS)

    Roy, Arunava

    2011-12-01

    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 Society1 website featured an article on BH formation at the LHC.2 This article examines some aspects of mini BHs and explores the possibility of their detection at the LHC.

  8. Small t physics at the Tevatron Collider

    SciTech Connect

    Bertani, M.; Giacomalli, G.; Maleyran, R.; Manarin, A.; Amos, N.; DeSalvo, R.; Baker, W.; Ellsworth, R.; Dimitroyannis, D.; Block, M.

    1987-05-11

    The first physics run of the superconducting Tevatron Collider at Fermilab ended this morning. A status report will be presented on the progress of the small angle elastic scattering and total cross section experiment, E710. The goals of this experiment are to measure the total proton-antiproton cross section from ..sqrt..s = 300 to 2000 GeV, the slope of the diffraction peak and rho, the ratio of the real to imaginary part of the forward scattering amplitude, at these energies. 1 ref., 8 figs.

  9. SUSY Without Prejudice at Linear Colliders

    SciTech Connect

    Rizzo, Thomas G.

    2008-12-11

    We explore the physics of the general CP-conserving MSSM with Minimal Flavor Violation, the pMSSM. The 19 soft SUSY breaking parameters are chosen so to satisfy all existing experimental and theoretical constraints assuming that the WIMP is the lightest neutralino. We scan this parameter space twice using both flat and log priors and compare the results which yield similar conclusions. Constraints from both LEP and the Tevatron play an important role in obtaining our final model samples. Implications for future TeV-scale e{sup +}e{sup -} linear colliders (LC) are discussed.

  10. A COMPLETE SCHEME FOR A MUON COLLIDER.

    SciTech Connect

    PALMER,R.B.; BERG, J.S.; FERNOW, R.C.; GALLARDO, J.C.; KIRK, H.G.; ALEXAHIN, Y.; NEUFFER, D.; KAHN, S.A.; SUMMERS, D.

    2007-09-01

    A complete scheme for production, cooling, acceleration, and ring for a 1.5 TeV center of mass muon collider is presented, together with parameters for two higher energy machines. The schemes starts with the front end of a proposed neutrino factory that yields bunch trains of both muon signs. Six dimensional cooling in long-period helical lattices reduces the longitudinal emittance until it becomes possible to merge the trains into single bunches, one of each sign. Further cooling in all dimensions is applied to the single bunches in further helical lattices. Final transverse cooling to the required parameters is achieved in 50 T solenoids.

  11. Broader Impacts of the International Linear Collider

    SciTech Connect

    Bardeen, M.; Ruchti, R.

    2005-08-01

    Large-scale scientific endeavors such as the International Linear Collider Project can have a lasting impact on education and outreach to our society. The ILC will provide a discovery platform for frontier physical science and it will also provide a discovery platform for broader impacts and social science. The importance of Broader Impacts of Science in general and the ILC in particular are described. Additionally, a synopsis of education and outreach activities carried out as an integral part of the Snowmass ILC Workshop is provided.

  12. Next linear collider test accelerator injector upgrade

    SciTech Connect

    Yeremian, A.D.; Miller, R.H.

    1995-12-31

    The Next Linear Collider Test Accelerator (NLCTA) is being constructed at SLAC to demonstrate multibunch beam loading compensation, suppression of higher order deflecting modes and measure transverse components of the accelerating fields in X-band accelerating structures. Currently a simple injector which provides the average current necessary for the beam loading compensations studies is under construction. An injector upgrade is planned to produce bunch trains similar to that of the NLC with microbunch intensity, separation and energy spread, identical to that of NLC. We discuss the design of the NLCTA injector upgrade.

  13. Signatures for Majorana neutrinos at hadron colliders.

    PubMed

    Han, Tao; Zhang, Bin

    2006-10-27

    The Majorana nature of neutrinos may only be experimentally verified via lepton-number violating processes involving charged leptons. We explore the Delta L = 2 like-sign dilepton production at hadron colliders to search for signals of Majorana neutrinos. We find significant sensitivity for resonant production of a Majorana neutrino in the mass range of 10-80 GeV at the current run of the Tevatron with 2 fb(-1) integrated luminosity and in the range of 10-400 GeV at the CERN LHC with 100 fb(-1).

  14. Drell-Yan production at collider energies

    SciTech Connect

    Neerven, W.L. Van

    1995-07-01

    We present some results of the Drell-Yan cross sections d{sigma}/dm and {sigma}{sub tot} which includes the O ({alpha}{sub s}{sup 2}) contribution to the coefficient function. In particular we study the total cross section {sigma}{sub tot} for vector boson production and d{sigma}/dm for low invariant masses m of the lepton pairs at large hadron collider energies. This study includes a detailed discussion of the dependence of the cross sections on the chosen scheme ({bar M}S versus DIS) and the factorization scale.

  15. Electron Ion Collider transverse spin physics

    SciTech Connect

    Prokudin, Alexei

    2011-07-01

    Electron Ion Collider is a future high energy facility for studies of the structure of the nucleon. Three-dimensional parton structure is one of the main goals of EIC. In momentum space Transverse Momentum Dependent Distributions (TMDs) are the key ingredients to map such a structure. At leading twist spin structure of spin-1/2 hadron can be described by 8 TMDs. Experimentally these functions can be studied in polarised SIDIS experiments. We discuss Sivers distribution function that describes distribution of unpolarised quarks in a transversely polarised nucleon and transversity that measures distribution of transversely polarised quarks in a transversely polarised nucleon

  16. Electron Ion Collider transverse spin physics

    SciTech Connect

    Prokudin, Alexei

    2011-07-15

    Electron Ion Collider is a future high energy facility for studies of the structure of the nucleon. Three-dimensional parton structure is one of the main goals of EIC. In momentum space Transverse Momentum Dependent Distributions (TMDs) are the key ingredients to map such a structure. At leading twist spin structure of spin-1/2 hadron can be described by 8 TMDs. Experimentally these functions can be studied in polarised SIDIS experiments. We discuss Sivers distribution function that describes distribution of unpolarised quarks in a transversely polarised nucleon and transversity that measures distribution of transversely polarised quarks in a transversely polarised nucleon.

  17. Characterization of an equine herpesvirus type 1 gene encoding a glycoprotein (gp13) with homology to herpes simplex virus glycoprotein C.

    PubMed

    Allen, G P; Coogle, L D

    1988-08-01

    The molecular structure of the equine herpesvirus type 1 (EHV-1) gene encoding glycoprotein 13 (gp13) was analyzed. The gene is contained within a 1.8-kilobase AccI-EcoRI restriction fragment mapping at map coordinates 0.136 to 0.148 in the UL region of the EHV-1 genome and is transcribed from right to left. Determination of the nucleotide sequence of the DNA fragment revealed a complete transcriptional unit composed of typical regulatory promoter elements upstream to a long open reading frame (1,404 base pairs) that encoded a 468-amino-acid primary translation product of 51 kilodaltons. The predicted protein has the characteristic features of a membrane-spanning protein: an N-terminal signal sequence, a hydrophobic membrane anchor region, a charged C-terminal cytoplasmic tail, and an exterior domain with nine potential N-glycosylation sites. The EHV-1 DNA sequences expressed in lambda gt11 as gp13 epitopes were present in the open reading frame. Amino acid sequences composing a major antigenic site, recognized by 35% of a panel of 42 anti-gp13 monoclonal antibodies, were identified in the N-terminal surface domain of the deduced gp13 molecule. Comparison of the EHV-1 gp13 DNA sequence with that encoding glycoproteins of other alphaherpesviruses revealed no detectable homology. However, a search for homology at the amino acid level showed regions of significant sequence similarity between the amino acids of the carboxy half of EHV-1 gp13 and those of the same region of gC-like glycoproteins of herpes simplex virus (gC-1 and gC-2), pseudorabies herpesvirus (gIII), and varicella-zoster virus (gp66). The sequences of the N-terminal portion of gp13, by contrast, were much less conserved. The results of these studies indicate that EHV-1 gp13 is the structural homolog of herpes simplex virus glycoprotein C and further suggest that the epitope-containing N-terminal amino acid sequences of the herpesvirus gC-like glycoproteins have undergone more extensive evolutionary

  18. Enzyme-Linked Immunosorbent Assay with Conserved Immunoreactive Glycoproteins gp36 and gp19 Has Enhanced Sensitivity and Provides Species-Specific Immunodiagnosis of Ehrlichia canis Infection▿

    PubMed Central

    Cárdenas, Ana Maria; Doyle, C. Kuyler; Zhang, Xiaofeng; Nethery, Kimberly; Corstvet, Richard E.; Walker, David H.; McBride, Jere W.

    2007-01-01

    Ehrlichia canis is the primary etiologic agent of canine monocytic ehrlichiosis, a globally distributed and potentially fatal disease of dogs. We previously reported on the identification of two conserved major immunoreactive antigens, gp36 and gp19, which are the first proteins to elicit an E. canis-specific antibody response, and gp200 and p28, which elicit strong antibody responses later in the acute phase of the infection. In this report, the sensitivities and specificities of five recombinant E. canis proteins for the immunodiagnosis of E. canis infection by an enzyme-linked immunosorbent assay (ELISA) were evaluated. Recombinant polypeptides gp36, gp19, and gp200 (N and C termini) exhibited 100% sensitivity and specificity for immunodiagnosis by the recombinant glycoprotein ELISA compared with the results obtained by an indirect fluorescent-antibody assay (IFA) for the detection of antibodies in dogs that were naturally infected with E. canis. Moreover, the enhanced sensitivities of gp36 and gp19 for immunodiagnosis by the recombinant glycoprotein ELISA compared to those obtained by IFA were demonstrated with dogs experimentally infected with E. canis, in which antibodies were detected as much as 2 weeks earlier, on day 14 postinoculation. gp36 and gp19 were not cross-reactive with antibodies in sera from E. chaffeensis-infected dogs and thus provided species-specific serologic discrimination between E. canis and E. chaffeensis infections. This is the first demonstration of the improved detection capability of the recombinant protein technology compared to the capability of the “gold standard” IFA and may eliminate the remaining obstacles associated with the immunodiagnosis of E. canis infections, including species-specific identification and the lack of sensitivity associated with low antibody titers early in the acute phase of the infection. PMID:17151186

  19. Circular lepton colliders as an option for a Higgs factory: The highest energy circular lepton collider

    NASA Astrophysics Data System (ADS)

    Zimmermann, Frank

    With a maximum centre-of-mass energy of 209 GeV, LEP2, in operation at CERN until 2001, has been the highest energy e+e-. collider so far. The discovery, in 2012 by two LHC experiments, of a Higgs-like boson at an energy reachable by a collider slightly more energetic than LEP2, together with the excellent performance achieved in the two B factories PEP-II and KEKB during the first decade of the 21st century, have led to new proposals for a next-generation circular e+e-. collider at the energy frontier [1-5]. In order to serve as a Higgs factory such a collider needs to be able to operate at least at a centre-of-mass energy of 240 GeV (for efficient e+e- → ZH production), i.e. 15% above the LEP2 peak energy. Reaching even higher energies, e.g. 350 GeV centre-of-mass (CM), for tbar t production or 500 GeV for ZHH and Ztbar t studies would be possible for a new ring of larger circumference...

  20. Linear collider approach to a B anti B factory

    SciTech Connect

    Wilson, P.B.

    1987-06-01

    In this paper we consider the basic design expression and principal design constraints for a linear collider suitable for a B anti-B factory: Energy approx. =10 GeV, luminosity 10/sup 33/-10/sup 34/ cm/sup -2/s/sup -1/, energy resolution approx. =10/sup -2/. The design of room temperature linear colliders for a B factory is discussed. In such colliders, the rf energy stored in the linac structure is thrown away after each linac pulse. Linear colliders using superconducting rf cavities are considered. Some brief conclusions are presented.

  1. Klystron switching power supplies for the Internation Linear Collider

    SciTech Connect

    Fraioli, Andrea; /Cassino U. /INFN, Pisa

    2009-12-01

    The International Linear Collider is a majestic High Energy Physics particle accelerator that will give physicists a new cosmic doorway to explore energy regimes beyond the reach of today's accelerators. ILC will complement the Large Hadron Collider (LHC), a proton-proton collider at the European Center for Nuclear Research (CERN) in Geneva, Switzerland, by producing electron-positron collisions at center of mass energy of about 500 GeV. In particular, the subject of this dissertation is the R&D for a solid state Marx Modulator and relative switching power supply for the International Linear Collider Main LINAC Radio Frequency stations.

  2. Numerical calculation of ion polarization in the NICA collider

    NASA Astrophysics Data System (ADS)

    Kovalenko, A. D.; Butenko, A. V.; Kekelidze, V. D.; Mikhaylov, V. A.; Kondratenko, M. A.; Kondratenko, A. M.; Filatov, Yu N.

    2016-02-01

    The NICA Collider with two solenoid Siberian snakes is “transparent” to the spin. The collider transparent to the spin provides a unique capability to control any polarization direction of protons and deuterons using additional weak solenoids without affecting orbital parameters of the beam. The spin tune induced by the control solenoids must significantly exceed the strength of the zero-integer spin resonance, which contains a coherent part associated with errors in the collider's magnetic structure and an incoherent part associated with the beam emittances. We present calculations of the coherent part of the resonance strength in the NICA collider for proton and deuteron beams.

  3. Far Future Colliders and Required R&D Program

    SciTech Connect

    Shiltsev, V.; /Fermilab

    2012-06-01

    Particle colliders for high energy physics have been in the forefront of scientific discoveries for more than half a century. The accelerator technology of the collider has progressed immensely, while the beam energy, luminosity, facility size and the cost have grown by several orders of magnitude. The method of colliding beams has not fully exhausted its potential but its pace of progress has greatly slowed down. In this paper we very briefly review the R&D toward near future colliders and make an attempt to look beyond the current horizon and outline the changes in the paradigm required for the next breakthroughs.

  4. Priming of reovirus transcription by GppppG and formation of CpG(5')GpC.

    PubMed Central

    Yamakawa, M; Furuichi, Y; Shatkin, A J

    1982-01-01

    Compounds of general structure N(5')pn(5')N were used by the reovirus-associated RNA polymerase as primers for template-directed synthesis of virus-specific oligonucleotides and RNA. Structural requirements for activity included a guanosine residue and at least four phosphates--i.e., G(5')pppp(5')N. Gp4G incubated with viral cores in the presence of CTP yielded Gp4GpC and CpGp4GpC. In a complete transcription mixture, Gp4G was also incorporated into the 5' termini of full-length transcripts in the unmethylated forms Gp4GpC and CpGp4GpC, in contrast to viral mRNAs that contain 5'-terminal m7GpppGmpC formed de novo. Gp5G, Gp6G, and Gp4A but not Gp2G, Gp3G, and Ap4A also primed reovirus transcription and inhibited RNA methylation. Images PMID:6959105

  5. Progress towards next generation hadron colliders: FCC-hh, HE-LHC, and SPPC

    NASA Astrophysics Data System (ADS)

    Zimmermann, Frank; EuCARD-2 Extreme Beams Collaboration; Future Circular Collider (FCC) Study Collaboration

    2017-01-01

    A higher-energy circular proton collider is generally considered to be the only path available in this century for exploring energy scales well beyond the reach of the Large Hadron Collider (LHC) presently in operation at CERN. In response to the 2013 Update of the European Strategy for Particle Physics and aligned with the 2014 US ``P5'' recommendations, the international Future Circular Collider (FCC) study, hosted by CERN, is designing such future frontier hadron collider. This so-called FCC-hh will provide proton-proton collisions at a centre-of-mass energy of 100 TeV, with unprecedented luminosity. The FCC-hh energy goal is reached by combining higher-field, 16 T magnets, based on Nb3Sn superconductor, and a new 100 km tunnel connected to the LHC complex. In addition to the FCC-hh proper, the FCC study is also exploring the possibility of a High-Energy LHC (HE-LHC), with a centre-of-mass energy of 25-27 TeV, as could be achieved in the existing 27 km LHC tunnel using the FCC-hh magnet technology. A separate design effort centred at IHEP Beijing aims at developing and constructing a similar collider in China, with a smaller circumference of about 54 km, called SPPC. Assuming even higher-field 20 T magnets, by relying on high-temperature superconductor, the SPPC could reach a c.m. energy of about 70 TeV. This presentation will report the motivation and the present status of the R&D for future hadron colliders, a comparison of the three designs under consideration, the major challenges, R&D topics, the international technology programs, and the emerging global collaboration. Work supported by the European Commission under Capacities 7th Framework Programme project EuCARD-2, Grant Agreement 312453, and the HORIZON 2020 project EuroCirCol, Grant Agreement 654305.

  6. Molecular transduction mechanisms of cytokine-hormone interactions: role of gp130 cytokines.

    PubMed

    Gerez, Juan; Bonfiglio, José; Sosa, Sebastian; Giacomini, Damiana; Acuña, Matias; Nagashima, Alberto Carbia; Perone, Marcelo J; Silberstein, Susana; Renner, Ulrich; Stalla, Günter K; Arzt, Eduardo

    2007-09-01

    Highly sophisticated mechanisms confer on the immune system the capacity to respond with a certain degree of autonomy. However, the final outcome of an immune response depends on the interaction of the immune system with other systems. The immune and neuroendocrine systems have an intimate cross-communication that makes possible a satisfactory response to environmental changes. Part of this interaction occurs through cytokines and steroid hormones. The last step of this cross-talk is the molecular level. As a model of interaction, this review focuses on the gp130 cytokine family. These cytokines, as well as their receptors, are expressed in pituitary cells. They regulate hormone production as well as growth of pituitary cells. During acute or chronic inflammation or infection, systemic, hypothalamic and hypophyseal gp130 cytokines act on anterior pituitary cells, integrating the neuroendocrine-immune response. Disruptions of these pathways may lead not only to abnormal growth of pituitary cells but also to immune disorders, for which, based on recent findings, targeting these cytokines might be a novel therapeutic approach.

  7. Scaffold optimization in discontinuous epitope containing protein mimics of gp120 using smart libraries.

    PubMed

    Mulder, Gwenn E; Quarles van Ufford, H Linda C; van Ameijde, Jeroen; Brouwer, Arwin J; Kruijtzer, John A W; Liskamp, Rob M J

    2013-04-28

    A diversity of protein surface discontinuous epitope mimics is now rapidly and efficiently accessible. Despite the important role of protein-protein interactions involving discontinuous epitopes in a wide range of diseases, mimicry of discontinuous epitopes using peptide-based molecules remains a major challenge. Using copper(I) catalyzed azide-alkyne cycloaddition (CuAAC), we have developed a general and efficient method for the synthesis of collections of discontinuous epitope mimics. Up to three different cyclic peptides, representing discontinuous epitopes in HIV-gp120, were conjugated to a selection of scaffold molecules. Variation of the scaffold molecule, optimization of the ring size of the cyclic peptides and screening of the resulting libraries for successful protein mimics led to an HIV gp120 mimic with an IC50 value of 1.7 μM. The approach described here provides rapid and highly reproducible access to clean, smart libraries of very complex bio-molecular constructs representing protein mimics for use as synthetic vaccines and beyond.

  8. Mass reach scaling for future hadron colliders

    NASA Astrophysics Data System (ADS)

    Rizzo, Thomas G.

    2015-04-01

    The primary goal of any future hadron collider is to discover new physics (NP) associated with a high mass scale, , beyond the range of the LHC. In order to maintain the same relative mass reach for rate-limited NP, , as increases, Richter recently reminded us that the required integrated luminosity obtainable at future hadron colliders (FHC) must grow rapidly, , in the limit of naive scaling. This would imply, e.g., a 50-fold increase in the required integrated luminosity when going from the 14 TeV LHC to a FHC with TeV, an increase that would prove quite challenging on many different fronts. In this paper we point out, due to the scaling violations associated with the evolution of the parton density functions (PDFs) and the running of the strong coupling, , that the actual luminosity necessary in order to maintain any fixed value of the relative mass reach is somewhat greater than this scaling result indicates. However, the actual values of the required luminosity scaling are found to be dependent upon the detailed nature of the NP being considered. Here we elucidate this point explicitly by employing several specific benchmark examples of possible NP scenarios and briefly discuss the (relatively weak) search impact in each case if these luminosity goals are not met.

  9. ICOOL: A TOOL FOR MUON COLLIDER SIMULATIONS.

    SciTech Connect

    FERNOW,R.C.

    2001-09-28

    Current ideas for designing neutrino factories [ 1,2] and muon colliders [3] require unique configurations of fields and materials to prepare the muon beam for acceleration. This so-called front end system must accomplish the goals of phase rotation, bunching and cooling. We have continued the development of a 3-D tracking code, ICOOL [4], for examining possible muon collider front end configurations. A system is described in terms of a series of longitudinal regions with associated material and field properties. The tracking takes place in a coordinate system that follows a reference orbit through the system. The code takes into account decays and interactions of {approx}50-500 MeV/c muons in matter. Material geometry regions include cylinders and wedges. A number of analytic models are provided for describing the field configurations. Simple diagnostics are built into the code, including calculation of emittances and correlations, longitudinal traces, histograms and scatter plots. A number of auxiliary codes can be used for pre-processing, post-processing and optimization.

  10. Magnetic Turbulence in colliding laser produced plasmas

    NASA Astrophysics Data System (ADS)

    Gekelman, Walter; Collette, Andrew

    2006-10-01

    We describe a series of experiments, which involve the collision of two dense (initially, δnlpp/n0>>1) laser-produced plasmas (llp) within an ambient, highly magnetized (RciColliding plasmas can be used to study generation of magnetic turbulence and spontaneous generation of magnetic fields. The plasma column (He, Ne, 1-4 X10^12 cm^3) is 18 m long and 60 cm in diameter, 15 ms duration and pulsed at 1 Hz. Two carbon targets are struck by 1.5 J (10 ns,10 μ, 1 Hz) laser beams. The lpp's form diamagnetic bubbles in which a large percentage of the background magnetic field (600G collide. Fast camera (3 ns) photographs show the bubble surfaces become corrugated after the collision. Small magnetic field probes are used to study the magnetic turbulence. One probe is fixed and the second moved in a small volume close to the targets. An ensemble each location within the volume is used to determine correlations and cross-spectral functions of the magnetic turbulence. The current systems of the waves are fully three-dimensional and are reported in the adjacent poster by Collette et al. [1] M. Van Zeeland, W. Gekelman, Laser Plasma Diamagnetism in the presence of an ambient magnetized plasma, Phys. Plasmas, 11, 320 (2004)

  11. Collider signatures of flavorful Higgs bosons

    DOE PAGES

    Altmannshofer, Wolfgang; Eby, Joshua; Gori, Stefania; ...

    2016-12-30

    Motivated by our limited knowledge of the Higgs couplings to the first two generation fermions, we analyze the collider phenomenology of a class of two Higgs doublet models (2HDMs) with a nonstandard Yukawa sector. One Higgs doublet is mainly responsible for the masses of the weak gauge bosons and the third-generation fermions, while the second Higgs doublet provides mass for the lighter fermion generations. The characteristic collider signatures of this setup differ significantly from well-studied 2HDMs with natural flavor conservation, flavor alignment, or minimal flavor violation. New production mechanisms for the heavy scalar, pseudoscalar, and charged Higgs involving second-generation quarksmore » can become dominant. The most interesting decay modes include H/A → cc,tc,μμ,τμ and H± → cb,cs,μν. As a result, searches for low-mass dimuon resonances are currently among the best probes of the heavy Higgs bosons in this setup.« less

  12. Dark Matter: Collider vs. direct searches

    NASA Astrophysics Data System (ADS)

    Jacques, T.

    2016-07-01

    Effective Field Theories (EFTs) are a useful tool across a wide range of DM searches, including LHC searches and direct detection. Given the current lack of indications about the nature of the DM particle and its interactions, a model independent interpretation of the collider bounds appears mandatory, especially in complementarity with the reinterpretation of the exclusion limits within a choice of simplified models, which cannot exhaust the set of possible completions of an effective Lagrangian. However EFTs must be used with caution at LHC energies, where the energy scale of the interaction is at a scale where the EFT approximation can no longer be assumed to be valid. Here we introduce some tools that allow the validity of the EFT approximation to be quantified, and provide case studies for two operators. We also show a technique that allows EFT constraints from collider searches to be made substantially more robust, even at large center-of-mass energies. This allows EFT constraints from different classes of experiment to be compared in a much more robust manner.

  13. First results from the SPS collider

    SciTech Connect

    Meinke, R.B.

    1982-01-01

    First results from experiment UA5 at the CERN SPS collider studying anti pp collisions at ..sqrt.. s = 540 GeV are presented. The central region pseudorapidity density is 3.0 +/- 0.1 for non-diffractive events. The FWHM of the observed pseudorapidity distribution is narrower than expected from a simple extrapolation of ISR data which can be interpreted as an increase in the mean P/sub t/ for hadron production. A value of 27.4 +/- 2.0 is obtained for the mean charged multiplicity (n/sub ch/) of produced hadrons. This is not in disagreement with an extrapolation using a quadratic fit in lns to previous lower energy data up to ISR energies, but excludes an s/sup 1/4/ or stronger dependence of (n/sub ch/) on s. Correlations between charged particles of positive and negative c.m.s. pseudorapidity have been analysed. In contrast to ISR energies, where long range correlations have been found to be small, they appear to be as important as short range correlations at collider energies. Preliminary results on correlations between charged particles and photons over a limited acceptance in the central region of pseudo-rapidity are given.

  14. Collider signatures of flavorful Higgs bosons

    SciTech Connect

    Altmannshofer, Wolfgang; Eby, Joshua; Gori, Stefania; Lotito, Matteo; Martone, Mario; Tuckler, Douglas

    2016-12-30

    Motivated by our limited knowledge of the Higgs couplings to the first two generation fermions, we analyze the collider phenomenology of a class of two Higgs doublet models (2HDMs) with a nonstandard Yukawa sector. One Higgs doublet is mainly responsible for the masses of the weak gauge bosons and the third-generation fermions, while the second Higgs doublet provides mass for the lighter fermion generations. The characteristic collider signatures of this setup differ significantly from well-studied 2HDMs with natural flavor conservation, flavor alignment, or minimal flavor violation. New production mechanisms for the heavy scalar, pseudoscalar, and charged Higgs involving second-generation quarks can become dominant. The most interesting decay modes include H/A → cc,tc,μμ,τμ and H± → cb,cs,μν. As a result, searches for low-mass dimuon resonances are currently among the best probes of the heavy Higgs bosons in this setup.

  15. An Energy Recovery Electron Linac On Ring Collider

    SciTech Connect

    Nikolitsa Merminga; Geoffrey Krafft; Valeri Lebedev; Ilan Ben-Zvi

    2001-09-01

    Electron-proton/ion colliders with center of mass energies between 14 GeV and 100 GeV (protons) or 63 GeV/A (ions) and luminosities at the 10{sup 33} (per nucleon) level have been proposed recently as a means for studying hadronic structure. Electron beam polarization appears to be crucial for many of the experiments. Two accelerator design scenarios have been examined in detail: colliding rings and recirculating linac-on-ring. Although the linac-on-ring scenario is not as well developed as the ring-ring scenario, comparable luminosities appear feasible. The linac-on-ring option presents significant advantages with respect to: (1) spin manipulations; (2) reduction of the synchrotron radiation load in the detectors; (3) a wide range of continuous energy variability. Rf power and beam dump considerations require that the electron linac recover the beam energy. This technology has been demonstrated at Jefferson Lab's IR FEL with cw current up to 5 mA and beam energy up to 50 MeV. Based on extrapolations from actual measurements and calculations, energy recovery is expected to be feasible at higher currents (a few hundred mA) and higher energies (a few GeV) as well. The report begins with a brief overview of Jefferson Lab's experience with energy recovery and summarize its benefits. Luminosity projections for the linac-ring scenario based on fundamental limitations are presented next. The feasibility of an energy recovery electron linac-on-proton ring collider is investigated and four conceptual point designs are shown corresponding to electron to proton energies of: 3 GeV on 15 GeV, 5 GeV on 50 GeV and 10 GeV on 250 GeV, and for gold ions with 100 GeV/A. The last two designs assume that the protons or ions are stored in the existing RHIC accelerator. Accelerator physics issues relevant to proton rings and energy recovery linacs are discussed next and a list of required R and D for the realization of such a design is presented.

  16. Healthcare use among preschool children attending GP-led urgent care centres: a descriptive, observational study

    PubMed Central

    Gnani, S; Ramzan, F; Davison, M; Ladbrooke, T; Saxena, S

    2016-01-01

    Objective Urgent care centres’ (UCCs) hours were developed with the aim of reducing inappropriate emergency department (ED) attendances in England. We aimed to examine the presenting complaint and outcomes of care in 2 general practitioner (GP)-led UCCs with extended opening times. Design Retrospective observational epidemiological study using routinely collected data. Setting 2 GP-led UCCs in London, colocated with a hospital ED. Participants All children aged under 5 years, attending 2 GP-led UCCs over a 3-year period. Outcomes Outcomes of care for the children including: primary diagnosis; registration status with a GP; destination following review within the UCC; and any medication prescribed. Comparison between GP-led UCC visit rates and routine general practices was also made. Results 3% (n=7747/282 947) of all attenders at the GP-led UCCs were children aged under 5 years. The most common reason for attendance was a respiratory illness (27%), followed by infectious illness (17%). 18% (n=1428) were either upper respiratory tract infections or viral infections. The majority (91%) of children attending were registered with a GP, and over two-thirds of attendances were ‘out of hours’. Overall 79% were seen and discharged home. Preschool children were more likely to attend their GP (47.0 per 100) than a GP-led UCC (9.4 per 100; 95% CI 8.9 to 10.0). Conclusions Two-thirds of preschool children attending GP-led UCCs do so out of hours, despite the majority being registered with a GP. The case mix is comparable with those presenting to an ED setting, with the majority managed exclusively by the GPs in the UCC before discharge home. Further work is required to understand the benefits of a GP-led urgent system in influencing future use of services especially emergency care. PMID:27288373

  17. Antibody responses to the immunodominant Cryptosporidium gp15 antigen and gp15 polymorphisms in a case-control study of cryptosporidiosis in children in Bangladesh.

    PubMed

    Allison, Genève M; Rogers, Kathleen A; Borad, Anoli; Ahmed, Sabeena; Karim, Mohammad Mahbubul; Kane, Anne V; Hibberd, Patricia L; Naumova, Elena N; Calderwood, Stephen B; Ryan, Edward T; Khan, Wasif A; Ward, Honorine D

    2011-07-01

    Although Cryptospridium hominis is the dominant Cryptosporidium species infecting humans, immune responses to cognate antigens in C. hominis-infected persons have not been reported. We investigated antibody responses to the immunodominant gp15 antigen from C. hominis and C. parvum, in C. hominis-infected Bangladeshi children less than five years of age with diarrhea (cases) and uninfected children with diarrhea (controls). We also investigated polymorphisms in the C. hominis gp15 sequence from cases. Serum IgG responses to gp15 from both species were significantly greater in cases than controls. In spite of polymorphisms in the gp15 sequence, there was a significant correlation between antibody levels to gp15 from both species, indicating cross-reactivity to conserved epitopes. Cases with acute diarrhea had a significantly greater serum IgA response to gp15 compared with those with persistent diarrhea, suggesting that this response may be associated with protection from prolonged disease. These findings support further investigation of gp15 as a vaccine candidate.

  18. STAR FORMATION IN TURBULENT MOLECULAR CLOUDS WITH COLLIDING FLOW

    SciTech Connect

    Matsumoto, Tomoaki; Dobashi, Kazuhito; Shimoikura, Tomomi

    2015-03-10

    Using self-gravitational hydrodynamical numerical simulations, we investigated the evolution of high-density turbulent molecular clouds swept by a colliding flow. The interaction of shock waves due to turbulence produces networks of thin filamentary clouds with a sub-parsec width. The colliding flow accumulates the filamentary clouds into a sheet cloud and promotes active star formation for initially high-density clouds. Clouds with a colliding flow exhibit a finer filamentary network than clouds without a colliding flow. The probability distribution functions (PDFs) for the density and column density can be fitted by lognormal functions for clouds without colliding flow. When the initial turbulence is weak, the column density PDF has a power-law wing at high column densities. The colliding flow considerably deforms the PDF, such that the PDF exhibits a double peak. The stellar mass distributions reproduced here are consistent with the classical initial mass function with a power-law index of –1.35 when the initial clouds have a high density. The distribution of stellar velocities agrees with the gas velocity distribution, which can be fitted by Gaussian functions for clouds without colliding flow. For clouds with colliding flow, the velocity dispersion of gas tends to be larger than the stellar velocity dispersion. The signatures of colliding flows and turbulence appear in channel maps reconstructed from the simulation data. Clouds without colliding flow exhibit a cloud-scale velocity shear due to the turbulence. In contrast, clouds with colliding flow show a prominent anti-correlated distribution of thin filaments between the different velocity channels, suggesting collisions between the filamentary clouds.

  19. Physics potential and motivations for a muon collider

    NASA Astrophysics Data System (ADS)

    Greco, Mario

    2016-06-01

    The discovery of the Higgs particle is demanding a detailed knowledge of the properties of this fundamental component of the Standard Model. From the available data however, it cannot be concluded yet that we have found the SM Higgs boson and not one of the scalars postulated within the possible extensions of the SM. It is shown that a Higgs factory through a muon collider is particularly appropriate for precision studies of the properties of this particle. However sizable QED radiative effects — of order of 50% — must be carefully taken into account for a precise measurement of the leptonic and total widths of the Higgs particle. The results presented here are mainly based on a recent work in collaboration of Tao Han and Zhen Liu.

  20. 120 MW, 800 MHz Magnicon for a Future Muon Collider

    SciTech Connect

    Jay L. Hirshfield

    2005-12-15

    Development of a pulsed magnicon at 800 MHz was carried out for the muon collider application, based on experience with similar amplifiers in the frequency range between 915 MHz and 34.3 GHz. Numerical simulations using proven computer codes were employed for the conceptual design, while established design technologies were incorporated into the engineering design. A cohesive design for the 800 MHz magnicon amplifier was carried out, including design of a 200 MW diode electron gun, design of the magnet system, optimization of beam dynamics including space charge effects in the transient and steady-state regimes, design of the drive, gain, and output cavities including an rf choke in the beam exit aperture, analysis of parasitic oscillations and design means to eliminate them, and design of the beam collector capable of 20 kW average power operation.

  1. Magnet designs for muon collider ring and interactions regions

    SciTech Connect

    Zlobin, A.V.; Alexahin, Y.I.; Kashikhin, V.V.; Mokhov, N.V.; /Fermilab

    2010-05-01

    Conceptual designs of superconducting magnets for the storage ring of a Muon Collider with a 1.5 TeV c.o.m. energy and an average luminosity of 10{sup 34} cm{sup -2}s{sup -1} are presented. All magnets are based on Nb{sub 3}Sn superconductor and designed to provide an adequate operating field/field gradient in the aperture with the critical current margin required for reliable magnet operation in the machine. Magnet cross-sections were optimized to achieve the accelerator field quality in the magnet aperture occupied with beams. The magnets and corresponding protective measures are designed to handle about 0.5 kW/m of dynamic heat load from the muon beam decays. Magnet parameters are reported and compared with the requirements.

  2. Physics Potential and Motivations for a Muon Collider

    NASA Astrophysics Data System (ADS)

    Greco, Mario

    The discovery of the Higgs particle is demanding a detailed knowledge of the properties of this fundamental component of the Standard Model. From the available data however, it cannot be concluded yet that we have found the SM Higgs boson and not one of the scalars postulated within the possible extensions of the SM. It is shown that a Higgs factory through a muon collider is particularly appropriate for precision studies of the properties of this particle. However sizable QED radiative effects - of order of 50% - must be carefully taken into account for a precise measurement of the leptonic and total widths of the Higgs particle. The results presented here are mainly based on a recent work in collaboration of Tao Han and Zhen Liu.

  3. Acccelerator Physics Issues of a Very Large Hadron Collider

    SciTech Connect

    Chou, W.

    1997-06-01

    A Very Large Hadron Collider (VLHC) was proposed for the post-LHC future. This paper gives a quick survey of a number of accelerator physics issues based on the information obtained from a parameter spreadsheet SSP. The main technical challenges to build such a machine appear to be: the large number of events per crossing (in hundreds), enormous beam stored energy (equivalent to tens tons of TNT), ground motion (which is particularly harmful when the synchrotron frequency is in the sub-Hertz range), small dynamic aperture (due to long filling time), fast growth of the resistive wall instability (in a fraction of one turn), low threshold of the single bunch transverse instability (due to big machine size), strong synchrotron radiation (at a level close to the LEP) and short radiation damage lifetime, etc. Possible solutions to some of these problems will also be discussed.

  4. New fast beam profile monitor for electron-positron colliders

    SciTech Connect

    Bogomyagkov, A. V.; Gurko, V. F.; Zhuravlev, A. N.; Zubarev, P. V.; Kiselev, V. A.; Meshkov, O. I.; Muchnoi, N. Yu.; Selivanov, A. N.; Smaluk, V. V.; Khilchenko, A. D.

    2007-04-15

    A new fast beam profile monitor has been developed at the Budker Institute of Nuclear Physics. This monitor is based on the Hamamatsu multianode photomultiplier with 16 anode strips and provides turn-by-turn measurement of the transverse beam profile. The device is equipped with an internal memory, which has enough capacity to store 131 072 samples of the beam profile. The dynamic range of the beam profile monitor allows us to study turn-by-turn beam dynamics within the bunch charge range from 1 pC up to 10 nC. Using this instrument, we have investigated at the VEPP-4M electron-positron collider a number of beam dynamics effects which cannot be observed by other beam diagnostics tools.

  5. Intracellular mannose binding lectin mediates subcellular trafficking of HIV-1 gp120 in neurons.

    PubMed

    Teodorof, C; Divakar, S; Soontornniyomkij, B; Achim, C L; Kaul, M; Singh, K K

    2014-09-01

    Human immunodeficiency virus-1 (HIV-1) enters the brain early during infection and leads to severe neuronal damage and central nervous system impairment. HIV-1 envelope glycoprotein 120 (gp120), a neurotoxin, undergoes intracellular trafficking and transport across neurons; however mechanisms of gp120 trafficking in neurons are unclear. Our results show that mannose binding lectin (MBL) that binds to the N-linked mannose residues on gp120, participates in intravesicular packaging of gp120 in neuronal subcellular organelles and also in subcellular trafficking of these vesicles in neuronal cells. Perinuclear MBL:gp120 vesicular complexes were observed and MBL facilitated the subcellular trafficking of gp120 via the endoplasmic reticulum (ER) and Golgi vesicles. The functional carbohydrate recognition domain of MBL was required for perinuclear organization, distribution and subcellular trafficking of MBL:gp120 vesicular complexes. Nocodazole, an agent that depolymerizes the microtubule network, abolished the trafficking of MBL:gp120 vesicles, suggesting that these vesicular complexes were transported along the microtubule network. Live cell imaging confirmed the association of the MBL:gp120 complexes with dynamic subcellular vesicles that underwent trafficking in neuronal soma and along the neurites. Thus, our findings suggest that intracellular MBL mediates subcellular trafficking and transport of viral glycoproteins in a microtubule-dependent mechanism in the neurons.

  6. Reversal of P-gp-mediated multidrug resistance in colon cancer by cinobufagin.

    PubMed

    Yuan, Zeting; Shi, Xiaojing; Qiu, Yanyan; Jia, Tingting; Yuan, Xia; Zou, Yu; Liu, Cheng; Yu, Hui; Yuan, Yuxia; He, Xue; Xu, Ke; Yin, Peihao

    2017-03-01

    Cinobufagin (CBF) is isolated from the skin and posterior auricular glands of the Asiatic toad (Bufo gargarizans). This study investigated the reversal effect of CBF on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in colon cancer. The effect of CBF on the cytotoxicity of anticancer drugs in P-gp overexpressing LoVo/ADR, HCT116/L, Cao-2/ADR cells and their parental cells was determined using CCK-8 assay. Apoptosis of anti-cancer drugs and accumulation of doxorubicin (DOX) and Rhodamine 123 (Rho123) in P-gp overexpressing cells were evaluated by flow cytometry. Results indicated that CBF significantly enhanced the sensitivity of P-gp substrate drugs on P-gp overexpressing cells, but had no effect on their parental cells. CBF enhanced the effect of DOX against P-gp-overexpressing LoVo/ADR cell xenografts in nude mice. Moreover, CBF also increased cell apoptosis of chemotherapy agents and intracellular accumulation of DOX and Rho123 in the MDR cells. Further research on the mechanisms revealed non-competitive inhibition of P-gp ATPase activity, but without altering the expression of P-gp. These findings demonstrated that CBF could be further developed into a safe and potent P-gp modulator for combination use with anticancer drugs in cancer chemotherapy.

  7. Intracellular Mannose Binding Lectin Mediates Subcellular Trafficking of HIV-1 gp120 in Neurons

    PubMed Central

    Teodorof, C; Divakar, S; Soontornniyomkij, B; Achim, CL; Kaul, M; Singh, KK

    2014-01-01

    Human immunodeficiency virus -1 (HIV-1) enters the brain early during infection and leads to severe neuronal damage and central nervous system impairment. HIV-1 envelope glycoprotein 120 (gp120), a neurotoxin, undergoes intracellular trafficking and transport across neurons; however mechanisms of gp120 trafficking in neurons are unclear. Our results show that mannose binding lectin (MBL) that binds to the N-linked mannose residues on gp120, participates in intravesicular packaging of gp120 in neuronal subcellular organelles and also in subcellular trafficking of these vesicles in neuronal cells. Perinuclear MBL:gp120 vesicular complexes were observed and MBL facilitated the subcellular trafficking of gp120 via the endoplasmic reticulum (ER) and Golgi vesicles. The functional carbohydrate recognition domain of MBL was required for perinuclear organization, distribution and subcellular trafficking of MBL:gp120 vesicular complexes. Nocodazole, an agent that depolymerizes the microtubule network, abolished the trafficking of MBL:gp120 vesicles, suggesting that these vesicular complexes were transported along the microtubule network. Live cell imaging confirmed the association of the MBL:gp120 complexes with dynamic subcellular vesicles that underwent trafficking in neuronal soma and along the neurites. Thus, our findings suggest that intracellular MBL mediates subcellular trafficking and transport of viral glycoproteins in a microtubule-dependent mechanism in the neurons. PMID:24825317

  8. Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

    SciTech Connect

    Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B. )

    1991-05-01

    Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-(1-14C) glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection.

  9. A bipartite signal regulates the faithful delivery of apical domain marker podocalyxin/Gp135.

    PubMed

    Yu, Chun-Ying; Chen, Jen-Yau; Lin, Yu-Yu; Shen, Kuo-Fang; Lin, Wei-Ling; Chien, Chung-Liang; ter Beest, Martin B A; Jou, Tzuu-Shuh

    2007-05-01

    Podocalyxin/Gp135 was recently demonstrated to participate in the formation of a preapical complex to set up initial polarity in MDCK cells, a function presumably depending on the apical targeting of Gp135. We show that correct apical sorting of Gp135 depends on a bipartite signal composed of an extracellular O-glycosylation-rich region and the intracellular PDZ domain-binding motif. The function of this PDZ-binding motif could be substituted with a fusion construct of Gp135 with Ezrin-binding phosphoprotein 50 (EBP50). In accordance with this observation, EBP50 binds to newly synthesized Gp135 at the Golgi apparatus and facilitates oligomerization and sorting of Gp135 into a clustering complex. A defective connection between Gp135 and EBP50 or EBP50 knockdown results in a delayed exit from the detergent-resistant microdomain, failure of oligomerization, and basolateral missorting of Gp135. Furthermore, the basolaterally missorted EBP50-binding defective mutant of Gp135 was rapidly retrieved via a PKC-dependent mechanism. According to these findings, we propose a model by which a highly negative charged transmembrane protein could be packed into an apical sorting platform with the aid of its cytoplasmic partner EBP50.

  10. A Betabaculovirus-Encoded gp64 Homolog Codes for a Functional Envelope Fusion Protein

    PubMed Central

    Ardisson-Araújo, Daniel M. P.; Melo, Fernando L.; Clem, Rollie J.; Wolff, José L. C.

    2015-01-01

    The GP64 envelope fusion protein is a hallmark of group I alphabaculoviruses. However, the Diatraea saccharalis granulovirus genome sequence revealed the first betabaculovirus species harboring a gp64 homolog (disa118). In this work, we have shown that this homolog encodes a functional envelope fusion protein and could enable the infection and fusogenic abilities of a gp64-null prototype baculovirus. Therefore, GP64 may complement or may be in the process of replacing F protein activity in this virus lineage. PMID:26537678

  11. Introduction and recent developments in γγ, γe colliders

    NASA Astrophysics Data System (ADS)

    Telnov, Valery

    2001-08-01

    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 mainly 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 luminosity in the high energy part of spectrum can reach 0.3-0.5 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 that in e+e- collisions. The key new element in photon colliders is a very powerful laser system. The most straightforward solution is "an optical storage ring (optical trap)" with diode pumped laser injector which is today technically feasible. This paper briefly reviews the status of a photon collider based at TESLA, its possible parameters.

  12. e-A PHYSICS AT A COLLIDER.

    SciTech Connect

    G. T. GARVEY

    2001-01-09

    An electron-nucleus (e-A) collider with center-of-mass energy in excess of 50 GeV per electron-nucleon collision will allow the physics community to obtain unprecedented new knowledge of the partonic structure of nuclei. If reliable information is to be extracted on these partonic densities, it is essential to realize that with our current level of understanding of QCD, momentum transfers to the struck partons greater than 1 GeV/c are necessary. This requirement puts a priority on high center-of-mass energy if partonic densities are to be measured over a wide range. Comparing the partonic structure of the free nucleon to that of bound nucleons and measuring the systematic changes in that structure as a function of nucleon number (A) will provide deeper insight into the origins and dynamics of nuclear binding. In addition, e-A collisions will allow the exploration of partonic densities appreciably higher than is accessible in e-p collisions. An e-A collider will allow one to measure the gluonic structure functions of nuclei down to x {approx} 10{sup -3}, information valuable in its own right and essential to a quantitative understanding of highly relativistic A-A collisions. The time-space evolution of partons can only be investigated by studying the modifications of hard collisions that take place when nuclear targets are employed. In a hard collision the partonic fragments interact, hadronize, and reinteract on their way to the distant detectors without revealing their evolution into the hadrons finally detected. Nuclear targets of differing A place varying amounts of nuclear matter in proximity to the hard collision producing unique information about the quantum fluctuations of incident projectile prior to the collision and on the early evolution of the produced partons. Using charged leptons (e, {mu}) to investigate this physics has been the richest source of information to date and extending the reach of these investigations by the constructing an e -A collider

  13. Differential Antibody Responses to Conserved HIV-1 Neutralizing Epitopes in the Context of Multivalent Scaffolds and Native-Like gp140 Trimers

    PubMed Central

    Morris, Charles D.; Azadnia, Parisa; de Val, Natalia; Vora, Nemil; Honda, Andrew; Giang, Erick; Saye-Francisco, Karen; Cheng, Yushao; Lin, Xiaohe; Mann, Colin J.; Tang, Jeffrey; Sok, Devin; Burton, Dennis R.; Law, Mansun; Ward, Andrew B.

    2017-01-01

    ABSTRACT Broadly neutralizing antibodies (bNAbs) have provided valuable insights into the humoral immune response to HIV-1. While rationally designed epitope scaffolds and well-folded gp140 trimers have been proposed as vaccine antigens, a comparative understanding of their antibody responses has not yet been established. In this study, we probed antibody responses to the N332 supersite and the membrane-proximal external region (MPER) in the context of heterologous protein scaffolds and native-like gp140 trimers. Ferritin nanoparticles and fragment crystallizable (Fc) regions were utilized as multivalent carriers to display scaffold antigens with grafted N332 and MPER epitopes, respectively. Trimeric scaffolds were also identified to stabilize the MPER-containing BG505 gp140.681 trimer in a native-like conformation. Following structural and antigenic evaluation, a subset of scaffold and trimer antigens was selected for immunization in BALB/c mice. Serum binding revealed distinct patterns of antibody responses to these two bNAb targets presented in different structural contexts. For example, the N332 nanoparticles elicited glycan epitope-specific antibody responses that could also recognize the native trimer, while a scaffolded BG505 gp140.681 trimer generated a stronger and more rapid antibody response to the trimer apex than its parent gp140.664 trimer. Furthermore, next-generation sequencing (NGS) of mouse splenic B cells revealed expansion of antibody lineages with long heavy-chain complementarity-determining region 3 (HCDR3) loops upon activation by MPER scaffolds, in contrast to the steady repertoires primed by N332 nanoparticles and a soluble gp140.664 trimer. These findings will facilitate the future development of a coherent vaccination strategy that combines both epitope-focused and trimer-based approaches. PMID:28246356

  14. The Threshold of Embedded M Collider Bias and Confounding Bias

    ERIC Educational Resources Information Center

    Kelcey, Benjamin; Carlisle, Joanne

    2011-01-01

    Of particular import to this study, is collider bias originating from stratification on retreatment variables forming an embedded M or bowtie structural design. That is, rather than assume an M structural design which suggests that "X" is a collider but not a confounder, the authors adopt what they consider to be a more reasonable…

  15. Comparison of two approaches to linear collider design

    SciTech Connect

    Schnell, W.

    1987-11-01

    This paper reviews linear collider parameters. It aims at analyzing two specific design approachs - the ones for CLIC at CERN and for a TeV linear collider at SLAC - which appear to lead into remarkably different directions although they start from the same premises and try to respect the same boundary conditions. 19 refs.

  16. Nonrandom distribution of cryptic repeating triplets of purines and pyrimidines (RNY)(n) in gp120 of HIV Type1.

    PubMed

    De Crignis, Elisa; Guglietta, Silvia; Foley, Brian T; Negroni, Matteo; Di Narzo, Antonio Fabio; Waelti Da Costa, Vreneli; Cavassini, Matthias; Bart, Pierre-Alexandre; Pantaleo, Giuseppe; Graziosi, Cecilia

    2012-05-01

    We have analyzed purine (R) and pyrimidine (Y) codon patterns in variable and constant regions of HIV-1 gp120 in seven patients infected with different HIV-1 subtypes and naive to antiretroviral therapy. We have calculated the relative frequency of each in-frame codon RNY, YNR, RNR, and YNY (N=any nucleotide) in variable and constant regions of gp120, in the sequence within indels and at indels' flanking sites. Our data show that hypervariable regions V1, V2, V4, and V5 are characterized by the presence of long stretches of RNY codons constituting the majority of the sequence portion within insertions/deletions. In full-length gp120 and within inserted/deleted fragments the number of AVT (V=A, C, G) codons did not exceed 50% of the total RNY codons. RNY strings in variable regions spanned up to 21 codons and were always in frame. In contrast, RNY strings in constant regions were mostly out of frame and their length was limited to five codons. The frequency of the codon RNY was found to be significantly higher in variable regions (p<0.0001; t-test), within indels, and at indels' flanking sites (p<0.0001; χ(2) test). Analysis of the distribution of RNY strings equal to or longer than five codons in the full genome of HXB2 also shows that these sequences are mostly out of frame, unless they contain a potential N-glycosylation site or an asparagine. These data suggest that cryptic repeats of RNY may play a role in the genesis of multiple base insertions and deletions in hypervariable regions of gp120.

  17. The Teamwork Study: enhancing the role of non-GP staff in chronic disease management in general practice.

    PubMed

    Black, D A; Taggart, J; Jayasinghe, U W; Proudfoot, J; Crookes, P; Beilby, J; Powell-Davis, G; Wilson, L A; Harris, M F

    2013-01-01

    There is evidence for a team-based approach in the management of chronic disease in primary health care. However, the standard of care is variable, probably reflecting the limited organisational capacity of health services to provide the necessary structured and organised care for this group of patients. This study aimed to evaluate the impact of a structured intervention involving non-GP staff in GP practices on the quality of care for patients with diabetes or cardiovascular disease. A cluster randomised trial was undertaken across 60 GP practices. The intervention was implemented in 30 practices with staff and patients interviewed at baseline and at 12-15 months follow up. The change in team roles was evaluated using a questionnaire completed by practice staff. The quality of care was evaluated using the Patient Assessment of Chronic Illness Care questionnaire. We found that although the team roles of staff improved in the intervention practices and there were significant differences between practices, there was no significant difference between those in the intervention and control groups in patient-assessed quality of care after adjusting for baseline-level score and covariates at the 12-month follow up. Practice team roles were not significantly associated with change in Patient Assessment of Chronic Illness Care scores. Patients with multiple conditions were more likely to assess their quality of care to be better. Thus, although previous research has shown a cross-sectional association between team work and quality of care, we were unable to replicate these findings in the present study. These results may be indicative of insufficient time for organisational change to result in improved patient-assessed quality of care, or because non-GP staff roles were not sufficiently focussed on the aspects of care assessed. The findings provide important information for researchers when designing similar studies.

  18. Qualitative study of depression management in primary care: GP and patient goals, and the value of listening

    PubMed Central

    Johnston, Olwyn; Kumar, Satinder; Kendall, Kathleen; Peveler, Robert; Gabbay, John; Kendrick, Tony

    2007-01-01

    Background Guidelines for depression management have been developed but little is known about GP and patient goals, which are likely to influence treatment offers, uptake, and adherence. Aim To identify issues of importance to GPs, patients, and patients' supporters regarding depression management. GP and patient goals for depression management became a focus of the study. Design of study Grounded theory-based qualitative study. Setting GPs were drawn from 28 practices. The majority of patients and supporters were recruited from 10 of these practices. Method Sixty-one patients (28 depressed, 18 previously depressed, 15 never depressed), 18 supporters, and 32 GPs were interviewed. Results GPs described encouraging patients to view depression as separate from the self and ‘normal’ sadness. Patients and supporters often questioned such boundaries, rejecting the notion of a medical cure and emphasising self-management. The majority of participants who were considering depression-management strategies wanted to ‘get out’ of their depression. However, a quarter did not see this as immediately relevant or achievable. They focused on getting by from day to day, which had the potential to clash with GP priorities. GP frustration and uncertainty could occur when depression was resistant to cure. Participants identified the importance of GPs listening to patients, but often felt that this did not happen. Conclusion Physicians need greater awareness of the extent to which their goals for the management of depression are perceived as relevant or achievable by patients. Future research should explore methods of negotiating agreed strategies for management. PMID:17976282

  19. Membrane-Proximal External HIV-1 gp41 Motif Adapted for Destabilizing the Highly Rigid Viral Envelope

    PubMed Central

    Apellániz, Beatriz; Ivankin, Andrey; Nir, Shlomo; Gidalevitz, David; Nieva, José L.

    2011-01-01

    Electron microscopy structural determinations suggest that the membrane-proximal external region (MPER) of glycoprotein 41 (gp41) may associate with the HIV-1 membrane interface. It is further proposed that MPER-induced disruption and/or deformation of the lipid bilayer ensue during viral fusion. However, it is predicted that the cholesterol content of this membrane (∼45 mol %) will act against MPER binding and restructuring activity, in agreement with alternative structural models proposing that the MPER constitutes a gp41 ectodomain component that does not insert into the viral membrane. Here, using MPER-based peptides, we test the hypothesis that cholesterol impedes the membrane association and destabilizing activities of this gp41 domain. To that end, partitioning and leakage assays carried out in lipid vesicles were combined with x-ray reflectivity and grazing-incidence diffraction studies of monolayers. CpreTM, a peptide combining the carboxyterminal MPER sequence with aminoterminal residues of the transmembrane domain, bound and destabilized effectively cholesterol-enriched membranes. Accordingly, virion incubation with this peptide inhibited cell infection potently but nonspecifically. Thus, CpreTM seems to mimic the envelope-perturbing function of the MPER domain and displays antiviral activity. As such, we infer that CpreTM bound to cholesterol-enriched membranes would represent a relevant target for anti-HIV-1 immunogen and inhibitor development. PMID:22098741

  20. All-atom models of the membrane-spanning domain of HIV-1 gp41 from metadynamics.

    PubMed

    Gangupomu, Vamshi K; Abrams, Cameron F

    2010-11-17

    The 27-residue membrane-spanning domain (MSD) of the HIV-1 glycoprotein gp41 bears conserved sequence elements crucial to the biological function of the virus, in particular a conserved GXXXG motif and a midspan arginine. However, structure-based explanations for the roles of these and other MSD features remain unclear. Using molecular dynamics and metadynamics calculations of an all-atom, explicit solvent, and membrane-anchored model, we study the conformational variability of the HIV-1 gp41 MSD. We find that the MSD peptide assumes a stable tilted α-helical conformation in the membrane. However, when the side chain of the midspan Arg (694) "snorkels" to the outer leaflet of the viral membrane, the MSD assumes a metastable conformation where the highly-conserved N-terminal core (between Lys(681) and Arg(694) and containing the GXXXG motif) unfolds. In contrast, when the Arg(694) side chain snorkels to the inner leaflet, the MSD peptide assumes a metastable conformation consistent with experimental observations where the peptide kinks at Phe(697) to facilitate Arg(694) snorkeling. Both of these models suggest specific ways that gp41 may destabilize viral membrane, priming the virus for fusion with a target cell.

  1. Big Science and the Large Hadron Collider

    NASA Astrophysics Data System (ADS)

    Giudice, Gian Francesco

    2012-03-01

    The Large Hadron Collider (LHC), the particle accelerator operating at CERN, is probably the most complex and ambitious scientific project ever accomplished by humanity. The sheer size of the enterprise, in terms of financial and human resources, naturally raises the question whether society should support such costly basic-research programs. I address this question by first reviewing the process that led to the emergence of Big Science and the role of large projects in the development of science and technology. I then compare the methodologies of Small and Big Science, emphasizing their mutual linkage. Finally, after examining the cost of Big Science projects, I highlight several general aspects of their beneficial implications for society.

  2. Beam Dynamics Considerations in Electron Ion Colliders

    NASA Astrophysics Data System (ADS)

    Krafft, Geoffrey

    2015-04-01

    The nuclear physics community is converging on the idea that the next large project after FRIB should be an electron-ion collider. Both Brookhaven National Lab and Thomas Jefferson National Accelerator Facility have developed accelerator designs, both of which need novel solutions to accelerator physics problems. In this talk we discuss some of the problems that must be solved and their solutions. Examples in novel beam optics systems, beam cooling, and beam polarization control will be presented. Authored by Jefferson Science Associates, LLC under U.S. DOE Contract No. DE-AC05-06OR23177. The U.S. Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce this manuscript for U.S. Government purposes.

  3. Minimal walking technicolor: Setup for collider physics

    SciTech Connect

    Foadi, Roshan; Frandsen, Mads T.; Ryttov, Thomas A.; Sannino, Francesco

    2007-09-01

    Different theoretical and phenomenological aspects of the minimal and nonminimal walking technicolor theories have recently been studied. The goal here is to make the models ready for collider phenomenology. We do this by constructing the low energy effective theory containing scalars, pseudoscalars, vector mesons, and other fields predicted by the minimal walking theory. We construct their self-interactions and interactions with standard model fields. Using the Weinberg sum rules, opportunely modified to take into account the walking behavior of the underlying gauge theory, we find interesting relations for the spin-one spectrum. We derive the electroweak parameters using the newly constructed effective theory and compare the results with the underlying gauge theory. Our analysis is sufficiently general such that the resulting model can be used to represent a generic walking technicolor theory not at odds with precision data.

  4. Small air showers and collider physics

    NASA Technical Reports Server (NTRS)

    Capdevielle, J. N.; Gawin, J.; Grochalska, B.

    1985-01-01

    At energies lower than 2.5 X 10 to the 5 GeV (in Lab. system), more accurate information on nucleon-nucleon collision (p-p collider and on primary composition now exist. The behavior of those both basic elements in cosmic ray phenomenology from ISR energy suggests some tendencies for reasonable extrapolation in the next decade 2.0x10 to the 5 to 2.0x10 to the 6 GeV. Small showers in altitude, recorded in the decade 2 X 10 to the 4 to 2 X 10 to the 5 GeV offers a good tool to testify the validity of all the Monte-Carlo simulation analysis and appreciate how nucleon-air collision are different from nucleon-nucleon collisions.

  5. The Structure of Jets at Hadron Colliders

    SciTech Connect

    Larkoski, Andrew James

    2012-08-01

    Particle physics seeks to understand the interactions and properties of the fundamental particles. To gain understanding, there is an interplay between theory and experiment. Models are proposed to explain how particles behave and interact. These models make precise predictions that can be tested. Experiments are built and executed to measure the properties of these particles, providing necessary tests for the theories that attempt to explain the realm of fundamental particles. However, there is also another level of interaction between theory and experiment; the development of new experiments demands the study of how particles will behave with respect to the measured observables toward the goal of understanding the details and idiosyncrasies of the measurements very well. Only once these are well-modeled and understood can one be con dent that the data that are measured is trustworthy. The modeling and interpretation of the physics of a proton collider, such as the LHC, is the main topic of this thesis.

  6. Performance of the SLAC Linear Collider klystrons

    SciTech Connect

    Allen, M.A.; Fowkes, W.R.; Koontz, R.F.; Schwarz, H.D.; Seeman, J.T.; Vlieks, A.E.

    1987-01-01

    There are now 200 new, high power 5045 klystrons installed on the two-mile Stanford Linear Accelerator. Peak power per klystron averages over 63 MW. Average energy contribution is above 240 MeV per station. Electron beam energy has been measured as high as 53 GeV. Energy instability due to klystron malfunction is less than 0.2%. The installed klystrons have logged over one million operating hours with close to 20,000 klystron hours cumulative operating time between failures. Data are being accumulated on klystron operation and failure modes with failure signatures starting to become apparent. To date, no wholesale failure modes have surfaced that would impair the SLAC Linear Collider (SLC) program.

  7. Illuminating new electroweak states at hadron colliders

    NASA Astrophysics Data System (ADS)

    Ismail, Ahmed; Izaguirre, Eder; Shuve, Brian

    2016-07-01

    In this paper, we propose a novel powerful strategy to perform searches for new electroweak states. Uncolored electroweak states appear in generic extensions of the Standard Model (SM) and yet are challenging to discover at hadron colliders. This problem is particularly acute when the lightest state in the electroweak multiplet is neutral and all multiplet components are approximately degenerate. In this scenario, production of the charged fields of the multiplet is followed by decay into nearly invisible states; if this decay occurs promptly, the only way to infer the presence of the reaction is through its missing energy signature. Our proposal relies on emission of photon radiation from the new charged states as a means of discriminating the signal from SM backgrounds. We demonstrate its broad applicability by studying two examples: a pure Higgsino doublet and an electroweak quintuplet field.

  8. Optimal, real-time control--colliders

    SciTech Connect

    Spencer, J.E.

    1991-05-01

    With reasonable definitions, optimal control is possible for both classical and quantal systems with new approaches called PISC(Parallel) and NISC(Neural) from analogy with RISC (Reduced Instruction Set Computing). If control equals interaction, observation and comparison to some figure of merit with interaction via external fields, then optimization comes from varying these fields to give design or operating goals. Structural stability can then give us tolerance and design constraints. But simulations use simplified models, are not in real-time and assume fixed or stationary conditions, so optimal control goes far beyond convergence rates of algorithms. It is inseparable from design and this has many implications for colliders. 12 refs., 3 figs.

  9. Illuminating new electroweak states at hadron colliders

    DOE PAGES

    Ismail, Ahmed; Izaguirre, Eder; Shuve, Brian

    2016-07-01

    In this paper, we propose a novel powerful strategy to perform searches for new electroweak states. Uncolored electroweak states appear in generic extensions of the Standard Model (SM) and yet are challenging to discover at hadron colliders. This problem is particularly acute when the lightest state in the electroweak multiplet is neutral and all multiplet components are approximately degenerate. In this scenario, production of the charged fields of the multiplet is followed by decay into nearly invisible states; if this decay occurs promptly, the only way to infer the presence of the reaction is through its missing energy signature. Ourmore » proposal relies on emission of photon radiation from the new charged states as a means of discriminating the signal from SM backgrounds. Lastly, we demonstrate its broad applicability by studying two examples: a pure Higgsino doublet and an electroweak quintuplet field.« less

  10. Illuminating new electroweak states at hadron colliders

    SciTech Connect

    Ismail, Ahmed; Izaguirre, Eder; Shuve, Brian

    2016-07-01

    In this paper, we propose a novel powerful strategy to perform searches for new electroweak states. Uncolored electroweak states appear in generic extensions of the Standard Model (SM) and yet are challenging to discover at hadron colliders. This problem is particularly acute when the lightest state in the electroweak multiplet is neutral and all multiplet components are approximately degenerate. In this scenario, production of the charged fields of the multiplet is followed by decay into nearly invisible states; if this decay occurs promptly, the only way to infer the presence of the reaction is through its missing energy signature. Our proposal relies on emission of photon radiation from the new charged states as a means of discriminating the signal from SM backgrounds. Lastly, we demonstrate its broad applicability by studying two examples: a pure Higgsino doublet and an electroweak quintuplet field.

  11. SSC collider dipole magnets field angle data

    SciTech Connect

    Kuchnir, M.; Bleadon, M.; Schmidt, E.; Bossert, R.; Carson, J.; Delchamps, S.W.; Gourlay, S.; Hanft, R.; Koska, W.; Lamm, M.J.; Mazur, P.O.; Orris, D.; Ozelis, J.; Strait, J.; Wake, M. ); DiMarco, J.; Devred, A.; Kuzminski, J.; Yu, Y.; Zheng, H. ); Ogitsu, T. (Superconducting Super Collider

    1992-09-01

    In the fabrication of both 40 and 50 mm collider dipole superconducting magnets, surveys of the direction of the magnetic field along their length have been taken. This data besides being used for certifying compliance with the specifications for the finished magnet, yields interesting information on the straightness and rigidity of the coil placement between some stages in their manufacture and testing. A discussion on the measuring equipment and procedures is given. All of the 40 mm magnets that were built or cryostat at Fermilab have at least one of these surveys, and a summary of the data on them is presented. Most of the 50 mm magnets built and cold tested at Fermilab have been surveyed before and after insertion in the cryostat and before and after being cold tested. A summary of this data is also presented.

  12. Tracking study of hadron collider boosters

    SciTech Connect

    Machida, S.; Bourianoff, G.; Huang, Y.; Mahale, N.

    1992-07-01

    A simulation code SIMPSONS (previously called 6D-TEASE T) of single- and multi-particle tracking has been developed for proton synchrotrons. The 6D phase space coordinates are calculated each time step including acceleration with an arbitrary ramping curve by integration of the rf phase. Space-charge effects are modelled by means of the Particle In Cell (PIC) method. We observed the transverse emittance growth around the injection energy of the Low Energy Booster (LEB) of the Superconducting Super Collider (SSC) with and without second harmonic rf cavities which reduce peak line density. We also employed the code to see the possible transverse emittance deterioration around the transition energy in the Medium Energy Booster (MEB) and to estimate the emittance dilution due to an injection error of the MEB.

  13. Sfermion precision measurements at a linear collider

    SciTech Connect

    A. Freitas et al.

    2003-09-25

    At future e{sup +}e{sup -} linear colliders, the event rates and clean signals of scalar fermion production--in particular for the scalar leptons--allow very precise measurements of their masses and couplings and the determination of their quantum numbers. Various methods are proposed for extracting these parameters from the data at the sfermion thresholds and in the continuum. At the same time, NLO radiative corrections and non-zero width effects have been calculated in order to match the experimental accuracy. The substantial mixing expected for the third generation sfermions opens up additional opportunities. Techniques are presented for determining potential CP-violating phases and for extracting tan {beta} from the stau sector, in particular at high values. The consequences of possible large mass differences in the stop and sbottom system are explored in dedicated analyses.

  14. Ground motion data for International Collider models

    SciTech Connect

    Volk, J.T.; LeBrun, P.; Shiltsev, V.; Singatulin, S.; /Fermilab

    2007-11-01

    The proposed location for the International Linear Collider (ILC) in the Americas region is Fermilab in Batavia Illinois. If built at this location the tunnels would be located in the Galena Platteville shale at a depth of 100 or more meters below the surface. Studies using hydro static water levels and seismometers have been conducted in the MINOS hall and the LaFrange Mine in North Aurora Illinois to determine the level of ground motion. Both these locations are in the Galena Platteville shale and indicate the typical ground motion to be expected for the ILC. The data contains both natural and cultural noise. Coefficients for the ALT law are determined. Seismic measurements at the surface and 100 meters below the surface are presented.

  15. Time resolved diagnostics of ions in colliding carbon plasmas

    SciTech Connect

    Singh, Ravi Pratap; Gupta, Shyam L.; Thareja, Raj K.

    2014-11-14

    We report a comparative study of the dynamic behaviour of ions at different pressures in laser ablated colliding and single plasma plumes using 2D imaging, optical emission spectroscopy (OES) and a retarding field analyser (RFA). 2D imaging shows the splitting of plasma plumes due to different velocities of various plasma species. OES shows enhancement in abundance of ionic species with their presence for a longer time in colliding plume. C{sub 2} molecular formation is seen at later time in colliding plume compared to single plume and is attributed to dominating collisional processes in the colliding region of the plumes. The time of flight distribution of ions traced by the RFA shows the variation with change in fluence as well as ambient pressure for both colliding and single plume. Time of flight analysis of ions also shows the appearance of a fast peak in ion signal due to acceleration of ions at larger fluence.

  16. Detectors for Linear Colliders: Calorimetry at a Future Electron-Positron Collider (3/4)

    ScienceCinema

    None

    2016-07-12

    Calorimetry will play a central role in determining the physics reach at a future e+e- collider. The requirements for calorimetry place the emphasis on achieving an excellent jet energy resolution. The currently favoured option for calorimetry at a future e+e- collider is the concept of high granularity particle flow calorimetry. Here granularity and a high pattern recognition capability is more important than the single particle calorimetric response. In this lecture I will describe the recent progress in understanding the reach of high granularity particle flow calorimetry and the related R&D; efforts which concentrate on test beam demonstrations of the technological options for highly granular calorimeters. I will also discuss alternatives to particle flow, for example the technique of dual readout calorimetry.

  17. Detectors for Linear Colliders: Calorimetry at a Future Electron-Positron Collider (3/4)

    SciTech Connect

    2010-02-17

    Calorimetry will play a central role in determining the physics reach at a future e+e- collider. The requirements for calorimetry place the emphasis on achieving an excellent jet energy resolution. The currently favoured option for calorimetry at a future e+e- collider is the concept of high granularity particle flow calorimetry. Here granularity and a high pattern recognition capability is more important than the single particle calorimetric response. In this lecture I will describe the recent progress in understanding the reach of high granularity particle flow calorimetry and the related R&D; efforts which concentrate on test beam demonstrations of the technological options for highly granular calorimeters. I will also discuss alternatives to particle flow, for example the technique of dual readout calorimetry.

  18. Collider Phenomenology with Split-UED

    SciTech Connect

    Kong, Kyoungchul; Park, Seong Chan; Rizzo, Thomas G.; /SLAC

    2011-12-15

    We investigate the collider implications of Split Universal Extra Dimensions. The non-vanishing fermion mass in the bulk, which is consistent with the KK-parity, largely modifies the phenomenology of Minimal Universal Extra Dimensions. We scrutinize the behavior of couplings and study the discovery reach of the Tevatron and the LHC for level-2 Kaluza-Klein modes in the dilepton channel, which would indicates the presence of the extra dimensions. Observation of large event rates for dilepton resonances can result from a nontrivial fermion mass profile along the extra dimensions, which, in turn, may corroborate extra dimensional explanation for the observation of the positron excess in cosmic rays. The Minimal Universal Extra Dimensions scenario has received great attention. Recently non-vanishing bulk fermion masses have been introduced without spoiling the virtue of KK-parity. The fermion profiles are no longer simple sine/cosine functions and depend upon the specific values of bulk parameters. The profiles of fermions are split along the extra dimensions while the wave functions of the bosons remain the same as in UED. A simple introduction of a KK-parity conserving bulk fermion mass has significant influences on collider aspects as well as astrophysical implications of UED. For instance, the DM annihilation fraction into certain SM fermion pairs is either enhanced or reduced (compared to the MUED case) so that one can perhaps explain the PAMELA positron excess while suppressing the anti-proton flux. In this paper, we have concentrated on collider phenomenology of Split Universal Extra Dimensions. We have revisited the KK decomposition in detail and analyzed wave function overlaps to compute relevant couplings for collider studies. We have discussed general collider implication for level-1 KK modes and level-2 KK with non-zero bulk mass and have computed LHC reach for the EW level-2 KK bosons, {gamma}{sub 2} and Z{sub 2}, in the dilepton channel. The LHC should

  19. Status and future directions for advanced accelerator research - conventional and non-conventional collider concepts

    SciTech Connect

    Siemann, R.H.

    1997-01-01

    The relationship between advanced accelerator research and future directions for particle physics is discussed. Comments are made about accelerator research trends in hadron colliders, muon colliders, and e{sup +}3{sup {minus}} linear colliders.

  20. Actinomycin D binds strongly to d(TGTCATTG), a single-stranded DNA devoid of GpC sites.

    PubMed

    Chen, F M; Sha, F

    2001-05-01

    Despite the absence of the GpC sequence and complete self-complementarity, d(CGTCGTCG) has recently been shown to bind strongly to actinomycin D (ACTD) with a binding density of about one drug molecule per strand. To further elucidate the nature of such a binding, studies are herein made with single-base G --> A and C --> T replacements in d(CGTCGTCG) to identify the DNA bases that play important roles in the strong ACTD binding of this oligomer. On the basis of these results, the octamer d(TGTCATTG) has been identified as a potentially strong ACTD binder. Indeed, binding titration confirms such an expectation and reveals an ACTD binding constant of about 1 x 10(7) M(-1) and a binding density of roughly 0.8 drug molecule per DNA strand for this strong binding mode. Similar binding studies with single-base substitutions on d(TGTCATTG) further reveal the relative importance of the C and G bases on its ACTD binding, with the 3'-terminus G appearing to be the most crucial base. Further base substitutions lead to the conclusion that these C and G bases act in concert rather than individually in the ACTD binding of d(TGTCATTG). Spectral comparisons with the apparently single-stranded GpC-containing d(TGCTTTG) led to the proposal of a speculated monomeric hairpin binding model to account for the experimental observations. This model makes use of the notion that ACTD prefers to have the 3'-sides of both G bases stacking on the opposite faces of its planar phenoxazone chromophore, a principle akin to its classic preference for the GpC sequence in duplex form. The finding that ACTD can bind strongly to single-stranded DNA of special sequence motifs may have important implications.