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. Musculoskeletal (MSK) and Sport and Exercise Medicine (SEM) in General Practice (GP): A Novel GP-based MSK and SEM Clinic for Managing Musculoskeletal symptoms in a GP

    PubMed Central

    Heron, Neil

    2015-01-01

    Musculoskeletal (MSK) complaints are common within primary care (1) (2) (3) but some General Practitioners (GPs)/family physicians do not feel comfortable managing these symptoms (3), preferring to refer onto hospital specialists or Integrated Clinical Assessment and Treatment Services (ICATs). Long waiting times for hospital outpatient reviews are a major cause of patient inconvenience and complaints (4). We therefore aimed to establish a GP-ran MSK and sport and exercise medicine (SEM) clinic based within a Belfast GP surgery that would contribute to a sustainable improvement in managing these common conditions within primary care as well as reducing waiting times for patients with these conditions to see a specialist. This shift from hospital-based to community-based management is in-keeping with recent policy changes within the UK health-system, including Transforming Your Care within Northern Ireland (NI) (5). The GP-ran MSK and SEM clinic was held monthly within a Belfast GP practice, staffed by one GP with a specialist interest in MSK and SEM conditions and its performance was reviewed over a three month period. Parameters audited included cases seen, orthopaedic and x-ray referral rates and secondary care referrals comparing the GP practice's performance to the same time period in the previous year as well as patient satisfaction questionnaires. PMID:26733320

  3. Musculoskeletal (MSK) and Sport and Exercise Medicine (SEM) in General Practice (GP): A Novel GP-based MSK and SEM Clinic for Managing Musculoskeletal symptoms in a GP.

    PubMed

    Heron, Neil

    2015-01-01

    Musculoskeletal (MSK) complaints are common within primary care (1) (2) (3) but some General Practitioners (GPs)/family physicians do not feel comfortable managing these symptoms (3), preferring to refer onto hospital specialists or Integrated Clinical Assessment and Treatment Services (ICATs). Long waiting times for hospital outpatient reviews are a major cause of patient inconvenience and complaints (4). We therefore aimed to establish a GP-ran MSK and sport and exercise medicine (SEM) clinic based within a Belfast GP surgery that would contribute to a sustainable improvement in managing these common conditions within primary care as well as reducing waiting times for patients with these conditions to see a specialist. This shift from hospital-based to community-based management is in-keeping with recent policy changes within the UK health-system, including Transforming Your Care within Northern Ireland (NI) (5). The GP-ran MSK and SEM clinic was held monthly within a Belfast GP practice, staffed by one GP with a specialist interest in MSK and SEM conditions and its performance was reviewed over a three month period. Parameters audited included cases seen, orthopaedic and x-ray referral rates and secondary care referrals comparing the GP practice's performance to the same time period in the previous year as well as patient satisfaction questionnaires.

  4. A gp63 based vaccine candidate against Visceral Leishmaniasis

    PubMed Central

    Sinha, Sukrat; Sundaram, Shanthy; Singh, Anand Prakash; Tripathi, Ashutosh

    2011-01-01

    Visceral leishmaniasis is a macrophage associated disorder which leads to a profound decrease in the natural immunotherapeutic potential of the infected subjects to combat the disease. The major surface glycoprotein gp63 has been found to be a significant vaccine candidate against visceral leishmaniasis. The current study addresses the levels of similarity and identity in the gp63 obtained from different species of Leishmania viz donovoni, chagasi and infantum linked to the cause of visceral leishmaniasis. The results from BLAST, Phylogram and Cladogram studies indicate significant identity, similarity and conservation of important residues in the protein which lead us to conclude that a common gp63 based vaccine can be used as a therapeutical tool against visceral leishmaniasis caused by different species strains of leishmania. PMID:21383918

  5. Eliciting neutralizing antibodies with gp120 outer domain constructs based on M-group consensus sequence.

    PubMed

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

    2014-08-01

    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

  6. 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

  7. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  9. Development and Application of a gp60-Based Typing Assay for Cryptosporidium viatorum

    PubMed Central

    Elwin, K.; Winiecka-Krusnell, J.; Chalmers, R. M.; Xiao, L.; Lebbad, M.

    2015-01-01

    The apicomplexan intestinal parasites of the genus Cryptosporidium take a major toll on human and animal health and are frequent causes of waterborne outbreaks. Several species and genotypes can infect humans, including Cryptosporidium viatorum, which, to date, has only been found in humans. Molecular characterization of Cryptosporidium spp., critical to epidemiological analyses, is commonly based on gp60 gene analysis, which appears to require bespoke species- or group-specific PCR primers due to extensive genetic diversity across the genus. In this study, we amplified, sequenced, and characterized the gp60 gene of C. viatorum for the first time. Moreover, we developed and validated a gp60 typing assay for this species and applied it to 27 isolates originating from Asia, Africa, and Central America. A single subtype family, XVa, was identified containing multiple alleles. PMID:25832304

  10. 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.

  11. Worrying about wasting GP time as a barrier to help-seeking: a community-based, qualitative study

    PubMed Central

    Cromme, Susanne K; Whitaker, Katriina L; Winstanley, Kelly; Renzi, Cristina; Smith, Claire Friedemann; Wardle, Jane

    2016-01-01

    Background Worrying about wasting GP time is frequently cited as a barrier to help-seeking for cancer symptoms. Aim To explore the circumstances under which individuals feel that they are wasting GP time. Design and setting Community-based, qualitative interview studies that took place in London, the South East and the North West of England. Method Interviewees (n = 62) were recruited from a sample (n = 2042) of adults aged ≥50 years, who completed a ‘health survey’ that included a list of cancer ‘alarm’ symptoms. Individuals who reported symptoms at baseline that were still present at the 3-month follow-up (n = 271), and who had also consented to be contacted (n = 215), constituted the pool of people invited for interview. Analyses focused on accounts of worrying about wasting GP time. Results Participants were worried about wasting GP time when time constraints were visible, while dismissive interactions with their GP induced a worry of unnecessary help-seeking. Many felt that symptoms that were not persistent, worsening, or life-threatening did not warrant GP attention. Additionally, patients considered it time-wasting when they perceived attention from nurses or pharmacists to be sufficient, or when appointment structures (for example, ‘one issue per visit’) were not adhered to. Close relationships with GPs eased worries about time-wasting, while some patients saw GPs as fulfilling a service financed by taxpayers. Conclusion Worrying about wasting GP time is a complex barrier to help-seeking. GP time and resource scarcity, symptom gravity, appointment etiquette, and previous GP interactions contribute to increasing worries. Friendly GP relationships, economic reasoning, and a focus on the GP’s responsibilities as a medical professional reduce this worry. PMID:27215569

  12. Fluctuation Dynamics Analysis of gp120 Envelope Protein Reveals a Topologically Based Communication Network

    PubMed Central

    Shrivastava, Indira; LaLonde, Judith M.

    2012-01-01

    HIV infection is initiated by binding of the viral glycoprotein gp120, to the cellular receptor CD4. Upon CD4 binding, gp120 undergoes conformational change, permitting binding to the chemokine receptor. Crystal structures of gp120 ternary complex reveal the CD4 bound conformation of gp120. We report here the application of Gaussian Network Model (GNM) to the crystal structures of gp120 bound to CD4 or CD4 mimic and 17b, to study the collective motions of the gp120 core and determine the communication propensities of the residue network. The GNM fluctuation profiles identify residues in the inner domain and outer domain that may facilitate conformational change or stability, respectively. Communication propensities delineate a residue network that is topologically suited for signal propagation from the Phe43 cavity throughout the gp120 outer domain. . These results provide a new context for interpreting gp120 core envelope structure-function relationships. PMID:20718047

  13. 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.

  14. ALV-J GP37 Molecular Analysis Reveals Novel Virus-Adapted Sites and Three Tyrosine-Based Env Species

    PubMed Central

    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. PMID:25849207

  15. 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.

  16. Linear Colliders

    NASA Astrophysics Data System (ADS)

    Yamamoto, Akira; Yokoya, Kaoru

    2015-02-01

    An overview of linear collider programs is given. The history and technical challenges are described and the pioneering electron-positron linear collider, the SLC, is first introduced. For future energy frontier linear collider projects, the International Linear Collider (ILC) and the Compact Linear Collider (CLIC) are introduced and their technical features are discussed. The ILC is based on superconducting RF technology and the CLIC is based on two-beam acceleration technology. The ILC collaboration completed the Technical Design Report in 2013, and has come to the stage of "Design to Reality." The CLIC collaboration published the Conceptual Design Report in 2012, and the key technology demonstration is in progress. The prospects for further advanced acceleration technology are briefly discussed for possible long-term future linear colliders.

  17. Linear Colliders

    NASA Astrophysics Data System (ADS)

    Yamamoto, Akira; Yokoya, Kaoru

    An overview of linear collider programs is given. The history and technical challenges are described and the pioneering electron-positron linear collider, the SLC, is first introduced. For future energy frontier linear collider projects, the International Linear Collider (ILC) and the Compact Linear Collider (CLIC) are introduced and their technical features are discussed. The ILC is based on superconducting RF technology and the CLIC is based on two-beam acceleration technology. The ILC collaboration completed the Technical Design Report in 2013, and has come to the stage of "Design to Reality." The CLIC collaboration published the Conceptual Design Report in 2012, and the key technology demonstration is in progress. The prospects for further advanced acceleration technology are briefly discussed for possible long-term future linear colliders.

  18. 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. PMID:27068655

  19. Design, synthesis and biological evaluation of small molecule inhibitors of CD4-gp120 binding based on virtual screening

    PubMed Central

    Elban, Mark A.; Courter, Joel R.; Sugawara, Akihiro; Soeta, Takahiro; Madani, Navid; Princiotto, Amy M.; Kwon, Young Do; Kwong, Peter D.; Schön, Arne; Freire, Ernesto; Sodroski, Joseph; Smith, Amos B.

    2011-01-01

    The low-molecular-weight compound JRC-II-191 inhibits infection of HIV-1 by blocking the binding of the HIV-1 envelope glycoprotein gp120 to the CD4 receptor and is therefore an important lead in the development of a potent viral entry inhibitor. Reported here is the use of two orthogonal screening methods, GOLD docking and ROCS shape-based similarity searching, to identify amine-building blocks that, when conjugated to the core scaffold, yield novel analogues that maintain similar affinity for gp120. Use of this computational approach to expand SAR produced analogues of equal inhibitory activity but with diverse capacity to enhance viral infection. The novel analogues provide additional lead scaffolds for the development of HIV-1 entry inhibitors that employ protein-ligand interactions in the vestibule of gp120 Phe 43 cavity. PMID:21169023

  20. Evaluation of a gp63–PCR Based Assay as a Molecular Diagnosis Tool in Canine Leishmaniasis in Tunisia

    PubMed Central

    Guerbouj, Souheila; Djilani, Fattouma; Bettaieb, Jihene; Lambson, Bronwen; Diouani, Mohamed Fethi; Ben Salah, Afif; Ben Ismail, Riadh; Guizani, Ikram

    2014-01-01

    A gp63PCR method was evaluated for the detection and characterization of Leishmania (Leishmania) (L.) parasites in canine lymph node aspirates. This tool was tested and compared to other PCRs based on the amplification of 18S ribosomal genes, a L. infantum specific repetitive sequence and kinetoplastic DNA minicircles, and to classical parasitological (smear examination and/or culture) or serological (IFAT) techniques on a sample of 40 dogs, originating from different L. infantum endemic regions in Tunisia. Sensitivity and specificity of all the PCR assays were evaluated on parasitologically confirmed dogs within this sample (N = 18) and control dogs (N = 45) originating from non–endemic countries in northern Europe and Australia. The gp63 PCR had 83.5% sensitivity and 100% specificity, a performance comparable to the kinetoplast PCR assay and better than the other assays. These assays had comparable results when the gels were southern transferred and hybridized with a radioactive probe. As different infection rates were found according to the technique, concordance of the results was estimated by (κ) test. Best concordance values were between the gp63PCR and parasitological methods (74.6%, 95% confidence intervals CI: 58.8–95.4%) or serology IFAT technique (47.4%, 95% CI: 23.5–71.3%). However, taken together Gp63 and Rib assays covered most of the samples found positive making of them a good alternative for determination of infection rates. Potential of the gp63PCR-RFLP assay for analysis of parasite genetic diversity within samples was also evaluated using 5 restriction enzymes. RFLP analysis confirmed assignment of the parasites infecting the dogs to L. infantum species and illustrated occurrence of multiple variants in the different endemic foci. Gp63 PCR assay thus constitutes a useful tool in molecular diagnosis of L. infantum infections in dogs in Tunisia. PMID:25153833

  1. 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.

  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. 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.

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

    PubMed Central

    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. PMID:26517259

  5. 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.

  6. 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.

  7. [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.

  8. 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.

  9. 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

  10. 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.

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

    PubMed

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

    2015-12-01

    The membrane-proximal external region (MPER) of HIV-1 gp41 is an attractive target for vaccine development. Thus, better understanding of its immunogenic properties in various structural contexts is important. We previously described the crystal structure of a trimeric protein complex named gp41-HR1-54Q, which consists of the heptad repeat regions 1 and 2 and the MPER. The protein was efficiently recognized by broadly neutralizing antibodies. Here, we describe its immunogenic properties in rabbits. The protein was highly immunogenic, especially the C-terminal end of the MPER containing 4E10 and 10E8 epitopes ((671)NWFDITNWLWYIK(683)). Although antibodies exhibited strong competition activity against 4E10 and 10E8, neutralizing activity was not detected. Detailed mapping analyses indicated that amino acid residues critical for recognition resided on faces of the alpha helix that are either opposite of or perpendicular to the epitopes recognized by 4E10 and 10E8. These results provide critical information for designing the next generation of MPER-based immunogens. PMID:26454663

  12. Photon collider Higgs factories

    NASA Astrophysics Data System (ADS)

    Telnov, V. I.

    2014-09-01

    The discovery of the Higgs boson (and still nothing else) have triggered appearance of many proposals of Higgs factories for precision measurement of the Higgs properties. Among them there are several projects of photon colliders (PC) without e+e- in addition to PLC based on e+e- linear colliders ILC and CLIC. In this paper, following a brief discussion of Higgs factories physics program I give an overview of photon colliders based on linear colliders ILC and CLIC, and of the recently proposed photon-collider Higgs factories with no e+e- collision option based on recirculation linacs in ring tunnels.

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

    PubMed

    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.

  14. 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

  15. 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.

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

    PubMed

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

    2016-08-01

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

  17. Comb-like amphiphilic polypeptide-based copolymer nanomicelles for co-delivery of doxorubicin and P-gp siRNA into MCF-7 cells.

    PubMed

    Suo, Aili; Qian, Junmin; Zhang, Yaping; Liu, Rongrong; Xu, Weijun; Wang, Hejing

    2016-05-01

    A comb-like amphiphilic copolymer methoxypolyethylene glycol-graft-poly(L-lysine)-block-poly(L-phenylalanine) (mPEG-g-PLL-b-Phe) was successfully synthesized. To synthesize mPEG-g-PLL-b-Phe, diblock copolymer PLL-b-Phe was first synthesized by successive ring-opening polymerization of α-amino acid N-carboxyanhydrides followed by the removal of benzyloxycarbonyl protecting groups, and then mPEG was grafted onto PLL-b-Phe by reductive amination via Schiff's base formation. The chemical structures of the copolymers were identified by (1)H NMR. mPEG-g-PLL-b-Phe copolymer had a critical micelle concentration of 6.0mg/L and could self-assemble in an aqueous solution into multicompartment nanomicelles with a mean diameter of approximately 78 nm. The nanomicelles could encapsulate doxorubicin (DOX) through hydrophobic and π-π stacking interactions between DOX molecules and Phe blocks and simultaneously complex P-gp siRNA with cationic PLL blocks via electrostatic interactions. The DOX/P-gp siRNA-loaded nanomicelles showed spherical morphology, possessed narrow particle size distribution and had a mean particle size of 120 nm. The DOX/P-gp siRNA-loaded nanomicelles exhibited pH-responsive release behaviors and displayed accelerated release under acidic conditions. The DOX/P-gp siRNA-loaded nanomicelles were efficiently internalized into MCF-7 cells, and DOX released could successfully reach nuclei. In vitro cytotoxicity assay demonstrated that the DOX/P-gp siRNA-loaded nanomicelles showed a much higher cytotoxicity in MCF-7 cells than DOX-loaded nanomicelles due to their synergistic killing effect and that the blank nanomicelles had good biocompatibility. Thus, the novel comb-like mPEG-g-PLL-b-Phe nanomicelles could be a promising vehicle for co-delivery of chemotherapeutic drug and genetic material.

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

    SciTech Connect

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

    2006-09-01

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

  19. 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.

  20. 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.

  1. Exploring GpG bases next to anticodon in tRNA subsets

    PubMed Central

    Srinivasan, Thangavelu; Kumaran, Kubendiran; Selvakumar, Rajendran; Velmurugan, Devadasan; Sudarsanam, Dorairaj

    2013-01-01

    Transfer RNA (tRNA) structure, modifications and functions are evolutionary and established in bacteria, archaea and eukaryotes. Typically the tRNA modifications are indispensable for its stability and are required for decoding the mRNA into amino acids for protein synthesis. A conserved methylation has been located on the anticodon loop specifically at the 37th position and it is next to the anticodon bases. This modification is called as m1G37 and it is catalyzed by tRNA (m1G37) methyltransferase (TrmD). It is deciphered that G37 positions occur on few additional amino acids specific tRNA subsets in bacteria. Furthermore, Archaea and Eukaryotes have more number of tRNA subsets which contains G37 position next to the anticodon and the G residue are located at different positions such as G36, G37, G38, 39, and G40. In eight bacterial species, G (guanosine) residues are presents at the 37th and 38th position except three tRNA subsets having G residues at 36th and 39th positions. Therefore we propose that m1G37 modification may be feasible at 36th, 37th, 38th, 39th and 40th positions next to the anticodon of tRNAs. Collectively, methylation at G residues close to the anticodon may be possible at different positions and without restriction of anticodon 3rd base A, C, U or G. PMID:23847401

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

    PubMed Central

    Powell, Sian; Easton, Graham

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  4. 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.

  5. Results from a Prototype Chicane-Based Energy Spectrometer for a Linear Collider

    SciTech Connect

    Lyapin, A.; Schreiber, H.J.; Viti, M.; Adolphsen, C.; Arnold, R.; Boogert, S.; Boorman, G.; Chistiakova, M.V.; Gournaris, F.; Duginov, V.; Hast, C.; Hildreth, M.; Hlaing, C.; Jackson, F.; Khainovsky, O.; Kolomensky, Yu.G.; Kostromin, S.; Kumar, K.; Maiheu, B.; McCormick, D.; Miller, D.J.; /University Coll. London /Dubna, JINR /UC, Berkeley /LBL, Berkeley /Caltech /UC, Berkeley /LBL, Berkeley /Cambridge U. /SLAC /Cambridge U. /Fermilab /University Coll. London /SLAC

    2011-02-28

    The International Linear Collider (ILC) and other proposed high energy e{sup +}e{sup -} machines aim to measure with unprecedented precision Standard Model quantities and new, not yet discovered phenomena. One of the main requirements for achieving this goal is a measurement of the incident beam energy with an uncertainty close to 10{sup -4}. This article presents the analysis of data from a prototype energy spectrometer commissioned in 2006-2007 in SLAC's End Station A beamline. The prototype was a 4-magnet chicane equipped with beam position monitors measuring small changes of the beam orbit through the chicane at different beam energies. A single bunch energy resolution close to 5 {center_dot} 10{sup -4} was measured, which is satisfactory for most scenarios. We also report on the operational experience with the chicane-based spectrometer and suggest ways of improving its performance.

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

    PubMed

    Rigby, Carolyn

    2010-11-01

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

  7. Requirement of the single base insertion at the 3' end of the env-related gene of Friend spleen focus-forming virus for pathogenic activity and its effect on localization of the glycoprotein product (gp55).

    PubMed Central

    Amanuma, H; Watanabe, N; Nishi, M; Ikawa, Y

    1989-01-01

    In order to obtain evidence for the essential role of the single base insertion occurring at the 3' end of the env-related gene of Friend spleen focus-forming virus (SFFV) encoding the leukemogenic glycoprotein (gp55) a mutant SFFV genome was constructed in which the segment of the gp55 gene of the polycythemia-inducing strain of SFFV containing the single base insertion and the 6-base-pair duplication was replaced by the corresponding sequence of the Friend murine leukemia virus env gene. The mutant SFFV-Friend murine leukemia virus complex did not induce symptoms of the erythroproliferative disease in adult DBA/2 mice. During passage through newborn DBA/2 mice, the mutant virus complex invariably gave rise to weakly pathogenic variant SFFVs. All of the variant SFFVs induced in adult DBA/2 mice a transient mild splenomegaly associated with normal or slightly low hematocrit value, and they produced gp55 with a molecular weight similar to that of gp55 of the wild-type SFFV. For the two isolates of variant SFFV, the 3' portion of the viral DNA intermediate containing the 3' portion of the gp55 gene was molecularly cloned. Nucleotide sequences of these biologically active cloned DNAs were determined and showed that the variant SFFV genomes arose from the mutant SFFV genome by regaining the single base insertion, indicating that the single base insertion is essential for the biological activity of gp55. Evidence is presented indicating that the single base insertion which causes a loss of the cytoplasmic domain of the env-related protein is not related to the localization of the further-glycosylated form of gp55 in the plasma membrane but is involved with the release of gp55 from cells. Images PMID:2552155

  8. 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.

  9. 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

  10. 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

  11. Bylaws for GP Section

    NASA Astrophysics Data System (ADS)

    Individual sections of AGU are governed by collections of bylaws adopted by each membership. The GP Section, at the present time, has no bylaws. Such a document would include articles defining the name, objectives, and membership of the section. Also present would be a description of officers (president, president-elect, and secretary), their duties, nomination and election procedures, and information on committees, meetings, and publications. The GP Section now functions by following some standard, although unwritten, procedures. The usual bylaws used by AGU sections would not change any of the functions or procedures used by our section but would put in writing the structure that we follow. It is possible, in the membership clause, to allow members to be affiliated with more than one section and to no longer claim only a “primary” section. The GP Executive Committee intends to discuss the possibility of adopting our own bylaws at the spring business meeting. We would appreciate any input from GP membership on this topic prior to May. Please direct your comments to Laurie Brown or Subir Banerjee (addresses above).

  12. 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.

  13. Proposing a Laser Based Beam Size Monitor for the Future Linear Collider

    SciTech Connect

    Ross, Marc C

    2001-12-10

    Compton scattering techniques for the measurement of the transverse beam size of particle beams at future linear colliders (FLC) are proposed. At several locations of the beam delivery system (BDS) of the FLC, beam spot sizes ranging from several hundreds to a few micrometers have to be measured. This is necessary to verify beam optics, to obtain the transverse beam emittance, and to achieve the highest possible luminosity. The large demagnification of the beam in the BDS and the high beam power puts extreme conditions on any measuring device. With conventional techniques at their operational limit in FLC scenarios, new methods for the detection of the transverse beam size have to be developed. For this laser based techniques are proposed capable of measuring high power beams with sizes in the micrometer range. In this paper general aspects and critical issues of a generic device are outlined and specific solutions proposed. Plans to install a laser wire experiment at an accelerator test facility are presented.

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

    NASA Astrophysics Data System (ADS)

    Lednicky, R.

    2008-09-01

    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 √ s NN = 9 GeV and averaged luminosity 1027 cm-2 s-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. 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.

  16. 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.

  17. Muon Collider

    SciTech Connect

    Palmer, R.

    2009-10-19

    Parameters are given of muon colliders with center of mass energies of 1.5 and 3 TeV. Pion production is from protons on a mercury target. Capture, decay, and phase rotation yields bunch trains of both muon signs. Six dimensional cooling reduces the emittances until the trains are merged into single bunches, one of each sign. Further cooling in 6 dimensions is then applied, followed by final transverse cooling in 50 T solenoids. After acceleration the muons enter the collider ring. Ongoing R&D is discussed.

  18. ELIC: A High Luminosity And Efficient Spin Manipulation Electron-Light Ion Collider Based At CEBAF

    SciTech Connect

    Lia Merminga; Yaroslav Derbenev

    2004-02-01

    Electron-light ion colliders with center of mass energy between 20 and 100 GeV, luminosity between 10{sup 33} and 10{sup 35} cm{sup -2} sec{sup -1}, and polarization of both beams at or above 80% have been proposed for the study of hadronic structure. The Electron-Light Ion Collider (ELIC) facility would require the upgrade of CEBAF to 5-7 GeV energy recovering linac and the realization of an ion storage ring complex, accelerating and storing light ions of up to 150 GeV. In this report several innovative features of electron and ion beam designs and their advantages in delivering the luminosity and spin are described. These features include: electron circulator ring to reduce electron polarized source and energy recovering linac requirements, twisted spin booster and collider ring; interaction points with low beta-star and crab-crossing using the short, cooled ion bunches. Accelerator physics and technology issues for both protons/ions and electrons are presented. The feasibility of an integrated fixed target program at 25 GeV and collider program with center of mass energy between 20 and 65 GeV is explored.

  19. Muon collider design

    SciTech Connect

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

    1996-03-01

    The possibility of muon colliders was introduced by Skrinsky et al., Neuffer, and others. More recently, several workshops and collaboration meetings have greatly increased the level of discussion. In this paper we present scenarios for 4 TeV and 0.5 TeV colliders based on an optimally designed proton source, and for a lower luminosity 0.5 TeV demonstration based on an upgraded version of the AGS. It is assumed that a demonstration version based on upgrades of the FERMILAB machines would also be possible. 53 refs., 25 figs., 8 tabs.

  20. The Impact of Proposed delta Gp Limits on Glass Formulation Efforts: Part 1:. Model-Based Assessments

    SciTech Connect

    PEELER, DAVID

    2004-07-01

    The Savannah River National Laboratory (SRNL) has initiated studies to assess alternative durability options that may provide access to compositional regions of interest in support of the accelerated cleanup mission at the Defense Waste Processing Facility (DWPF). One of the options being pursued is the redefinition of the durability model acceptability limits. Some of the conservative steps used in establishing the current limits without comprising the high confidence required for meeting the specification on the wasteform quality were identified and eliminated. The results led to a set of three new Property Acceptability Region (PAR) values for the preliminary glass dissolution estimator or free energy of hydration durability model which have the potential to allow access to compositional regions of interest to improve melt rate or waste throughput. Although these limits are available for implementation, there is currently no driving force to do so (i.e., the current Frit 418 - Sludge Batch 3 (SB3) system is liquidus temperature (TL) limited). In this report, glass formulations were identified with the intent of generating incentive for applying the new durability limits for SB3. More specifically, higher alkali frit compositions were identified or developed to transition into and through the region of .Gp acceptability as defined by the current and proposed durability limits. All other property prediction criteria were satisfied. An eight glass test matrix has been identified to meet these objectives. These glasses will be fabricated in the laboratory and their durability measured and compared to model predictions (and to the assessments by the index system). Although incentive for implementation of the proposed durability limits could be demonstrated through the measured durability response for these higher alkali systems, assessments of melt rate should also be performed to establish a clear motive or driver to implement a frit change. More specifically, a

  1. Linear collider development at SLAC

    SciTech Connect

    Irwin, J.

    1993-08-01

    Linear collider R&D at SLAC comprises work on the present Stanford Linear Collider (SLC) and work toward the next linear collider (NLC). Recent SLC developments are summarized. NLC studies are divided into hardware-based and theoretical. We report on the status of the NLC Test Accelerator (NLCTA) and the final focus test beam (FFTB), describe plans for ASSET, an installation to measure accelerator structure wakefields, and mention IR design developments. Finally we review recent NLC theoretical studies, ending with the author`s view of next linear collider parameter sets.

  2. 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.

  3. 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.

  4. Collider physics

    SciTech Connect

    Not Available

    1991-01-01

    This past year our group participated in both the D0 experiment at Fermilab and the SDC experiment at the SSC. Most of our effort was concentrated on the D0 project, where we contributed as much manpower as possible to the commissioning of the detector in preparation for the coming collider run. Our SDC work consisted of the investigation of one of the candidate technologies for the forward calorimeter. On the D0 experiment, our primary responsibilities have been in the areas of electronics commissioning and in the establishment of triggers for the coming collider run. We have also actively participated in the physics studies and have contributed to the upgrade effort as much as time has permitted. Our group has also participated in the cosmic ray run and in the D0 test beam. In view of our contributions, James White was selected as a member of the D0 Trigger board, and Jay Wightman is being trained as one of the global experts'' who are responsible for keeping the detector operational during the run. In addition, Amber Boehnlein has played a major role in the Level-2 trigger commissioning. A more detailed description of these activities is given in this paper.

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

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

    2007-04-10

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

  7. (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.

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

    NASA Astrophysics Data System (ADS)

    Zha, Hao; Latina, Andrea; Grudiev, Alexej; De Michele, Giovanni; Solodko, Anastasiya; Wuensch, Walter; Schulte, Daniel; Adli, Erik; Lipkowitz, Nate; Yocky, Gerald S.

    2016-01-01

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

  9. 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

  10. 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. PMID:25750031

  11. Acid-base properties of the nucleic-acid model 2'-deoxyguanylyl(5'-->3')-2'-deoxy-5'-guanylate, d(pGpG)3-, and of related guanine derivatives.

    PubMed

    Knobloch, Bernd; Sigel, Helmut; Okruszek, Andrzej; Sigel, Roland K O

    2006-03-21

    The dinucleotide d(pGpG) is an often employed DNA model to study various kinds of interactions between DNA and metal ions, but its acid-base properties were not yet described in detail. In this study the six deprotonation reactions of H4[d(pGpG)]+ are quantified. The acidity constants for the release of the first proton from the terminal P(O)(OH)2 group (pKa = 0.65) and for one of the (N7)H+ sites (pKa = 2.4) are estimated. The acidity constants of the remaining four deprotonation reactions were measured by potentiometric pH titrations in aqueous solution (25 degrees C; I = 0.1 M, NaNO3): The pKa values for the deprotonations of the second (N7)H+, the P(O)2(OH)-, and the two (N1)H sites are 2.98, 6.56, 9.54 and 10.11, respectively. Based on these results we show how to estimate acidity constants for related systems that have not been studied, e.g. pGpG, which is involved in the initiation step of a rotavirus RNA polymerase. The relevance of our results for nucleic acids in general is briefly indicated.

  12. 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

  13. Beam collimation at hadron colliders

    SciTech Connect

    Nikolai V. Mokhov

    2003-08-12

    Operational and accidental beam losses in hadron colliders can have a serious impact on machine and detector performance, resulting in effects ranging from minor to catastrophic. Principles and realization are described for a reliable beam collimation system required to sustain favorable background conditions in the collider detectors, provide quench stability of superconducting magnets, minimize irradiation of accelerator equipment, maintain operational reliability over the life of the machine, and reduce the impact of radiation on personnel and the environment. Based on detailed Monte-Carlo simulations, such a system has been designed and incorporated in the Tevatron collider. Its performance, comparison to measurements and possible ways to further improve the collimation efficiency are described in detail. Specifics of the collimation systems designed for the SSC, LHC, VLHC, and HERA colliders are discussed.

  14. 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

  15. Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

    PubMed

    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 (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 (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-electron microscopy 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. We also 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 towards differently structured products of the GP gene. PMID:27562261

  16. Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

    PubMed

    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

    2016-08-08

    The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (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 (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-electron microscopy 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. We also 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 towards differently structured products of the GP gene.

  17. 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...

  18. 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

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

    PubMed

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

    2015-11-28

    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. PMID:26495445

  20. Gamma-gamma colliders

    SciTech Connect

    Kim, K.J.; Sessler, A.

    1996-06-01

    Gamma-gamma colliders make intense beams of gamma rays and have them collide so as to make elementary particles. The authors show, in this article, that constructing a gamma-gamma collider as an add-on to an electron-positron linear collider is possible with present technology and that it does not require much additional cost. Furthermore, they show that the resulting capability is very interesting from a particle physics point of view. An overview of a linear collider, with a second interaction region devoted to {gamma}{gamma} collisions is shown.

  1. Period change in GP And

    NASA Astrophysics Data System (ADS)

    Rodriguez, E.; Rolland, A.; Lopez de Coca, P.

    1993-05-01

    GP And is a high amplitude d Scuti type star with V~10.m75, DV~0.m55, P=0.d0787 and spectral type A3 (Lopez de Coca et al. 1990, A & A 83, 51). To study the stability of its fundamental pulsation we have carried out simultaneous uvby photometry of this star in the years 1987 and 1992 at Sierra Nevada and Caltar Alto observatories, both in Spain. Ten new times of light maxima were obtained. In total, forty-one time s of light maxima (from 1973 to 1992, collected from Splittgerber 1976, Mitt. Veraend. Sterne 7, 137; Eggen 1978, IBVS 1517; Gieseking et al. 1979, A & AS 36, 457; Burchi et al. 1992, Mem. Soc. Astron. Ital. 63, 87 and us) were used to determinate the ephemeris of the light curve of GP And by means of the classical O-C method.

  2. Challenges in future linear colliders

    SciTech Connect

    Swapan Chattopadhyay; Kaoru Yokoya

    2002-09-02

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

  3. 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.

  4. Results from hadron colliders

    SciTech Connect

    Pondrom, L.G. )

    1990-12-14

    The present status of hadron collider physics is reviewed. The total cross section for {bar p} + p has been measured at 1.8 TeV: {sigma}{sub tot} = 72.1 {plus minus} 3.3 mb. New data confirm the UA2 observation of W/Z {yields} {bar q}q. Precision measurements of M{sub W} by UA2 and CDF give an average value M{sub W} = 80.13 {plus minus} 0.30 GeV/c{sup 2}. When combined with measurements of M{sub Z} from LEP and SLC this number gives sin{sup 2}{theta}{sub W} = 0.227 {plus minus} 0.006, or m{sub top} = 130{sub {minus}60}{sup +40} GeV/c{sup 2} from the EWK radiative correction term {Delta}r. Evidence for hadron colliders as practical sources of b quarks has been strengthened, while searches for t quarks have pushed the mass above M{sub W}: m{sub top} > 89 GeV/c{sup 2} 95% cl (CDF Preliminary). Searches beyond the standard model based on the missing E{sub T} signature have not yet produced any positive results. Future prospects for the discovery of the top quark in the range m{sub top} < 200 GeV/c{sup 2} look promising. 80 refs., 35 figs., 7 tabs.

  5. On-orbit GP-B Operations

    NASA Astrophysics Data System (ADS)

    Muhlfelder, B.; Green, G.; Keiser, G. M.; Smith, M.

    Gravity Probe B (GP-B) is a space-based experiment designed to measure two non-Newtonian precessions of precision gyroscopes in orbit about the Earth. The on-orbit mission is divided into three phases: initialization, science, and post-science calibration. The initialization phase configures the space vehicle for science and spans the first two months of the 18 month on-orbit dewar lifetime. Initialization consists of adjusting the vehicle's 640 km orbit to within 0.003 degrees of a nearly polar orbit, use of an on-board tracking telescope to point the vehicle to a distant fixed reference star, and spinning each of the science gyroscopes to approximately 100 Hz. After initialization, science data are collected for each gyroscope. A London Moment based gyroscope readout system provides a measurement of the precession of the gyroscope spin axis orientation. Following the collection of the science data, the Newtonian drift rates of the gyroscopes are intentionally enhanced. This calibration provides a bound of the amount of Newtonian gyroscope precession present in the science phase, gyroscope data. All vehicle commanding and data collection will be performed using the GP-B ground station. The team is now readying for the planned April 2004 launch.

  6. The Large Hadron Collider

    NASA Astrophysics Data System (ADS)

    Myers, Stephen

    The Large Hadron Collider (LHC) was first suggested (in a documented way) in 1983 [1] as a possible future hadron collider to be installed in the 27 km "LEP" tunnel. More than thirty years later the collider has been operated successfully with beam for three years with spectacular performance and has discovered the long-sought-after Higgs boson. The LHC is the world's largest and most energetic particle collider. It took many years to plan and build this large complex machine which promises exciting, new physics results for many years to come...

  7. The development of colliders

    SciTech Connect

    Sessler, A.M.

    1997-03-01

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

  8. An Afterburner at the ILC: The Collider Viewpoint

    SciTech Connect

    Raubenheimer, Tor O.

    2004-12-07

    The concept of a high-gradient plasma wakefield accelerator is considered as an upgrade path for the International Linear Collider, a future linear collider. Basic parameters are presented based on those developed for the SLC 'Afterburner'. Basic layout considerations are described and the primary concerns related to the collider operation are discussed.

  9. An Afterburner at the ILC: The Collider Viewpoint

    SciTech Connect

    Raubenheimer, T

    2004-09-01

    The concept of a high-gradient plasma wakefield accelerator is considered as an upgrade path for the International Linear Collider, a future linear collider. Basic parameters are presented based on those developed for the SLC ''Afterburner.'' Basic layout considerations are described and the primary concerns related to the collider operation are discussed.

  10. 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.

  11. 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.

  12. A novel tetrameric gp350 1-470 as a potential Epstein-Barr virus vaccine.

    PubMed

    Cui, Xinle; Cao, Zhouhong; Sen, Goutam; Chattopadhyay, Gouri; Fuller, Deborah H; Fuller, James T; Snapper, Dustin M; Snow, Andrew L; Mond, James J; Snapper, Clifford M

    2013-06-26

    Infectious mononucleosis and B-cell transformation in response to infection with Epstein-Barr virus (EBV) is dependent upon binding of the EBV envelope glycoprotein gp350 to CD21 on B-cells. Gp350-specific antibody comprises most of the EBV neutralizing activity in the serum of infected patients, making this protein a promising target antigen for a prophylactic EBV vaccine. We describe a novel, tetrameric gp350-based vaccine that exhibits markedly enhanced immunogenicity relative to its monomeric counterpart. Plasmid DNA was constructed for synthesis, within transfected CHO cells, of a tetrameric, truncated (a.a. 1-470) gp350 protein (gp350(1-470)). Tetrameric gp350(1-470) induced ≈ 20-fold higher serum titers of gp350(1-470)-specific IgG and >19-fold enhancements in neutralizing titers at the highest dose, and was >25-fold more immunogenic on a per-weight basis than monomeric gp350(1-470). Further, epidermal immunization with plasmid DNA encoding gp350(1-470) tetramer induced 8-fold higher serum titers of gp350(1-470)-specific IgG relative to monomer. Tetrameric gp350(1-470) binding to human CD21 was >24-fold more efficient on a per-weight basis than monomer, but neither tetramer nor monomer mediated polyclonal human B-cell activation. Finally, the introduction of strong, universal tetanus toxoid (TT)-specific CD4+ T-cell epitopes into the tetrameric gp350(1-470) had no effect on the gp350(1-470)-specific IgG response in naïve mice, and resulted in suppressed gp350(1-470)-specific IgG responses in TT-primed mice. Collectively, these data suggest that tetrameric gp350(1-470) is a potentially promising candidate for testing as a prophylactic EBV vaccine, and that protein multimerization, using the approach described herein, is likely to be clinically relevant for enhancing the immunogenicity of other proteins of vaccine interest.

  13. A novel tetrameric gp3501-470 as a potential Epstein-Barr virus vaccine

    PubMed Central

    Cui, Xinle; Cao, Zhouhong; Sen, Goutam; Chattopadhyay, Gouri; Fuller, Deborah H.; Fuller, James T.; Snapper, Dustin M.; Snow, Andrew; Mond, James J.; Snapper, Clifford M.

    2013-01-01

    Infectious mononucleosis and B-cell transformation in response to infection with Epstein-Barr virus (EBV) is dependent upon binding of the EBV envelope glycoprotein gp350 to CD21 on B-cells. Gp350-specific antibody comprises most of the EBV neutralizing activity in the serum of infected patients, making this protein a promising target antigen for a prophylactic EBV vaccine. We describe a novel, tetrameric gp350-based vaccine that exhibits markedly enhanced immunogenicity relative to its monomeric counterpart. Plasmid DNA was constructed for synthesis, within transfected CHO cells, of a tetrameric, truncated (a.a. 1-470) gp350 protein (gp3501-470). Tetrameric gp3501-470 induced ~20-fold higher serum titers of gp3501-470-specific IgG and >19-fold enhancements in neutralizing titers at the highest dose, and was >25-fold more immunogenic on a per-weight basis than monomeric gp3501-470. Further, epidermal immunization with plasmid DNA encoding gp3501-470 tetramer induced 8-fold higher serum titers of gp3501-470-specific IgG relative to monomer. Tetrameric gp3501-470 binding to human CD21 was >24-fold more efficient on a per-weight basis than monomer, but neither tetramer nor monomer mediated polyclonal human B-cell activation. Finally, the introduction of strong, universal tetanus toxoid (TT)-specific CD4+ T-cell epitopes into the tetrameric gp3501-470 had no effect on the gp3501-470-specific IgG response in naïve mice, and resulted in suppressed gp3501-470-specific IgG responses in TT-primed mice. Collectively, these data suggest that tetrameric gp3501-470 is a potentially promising candidate for testing as a prophylactic EBV vaccine, and that protein multimerization, using the approach described herein, is likely to be clinically relevant for enhancing the immunogenicity of other proteins of vaccine interest. PMID:23665339

  14. 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.

  15. 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.

  16. 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

  17. Screening and Identification of ssDNA Aptamer for Human GP73.

    PubMed

    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.

  18. 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.

  19. 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.

  20. Hadron hadron collider group

    SciTech Connect

    Palmer, R.; Peoples, J.; Ankenbrandt, C.

    1982-01-01

    The objective of this group was to make a rough assessment of the characteristics of a hadron-hadron collider which could make it possible to study the 1 TeV mass scale. Since there is very little theoretical guidance for the type of experimental measurements which could illuminate this mass scale, we chose to extend the types of experiments which have been done at the ISR, and which are in progress at the SPS collider to these higher energies.

  1. 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.

  2. Free gp70 from FeLV: enrichment from cell culture fluid by ferric oxide-agarose chromatography.

    PubMed

    Zelikman, I; Akerblom, L; Hjertèn, S; Morein, B

    1989-04-01

    A new chromatographic material based on beads of macroporous crosslinked agarose containing ferric oxide particles was used for enrichment of gp70--the envelope glycoprotein of feline leukemia virus (FeLV). Free gp70 was purified from cell culture fluid in one step with a recovery of 50 to 60% and a purification of about 60 times. The described procedure is a suitable first step for the purification of gp70 from large volumes of cell culture fluid.

  3. Test facilities for future linear colliders

    SciTech Connect

    Ruth, R.D.

    1995-12-01

    During the past several years there has been a tremendous amount of progress on Linear Collider technology world wide. This research has led to the construction of the test facilities described in this report. Some of the facilities will be complete as early as the end of 1996, while others will be finishing up around the end 1997. Even now there are extensive tests ongoing for the enabling technologies for all of the test facilities. At the same time the Linear Collider designs are quite mature now and the SLC is providing the key experience base that can only come from a working collider. All this taken together indicates that the technology and accelerator physics will be ready for a future Linear Collider project to begin in the last half of the 1990s.

  4. Photon-photon colliders

    SciTech Connect

    Sessler, Andrew M.

    1996-01-01

    Since the seminal work by Ginsburg, et al., the subject of giving the Next Linear Collider photon-photon capability, as well as electron-positron capability, has drawn much attention [1]. A 1990 article by V.I. Telnov describes the situation at that time [2]. In March 1994, the first workshop on this subject was held [3]. This report briefly reviews the physics that can be achieved through the photon-photon channel and then focuses on the means of achieving such a collider. Also reviewed is the spectrum of backscattered Compton photons—the best way of obtaining photons. We emphasize the spectrum actually obtained in a collider with both polarized electrons and photons (peaked at high energy and very different from a Compton spectrum). Luminosity is estimated for the presently considered colliders, and interaction and conversion-point geometries are described. Also specified are laser requirements (such as wavelength, peak power, and average power) and the lasers that might be employed. These include conventional and free-electron lasers. Finally, we describe the R&D necessary to make either of these approaches viable and explore the use of the SLC as a test bed for a photon-photon collider of very high energy.

  5. Photon-photon colliders

    SciTech Connect

    Sessler, A.M.

    1995-04-01

    Since the seminal work by Ginsburg, et at., the subject of giving the Next Linear Collider photon-photon capability, as well as electron-positron capability, has drawn much attention. A 1990 article by V.I. Teinov describes the situation at that time. In March 1994, the first workshop on this subject was held. This report briefly reviews the physics that can be achieved through the photon-photon channel and then focuses on the means of achieving such a collider. Also reviewed is the spectrum of backscattered Compton photons -- the best way of obtaining photons. We emphasize the spectrum actually obtained in a collider with both polarized electrons and photons (peaked at high energy and very different from a Compton spectrum). Luminosity is estimated for the presently considered colliders, and interaction and conversion-point geometries are described. Also specified are laser requirements (such as wavelength, peak power, and average power) and the lasers that might be employed. These include conventional and free-electron lasers. Finally, we describe the R&D necessary to make either of these approaches viable and explore the use of the SLC as a test bed for a photon-photon collider of very high energy.

  6. Military GP training-the future.

    PubMed

    Herod, T P; Johnson, G A

    2013-01-01

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

  7. 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.

  8. The Large Hadron Collider.

    PubMed

    Evans, Lyndon

    2012-02-28

    The construction of the Large Hadron Collider (LHC) has been a massive endeavour spanning almost 30 years from conception to commissioning. Building the machine with the highest possible energy (7 TeV) in the existing large electron-positron (LEP) collider tunnel of 27 km circumference and with a tunnel diameter of only 3.8 m has required considerable innovation. The first was the development of a two-in-one magnet, where the two rings are integrated into a single magnetic structure. This compact two-in-one structure was essential for the LHC owing to the limited space available in the existing LEP collider tunnel and the cost. The second was a bold move to the use of superfluid helium cooling on a massive scale, which was imposed by the need to achieve a high (8.3 T) magnetic field using an affordable Nb-Ti superconductor.

  9. 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.

  10. 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.

  11. The large hadron collider

    NASA Astrophysics Data System (ADS)

    Brüning, O.; Burkhardt, H.; Myers, S.

    2012-07-01

    The Large Hadron Collider (LHC) is the world’s largest and most energetic particle collider. It took many years to plan and build this large complex machine which promises exciting, new physics results for many years to come. We describe and review the machine design and parameters, with emphasis on subjects like luminosity and beam conditions which are relevant for the large community of physicists involved in the experiments at the LHC. First collisions in the LHC were achieved at the end of 2009 and followed by a period of a rapid performance increase. We discuss what has been learned so far and what can be expected for the future.

  12. 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.

  13. optGpSampler: An Improved Tool for Uniformly Sampling the Solution-Space of Genome-Scale Metabolic Networks

    PubMed Central

    Megchelenbrink, Wout; Huynen, Martijn; Marchiori, Elena

    2014-01-01

    Constraint-based models of metabolic networks are typically underdetermined, because they contain more reactions than metabolites. Therefore the solutions to this system do not consist of unique flux rates for each reaction, but rather a space of possible flux rates. By uniformly sampling this space, an estimated probability distribution for each reaction’s flux in the network can be obtained. However, sampling a high dimensional network is time-consuming. Furthermore, the constraints imposed on the network give rise to an irregularly shaped solution space. Therefore more tailored, efficient sampling methods are needed. We propose an efficient sampling algorithm (called optGpSampler), which implements the Artificial Centering Hit-and-Run algorithm in a different manner than the sampling algorithm implemented in the COBRA Toolbox for metabolic network analysis, here called gpSampler. Results of extensive experiments on different genome-scale metabolic networks show that optGpSampler is up to 40 times faster than gpSampler. Application of existing convergence diagnostics on small network reconstructions indicate that optGpSampler converges roughly ten times faster than gpSampler towards similar sampling distributions. For networks of higher dimension (i.e. containing more than 500 reactions), we observed significantly better convergence of optGpSampler and a large deviation between the samples generated by the two algorithms. Availability: optGpSampler for Matlab and Python is available for non-commercial use at: http://cs.ru.nl/~wmegchel/optGpSampler/. PMID:24551039

  14. 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

  15. The Stanford Linear Collider

    SciTech Connect

    Rees, J.R.

    1989-10-01

    April, 1989, the first Z zero particle was observed at the Stanford Linear Collider (SLC). The SLC collides high-energy beams of electrons and positrons into each other. In break with tradition the SLC aims two linear beams at each other. Strong motives impelled the Stanford team to choose the route of innovation. One reason being that linear colliders promise to be less expensive to build and operate than storage ring colliders. An equally powerful motive was the desire to build an Z zero factory, a facility at which the Z zero particle can be studied in detail. More than 200 Z zero particles have been detected at the SLC and more continue to be churned out regularly. It is in measuring the properties of the Z zero that the SLC has a seminal contribution to make. One of the primary goals of the SLC experimental program is to determine the mass of the Z zero as precisely as possible.In the end, the SLC's greatest significance will be in having proved a new accelerator technology. 7 figs.

  16. 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.

  17. 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.

  18. High luminosity muon collider design

    SciTech Connect

    Palmer, R.; Gallardo, J.

    1996-10-01

    Muon Colliders have unique technical and physics advantages and disadvantages when compared with both hadron and electron machines. They should be regarded as complementary. Parameters are given of 4 TeV high luminosity {mu}{sup +}{mu}{sup {minus}} collider, and of a 0.5 TeV lower luminosity demonstration machine. We discuss the various systems in such muon colliders.

  19. 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.

  20. Natural flavonoids silymarin and quercetin improve the brain distribution of co-administered P-gp substrate drugs.

    PubMed

    Ravikumar Reddy, D; Khurana, Amit; Bale, Swarna; Ravirala, Ramu; Samba Siva Reddy, V; Mohankumar, M; Godugu, Chandraiah

    2016-01-01

    P-glycoprotein (P-gp), a well known efflux transporter in the blood brain barrier inhibits the uptake of substrate drugs into brain. The main aim of this study is to evaluate the effect of natural product based P-gp inhibitors on brain penetration of various CNS drugs which are P-gp substrates. In this study, we have evaluated the inhibitory effects of natural bioflavonoids (quercetin and silymarin) on P-gp by using digoxin and quinidine as model P-gp model substrate drugs. In vitro inhibitory effects were evaluated in Caco-2 cell lines using digoxin as a model drug and in vivo P-gp inhibiting effect was evaluated in mice model using quinidine as model drug. The accumulation and bidirectional transport of digoxin in Caco-2 cells was determined in presence and absence of quercetin and silymarin. Elacridar was used as standard P-gp inhibitor and used to compare the inhibitory effects of test compounds. The apical to basolateral transport of digoxin was increased where as basolateral to apical transport of digoxin was decreased in concentration dependent manner in the presence of elacridar, quercetin and silymarin. After intravenous administration of P-gp inhibitors, brain levels of quinidine were estimated using LC-MS method. Increased brain uptake was observed with quercetin (2.5-fold) and silymarin (3.5-fold). Though the brain penetration potential of P-gp substrates was lower than that observed in elacridar, both quercetin and silymarin improved plasma quinidine levels. Caco-2 permeability studies and brain uptake indicate that both quercetin and silymarin can inhibit P-gp mediated efflux of drug into brain. Our results suggest that both silymarin and quercetin could potentially increase the brain distribution of co-administered drugs that are P-gp substrates.

  1. Natural flavonoids silymarin and quercetin improve the brain distribution of co-administered P-gp substrate drugs.

    PubMed

    Ravikumar Reddy, D; Khurana, Amit; Bale, Swarna; Ravirala, Ramu; Samba Siva Reddy, V; Mohankumar, M; Godugu, Chandraiah

    2016-01-01

    P-glycoprotein (P-gp), a well known efflux transporter in the blood brain barrier inhibits the uptake of substrate drugs into brain. The main aim of this study is to evaluate the effect of natural product based P-gp inhibitors on brain penetration of various CNS drugs which are P-gp substrates. In this study, we have evaluated the inhibitory effects of natural bioflavonoids (quercetin and silymarin) on P-gp by using digoxin and quinidine as model P-gp model substrate drugs. In vitro inhibitory effects were evaluated in Caco-2 cell lines using digoxin as a model drug and in vivo P-gp inhibiting effect was evaluated in mice model using quinidine as model drug. The accumulation and bidirectional transport of digoxin in Caco-2 cells was determined in presence and absence of quercetin and silymarin. Elacridar was used as standard P-gp inhibitor and used to compare the inhibitory effects of test compounds. The apical to basolateral transport of digoxin was increased where as basolateral to apical transport of digoxin was decreased in concentration dependent manner in the presence of elacridar, quercetin and silymarin. After intravenous administration of P-gp inhibitors, brain levels of quinidine were estimated using LC-MS method. Increased brain uptake was observed with quercetin (2.5-fold) and silymarin (3.5-fold). Though the brain penetration potential of P-gp substrates was lower than that observed in elacridar, both quercetin and silymarin improved plasma quinidine levels. Caco-2 permeability studies and brain uptake indicate that both quercetin and silymarin can inhibit P-gp mediated efflux of drug into brain. Our results suggest that both silymarin and quercetin could potentially increase the brain distribution of co-administered drugs that are P-gp substrates. PMID:27652191

  2. Agar gel immunodiffusion analysis using baculovirus-expressed recombinant bovine leukemia virus envelope glycoprotein (gp51/gp30(T-)).

    PubMed

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

    2009-12-01

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

  3. 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

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

    2015-10-30

    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

  4. 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.

  5. Muon Collider Progress: Accelerators

    SciTech Connect

    Zisman, Michael S.

    2011-09-10

    A muon collider would be a powerful tool for exploring the energy-frontier with leptons, and would complement the studies now under way at the LHC. Such a device would offer several important benefits. Muons, like electrons, are point particles so the full center-of-mass energy is available for particle production. Moreover, on account of their higher mass, muons give rise to very little synchrotron radiation and produce very little beamstrahlung. The first feature permits the use of a circular collider that can make efficient use of the expensive rf system and whose footprint is compatible with an existing laboratory site. The second feature leads to a relatively narrow energy spread at the collision point. Designing an accelerator complex for a muon collider is a challenging task. Firstly, the muons are produced as a tertiary beam, so a high-power proton beam and a target that can withstand it are needed to provide the required luminosity of ~1 × 10{sup 34} cm{sup –2}s{sup –1}. Secondly, the beam is initially produced with a large 6D phase space, which necessitates a scheme for reducing the muon beam emittance (“cooling”). Finally, the muon has a short lifetime so all beam manipulations must be done very rapidly. The Muon Accelerator Program, led by Fermilab and including a number of U.S. national laboratories and universities, has undertaken design and R&D activities aimed toward the eventual construction of a muon collider. Design features of such a facility and the supporting R&D program are described.

  6. Immune Focusing and Enhanced Neutralization Induced by HIV-1 gp140 Chemical Cross-Linking

    PubMed Central

    Schiffner, T.; Kong, L.; Duncan, C. J. A.; Back, J. W.; Benschop, J. J.; Shen, X.; Huang, P. S.; Stewart-Jones, G. B.; DeStefano, J.; Seaman, M. S.; Tomaras, G. D.; Montefiori, D. C.; Schief, W. R.

    2013-01-01

    Experimental vaccine antigens based upon the HIV-1 envelope glycoproteins (Env) have failed to induce neutralizing antibodies (NAbs) against the majority of circulating viral strains as a result of antibody evasion mechanisms, including amino acid variability and conformational instability. A potential vaccine design strategy is to stabilize Env, thereby focusing antibody responses on constitutively exposed, conserved surfaces, such as the CD4 binding site (CD4bs). Here, we show that a largely trimeric form of soluble Env can be stably cross-linked with glutaraldehyde (GLA) without global modification of antigenicity. Cross-linking largely conserved binding of all potent broadly neutralizing antibodies (bNAbs) tested, including CD4bs-specific VRC01 and HJ16, but reduced binding of several non- or weakly neutralizing antibodies and soluble CD4 (sCD4). Adjuvanted administration of cross-linked or unmodified gp140 to rabbits generated indistinguishable total gp140-specific serum IgG binding titers. However, sera from animals receiving cross-linked gp140 showed significantly increased CD4bs-specific antibody binding compared to animals receiving unmodified gp140. Moreover, peptide mapping of sera from animals receiving cross-linked gp140 revealed increased binding to gp120 C1 and V1V2 regions. Finally, neutralization titers were significantly elevated in sera from animals receiving cross-linked gp140 rather than unmodified gp140. We conclude that cross-linking favors antigen stability, imparts antigenic modifications that selectively refocus antibody specificity and improves induction of NAbs, and might be a useful strategy for future vaccine design. PMID:23843636

  7. 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. PMID:26730512

  8. Glycoprotein gp50-negative pseudorabies virus: a novel approach toward a nonspreading live herpesvirus vaccine.

    PubMed Central

    Heffner, S; Kovács, F; Klupp, B G; Mettenleiter, T C

    1993-01-01

    V-infected animals exhibited severe symptoms, whereas the gp50- PrV-infected pigs showed a significant level of protection. In conclusion, vaccination with a PrV mutant lacking glycoprotein gp50, which is unable to spread between animals because of a lack of formation of free infectious virions, can confer on pigs protection against challenge infection. These results provide the basis for the development of new, nonspreading live herpesvirus vaccines based on gp50- PrV mutants. Images PMID:8382308

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

    PubMed Central

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

    2015-01-01

    Objective. To explore experienced general practitioner (GP) tutor perceptions of a skilled GP tutor of medical students. Design. Interview study based on focus groups. Setting. Twenty GPs experienced in tutoring medical students at primary health care centres in two Swedish regions were interviewed. Method. Four focus-group interviews were analysed using qualitative content analysis. Subjects. Twenty GP tutors, median age 50, specifically selected according to age, gender, and location participated in two focus groups in Gothenburg and Malmö, respectively. Main outcome measures. Meaning units in the texts were extracted, coded and condensed into categories and themes. Results. Three main themes emerged: “Professional as GP and ambassador to general practice”, “Committed and student-centred educator”, and “Coordinator of the learning environment”. Conclusion. Experienced GP tutors describe their skills as a clinical tutor as complex and diversified. A strong professional identity within general practice is vital and GP tutors describe themselves as ambassadors to general practice, essential to the process of recruiting a new generation of general practitioners. Leaders of clinical education and health care planners must understand the complexity in a clinical tutor's assignment and provide adequate support, time, and resources in order to facilitate a sustainable tutorship and a good learning environment, which could also improve the necessary recruitment of future GPs. PMID:26158585

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

    PubMed

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

    2016-04-01

    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. PMID:26874586

  11. 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.

  12. 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

  13. RF sources for future colliders

    NASA Astrophysics Data System (ADS)

    Phillips, Robert M.

    1997-02-01

    As we push particle colliders to 1-TeV center-of-mass collision energy and beyond, we require much more from our RF energy sources, both in terms of the RF performance and the number required for a given machine. In order to conserve real estate, the operating frequency of future colliders is apt to be higher than the S-band used for the SLAC SLC. It is this inevitable trend toward higher frequencies which presents the source designer with the greatest challenge. This paper is about that challenge. For reasons which will become clear, as we go to frequencies substantially above X-band, we will require sources other than klystrons, probably of the type referred to as "fast-wave devices," such as FEL or gyro-based amplifiers, or two-beam accelerators. Because these are discussed elsewhere in this conference, I will stick to the klystron as my model in describing the challenges to be overcome, as well as the criteria which must be met by alternative sources for new accelerators.

  14. Experiment and Radiation Safety at Colliders

    NASA Astrophysics Data System (ADS)

    Pugatch, V.

    The emphasis is made on the novel radiation monitoring systems at colliders based on the Metal Foil Detector technology. The radiation monitoring systems for the HERA-B experiment (DESY, Hamburg) as well as for the Silicon Tracker of the LHCb experiment (CERN, Geneva) are described. The micro-strip Metal Foil Detector used for the beam profile monitoring is briefly presented.

  15. Linear Collider Accelerator Physics Issues Regarding Alignment

    SciTech Connect

    Seeman, J.T.; /SLAC

    2005-08-12

    The next generation of linear colliders will require more stringent alignment tolerances than those for the SLC with regard to the accelerating structures, quadrupoles, and beam position monitors. New techniques must be developed to achieve these tolerances. A combination of mechanical-electrical and beam-based methods will likely be needed.

  16. 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. PMID:24134857

  17. 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:…

  18. The super collider revisited

    SciTech Connect

    Hussein, M.S.; Pato, M.P. )

    1992-05-20

    In this paper, the authors suggest a revised version of the Superconducting Super Collider (SSC) that employs the planned SSC first stage machine as an injector of 0.5 TeV protons into a power laser accelerator. The recently developed Non-linear Amplification of Inverse Bremsstrahlung Acceleration (NAIBA) concept dictates the scenario of the next stage of acceleration. Post Star Wars lasers, available at several laboratories, can be used for the purpose. The 40 TeV CM energy, a target of the SSC, can be obtained with a new machine which can be 20 times smaller than the planned SSC.

  19. Hadron-hadron colliders

    SciTech Connect

    Month, M.; Weng, W.T.

    1983-06-21

    The objective is to investigate whether existing technology might be extrapolated to provide the conceptual framework for a major hadron-hadron collider facility for high energy physics experimentation for the remainder of this century. One contribution to this large effort is to formalize the methods and mathematical tools necessary. In this report, the main purpose is to introduce the student to basic design procedures. From these follow the fundamental characteristics of the facility: its performance capability, its size, and the nature and operating requirements on the accelerator components, and with this knowledge, we can determine the technology and resources needed to build the new facility.

  20. Muon Colliders and Neutrino Factories *

    NASA Astrophysics Data System (ADS)

    Geer, Steve

    2009-11-01

    Over the past decade, there has been significant progress in developing the concepts and technologies needed to produce, capture, and accelerate O(1021) 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.

  1. 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.

  2. 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.

  3. 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.

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

    SciTech Connect

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

    2008-03-01

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

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

    PubMed

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

    1996-08-01

    The recently cloned factor thrombopoietin (TPO) has been shown to exhibit megakaryocyte colony-stimulating activity in vitro. In this investigation, to further evaluate the action of TPO on megakaryocyte progenitor cells (colony-forming units-megakaryocyte [CFU-MK]), GpIIb/IIIa+ and GpIIb/IIIa- populations of CFU-MK were prepared from rat bone marrow cells based on their reactivity with P55 antibody, a monoclonal antibody against rat GpIIb/IIIa, and their responsiveness to recombinant human TPO (rhTPO) and recombinant rat interleukin-3 (rrIL-3) was examined using a megakaryocyte colony-forming assay (Meg-CSA). rhTPO supported only megakaryocyte colony growth from both fractions in a dose-dependent fashion. The mean colony size observed with the GpIIb/IIIa+ population was smaller than that seen with the GpIIb/IIIa- population. With the optimal concentration of either rhTPO or rrIL-3, similar numbers of megakaryocyte colonies were formed from the GpIIb/IIIa+ population previously shown to be highly enriched for CFU-MK. In contrast, the maximum number of megakaryocyte colonies from the GpIIb/IIIa- population stimulated by rhTPO was only 24.2% of that achieved with rrIL-3. Morphologic analysis of rhTPO-promoted megakaryocyte colonies from the GpIIb/IIIa+ population showed that the average colony size was smaller but that the mean diameter of individual megakaryocytes was larger than in megakaryocyte colonies promoted with rrIL-3. rhTPO plus rrIL-3, each at suboptimal concentrations, had an additive effect on proliferation of CFU-MK in the GpIIb/IIIa+ fraction, whereas rhTPO plus murine IL-6 or murine granulocyte-macrophage colony-stimulating factor (mG-M-CSF) modestly but significantly reduced megakaryocyte colony growth. These results indicate that TPO preferentially acts on GpIIb/IIIa+ late CFU-MK with lower proliferative capacity and interacts with some other cytokines in CFU-MK development. PMID:8765496

  6. 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.

  7. 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.

  8. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility

    SciTech Connect

    Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E.; Schief, William R.; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D.

    2010-04-15

    The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded {beta}-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate - and structurally plastic - layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated {beta}-sandwich and providing for conformational diversity used in immune evasion. A 'layered' gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a {beta}-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

  9. Progress in the Next Linear Collider Design

    NASA Astrophysics Data System (ADS)

    Raubenheimer, T. O.

    2001-07-01

    An electron/positron linear collider with a center-of-mass energy between 0.5 and 1 TeV would be an important complement to the physics program of the LHC. The Next Linear Collider (NLC) is being designed by a US collaboration (FNAL, LBNL, LLNL, and SLAC) which is working closely with the Japanese collaboration that is designing the Japanese Linear Collider (JLC). The NLC main linacs are based on normal conducting 11 GHz rf. This paper will discuss the technical difficulties encountered as well as the many changes that have been made to the NLC design over the last year. These changes include improvements to the X-band rf system as well as modifications to the injector and the beam delivery system. They are based on new conceptual solutions as well as results from the R&D programs which have exceeded initial specifications. The net effect has been to reduce the length of the collider from about 32 km to 25 km and to reduce the number of klystrons and modulators by a factor of two. Together these lead to significant cost savings.

  10. Collider Detector at Fermilab (CDF)

    SciTech Connect

    Jensen, H.B.

    1985-10-01

    A description of the Collider Detector at Fermilab (CDF) is given. It is a calorimetric detector, which covers almost the complete solid angle around the interaction region with segmented calorimeter ''towers''. A 1.5 Tesla superconducting solenoid, 3m in diameter and 5m long, provides a uniform magnetic field in the central region for magnetic analysis of charged particles. The magnetic field volume is filled with a large cylindrical drift chamber and a set of Time Projection Chambers. Muon detection is accomplished with drift chambers outside the calorimeters in the central region and with large magnetized steel toroids and associated drift chambers in the forward-backward regions. The electronics has a large dynamic range to allow measurement of both high energy clusters and small energy depositions made by penetrating muons. Interesting events are identified by a trigger system which, together with the rest of the data acquisition system, is FASTBUS based.

  11. 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.

  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. Topological Layers in the HIV-1 gp120 Inner Domain Regulate gp41 Interaction and CD4-Triggered Conformational Transitions

    PubMed Central

    Finzi, Andrés; Xiang, Shi-Hua; Pacheco, Beatriz; Wang, Liping; Haight, Jessica; Kassa, Aemro; Danek, Brenda; Pancera, Marie; Kwong, Peter D.; Sodroski, Joseph

    2010-01-01

    SUMMARY The entry of human immunodeficiency virus (HIV-1) into cells is initiated by binding of the gp120 exterior envelope glycoprotein to the receptor, CD4. How does CD4 binding trigger conformational changes in gp120 that allow the gp41 transmembrane envelope glycoprotein to mediate viral-cell membrane fusion? The transition from the unliganded to the CD4-bound state is regulated by two potentially flexible topological layers (“Layers 1 and 2”) in the gp120 inner domain. Both layers apparently contribute to the non-covalent association of unliganded gp120 with gp41. After CD4 makes initial contact with the gp120 outer domain, Layer 1-Layer 2 interactions strengthen gp120-CD4 binding by reducing the off-rate. Layer 1-Layer 2 interactions also destabilize the activated state induced on HIV-1 by treatment with soluble CD4. Thus, despite lack of contact with CD4, the gp120 inner domain layers govern CD4 triggering by participating in conformational transitions within gp120 and regulating the interaction with gp41. PMID:20227370

  15. 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)

  16. 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.

  17. 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.

  18. Muon Collider design status

    SciTech Connect

    Alexahin, Y.; /Fermilab

    2010-09-01

    Muon Collider (MC) - proposed by G.I. Budker and A.N. Skrinsky a few decades ago - is now considered as the most exciting option for the energy frontier machine in the post-LHC era. A national Muon Accelerator Program (MAP) is being formed in the USA with the ultimate goal of building a MC at the Fermilab site with c.o.m. energy in the range 1.5-3 TeV and luminosity of {approx} 1.5 {center_dot} 10{sup 34} cm{sup -2} s{sup -1}. As the first step on the way to MC it envisages construction of a Neutrino Factory (NF) for high-precision neutrino experiments. The baseline scheme of the NF-MC complex is presented and possible options for its main components are discussed.

  19. 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.

  20. An essential role for the baseplate protein Gp45 in phage adsorption to Staphylococcus aureus

    PubMed Central

    Li, Xuehua; Koç, Cengiz; Kühner, Petra; Stierhof, York-Dieter; Krismer, Bernhard; Enright, Mark C.; Penadés, José R.; Wolz, Christiane; Stehle, Thilo; Cambillau, Christian; Peschel, Andreas; Xia, Guoqing

    2016-01-01

    Despite the importance of phages in driving horizontal gene transfer (HGT) among pathogenic bacteria, the underlying molecular mechanisms mediating phage adsorption to S. aureus are still unclear. Phage ϕ11 is a siphovirus with a high transducing efficiency. Here, we show that the tail protein Gp45 localized within the ϕ11 baseplate. Phage ϕ11 was efficiently neutralized by anti-Gp45 serum, and its adsorption to host cells was inhibited by recombinant Gp45 in a dose-dependent manner. Flow cytometry analysis demonstrated that biotin-labelled Gp45 efficiently stained the wild-type S. aureus cell but not the double knockout mutant ΔtarM/S, which lacks both α- and β-O-GlcNAc residues on its wall teichoic acids (WTAs). Additionally, adsorption assays indicate that GlcNAc residues on WTAs and O-acetyl groups at the 6-position of muramic acid residues in peptidoglycan are essential components of the ϕ11 receptor. The elucidation of Gp45-involved molecular interactions not only broadens our understanding of siphovirus-mediated HGT, but also lays the groundwork for the development of sensitive affinity-based diagnostics and therapeutics for S. aureus infection. PMID:27212064

  1. Topological analysis of HIV-1 glycoproteins expressed in situ on virus surfaces reveals tighter packing but greater conformational flexibility than for soluble gp120.

    PubMed

    Tong, Tommy; Osawa, Keiko; Robinson, James E; Crooks, Ema T; Binley, James M

    2013-08-01

    In natural infection, antibodies interact with HIV-1 primarily through nonfunctional forms of envelope glycoproteins (Env), including uncleaved (UNC) gp160 and gp41 stumps. These antigens are important to fully characterize, as they may be decoys that promote nonneutralizing responses and may also be targets for nonneutralizing effector responses. In this study, we compared the antigenic properties of Env expressed in situ on pseudovirion virus-like particle (VLP) surfaces and soluble gp120 using harmonized enzyme-linked immunosorbent assays (ELISAs) and a panel of 51 monoclonal antibodies (MAbs). Only 32 of 46 soluble gp120-reactive MAbs recognized the primary UNC gp160 antigen of VLPs. Indeed, many epitopes were poorly exposed (C1, V2, C1-C4, C4, C4-V3, CD4 induced [CD4i], and PGT group 3) or obscured (C2, C5, and C1-C5) on VLPs. In further studies, VLP Env exhibited an increased degree of inter-MAb competition, the epicenter of which was the base of the V3 loop, where PGT, 2G12, V3, and CD4 binding site specificities competed. UNC gp160 also underwent more drastic soluble CD4 (sCD4)-induced conformational changes than soluble gp120, exposing CD4i, C1-C4, and V2 epitopes. A greater propensity of UNC gp160 to undergo conformational changes was also suggested by the induction of CD4i MAb binding to VLPs by a V3 MAb as well as by soluble CD4. The same effect was not observed for soluble gp120. Taken together, our data suggest that membrane-expressed UNC gp160 exists in a less "triggered" conformational state than soluble gp120 and that MAb binding to UNC gp160 tends to have greater conformational consequences.

  2. 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

  3. Quantum-beamsstrahlung laser collider

    SciTech Connect

    Tajima, T.; Chattopadyay, S.; Xie, M.

    1997-11-01

    An e{sup +}e{sup {minus}} linear collider at energies beyond a TeV runs into a problem of severe beamsstrahlung, characterized by {Upsilon} on the order of unity (and beyond). In the regime of extremely high {Upsilon} the beamsstrahlung may be largely suppressed due to the quantum effect. In the design of an e{sup +}e{sup {minus}} collider there are two ways to satisfy the collider physics constraints. One is to decrease the number of particles per bunch (and thus to increase the repetition rate) and the other is to decrease the longitudinal bunch length. The former approach can limit {Upsilon}, while the latter boosts it. (It may be useful to reevaluate the future collider parameters in view of this.) The laser wakefield driver for a collider in comparison with the microwave driver naturally offers a very short bunch length, which is appropriate for the latter collider option. The authors show that this choice of collider design with a short bunch length and high {Upsilon} has advantages and provide sample design parameters at 5 TeV. Such sample design parameters challenge them in a number of fronts, such as the preservation of high quality bunches, efficient high repetition rate lasers, etc. The collision point physics simulated by the CAIN code shows a surprisingly well preserved luminosity spectrum.

  4. Doctors telling stories: the place of anecdote in GP registrar training.

    PubMed

    Alderson, T St J; Bateman, H

    2002-11-01

    Observational studies within a hospital setting confirm the widespread use of anecdotes in hospital-based medical education and hypothesize a number of reasons for this. Whilst anecdotes may be used effectively in teaching there can be dangers in their inappropriate use. There is no information on the level and nature of the use of anecdotes within medical education in the community. The authors undertook a questionnaire study that asked GP trainers about how they used anecdote in their GP registrar teaching. The results suggested that GP trainers use anecdotes frequently in their registrar teaching, recognize the use of anecdotes described in the literature and have little concern that anecdotes might mislead. The authors discuss how anecdotes may be used to help build registrars' illness scripts, and to develop ways of thinking and working congruent with the existing professional community.

  5. 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.

  6. 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.

  7. Vanilla technicolor at linear colliders

    NASA Astrophysics Data System (ADS)

    Frandsen, Mads T.; Järvinen, Matti; Sannino, Francesco

    2011-08-01

    We analyze the reach of linear colliders for models of dynamical electroweak symmetry breaking. We show that linear colliders can efficiently test the compositeness scale, identified with the mass of the new spin-one resonances, until the maximum energy in the center of mass of the colliding leptons. In particular we analyze the Drell-Yan processes involving spin-one intermediate heavy bosons decaying either leptonically or into two standard model gauge bosons. We also analyze the light Higgs production in association with a standard model gauge boson stemming also from an intermediate spin-one heavy vector.

  8. Laser cooling of electron beams for linear colliders

    SciTech Connect

    Telnov, V.

    1996-10-01

    A novel method of electron beam cooling is considered which can be used for linear colliders. The electron beam is cooled during collision with focused powerful laser pulse. With reasonable laser parameters (laser flash energy about 10 J) one can decrease transverse beam emittances by a factor about 10 per one stage. The ultimate transverse emittances are much below that given by other methods. Depolarization of a beam during the cooling is about 5--15% for one stage. This method is especially useful for photon colliders and open new possibilities for e{sup +}e{sup {minus}} colliders and x-ray FEL based on high energy linacs.

  9. Presentations from the 3rd Workshop On Super Flavor Factory Based On Linear Collider Technology (Super B III) ,14-16 Jun 2006, Menlo Park, California

    SciTech Connect

    MacFarlane, D.

    2006-11-10

    This workshop was aimed at continuing discussions of the design for a very high luminosity e{sup +}e{sup -} collider using many of the same technical approaches as for the International Linear Collider. On this basis, the previous two meetings at Frascati have explored several new and promising ideas for reaching luminosities as high as 10{sup 36} cm{sup -2} s{sup -1} or more. We expect to continue the development of a coherent concept for the machine at the June meeting, ultimately aiming at a full written description of the concept by the end of 2006. The workshop also studied the capability of SuperB for a full range of flavor physics, and the corresponding requirements and demands on the associated detector.

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

    SciTech Connect

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

    1994-11-01

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

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

    SciTech Connect

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

    1995-06-01

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

  12. When Black Holes Collide

    NASA Technical Reports Server (NTRS)

    Baker, John

    2010-01-01

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

  13. 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.

  14. Collider Physics an Experimental Introduction

    NASA Astrophysics Data System (ADS)

    Elvezio Pagliarone, Carmine

    2011-04-01

    This paper reviews shortly a small part of the contents of a set of lectures, presented at the XIV International School of Particles and Fields in Morelia, state of Michoacán, Mexico, during November 2010. The main goal of those lectures was to introduce students to some of the basic ideas and tools required for experimental and phenomenological analysis of collider data. In particular, after an introduction to the scientific motivations, that drives the construction of powerful accelerator complexes, and the need of reaching high center of mass energies and luminosities, some basic concept about collider particle detectors will be discussed. A status about the present running colliders and collider experiments as well as future plans and research and development is also given.

  15. 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.

  16. Beam rounders for circular colliders

    SciTech Connect

    A. Burov and S. Nagaitsev

    2002-12-10

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

  17. 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).

  18. Pharmaceutical promotion and GP prescription behaviour.

    PubMed

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

    2006-01-01

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

  19. Polarized Electrons for Linear Colliders

    NASA Astrophysics Data System (ADS)

    Clendenin, J. E.; Brachmann, A.; Garwin, E. L.; Kirby, R. E.; Luh, D.-A.; Maruyama, T.; Prescott, C. Y.; Sheppard, J. C.; Turner, J.; Prepost, R.

    2005-08-01

    Future electron-positron linear colliders require a highly polarized electron beam with a pulse structure that depends primarily on whether the acceleration utilizes warm or superconducting RF structures. The International Linear Collider (ILC) will use cold structures for the main linac. It is shown that a DC-biased polarized photoelectron source such as successfully used for the SLC can meet the charge requirements for the ILC micropulse with a polarization approaching 90%.

  20. Polarized Electrons for Linear Colliders

    SciTech Connect

    Clendenin, J.

    2004-11-19

    Future electron-positron linear colliders require a highly polarized electron beam with a pulse structure that depends primarily on whether the acceleration utilizes warm or superconducting rf structures. The International Linear Collider (ILC) will use cold structures for the main linac. It is shown that a dc-biased polarized photoelectron source such as successfully used for the SLC can meet the charge requirements for the ILC micropulse with a polarization approaching 90%.

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

    NASA Technical Reports Server (NTRS)

    Colwell, Joshua E.

    2002-01-01

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

  2. 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…

  3. Physics at Future Circular Colliders

    NASA Astrophysics Data System (ADS)

    Kotwal, Ashutosh

    2016-03-01

    The Large Hadron Collider has been a grand success with the discovery of the Higgs boson, with bright prospects for additional discoveries since the recent increase in collider energy and the anticipated large datasets. Big open questions such as the nature of dark matter, the origin of the matter-antimatter asymmetry in the Universe, and the theoretical puzzle of the finely-tuned parameters in the Higgs sector, demand new physics principles that extend the established Standard Model paradigm. Future circular colliders in a substantially larger tunnel can house both a high luminosity electron-positron collider for precision measurements of Higgs and electroweak parameters, as well as a very high energy proton-proton collider which can directly manifest particles associated with these new physics principles. We discuss the physics goals of these future circular colliders, and the prospects for elucidating fundamental new laws of nature that will significantly extend our understanding of the Universe. Detailed studies of the discovery potential in specific benchmark models will be presented, with implications for detector design.

  4. 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.

  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. Structural characterization of HIV gp41 with the membrane-proximal external region.

    PubMed

    Shi, Wuxian; Bohon, Jen; Han, Dong P; Habte, Habtom; Qin, Yali; Cho, Michael W; Chance, Mark R

    2010-07-30

    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. PMID:20525690

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

    PubMed Central

    Shi, Wuxian; Bohon, Jen; Han, Dong P.; Habte, Habtom; Qin, Yali; Cho, Michael W.; Chance, Mark R.

    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. PMID:20525690

  8. Crystal Ball: On the Future High Energy Colliders

    SciTech Connect

    Shiltsev, Vladimir

    2015-09-20

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

  9. Development and validation of the GP frequency of interprofessional collaboration instrument (FICI-GP) in primary care.

    PubMed

    Van, Connie; Costa, Daniel; Mitchell, Bernadette; Abbott, Penny; Krass, Ines

    2012-07-01

    Existing validated measures of pharmacist-physician collaboration focus on measuring attitudes toward collaboration and do not measure frequency of interactions that comprise actual collaborative behavior. Therefore, the aim of this study was to develop and validate an instrument to measure the frequency of collaboration between general practitioners (GPs) and pharmacists from the GP's perspective. An 11-item Frequency of Interprofessional Collaboration Instrument for GPs (FICI-GP) was developed and administered to 1118 GPs in eight divisions of general practice in New South Wales, Australia. Two hundred and fifty-eight (23%) GP surveys were completed and returned. Principal component analysis suggested removal of one item for a final one-factor solution. The refined 10-item FICI-GP had a Cronbach's alpha of 0.87. After collapsing the original five-point response scale to a three-point response scale, the refined FICI-GP demonstrated fit to the Rasch model. Criterion validity of the FICI-GP was supported by the correlation of FICI-GP scores with scores on a previously validated physician-pharmacist collaboration instrument as well as by predicted differences in FICI-GP scores between subgroups of respondents stratified on age, co-location with pharmacists and interactions during residency. The refined 10-item FICI-GP was shown to have good internal consistency, criterion validity and fit to the Rasch model. PMID:22563657

  10. Solution structure of the HIV gp120 C5 domain.

    PubMed

    Guilhaudis, Laure; Jacobs, Amy; Caffrey, Michael

    2002-10-01

    In HIV the viral envelope protein is processed by a host cell protease to form gp120 and gp41. The C1 and C5 domains of gp120 are thought to directly interact with gp41 but are largely missing from the available X-ray structure. Biophysical studies of the HIV gp120 C5 domain (residues 489-511 of HIV-1 strain HXB2), which corresponds to the carboxy terminal region of gp120, have been undertaken. CD studies of the C5 domain suggest that it is unstructured in aqueous solutions but partially helical in trifluoroethanol/aqueous and hexafluoroisopropanol/aqueous buffers. The solution structure of the C5 peptide in 40% trifluoroethanol/aqueous buffer was determined by NMR spectroscopy. The resulting structure is a turn helix structural motif, consistent with the CD results. Fluorescence titration experiments suggest that HIV C5 forms a 1 : 1 complex with the HIV gp41 ectodomain in the presence of cosolvent with an apparent Kd of approximately 1.0 micro m. The absence of complex formation in the absence of cosolvent indicates that formation of the turn-helix structural motif of C5 is necessary for complex formation. Examination of the C5 structure provides insight into the interaction between gp120 and gp41 and provides a possible target site for future drug therapies designed to disrupt the gp120/gp41 complex. In addition, the C5 structure lends insight into the site of HIV envelope protein maturation by the host enzymes furin and PC7, which provides other possible targets for drug therapies.

  11. 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

  12. Fine definition of the epitope on the gp41 glycoprotein of human immunodeficiency virus type 1 for the neutralizing monoclonal antibody 2F5.

    PubMed

    Parker, C E; Deterding, L J; Hager-Braun, C; Binley, J M; Schülke, N; Katinger, H; Moore, J P; Tomer, K B

    2001-11-01

    Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS), in combination with proteolytic protection assays, has been used to identify the functional epitope on human immunodeficiency virus envelope glycoprotein gp41 for the broadly neutralizing anti-gp41 human monoclonal antibody 2F5. In this protection assay-based procedure, a soluble gp140 protein with a stabilizing intermolecular disulfide bond between the gp120 and gp41 subunits (SOS gp140) was affinity bound to immobilized 2F5 under physiological conditions. A combination of proteolytic enzymatic cleavages was then performed to remove unprotected residues. Residues of SOS gp140 protected by their binding to 2F5 were then identified based on their molecular weights as determined by direct MALDI-MS of the immobilized antibody beads. The epitope, NEQELLELDKWASLWN, determined by this MALDI-MS protection assay approach consists of 16 amino acid residues near the C terminus of gp41. It is significantly longer than the ELDKWA core epitope previously determined for 2F5 by peptide enzyme-linked immunosorbent assay. This new knowledge of the structure of the 2F5 epitope may facilitate the design of vaccine antigens intended to induce antibodies with the breadth and potency of action of the 2F5 monoclonal antibody. PMID:11602730

  13. 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

  14. 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...

  15. 77 FR 37663 - Northwest Pipeline GP; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-22

    ... Energy Regulatory Commission Northwest Pipeline GP; Notice of Application Take notice that on June 4, 2011, Northwest Pipeline GP (Northwest), 295 Chipeta Way, Salt Lake City, Utah 84108, filed in Docket... by removal of 10-inch diameter pipeline segments between mileposts 0.00 and 2.01 and mileposts...

  16. Status of the MEIC ion collider ring design

    SciTech Connect

    None, None

    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 super-conducting magnets. We describe complete ion collider optics including an independently-designed modular detector region.

  17. 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.

  18. Research and Development for an X-Band Linear Collider

    SciTech Connect

    Adolphsen, Chris

    1999-03-05

    At SLAC and KEK research is advancing toward a design for an electron-positron linear collider based on X-Band (11.4 GHz) rf accelerator technology. The nominal acceleration gradient in its main linacs will be about four times that in the Stanford Linear Collider (SLC). The design targets a 1.0 TeV center-of-mass energy but envisions initial operation at 0.5 TeV and allows for expansion to 1.5 TeV. A 1034 cm-2s-1 luminosity level will be achieved by colliding multiple bunches per pulse with bunch emittances about two orders of magnitude smaller than those in the SLC. The key components needed to realize such a collider are under development at SLAC and KEK. In this paper we review recent progress in the development of the linac rf system and discuss future R&D.

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

    PubMed

    St Pierre, Pascal; Nabi, Ivan R

    2012-02-01

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

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

    PubMed

    St Pierre, Pascal; Nabi, Ivan R

    2012-02-01

    The endoplasmic reticulum (ER) has been classically divided, based on electron microscopy analysis, into parallel ribosome-studded rough ER sheets and a tubular smooth ER network. Recent studies have identified molecular constituents of the ER, the reticulons and DP1, that drive ER tubule formation and whose expression determines expression of ER sheets and tubules and thereby rough and smooth ER. However, segregation of the ER into only two domains remains simplistic and multiple functionally distinct ER domains necessarily exist. In this review, we will discuss the sub-organization of the ER in different domains focusing on the localization and role of the gp78 ubiquitin ligase in the mitochondria-associated smooth ER and on the evidence for a quality control ERAD domain. PMID:22045301

  1. 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

    Jose, Davis; Weitzel, Steven E; Baase, Walter A; Michael, Miya M; von Hippel, Peter H

    2015-10-30

    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.

  2. 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

    Jose, Davis; Weitzel, Steven E; Baase, Walter A; Michael, Miya M; von Hippel, Peter H

    2015-10-30

    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

  3. Rf-driver linear colliders

    SciTech Connect

    Wilson, P.B.

    1987-05-01

    The next generation of linear collider after the SLC (Stanford Linear Collider) will probably have an energy in the range 300 GeV-1 TeV per linac. A number of exotic accelerating schemes, such as laser and plasma acceleration, have been proposed for linear colliders of the far future. However, the technology which is most mature and which could lead to a collider in the above energy range in the relatively near future is the rf-driven linac, in which externally produced rf is fed into a more or less conventional metallic accelerating structure. Two basic technologies have been proposed for producing the required high peak rf power: discrete microwave power sources, and various two-beam acceleration schemes in which the rf is produced by a high current driving beam running parallel to the main accelerator. The current status of experimental and analytic work on both the discrete source and the two-beam methods for producing rf is discussed. The implications of beam-beam related effects (luminosity, disruption and beamstrahlung) for the design of rf-driven colliders are also considered.

  4. 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.

  5. 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.

  6. 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

  7. Structural analysis of the varicella-zoster virus gp98-gp62 complex: posttranslational addition of N-linked and O-linked oligosaccharide moieties.

    PubMed

    Montalvo, E A; Parmley, R T; Grose, C

    1985-03-01

    Varicella-zoster virus specifies the formation of several glycoproteins, including the preponderant gp98-gp62 glycoprotein complex in the outer membranes of virus-infected cells. These viral glycoproteins are recognized and precipitated by a previously described monoclonal antibody designated monoclone 3B3. When an immunoblot analysis was performed, only gp98 was reactive with monoclone 3B3 antibody; likewise, titration in the presence of increased concentrations of sodium dodecyl sulfate during antigen-antibody incubations caused selective precipitation of gp98 but not gp62. Further structural analyses of gp98 were performed by using the glycosidases endo-beta-N-acetylglucosaminidase H (endoglycosidase H) and neuraminidase and two inhibitors of glycosylation (tunicamycin and monensin). In addition to gp98, antibody 3B3 reacted with several intermediate products, including gp90, gp88, gp81, and a nonglycosylated polypeptide, p73. Since gp98 was completely resistant to digestion with endoglycosidase H, it contained only complex carbohydrate moieties; conversely, gp81 contained mainly high-mannose residues. Polypeptide p73 was immunodetected in the presence of tunicamycin and designated as a nascent recipient of N-linked sugars, whereas gp88 was considered to contain O-linked oligosaccharides because its synthesis was not affected by tunicamycin. The ionophore monensin inhibited production of mature gp98, but other intermediate forms, including gp90, were detected. Since the latter product was similar in molecular weight to the desialated form of gp98, one effect of monensin treatment of varicella-zoster virus-infected cells was to block the addition of N-acetylneuraminic acid. Monensin also blocked insertion of gp98 into the plasma membrane and, as determined by electron microscopy, inhibited envelopment of the nucleocapsid and its transport within the cytoplasm. On the basis of this study, we reached the following conclusions: the primary antibody 3B3-binding

  8. 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.

  9. 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.

  10. 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.

  11. 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

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

    SciTech Connect

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

    1994-11-01

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

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

    SciTech Connect

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

    1995-07-05

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

  14. GP IIb/IIIa Blockade During Peripheral Artery Interventions

    SciTech Connect

    Tepe, Gunnar Wiskirchen, Jakub; Pereira, Philippe; Claussen, Claus D.; Miller, Stephen; Duda, Stephan H.

    2008-01-15

    The activation of the platelet GP IIb/IIIa receptor is the final and common pathway in platelet aggregation. By blocking this receptor, platelet aggregation can be inhibited independently of the stimulus prompted the targeting of this receptor. Several years ago, three drugs have been approved for coronary artery indications. Since that time, there is increasing evidence that GP IIb/IIIa receptor blockade might have also an important role in peripheral arterial intervention. This article summarizes the action and differences of GP Ilb/IIIa receptor inhibitors and its possible indication in peripheral arteries.

  15. Tevatron Collider Status and Prospects

    SciTech Connect

    Moore, Ronald S.

    2009-10-01

    The Tevatron proton-antiproton collider at Fermilab continues operation as the world's highest energy particle accelerator by delivering luminosity at a center-of-mass energy of 1.96 TeV. We review recent performance and plans for the remainder of Run 2.

  16. CERN's Large Hadron Collider project

    NASA Astrophysics Data System (ADS)

    Fearnley, Tom A.

    1997-03-01

    The paper gives a brief overview of CERN's Large Hadron Collider (LHC) project. After an outline of the physics motivation, we describe the LHC machine, interaction rates, experimental challenges, and some important physics channels to be studied. Finally we discuss the four experiments planned at the LHC: ATLAS, CMS, ALICE and LHC-B.

  17. 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.

  18. 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.

  19. Muon Colliders: The Next Frontier

    SciTech Connect

    Tourun, Yagmur

    2009-07-29

    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.

  20. Muon Colliders: The Next Frontier

    SciTech Connect

    Tourun, Yagmur

    2009-07-29

    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. Feedback Systems for Linear Colliders

    SciTech Connect

    1999-04-12

    Feedback systems are essential for stable operation of a linear collider, providing a cost-effective method for relaxing tight tolerances. In the Stanford Linear Collider (SLC), feedback controls beam parameters such as trajectory, energy, and intensity throughout the accelerator. A novel dithering optimization system which adjusts final focus parameters to maximize luminosity contributed to achieving record performance in the 1997-98 run. Performance limitations of the steering feedback have been investigated, and improvements have been made. For the Next Linear Collider (NLC), extensive feedback systems are planned as an integral part of the design. Feedback requirements for JLC (the Japanese Linear Collider) are essentially identical to NLC; some of the TESLA requirements are similar but there are significant differences. For NLC, algorithms which incorporate improvements upon the SLC implementation are being prototyped. Specialized systems for the damping rings, rf and interaction point will operate at high bandwidth and fast response. To correct for the motion of individual bunches within a train, both feedforward and feedback systems are planned. SLC experience has shown that feedback systems are an invaluable operational tool for decoupling systems, allowing precision tuning, and providing pulse-to-pulse diagnostics. Feedback systems for the NLC will incorporate the key SLC features and the benefits of advancing technologies.

  2. 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

  3. 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

  4. Physics at hadron colliders: Experimental view

    SciTech Connect

    Siegrist, J.L.

    1987-08-01

    The physics of the hadron-hadron collider experiment is considered from an experimental point of view. The problems encountered in determination of how well the standard model describes collider results are discussed. 53 refs., 58 figs.

  5. P{bar P} collider physics

    SciTech Connect

    Demarteau, M.

    1992-04-01

    A brief introduction to {bar p}p collider physics is given. Selected results from the collider experiments at the CERN S{bar p}pS and the Tevatron collider are described. The emphasis is on experimental aspects of {bar p}p collisions. Minimum bias physics and the production of jets, Intermediate Vector Bosons and heavy flavors is reviewed. The outlook for physics at hadron colliders for the near future is briefly discussed.

  6. From Neutrino Factory to Muon Collider

    SciTech Connect

    Geer, S.; /Fermilab

    2010-01-01

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

  7. Binding of Full-Length HIV-1 gp120 to CD4 Induces Structural Reorientation around the gp120 Core

    SciTech Connect

    Ashish,F.; Garg, R.; Anguita, J.; Krueger, J.

    2006-01-01

    Small-angle x-ray scattering data on the unliganded full-length fully glycosylated HIV-1 gp120, the soluble CD4 (domains 1-2) receptor and their complex in solution are presented. Ab initio structure restorations using these data provides the first look at the envelope shape for the unliganded and the complexed gp120 molecule. Fitting known crystal structures of the unliganded SIV and the complexed HIV gp120 core regions within our resultant shape constraints reveals movement of the V3 loop upon binding.

  8. HIGH ENERGY PHYSICS POTENTIAL AT MUON COLLIDERS

    SciTech Connect

    PARSA,Z.

    2000-04-07

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

  9. Recombinant expression, purification, and biophysical characterization of the transmembrane and membrane proximal domains of HIV-1 gp41

    PubMed Central

    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

    2014-01-01

    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. PMID:25155369

  10. Testing Relativity with Gp-B and Step

    NASA Astrophysics Data System (ADS)

    Worden, P. W.

    2011-12-01

    Gravity Probe B (GP-B) and the Satellite Test of the Equivalence Principle (STEP) are experiments designed to test General Relativity: GP-B tests two predictions, the geodetic effect and frame dragging, while STEP tests the assumption that the laws of physics are independent of the motion of the observer. Although differing in implementation, both experiments share important technology. This paper discusses the status of these experiments.

  11. Selection of an aptamer against mouse GP2 by SELEX.

    PubMed

    Hanazato, Misaho; Nakato, Gaku; Nishikawa, Fumiko; Hase, Koji; Nishikawa, Satoshi; Ohno, Hiroshi

    2014-01-01

    Microfold (M) cells are intestinal epithelial cells specialized for sampling and transport of luminal antigens to gut-associated lymphoid tissue for initiation of both mucosal and systemic immune responses. Therefore, M-cell targeted vaccination has the potential to be a better immunization strategy. Glycoprotein 2 (GP2), an antigen uptake receptor for FimH(+) bacteria on M cells, can be a good target for this purpose. Aptamers are oligonucleotides that bind to a variety of target molecules with high specificity and affinity. Together with its low toxic feature, aptamers serves as a tool of molecular-targeted delivery. In this study, we used Systematic Evolution of Ligands by EXponential enrichment (SELEX) to isolate aptamers specific to murine GP2 (mGP2). After ten rounds of SELEX, eleven different aptamer sequences were selected. Among them, the most frequently appeared sequence (~60%) were aptamer NO. 1 (Apt1), and the second most (~7%) were aptamer NO. 5 (Apt5). In vitro binding experiment confirmed that only Apt1 and Apt5 specifically bound to mGP2 among eleven aptamers initially selected. Apt1 showed the strongest affinity with mGP2, with the Kd value of 110±2.6 nM evaluated by BIACORE. Binding assays with mutants of Apt1 suggest that, in addition to the loop structure, the nucleotide sequence, AAAUA, in the loop is important for binding to mGP2. Furthermore, this aptamer was able to bind to mGP2 expressed on the cell surface. These results suggest that this mGP2-specific aptamer could serve as a valuable tool for testing M-cell-targeted vaccine delivery in the murine model system. PMID:24334484

  12. Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover

    PubMed Central

    Orr, Mona W.; Donaldson, Gregory P.; Severin, Geoffrey B.; Wang, Jingxin; Sintim, Herman O.; Waters, Christopher M.; Lee, Vincent T.

    2015-01-01

    The bacterial second messenger cyclic di-GMP (c-di-GMP) controls biofilm formation and other phenotypes relevant to pathogenesis. Cyclic-di-GMP is synthesized by diguanylate cyclases (DGCs). Phosphodiesterases (PDE-As) end signaling by linearizing c-di-GMP to 5ʹ-phosphoguanylyl-(3ʹ,5ʹ)-guanosine (pGpG), which is then hydrolyzed to two GMP molecules by yet unidentified enzymes termed PDE-Bs. We show that pGpG inhibits a PDE-A from Pseudomonas aeruginosa. In a dual DGC and PDE-A reaction, excess pGpG extends the half-life of c-di-GMP, indicating that removal of pGpG is critical for c-di-GMP homeostasis. Thus, we sought to identify the PDE-B enzyme(s) responsible for pGpG degradation. A differential radial capillary action of ligand assay-based screen for pGpG binding proteins identified oligoribonuclease (Orn), an exoribonuclease that hydrolyzes two- to five-nucleotide-long RNAs. Purified Orn rapidly converts pGpG into GMP. To determine whether Orn is the primary enzyme responsible for degrading pGpG, we assayed cell lysates of WT and ∆orn strains of P. aeruginosa PA14 for pGpG stability. The lysates from ∆orn showed 25-fold decrease in pGpG hydrolysis. Complementation with WT, but not active site mutants, restored hydrolysis. Accumulation of pGpG in the ∆orn strain could inhibit PDE-As, increasing c-di-GMP concentration. In support, we observed increased transcription from the c-di-GMP–regulated pel promoter. Additionally, the c-di-GMP–governed auto-aggregation and biofilm phenotypes were elevated in the ∆orn strain in a pel-dependent manner. Finally, we directly detect elevated pGpG and c-di-GMP in the ∆orn strain. Thus, we identified that Orn serves as the primary PDE-B enzyme that removes pGpG, which is necessary to complete the final step in the c-di-GMP degradation pathway. PMID:26305945

  13. Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover.

    PubMed

    Orr, Mona W; Donaldson, Gregory P; Severin, Geoffrey B; Wang, Jingxin; Sintim, Herman O; Waters, Christopher M; Lee, Vincent T

    2015-09-01

    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 5'-phosphoguanylyl-(3',5')-guanosine (pGpG), which is then hydrolyzed to two GMP molecules by yet unidentified enzymes termed PDE-Bs. We show that pGpG inhibits a PDE-A from Pseudomonas aeruginosa. In a dual DGC and PDE-A reaction, excess pGpG extends the half-life of c-di-GMP, indicating that removal of pGpG is critical for c-di-GMP homeostasis. Thus, we sought to identify the PDE-B enzyme(s) responsible for pGpG degradation. A differential radial capillary action of ligand assay-based screen for pGpG binding proteins identified oligoribonuclease (Orn), an exoribonuclease that hydrolyzes two- to five-nucleotide-long RNAs. Purified Orn rapidly converts pGpG into GMP. To determine whether Orn is the primary enzyme responsible for degrading pGpG, we assayed cell lysates of WT and ∆orn strains of P. aeruginosa PA14 for pGpG stability. The lysates from ∆orn showed 25-fold decrease in pGpG hydrolysis. Complementation with WT, but not active site mutants, restored hydrolysis. Accumulation of pGpG in the ∆orn strain could inhibit PDE-As, increasing c-di-GMP concentration. In support, we observed increased transcription from the c-di-GMP-regulated pel promoter. Additionally, the c-di-GMP-governed auto-aggregation and biofilm phenotypes were elevated in the ∆orn strain in a pel-dependent manner. Finally, we directly detect elevated pGpG and c-di-GMP in the ∆orn strain. Thus, we identified that Orn serves as the primary PDE-B enzyme that removes pGpG, which is necessary to complete the final step in the c-di-GMP degradation pathway. PMID:26305945

  14. The Role of NKG2D Signaling in Inhibition of Cytotoxic T-Lymphocyte Lysis by the Murine Cytomegalovirus Immunoevasin m152/gp40▿

    PubMed Central

    Pinto, Amelia K.; Jamieson, Amanda M.; Raulet, David H.; Hill, Ann B.

    2007-01-01

    Three proteins encoded by murine cytomegalovirus (MCMV)— gp34, encoded by m04 (m04/gp34), gp48, encoded by m06 (m06/gp48), and gp40, encoded by m152 (m152/gp40)—act together to powerfully impact the ability of primed cytotoxic CD8 T lymphocytes (CTL) to kill virus-infected cells. Of these three, the impact of m152/gp40 on CTL lysis appears greater than would be expected based on its impact on cell surface major histocompatibility complex (MHC) class I. In addition to MHC class I, m152/gp40 also downregulates the RAE-1 family of NKG2D ligands, which can provide costimulation for CD8 T cells. We hypothesized that m152/gp40 may impact CTL lysis so profoundly because it inhibits both antigen presentation and NKG2D-mediated costimulation. We therefore tested the extent to which m152/gp40's ability to inhibit CTL lysis of MCMV-infected cells could be accounted for by its inhibition of NKG2D signaling. As was predictable from the results reported in the literature, NKG2D ligands were not detected by NKG2D tetramer staining of cells infected with wild-type MCMV, whereas those infected with MCMV lacking m152/gp40 displayed measurable levels of the NKG2D ligand. To determine whether NKG2D signaling contributed to the ability of CTL to lyse these cells, we used a blocking anti-NKG2D antibody. Blocking NKG2D signaling did affect the killing of MCMV-infected cells for some epitopes. However, for all epitopes, the impact of m152/gp40 on CTL lysis was much greater than the impact of inhibition of NKG2D signaling. We conclude that the downregulation of NKG2D ligands by MCMV makes only a small contribution to the impact of m152/gp40 on CTL lysis and only for a small subset of CTL. PMID:17855532

  15. Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover.

    PubMed

    Orr, Mona W; Donaldson, Gregory P; Severin, Geoffrey B; Wang, Jingxin; Sintim, Herman O; Waters, Christopher M; Lee, Vincent T

    2015-09-01

    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 5'-phosphoguanylyl-(3',5')-guanosine (pGpG), which is then hydrolyzed to two GMP molecules by yet unidentified enzymes termed PDE-Bs. We show that pGpG inhibits a PDE-A from Pseudomonas aeruginosa. In a dual DGC and PDE-A reaction, excess pGpG extends the half-life of c-di-GMP, indicating that removal of pGpG is critical for c-di-GMP homeostasis. Thus, we sought to identify the PDE-B enzyme(s) responsible for pGpG degradation. A differential radial capillary action of ligand assay-based screen for pGpG binding proteins identified oligoribonuclease (Orn), an exoribonuclease that hydrolyzes two- to five-nucleotide-long RNAs. Purified Orn rapidly converts pGpG into GMP. To determine whether Orn is the primary enzyme responsible for degrading pGpG, we assayed cell lysates of WT and ∆orn strains of P. aeruginosa PA14 for pGpG stability. The lysates from ∆orn showed 25-fold decrease in pGpG hydrolysis. Complementation with WT, but not active site mutants, restored hydrolysis. Accumulation of pGpG in the ∆orn strain could inhibit PDE-As, increasing c-di-GMP concentration. In support, we observed increased transcription from the c-di-GMP-regulated pel promoter. Additionally, the c-di-GMP-governed auto-aggregation and biofilm phenotypes were elevated in the ∆orn strain in a pel-dependent manner. Finally, we directly detect elevated pGpG and c-di-GMP in the ∆orn strain. Thus, we identified that Orn serves as the primary PDE-B enzyme that removes pGpG, which is necessary to complete the final step in the c-di-GMP degradation pathway.

  16. Energetics of the HIV gp120-CD4 binding reaction.

    PubMed

    Myszka, D G; Sweet, R W; Hensley, P; Brigham-Burke, M; Kwong, P D; Hendrickson, W A; Wyatt, R; Sodroski, J; Doyle, M L

    2000-08-01

    HIV infection is initiated by the selective interaction between the cellular receptor CD4 and gp120, the external envelope glycoprotein of the virus. We used analytical ultracentrifugation, titration calorimetry, and surface plasmon resonance biosensor analysis to characterize the assembly state, thermodynamics, and kinetics of the CD4-gp120 interaction. The binding thermodynamics were of unexpected magnitude; changes in enthalpy, entropy, and heat capacity greatly exceeded those described for typical protein-protein interactions. These unusual thermodynamic properties were observed with both intact gp120 and a deglycosylated and truncated form of gp120 protein that lacked hypervariable loops V1, V2, and V3 and segments of its N and C termini. Together with previous crystallographic studies, the large changes in heat capacity and entropy reveal that extensive structural rearrangements occur within the core of gp120 upon CD4 binding. CD spectral studies and slow kinetics of binding support this conclusion. These results indicate considerable conformational flexibility within gp120, which may relate to viral mechanisms for triggering infection and disguising conserved receptor-binding sites from the immune system.

  17. 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

  18. 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.

  19. Immune evasion proteins gpUS2 and gpUS11 of human cytomegalovirus incompletely protect infected cells from CD8 T cell recognition.

    PubMed

    Besold, K; Wills, M; Plachter, B

    2009-08-15

    Human cytomegalovirus (HCMV) encodes four glycoproteins, termed gpUS2, gpUS3, gpUS6 and gpUS11 that interfere with MHC class I biosynthesis and antigen presentation. Despite gpUS2-11 expression, however, HCMV infection is efficiently controlled by cytolytic CD8 T lymphocytes (CTL). To address the role of gpUS2 and gpUS11 in antigen presentation during viral infection, HCMV mutants were generated that expressed either gpUS2 or gpUS11 alone without coexpression of the three other proteins. Fibroblasts infected with these viruses showed reduced HLA-A2 and HLA-B7 surface expression. Surprisingly, however, CTL directed against the tegument protein pp65 and the regulatory IE1 protein still recognized and lysed mutant virus infected fibroblasts. Yet, suppression of IE1 derived peptide presentation by gpUS2 or gpUS11 was far more pronounced. The results show that gpUS2 and gpUS11 alone only incompletely protect HCMV infected fibroblasts from CTL recognition and underline the importance of studying infected cells to elucidate HCMV immune evasion.

  20. 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.

  1. 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.

  2. SLC: The first linear collider

    NASA Astrophysics Data System (ADS)

    Phinney, Nan

    The Stanford Linear Collider (SLC) was built in the 1980s at the Stanford Linear Accelerator Center (SLAC) in California. Like LEP, it was designed to study the properties of the Z boson at a center-of-mass energy of about 91 GeV. The SLC was also a prototype for an entirely new approach to electron-positron colliders. The development of a new technology was motivated by the fact that in an electron storage ring, the electrons radiate synchrotron radiation as they are bent around the ring. To avoid excessive energy loss from this radiation, the circumference of the ring has to increase as the square of the desired energy, making very high energy rings prohibitively large and expensive. With a linear accelerator, the electrons do not need to bend and the tunnel length only grows linearly with energy...

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. String resonances at hadron colliders

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  8. 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.

  9. Fermilab Collider: Performance and plans

    SciTech Connect

    Finley, D.A.

    1993-12-01

    The Fermilab collider program has completed its first physics run with two major detectors, CDF and DO. Recent performance of the Fermilab accelerator complex during Run Ia is presented, along with plans to improve the luminosity of the collider. The beam-beam tune shift limitations of previous runs have been avoided by the successful implementation of electrostatic separators in the Tevatron. The simultaneous operation of two high luminosity sections is provided by two matched low beta inserts. The Antiproton Source has increased its performance over the previous run as measured by stack size and stacking rate. The Linac will be upgraded from 200 MeV to 400 MeV in order to lessen the space charge tune shift upon injection into the Booster and provide proton beams with increased intensity with the same emittance. Higher luminosity requires more bunches in the Tevatron to again avoid the limitation due to the beam-beam interaction. Until it is replaced with the Main Injector, the Main Ring will remain as the most significant bottleneck on the performance of the collider.

  10. Endoplasmic reticulum heat shock protein gp96 maintains liver homeostasis and promotes hepatocellular carcinogenesis

    PubMed Central

    Rachidi, Saleh; Sun, Shaoli; Wu, Bill X; Jones, Elizabeth; Drake, Richard R.; Ogretmen, Besim; Cowart, Ashley; Clarke, Christopher J.; Hannun, Yusuf A.; Chiosis, Gabriela; Liu, Bei; Li, Zihai

    2015-01-01

    Background & Aims gp96, or grp94, is an endoplasmic reticulum (ER) heat shock protein 90 paralog which acts as a protein chaperone and plays an important role in ER homeostasis. Previous work has demonstrated its role in ER stress, Wnt and integrin signaling, calcium homeostasis and others, which are vital processes in oncogenesis. However, the cancer-intrinsic function of gp96 remains controversial. Methods We studied the roles of gp96 in liver biology in mice via an albumin promoter-driven cre recombinase-mediated disruption of gp96 gene, hsp90b1. The impact of gp96 status on hepatic carcinogenesis in response to diethyl-nitrosoamine (DENA) was probed. The roles of gp96 on human hepatocellular carcinoma cells (HCC) were also examined pharmacologically with a targeted gp96 inhibitor. Results We demonstrated that gp96 maintains liver development and hepatocyte function in vivo, and its loss genetically promotes adaptive accumulation of long chain ceramides, accompanied by steatotic regeneration of residual gp96+ hepatocytes. The need for compensatory expansion of gp96+ cells in the gp96− background predisposes mice to develop carcinogen-induced hepatic hyperplasia and cancer from gp96+ but not gp96− hepatocytes. We also found that genetic and pharmacological inhibition of gp96 in human HCCs perturbs multiple growth signals, and attenuates their proliferation and expansion. Conclusions gp96 is a pro-oncogenic chaperone, and is an attractive therapeutic target for HCC. PMID:25463537

  11. Recombinant gp19 as a potential antigen for detecting anti-Ehrlichia canis antibodies in dog sera.

    PubMed

    Oliveira, Rômulo Silva de; Cunha, Rodrigo Casquero; Moraes-Filho, Jonas; Gonçales, Relber Aguiar; Lara, Ana Paula de Souza Stori de; Avila, Luciana Farias da Costa de; Labruna, Marcelo Bahia; Leite, Fábio Pereira Leivas

    2015-01-01

    The canine monocytic ehrlichiosis, caused by Ehrlichia canis, is endemic in several regions of Brazil. Some serological diagnostic techniques using immunodominant proteins of E. canis as antigens are available, but their specificities and sensitivities are questionable. Based on this, the objective of this study was to test the antigenic potential of the recombinant gp19 protein (rGP19) for subsequent use in diagnostic tests. The rGP19 expressed in the Escherichia coli strain BL21 (DE3) C41 was recognized in the sera from experimentally infected dogs using ELISA and Western blotting. Thus, it was possible to obtain a promising antigen with the ability to differentiate between E. canis-positive and -negative animals, even 1 week after infection. PMID:26291145

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Thermodynamics of peptide inhibitor binding to HIV-1 gp41.

    PubMed

    Cole, J L; Garsky, V M

    2001-05-15

    The gp41 subunit of the human immunodeficiency virus type 1 envelope glycoprotein mediates fusion of the cellular and viral membranes. The gp41 ectodomain is a trimer of alpha-helical hairpins, where N-terminal helices form a parallel three-stranded coiled-coil core and C-terminal helices pack around the core. A deep hydrophobic pocket on the N-terminal core represents an attractive target for antiviral therapeutics. We have employed a soluble derivative of the gp41 core ectodomain and small cyclic disulfide D-peptide inhibitors to define the stoichiometry, affinity, and thermodynamics of ligand binding to this pocket using isothermal titration calorimetry. These inhibitors bind with micromolar affinity to the pocket with the expected stoichiometry of three peptides per gp41 core trimer. There are no cooperative interactions among the three binding sites. Linear eight- or nine-residue D-peptides derived from the pocket-binding domain of the cyclic molecules also bind specifically. A negative heat capacity change is observed and is consistent with burial of hydrophobic surface upon binding. Contrary to expectations for a reaction dominated by the classical hydrophobic effect, peptide binding is enthalpically driven and is opposed by an unfavorable negative entropy change. The calorimetry data support models whereby dominant negative inhibitors bind to a transiently exposed surface on the prefusion intermediate state of gp41 and disrupt subsequent resolution to the fusion-active six-stranded hairpin conformation.

  20. 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.

  1. 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.

  2. Colliding-beam-accelerator lattice

    SciTech Connect

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

    1983-01-01

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

  3. 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.

  4. 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.

  5. 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.

  6. Colliders and brane vector phenomenology

    SciTech Connect

    Clark, T. E.; Love, S. T.; Xiong, C.; Nitta, Muneto; Veldhuis, T. ter

    2008-12-01

    Brane world oscillations manifest themselves as massive vector gauge fields. Their coupling to the standard model is deduced using the method of nonlinear realizations of the spontaneously broken higher dimensional space-time symmetries. Brane vectors are stable and weakly interacting and therefore escape particle detectors unnoticed. LEP and Tevatron data on the production of a single photon in conjunction with missing energy are used to delineate experimentally excluded regions of brane vector parameter space. The additional region of parameter space accessible to the LHC as well as a future lepton linear collider is also determined by means of this process.

  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 collider operations and plans

    SciTech Connect

    Peter H. Garbincius

    2004-06-17

    Fermilab's Tevatron is a proton-antiproton collider with center of mass energy of 1.96 TeV. The antiprotons are produced by 125 GeV protons from the Main Injector striking a stainless steel target. The 8 GeV antiprotons are collected and cooled in the Debuncher and Accumulator rings of the Antiproton Source and, just recently, in the Recycler ring before acceleration by the Main Injector and the Tevatron. In addition to energy, a vital parameter for generating physics data is the Luminosity delivered to the experiments given by a formula that is listed in detail in the paper.

  9. A New GP Recombination Method Using Random Tree Sampling

    NASA Astrophysics Data System (ADS)

    Tanji, Makoto; Iba, Hitoshi

    We propose a new program evolution method named PORTS (Program Optimization by Random Tree Sampling) which is motivated by the idea of preservation and control of tree fragments in GP (Genetic Programming). We assume that to recombine genetic materials efficiently, tree fragments of any size should be preserved into the next generation. PORTS samples tree fragments and concatenates them by traversing and transitioning between promising trees instead of using subtree crossover and mutation. Because the size of a fragment preserved during a generation update follows a geometric distribution, merits of the method are that it is relatively easy to predict the behavior of tree fragments over time and to control sampling size, by changing a single parameter. From experimental results on RoyalTree, Symbolic Regression and 6-Multiplexer problem, we observed that the performance of PORTS is competitive with Simple GP. Furthermore, the average node size of optimal solutions obtained by PORTS was simple than Simple GP's result.

  10. Estimates of Fermilab Tevatron collider performance

    SciTech Connect

    Dugan, G.

    1991-09-01

    This paper describes a model which has been used to estimate the average luminosity performance of the Tevatron collider. In the model, the average luminosity is related quantitatively to various performance parameters of the Fermilab Tevatron collider complex. The model is useful in allowing estimates to be developed for the improvements in average collider luminosity to be expected from changes in the fundamental performance parameters as a result of upgrades to various parts of the accelerator complex.

  11. '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. PMID:27054203

  12. 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.

  13. FUTURE LEPTON COLLIDERS AND LASER ACCELERATION

    SciTech Connect

    PARSA,Z.

    2000-05-30

    Future high energy colliders along with their physics potential, and relationship to new laser technology are discussed. Experimental approaches and requirements for New Physics exploration are also described.

  14. SLAC-Linac-Collider (SLC) Project

    SciTech Connect

    Wiedemann, H.

    1981-02-01

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

  15. How equitable are GP practice prescribing rates for statins?: an ecological study in four primary care trusts in North West England

    PubMed Central

    Ward, Paul R; Noyce, Peter R; St Leger, Antony S

    2007-01-01

    Background There is a growing body of literature highlighting inequities in GP practice prescribing rates for a number of drug therapies. The small amount of research on statin prescribing has either focussed on variations rather than equity per se, been based on populations other than GP practices or has used cost-based prescribing rates. Aim To explore the equity of GP practice prescribing rates for statins, using the theoretical framework of equity of treatment (also known as horizontal equity or comparative need). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates and health care needs indicators (HCNIs) were developed for all GP practices. Results Scatter-plots revealed large differences between individual GP practices, both within and between PCTs, in terms of the relationship between statin prescribing and healthcare need. In addition, there were large differences between GP practices in terms of the relationship between actual and expected prescribing rates for statins. Multiple regression analyses explained almost 30% of the variation in prescribing rates in the combined dataset, 25% in PCT1, 31% in PCT3, 51% in PC4 and 58% in PCT2. There were positive associations with variables relating to CHD hospital diagnoses and procedures and negative associations with variables relating to ethnicity, material deprivation, the proportion of patients aged over 75 years and single-handed GP practices. Conclusion Overall, this study found inequitable relationships between actual and expected prescribing rates, and possible inequities in statin prescribing rates on the basis of ethnicity, deprivation, single-handed practices and the proportion of patients aged over 75 years. PMID:17386118

  16. Antibodies with specificity to native gp120 and neutralization activity against primary human immunodeficiency virus type 1 isolates elicited by immunization with oligomeric gp160.

    PubMed Central

    VanCott, T C; Mascola, J R; Kaminski, R W; Kalyanaraman, V; Hallberg, P L; Burnett, P R; Ulrich, J T; Rechtman, D J; Birx, D L

    1997-01-01

    Current human immunodeficiency virus type 1 (HIV-1) envelope vaccine candidates elicit high antibody binding titers with neutralizing activity against T-cell line-adapted but not primary HIV-1 isolates. Serum antibodies from these human vaccine recipients were also found to be preferentially directed to linear epitopes within gp120 that are poorly exposed on native gp120. Systemic immunization of rabbits with an affinity-purified oligomeric gp160 protein formulated with either Alhydrogel or monophosphoryl lipid A-containing adjuvants resulted in the induction of high-titered serum antibodies that preferentially bound epitopes exposed on native forms of gp120 and gp160, recognized a restricted number of linear epitopes, efficiently bound heterologous strains of monomeric gp120 and cell surface-expressed oligomeric gp120/gp41, and neutralized several strains of T-cell line-adapted HIV-1. Additionally, those immune sera with the highest oligomeric gp160 antibody binding titers had neutralizing activity against some primary HIV-1 isolates, using phytohemagglutinin-stimulated peripheral blood mononuclear cell targets. Induction of an antibody response preferentially reactive with natively folded gp120/gp160 was dependent on the tertiary structure of the HIV-1 envelope immunogen as well as its adjuvant formulation, route of administration, and number of immunizations administered. These studies demonstrate the capacity of a soluble HIV-1 envelope glycoprotein vaccine to elicit an antibody response capable of neutralizing primary HIV-1 isolates. PMID:9151820

  17. Hadron colliders (SSC/LHC)

    SciTech Connect

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

    1992-12-31

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

  18. 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.

  19. 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

  20. 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.

  1. Autographa californica Multiple Nucleopolyhedrovirus GP64 Protein: Roles of Histidine Residues in Triggering Membrane Fusion and Fusion Pore Expansion▿†

    PubMed Central

    Li, Zhaofei; Blissard, Gary W.

    2011-01-01

    The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) GP64 protein mediates membrane fusion during entry. Fusion results from a low-pH-triggered conformational change in GP64 and subsequent interactions with the membrane bilayers. The low-pH sensor and trigger of the conformational change are not known, but histidine residues are implicated because the pKa of histidine is near the threshold for triggering fusion by GP64. We used alanine substitutions to examine the roles of all individual and selected clusters of GP64 histidine residues in triggering and mediating fusion by GP64. Three histidine residues (H152, H155, and H156), located in fusion loop 2, were identified as important for membrane fusion. These three histidine residues were important for efficient pore expansion but were not required for the pH-triggered conformational change. In contrast, a cluster of three histidine residues (H245, H304, and H430) located near the base of the central coiled coil was identified as a putative sensor for low pH. Three alanine substitutions in cluster H245/H304/H430 resulted in dramatically reduced membrane fusion and the apparent loss of the prefusion conformation at neutral pH. Thus, the H245/H304/H430 cluster of histidines may function or participate as a pH sensor by stabilizing the prefusion structure of GP64. PMID:21937651

  2. 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

  3. 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.

  4. Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region.

    PubMed Central

    Wyatt, R; Thali, M; Tilley, S; Pinter, A; Posner, M; Ho, D; Robinson, J; Sodroski, J

    1992-01-01

    Neutralizing antibodies that recognize the human immunodeficiency virus gp120 exterior envelope glycoprotein and are directed against either the third variable (V3) loop or conserved, discontinuous epitopes overlapping the CD4 binding region have been described. Here we report several observations that suggest a structural relationship between the V3 loop and amino acids in the fourth conserved (C4) gp120 region that constitute part of the CD4 binding site and the conserved neutralization epitopes. Treatment of the gp120 glycoprotein with ionic detergents resulted in a V3 loop-dependent masking of both linear C4 epitopes and discontinuous neutralization epitopes overlapping the CD4 binding site. Increased recognition of the native gp120 glycoprotein by an anti-V3 loop monoclonal antibody, 9284, resulted from from single amino acid changes either in the base of the V3 loop or in the gp120 C4 region. These amino acid changes also resulted in increased exposure of conserved epitopes overlapping the CD4 binding region. The replication-competent subset of these mutants exhibited increased sensitivity to neutralization by antibody 9284 and anti-CD4 binding site antibodies. The implied relationship of the V3 loop, which mediates post-receptor binding steps in virus entry, and components of the CD4 binding region may be important for the interaction of these functional gp120 domains and for the observed cooperativity of neutralizing antibodies directed against these regions. Images PMID:1279195

  5. Characterization of a Discontinuous Epitope of the HIV Envelope Protein gp120 Recognized by a Human Monoclonal Antibody Using Chemical Modification and Mass Spectrometric Analysis

    PubMed Central

    Hager-Braun, Christine; Hochleitner, Elisabeth O.; Gorny, Miroslaw K.; Zolla-Pazner, Susan; Bienstock, Rachelle J.; Tomer, Kenneth B.

    2010-01-01

    A subset of the neutralizing anti-HIV antibodies recognize epitopes on the envelope protein gp120 of the human immunodeficiency virus. These epitopes are exposed during conformational changes when gp120 binds to its primary receptor CD4. Based on chemical modification of lysine and arginine residues followed by mass spectrometric analysis, we determined the epitope on gp120 recognized by the human monoclonal antibody 559/64-D, which was previously found to be specific for the CD4 binding domain. Twenty-four lysine and arginine residues in recombinant full-length glycosylated gp120 were characterized; the relative reactivities of two lysine residues and five arginine residues were affected by the binding of 559/64-D. The data show that the epitope is discontinuous and is located in the proximity of the CD4-binding site. Additionally, the reactivities of a residue that is located in the secondary receptor binding region and several residues distant from the CD4 binding site were also altered by Ab binding. These data suggest that binding of 559/64-D induced conformational changes which result in altered surface exposure of specific amino acids distant from the CD4-binding site. Consequently, binding of 559/64-D to gp120 affects not only the CD4-binding site, which is recognized as the epitope, but appears to have a global effect on surface exposed residues of the full-length glycosylated gp120. PMID:20434359

  6. Systemically administered gp100 encoding DNA vaccine for melanoma using water-in-oil-in-water multiple emulsion delivery systems.

    PubMed

    Kalariya, Mayurkumar; Amiji, Mansoor M

    2013-09-10

    The purpose of this study was to develop a water-in-oil-in-water (W/O/W) multiple emulsions-based vaccine delivery system for plasmid DNA encoding the gp100 peptide antigen for melanoma immunotherapy. The gp100 encoding plasmid DNA was encapsulated in the inner-most aqueous phase of squalane oil containing W/O/W multiple emulsions using a two-step emulsification method. In vitro transfection ability of the encapsulated plasmid DNA was investigated in murine dendritic cells by transgene expression analysis using fluorescence microscopy and ELISA methods. Prophylactic immunization using the W/O/W multiple emulsions encapsulated the gp100 encoding plasmid DNA vaccine significantly reduced tumor volume in C57BL/6 mice during subsequent B16-F10 tumor challenge. In addition, serum Th1 cytokine levels and immuno-histochemistry of excised tumor tissues indicated activation of cytotoxic T-lymphocytes mediated anti-tumor immunity causing tumor growth suppression. The W/O/W multiple emulsions-based vaccine delivery system efficiently delivers the gp100 plasmid DNA to induce cell-mediated anti-tumor immunity.

  7. A charged performance by gp17 in viral packaging.

    PubMed

    Williams, R Scott; Williams, Gareth J; Tainer, John A

    2008-12-26

    Packaging of viral genomes into virus capsids requires powerful motors to overcome the repulsive force that builds as the nucleic acids are compressed. Through structural analyses of the T4 bacteriophage packaging motor gp17, Sun et al. (2008) now propose a packaging mechanism in which electrostatic forces cause the motor to alternate between tensed and relaxed conformational states. PMID:19109888

  8. 78 FR 25067 - Northwest Pipeline GP; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-29

    ... April 12, 2013, Northwest Pipeline GP (Northwest), 295 Chipeta Way, Salt Lake City, Utah 84108, filed in... authorizing Northwest to construct and operate the Blue Water Liquefied Natural Gas (LNG) Meter Station and associated appurtenances at Benton County, Washington. The Blue Water LNG Meter Station will include...

  9. The GP retainer scheme: report of a national survey.

    PubMed

    Lockyer, Lesley; Young, Pat; Main, Paul Gn; Morison, Jim

    2014-11-01

    The current context of organisational change and new working patterns, together with the high cost of medical training, mean it is of vital importance that the NHS retains its trained workforce. The GP retainer scheme supports doctors who for reasons of personal circumstance are restricted in their ability to compete for employment in medicine, and aims to facilitate the retention of their skills and confidence. This national study evaluates the experiences and views of current and past GP retainers and provides a rigorous assessment of the retainer scheme. It is a mixed method study: an online questionnaire was completed by 318 current and ex-retainers across the UK; follow-up telephone interviews were conducted with 30 respondents. The study finds that the GP retainer scheme is effective in retaining GPs through times of transition and provides evidence to support the continuing funding of the scheme across the UK. The scheme is beneficial for doctors who also have a role in caring for young children and is also highly valued by a minority of GP retainers who are using it to return to work after illness, or to practice in a more limited role, due to chronic illness or disability. This study found variations in the implementation of the educational entitlement which is fundamental to the scheme. A minority of retainers experienced problems with the implementation of the scheme and recommendations are made for improvements. PMID:25693154

  10. 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.

  11. 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).

  12. Bilepton production at hadron colliders

    NASA Astrophysics Data System (ADS)

    Dion, B.; Grégoire, T.; London, D.; Marleau, L.; Nadeau, H.

    1999-04-01

    We examine, as model-independently as possible, the production of bileptons at hadron colliders. When a particular model is necessary or useful, we choose the 3-3-1 model. We consider a variety of processes: qq¯-->Y++Y--, ud¯-->Y++Y-, ūd-->Y+Y--, qq¯-->Y++e-e-, qq¯-->φ++φ--, ud¯-->φ++φ-, and ūd-->φ+φ--, where Y and φ are vector and scalar bileptons, respectively. Given the present low-energy constraints, we find that, at the Fermilab Tevatron, vector bileptons are unobservable, while light scalar bileptons (Mφ<~300 GeV) are just barely observable. At the CERN LHC, the reach is extended considerably: vector bileptons of mass MY<~1 TeV are observable, as are scalar bileptons of mass Mφ<~850 GeV.

  13. Disformal dark energy at colliders

    NASA Astrophysics Data System (ADS)

    Brax, Philippe; Burrage, Clare; Englert, Christoph

    2015-08-01

    Disformally coupled, light scalar fields arise in many of the theories of dark energy and modified gravity that attempt to explain the accelerated expansion of the Universe. They have proved difficult to constrain with precision tests of gravity because they do not give rise to fifth forces around static nonrelativistic sources. However, because the scalar field couples derivatively to standard model matter, measurements at high-energy particle colliders offer an effective way to constrain and potentially detect a disformally coupled scalar field. Here we derive new constraints on the strength of the disformal coupling from LHC run 1 data and provide a forecast for the improvement of these constraints from run 2. We additionally comment on the running of disformal and standard model couplings in this scenario under the renormalization group flow.

  14. XXth Hadron Collider Physics Symposium

    NASA Astrophysics Data System (ADS)

    In 2009, the Hadron Collider Physics Symposium took place in Evian (France), on the shore of the Geneva Lake, from 16-20 November. It was jointly organised by CERN and the French HEP community (CNRS-IN2P3 and CEA-IRFU). This year's symposium come at an important time for both the Tevatron and LHC communities. It stimulated the completion of analyses for a significant Tevatron data sample, and it allowed an in-depth review of the readiness of the LHC and its detectors just before first collisions. The programme includes sessions on top-quark and electro-weak physics, QCD, B physics, new phenomena, electro-weak symmetry breaking, heavy ions, and the status and commissioning of the LHC machine and its experiments. Conference website : http://hcp2009.in2p3.fr/

  15. 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.

  16. 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.

  17. Functional Analysis of the Disulfide-Bonded Loop/Chain Reversal Region of Human Immunodeficiency Virus Type 1 gp41 Reveals a Critical Role in gp120-gp41 Association

    PubMed Central

    Maerz, Anne L.; Drummer, Heidi E.; Wilson, Kirilee A.; Poumbourios, Pantelis

    2001-01-01

    Human immunodeficiency virus type 1 (HIV-1) entry into cells is mediated by the surface-exposed envelope protein (SU) gp120, which binds to cellular CD4 and chemokine receptors, triggering the membrane fusion activity of the transmembrane (TM) protein gp41. The core of gp41 comprises an N-terminal triple-stranded coiled coil and an antiparallel C-terminal helical segment which is packed against the exterior of the coiled coil and is thought to correspond to a fusion-activated conformation. The available gp41 crystal structures lack the conserved disulfide-bonded loop region which, in human T-lymphotropic virus type 1 (HTLV-1) and murine leukemia virus TM proteins, mediates a chain reversal, connecting the antiparallel N- and C-terminal regions. Mutations in the HTLV-1 TM protein gp21 disulfide-bonded loop/chain reversal region adversely affected fusion activity without abolishing SU-TM association (A. L. Maerz, R. J. Center, B. E. Kemp, B. Kobe, and P. Poumbourios, J. Virol. 74:6614–6621, 2000). We now report that in contrast to our findings with HTLV-1, conservative substitutions in the HIV-1 gp41 disulfide-bonded loop/chain reversal region abolished association with gp120. While the mutations affecting gp120-gp41 association also affected cell-cell fusion activity, HIV-1 glycoprotein maturation appeared normal. The mutant glycoproteins were processed, expressed at the cell surface, and efficiently immunoprecipitated by conformation-dependent monoclonal antibodies. The gp120 association site includes aromatic and hydrophobic residues on either side of the gp41 disulfide-bonded loop and a basic residue within the loop. The HIV-1 gp41 disulfide-bonded loop/chain reversal region is a critical gp120 contact site; therefore, it is also likely to play a central role in fusion activation by linking CD4 plus chemokine receptor-induced conformational changes in gp120 to gp41 fusogenicity. These gp120 contact residues are present in diverse primate lentiviruses

  18. 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.

  19. 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.

  20. CGP lil-gp 2.1;1.02 User's Manual

    NASA Technical Reports Server (NTRS)

    Janikow, Cezary Z.; DeWeese, Scott W.

    1997-01-01

    This document describes extensions provided to lil-gp facilitating dealing with constraints. This document deals specifically with lil-gp 1.02, and the resulting extension is referred to as CGP lil-gp 2.1; 1.02 (the first version is for the extension, the second for the utilized lil-gp version). Unless explicitly needed to avoid confusion, version numbers are omitted.

  1. 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.

  2. 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

  3. Platelet GP IIb-IIIa Receptor Antagonists in Primary Angioplasty: Back to the Future.

    PubMed

    De Luca, Giuseppe; Savonitto, Stefano; van't Hof, Arnoud W J; Suryapranata, Harry

    2015-07-01

    Coronary artery disease and acute myocardial infarction still represent the leading cause of mortality in developed countries. Therefore, great efforts have been made in the last decades to improve reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite optimal epicardial recanalisation, a large proportion of patients still experience impaired reperfusion and in-stent thrombosis. The adjunctive use of glycoprotein (GP) IIb-IIIa inhibitors may certainly contribute in the reduction of such complications, especially when administered in the early phase of infarction. In fact, in this phase a larger platelet composition of the thrombus and the presence of a larger amount of viable myocardium, as compared to a delayed phase, may increase the benefits from this therapy and counterbalance the potential higher risk of bleeding. A large body of evidence has been accumulated on the benefits from GP IIb-IIIa inhibitors in terms of prevention of stent thrombosis, and benefits in mortality, especially among high-risk patients and as upstream strategy. Therefore, based on current available data, GP IIb-IIIa inhibitors can be recommended as early as possible (upstream strategy) among high-risk patients, such as those with advanced Killip class or anterior myocardial infarction (MI), and those presenting within the first three hours. Even though it is not universally accepted, in our opinion this strategy should be implemented in a pre-hospital setting (in ambulance) or at first hospital admission (Emergency Room or Coronary Care Unit, irrespective of whether they are in the spoke or hub hospitals). Peri-procedural intracoronary administration of GP IIb-IIIa inhibitors has not provided additional benefits as compared to intravenous administration and therefore cannot be recommended. Even though the vast majority of trials have been conducted with abciximab, several meta-analyses comparing small molecules (mainly high-dose tirofiban rather than eptifibatide

  4. 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.

  5. Conformational Characterization of Aberrant Disulfide-linked HIV-1 gp120 Dimers Secreted from Overexpressing Cells

    PubMed Central

    Finzi, Andrés; Pacheco, Beatriz; Zeng, Xin; Do Kwon, Young; Kwong, Peter D.; Sodroski, Joseph

    2010-01-01

    The envelope (Env) glycoproteins of human immunodeficiency virus (HIV-1) mediate viral entry and are also the primary target of neutralizing antibodies. The gp160 envelope glycoprotein precursor undergoes proteolytic cleavage in the Golgi complex to produce the gp120 exterior glycoprotein and the gp41 transmembrane glycoprotein, which remain associated non-covalently in the trimeric Env complex. Monomeric soluble gp120 has been used extensively to investigate conformational states, structure, antigenicity and immunogenicity of the HIV-1 Env glycoproteins. Expression of gp120 alone (without gp41) leads to the accumulation not only of monomeric gp120 but also an aberrant dimeric form. The gp120 dimers were sensitive to reducing agents. The formation of gp120 dimers was disrupted by a single amino acid change in the inner domain, and was reduced by removal of the V1/V2 variable loops or the N and C termini. Epitopes on the gp120 inner domain and the chemokine receptor-binding surface were altered or occluded by gp120 dimerization. Awareness of the existence and properties of gp120 dimers should assist interpretation of studies of this key viral protein. PMID:20471426

  6. 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.

  7. 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. PMID:23668610

  8. [Developing training in critical appraisal for GP trainees in the Eastern Region of Denmark].

    PubMed

    Tulinius, Charlotte; Nielsen, Anni Brit Sternhagen; Hermann, Christian; Hansen, Lars Jørgen; Vlasova, Lioudmila; Dalsted, Rikke

    2008-10-27

    In 2004 training in critical appraisal became a mandatory part of the Danish medical specialist training. In this article we describe how the course was designed and implemented on the basis of experience from previous research training initiatives targeting GPs and GP-trainees; and how we continuously develop the course and tailor the training of teachers for the course using a multi-method participatory evaluation design, theoretically based on Stenhouse's definition of the curriculum as a process and the teachers as researchers.

  9. 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.

  10. 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.

  11. 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)

  12. The principles and construction of linear colliders

    SciTech Connect

    Rees, J.

    1986-09-01

    The problems posed to the designers and builders of high-energy linear colliders are discussed. Scaling laws of linear colliders are considered. The problem of attainment of small interaction areas is addressed. The physics of damping rings, which are designed to condense beam bunches in phase space, is discussed. The effect of wake fields on a particle bunch in a linac, particularly the conventional disk-loaded microwave linac structures, are discussed, as well as ways of dealing with those effects. Finally, the SLAC Linear Collider is described. 18 refs., 17 figs. (LEW)

  13. 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

  14. Compensatable muon collider calorimeter with manageable backgrounds

    DOEpatents

    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.

  15. 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.

  16. CP violation and flavor-changing-currents at {mu}{sup +}{mu}{sup minus} colliders

    SciTech Connect

    Soni, A.

    1996-04-02

    Production and decay (CP) asymmetries at {mu}{sup +}{mu}{sup {minus}} collider, in extensions of the Standard Model (SM) are reported. Production asymmetries appear to be very promising for a large range of parameters, decays are less effective. Importance of flavor- changing scalar currents involving the top are emphasized. At lepton colliders, the top-anticharm final state is uniquely suited for such searches. At a muon collider there is the novel possibility of tree level {mu}{sup +}{mu}{sup {minus}} {r_arrow} t{ovr c}. This talk is based on works done in collaboration with David Atwood and Laura Reina. 10 refs., 8 figs.

  17. Gp120/CD4 blocking antibodies are frequently elicited in ART-naïve chronically HIV-1 infected individuals.

    PubMed

    Carrillo, Jorge; Molinos-Albert, Luis Manuel; Rodríguez de la Concepción, Maria Luisa; Marfil, Silvia; García, Elisabet; Derking, Ronald; Sanders, Rogier W; Clotet, Bonaventura; Blanco, Julià

    2015-01-01

    Antibodies with the ability to block the interaction of HIV-1 envelope glycoprotein (Env) gp120 with CD4, including those overlapping the CD4 binding site (CD4bs antibodies), can protect from infection by HIV-1, and their elicitation may be an interesting goal for any vaccination strategy. To identify gp120/CD4 blocking antibodies in plasma samples from HIV-1 infected individuals we have developed a competitive flow cytometry-based functional assay. In a cohort of treatment-naïve chronically infected patients, we showed that gp120/CD4 blocking antibodies were frequently elicited (detected in 97% plasma samples) and correlated with binding to trimeric HIV-1 envelope glycoproteins. However, no correlation was observed between functional CD4 binding blockade data and titer of CD4bs antibodies determined by ELISA using resurfaced gp120 proteins. Consistently, plasma samples lacking CD4bs antibodies were able to block the interaction between gp120 and its receptor, indicating that antibodies recognizing other epitopes, such as PGT126 and PG16, can also play the same role. Antibodies blocking CD4 binding increased over time and correlated positively with the capacity of plasma samples to neutralize the laboratory-adapted NL4.3 and BaL virus isolates, suggesting their potential contribution to the neutralizing workforce of plasma in vivo. Determining whether this response can be boosted to achieve broadly neutralizing antibodies may provide valuable information for the design of new strategies aimed to improve the anti-HIV-1 humoral response and to develop a successful HIV-1 vaccine. PMID:25803681

  18. 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.

  19. Gp120/CD4 Blocking Antibodies Are Frequently Elicited in ART-Naïve Chronically HIV-1 Infected Individuals

    PubMed Central

    Carrillo, Jorge; Molinos-Albert, Luis Manuel; de la Concepción, Maria Luisa Rodríguez; Marfil, Silvia; García, Elisabet; Derking, Ronald; Sanders, Rogier W.; Clotet, Bonaventura; Blanco, Julià

    2015-01-01

    Antibodies with the ability to block the interaction of HIV-1 envelope glycoprotein (Env) gp120 with CD4, including those overlapping the CD4 binding site (CD4bs antibodies), can protect from infection by HIV-1, and their elicitation may be an interesting goal for any vaccination strategy. To identify gp120/CD4 blocking antibodies in plasma samples from HIV-1 infected individuals we have developed a competitive flow cytometry-based functional assay. In a cohort of treatment-naïve chronically infected patients, we showed that gp120/CD4 blocking antibodies were frequently elicited (detected in 97% plasma samples) and correlated with binding to trimeric HIV-1 envelope glycoproteins. However, no correlation was observed between functional CD4 binding blockade data and titer of CD4bs antibodies determined by ELISA using resurfaced gp120 proteins. Consistently, plasma samples lacking CD4bs antibodies were able to block the interaction between gp120 and its receptor, indicating that antibodies recognizing other epitopes, such as PGT126 and PG16, can also play the same role. Antibodies blocking CD4 binding increased over time and correlated positively with the capacity of plasma samples to neutralize the laboratory-adapted NL4.3 and BaL virus isolates, suggesting their potential contribution to the neutralizing workforce of plasma in vivo. Determining whether this response can be boosted to achieve broadly neutralizing antibodies may provide valuable information for the design of new strategies aimed to improve the anti-HIV-1 humoral response and to develop a successful HIV-1 vaccine. PMID:25803681

  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. Results of dynamic testing of GP-B spherical gyroscopes

    NASA Technical Reports Server (NTRS)

    Keiser, G. M.; Breakwell, J. V.; Xiao, Y.; Feteih, S.

    1989-01-01

    Laboratory tests of the spherical electrostatically levitated cryogenically cooled coated gyroscope being developed for the Gravity Probe B (GP-B) spacecraft (Bardas et al., 1986) are reported. Spin speed and the dc components of the trapped magnetic field are measured with three orthogonal pickup loops attached to SQUID detectors as the levitated gyro is brought up to speed by an He gas jet. Data on the spin-vector time history, mass unbalance, higher rotor-shape harmonics, and spin-vector position are presented in extensive graphs and characterized in detail, and a mathematical model of the electrostatic suspension torques is derived. Prototype gyro 86-4 is found to have mass unbalance within the range required for the GP-B mission (to detect the geodetic and motional effects predicted by general relativity theory).

  2. 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.

  3. 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.

  4. Flavourful production at hadron colliders

    NASA Astrophysics Data System (ADS)

    Giudice, Gian Francesco; Gripaios, Ben; Sundrum, Raman

    2011-08-01

    We ask what new states may lie at or below the TeV scale, with sizable flavour-dependent couplings to light quarks, putting them within reach of hadron colliders via resonant production, or in association with Standard Model states. In particular, we focus on the compatibility of such states with stringent flavour-changing neutral current and electric-dipole moment constraints. We argue that the broadest and most theoretically plausible flavour structure of the new couplings is that they are hierarchical, as are Standard Model Yukawa couplings, although the hierarchical pattern may well be different. We point out that, without the need for any more elaborate or restrictive structure, new scalars with "diquark" couplings to standard quarks are particularly immune to existing constraints, and that such scalars may arise within a variety of theoretical paradigms. In particular, there can be substantial couplings to a pair of light quarks or to one light and one heavy quark. For example, the latter possibility may provide a flavour-safe interpretation of the asymmetry in top quark production observed at the Tevatron. We thereby motivate searches for diquark scalars at the Tevatron and LHC, and argue that their discovery represents one of our best chances for new insight into the Flavour Puzzle of the Standard Model.

  5. 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)]...

  6. Time evolution of the luminosity of colliding heavy-ion beams in BNL Relativistic Heavy Ion Collider and CERN Large Hadron Collider

    NASA Astrophysics Data System (ADS)

    Bruce, R.; Jowett, J. M.; Blaskiewicz, M.; Fischer, W.

    2010-09-01

    We have studied the time evolution of the heavy-ion luminosity and bunch intensities in the Relativistic Heavy Ion Collider (RHIC) at BNL, and in the Large Hadron Collider (LHC) at CERN. First, we present measurements from a large number of RHIC stores (from run-7), colliding 100GeV/nucleon Au79+197 beams without stochastic cooling. These are compared with two different calculation methods. The first is a simulation based on multiparticle tracking taking into account collisions, intrabeam scattering, radiation damping, and synchrotron and betatron motion. In the second, faster, method, a system of ordinary differential equations with terms describing the corresponding effects on emittances and bunch populations is solved numerically. Results of the tracking method agree very well with the RHIC data. With the faster method, significant discrepancies are found since the losses of particles diffusing out of the rf bucket due to intrabeam scattering are not modeled accurately enough. Finally, we use both methods to make predictions of the time evolution of the future Pb82+208 beams in the LHC at injection and collision energy. For this machine, the two methods agree well.

  7. Time evolution of the luminosity of colliding heavy-ion beams in BNL Relativistic Heavy Ion Collider and CERN Large Hadron Collider

    SciTech Connect

    Bruce, R.; Blaskiewicz, M.; Jowett, J.M.; Fischer, W.

    2010-09-07

    We have studied the time evolution of the heavy ion luminosity and bunch intensities in the Relativistic Heavy Ion Collider (RHIC), at BNL, and in the Large Hadron Collider (LHC), at CERN. First, we present measurements from a large number of RHIC stores (from Run 7), colliding 100 GeV/nucleon {sup 197}Au{sup 79}+ beams without stochastic cooling. These are compared with two different calculation methods. The first is a simulation based on multi-particle tracking taking into account collisions, intrabeam scattering, radiation damping, and synchrotron and betatron motion. In the second, faster, method, a system of ordinary differential equations with terms describing the corresponding effects on emittances and bunch populations is solved numerically. Results of the tracking method agree very well with the RHIC data. With the faster method, significant discrepancies are found since the losses of particles diffusing out of the RF bucket due to intrabeam scattering are not modeled accurately enough. Finally, we use both methods to make predictions of the time evolution of the future {sup 208}Pb+{sup 82+} beams in the LHC at injection and collision energy. For this machine, the two methods agree well.

  8. Oligomerization of the hydrophobic heptad repeat of gp41.

    PubMed Central

    Bernstein, H B; Tucker, S P; Kar, S R; McPherson, S A; McPherson, D T; Dubay, J W; Lebowitz, J; Compans, R W; Hunter, E

    1995-01-01

    The transmembrane protein of human immunodeficiency virus type 1 (HIV-1) contains a leucine zipper-like (hydrophobic heptad) repeat which has been predicted to form an amphipathic alpha helix. To evaluate the potential of the hydrophobic heptad repeat to induce protein oligomerization, this region of gp41 has been cloned into the bacterial expression vector pRIT2T. The resulting plasmid, pRIT3, expresses a fusion protein consisting of the Fc binding domain of monomeric protein A, a bacterial protein, and amino acids 538 to 593 of HIV-1 gp41. Gel filtration chromatography demonstrated the presence of oligomeric forms of the fusion protein, and analytical centrifugation studies confirmed that the chimeric protein formed a higher-order multimer that was greater than a dimer. Thus, we have identified a region of HIV-1 gp41 which is capable of directing the oligomerization of a fusion protein containing monomeric protein A. Point mutations, previously shown to inhibit the biological activity of the HIV-1 envelope glycoprotein, have been engineered into the segment of gp41 contained in the fusion protein, and expressed mutant proteins were purified and analyzed via fast protein liquid chromatography. A point mutation in the heptad repeat, which changed the central isoleucine to an alanine, caused a significant (> 60%) decrease in oligomerization, whereas changing the central isoleucine to aspartate or proline resulted in almost a complete loss of oligomerization. Deletions of one, two, or three amino acids following the first isoleucine also resulted in a profound decrease in oligomerization. The inhibitory effects of the mutations on oligomer formation correlated with the effects of the same mutations on envelope glycoprotein-mediated fusion. A possible role of the leucine zipper-like region in the fusion process and in an oligomerization event distinct from assembly of the envelope glycoprotein complex is discussed. PMID:7707497

  9. Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94

    PubMed Central

    Ansa-Addo, Ephraim A.; Thaxton, Jessica; Hong, Feng; Wu, Bill X.; Zhang, Yongliang; Fugle, Caroline W.; Metelli, Alessandra; Riesenberg, Brian; Williams, Katelyn; Gewirth, Daniel T.; Chiosis, Gabriela; Liu, Bei; Li, Zihai

    2016-01-01

    As an endoplasmic reticulum heat shock protein (HSP) 90 paralogue, glycoprotein (gp) 96 possesses immunological properties by chaperoning antigenic peptides for activation of T cells. Genetic studies in the last decade have unveiled that gp96 is also an essential master chaperone for multiple receptors and secreting proteins including Toll-like receptors (TLRs), integrins, the Wnt co-receptor, Low Density Lipoprotein Receptor-Related Protein 6 (LRP6), the latent TGFβ docking receptor, Glycoprotein A Repetitions Predominant (GARP), Glycoprotein (GP) Ib and insulin-like growth factors (IGF). Clinically, elevated expression of gp96 in a variety of cancers correlates with the advanced stage and poor survival of cancer patients. Recent preclinical studies have also uncovered that gp96 expression is closely linked to cancer progression in multiple myeloma, hepatocellular carcinoma, breast cancer and inflammation-associated colon cancer. Thus, gp96 is an attractive therapeutic target for cancer treatment. The chaperone function of gp96 depends on its ATPase domain, which is structurally distinct from other HSP90 members, and thus favors the design of highly selective gp96-targeted inhibitors against cancer. We herein discuss the strategically important oncogenic clients of gp96 and their underlying biology. The roles of cell-intrinsic gp96 in T cell biology are also discussed, in part because it offers another opportunity of cancer therapy by manipulating levels of gp96 in T cells to enhance host immune defense. PMID:27072698

  10. Polyubiquitylation of AMF requires cooperation between the gp78 and TRIM25 ubiquitin ligases.

    PubMed

    Wang, Ying; Ha, Seung-Wook; Zhang, Tianpeng; Kho, Dhong-Hyo; Raz, Avraham; Xie, Youming

    2014-04-30

    gp78 is a ubiquitin ligase that plays a vital role in endoplasmic reticulum (ER)-associated degradation (ERAD). Here we report that autocrine motility factor (AMF), also known as phosphoglucose isomerase (PGI), is a novel substrate of gp78. We show that polyubiquitylation of AMF requires cooperative interaction between gp78 and the ubiquitin ligase TRIM25 (tripartite motif-containing protein 25). While TRIM25 mediates the initial round of ubiquitylation, gp78 catalyzes polyubiquitylation of AMF. The E4-like activity of gp78 was illustrated by an in vitro polyubiquitylation assay using Ub-DHFR as a model substrate. We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78. This study uncovers a previously unknown functional link between gp78 and TRIM25 and provides mechanistic insight into gp78-mediated protein ubiquitylation.

  11. 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

  12. 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.

  13. Experimental examination of strain field within GP zone in an Al-Zn-Mg-Cu alloy

    NASA Astrophysics Data System (ADS)

    Bai, P. C.; Liu, F.; Hou, X. H.; Zhao, C. W.; Xing, Y. M.

    2012-11-01

    The strain field of GP zone plays a very important role in strengthening of the precipitation-hardened aluminum alloys by prohibiting movement of dislocations; however, quantitative analysis about the strain field of the GP zone in the aluminum alloys has been seldom reported elsewhere. In this paper, the microstructure of GP zone in an Al-Zn-Mg-Cu alloy was explored by using high-resolution transmission electron microscopy (HRTEM), and the displacement field of lattice planes within the GP zone was experimentally measured by geometric phase analysis (GPA) technique; then, the quantitative results about strains of the distorted lattice planes within the GP zone were also obtained. It is found that the GP zone core is convergence region of the strains, and the maximum value of the compressive strains within the GP zone is about 7.6%.

  14. Glycosylation of stress glycoprotein GP62 in cells exposed to heat-shock and subculturing.

    PubMed

    Dumić, J; Lauc, G; Flögel, M

    1999-11-01

    GP62 is a member of the stress glycoprotein family that was proposed to have a chaperone-like function in the heat-shock response. Using lectin blotting we have studied glycosylation of GP62 and determined that in addition to heat-shock, even simple subculturing of cells is a sufficient stimulus to provoke induction of GP62. Interestingly, both kinetics of induction and glycosylation of GP62 induced by subculturing were different than when GP62 was induced by heat-shock. While GP62 induced by heat-shock was recognized by SNA, DSA and PHA-E lectins, and not by BSA I, Con A, RCA I, SJA, UEA I, VVA, and WGA lectins, GP62 induced by subculturing was also recognized by RCA I and WGA lectins.

  15. Australian GP registrars' use of e-resources.

    PubMed

    Denny, Bianca; Chester, Andrea; Butler, Mexie; Brown, James

    2015-03-01

    Traditional face-to-face learning opportunities for Australian GP registrars are complemented by the use of e-resources. The current study aimed to investigate GP trainees' use of e-resources and their preferences for sourcing clinical information to inform the prospective direction and design of e-resources for the GP education and training sector. One-hundred and nineteen registrars completed a custom online survey measuring the type and frequency of use of e-resources, and preferences for their design and content. Results indicated that for the majority of registrars e-resources were the first preference for obtaining clinical information (77.3%). The most frequently used e-resources included non-medical search engines, medical journals and prescribing software. Factors relevant to registrars' selection and use of e-resources included the accuracy and comprehensiveness of the information. It is concluded that the use of e-resources provides a valuable supplement to registrars' learning and teaching. However, issues of quality and consistency raise some concerns regarding the use of e-resources for obtaining clinical information.

  16. 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.

  17. The Status of the International Linear Collider

    NASA Astrophysics Data System (ADS)

    Harrison, Michael

    2016-03-01

    The International Linear Collider is under consideration in Japan as the next major global high energy physics facility. In this talk we shall describe the site and accelerator footprint together with the latest technical information on the superconducting RF technology.

  18. Magnet R&D for future colliders

    SciTech Connect

    Sabbi, Gian Luca

    2001-06-14

    High-energy colliders complementing and expanding the physics reach of LHC are presently under study in the United States, Europe and Japan. The magnet system is a major cost driver for hadron colliders at the energy frontier, and critical to the successful operation of muon colliders. Under most scenarios, magnet design as well as vacuum and cryogenic systems are complicated by high radiation loads. Magnet R&D programs are underway worldwide to take advantage of new developments in superconducting materials, achieve higher efficiency and simplify fabrication while preserving accelerator-class field quality. A review of recent progress in magnet technology for future colliders is presented, with emphasis on the most innovative design concepts and fabrication techniques.

  19. 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.

  20. 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.

  1. World lays groundwork for future linear collider

    SciTech Connect

    Feder, Toni

    2010-07-15

    With the Large Hadron Collider at CERN finally working, the particle-physics community can now afford to divide its attention between achieving LHC results and preparing for the next machine on its wish list, an electron-positron linear collider. The preparations involve developing and deciding on the technology for such a machine, the mode of its governance, and how to balance regional and global particle- and accelerator-physics programs.

  2. RF pulse compression for future linear colliders

    NASA Astrophysics Data System (ADS)

    Wilson, Perry B.

    1995-07-01

    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 to 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-II system) can be used to reduce the klystron peak power by about a factor of two, or alternatively, 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.

  3. Regulation of the expression of chaperone gp96 in macrophages and dendritic cells.

    PubMed

    Wolfram, Lutz; Fischbeck, Anne; Frey-Wagner, Isabelle; Wojtal, Kacper A; Lang, Silvia; Fried, Michael; Vavricka, Stephan R; Hausmann, Martin; Rogler, Gerhard

    2013-01-01

    The chaperone function of the ER-residing heat shock protein gp96 plays an important role in protein physiology and has additionally important immunological functions due to its peptide-binding capacity. Low amounts of gp96 stimulate immunity; high quantities induce tolerance by mechanisms not fully understood. A lack of gp96 protein in intestinal macrophages (IMACs) from Crohn`s disease (CD) patients correlates with loss of tolerance against the host gut flora, leading to chronic inflammation. Since gp96 shows dose-dependent direction of immunological reactions, we studied primary IMACs and developed cell models to understand the regulation of gp96 expression. Induction of gp96-expression was higher in in vitro differentiated dendritic cells (i.v.DCs) than in in vitro differentiated macrophages (i.v.MACs), whereas monocytes (MOs) expressed only low gp96 levels. The highest levels of expression were found in IMACs. Lipopolysaccharide (LPS), muramyl dipeptide (MDP), tumour necrosis factor (TNF), and Interleukin (IL)-4 induced gp96-expression, while IL12, IL-17, IL-23 and interferon (IFN)-γ were not effective indicating that Th1 and Th17 cells are probably not involved in the induction of gp96. Furthermore, gp96 was able to induce its own expression. The ER-stress inducer tunicamycin increased gp96-expression in a concentration- and time-dependent manner. Both ulcerative colitis (UC) and CD patients showed significantly elevated gp96 mRNA levels in intestinal biopsies which correlated positively with the degree of inflammation of the tissue. Since gp96 is highly expressed on the one hand upon stress induction as during inflammation and on the other hand possibly mediating tolerance, these results will help to understand the whether gp96 plays a role in the pathophysiology of inflammatory bowel disease (IBD).

  4. Morphine and gp120 toxic interactions in striatal neurons are dependent on HIV-1 strain

    PubMed Central

    Podhaizer, Elizabeth M.; Zou, Shiping; Fitting, Sylvia; Samano, Kimberly L.; El-Hage, Nazira; Knapp, Pamela E.; Hauser, Kurt F.

    2011-01-01

    A rigorously controlled, cell culture paradigm was used to assess the role of HIV-1 gp120 ± morphine in mediating opioid-HIV interactive toxicity in striatal neurons. Computerized time-lapse microscopy tracked the fate of individual neurons co-cultured with mixed-glia from mouse striata during opioid and gp120 exposure. Subpopulations of neurons and astroglia displayed μ-opioid receptor, CXCR4, and CCR5 immunoreactivity. While gp120 alone was or tended to be neurotoxic irrespective of whether X4-tropic gp120IIIB, R5-tropic gp120ADA, or dual-tropic gp120MN was administered, interactive toxicity with morphine differed depending on HIV-1 strain. For example, morphine only transiently exacerbated gp120IIIB-induced neuronal death; however, in combination with gp120MN, morphine caused sustained increases in the rate of neuronal death compared to gp120MN alone that were prevented by naloxone. Alternatively, gp120ADA significantly increased the rate of neuron death, which was unaffected by morphine. The transient neurotoxic interactions between morphine and gp120IIIB were abrogated in the absence of glia suggesting that glia contribute significantly to the interactive pathology with chronic opiate abuse and neuroAIDS. To assess how mixed-glia might contribute to the neurotoxicity, the effects of morphine and/or gp120 on the production of reactive oxygen species (ROS) and on glutamate buffering were examined. All gp120 variants, and to a lesser extent morphine, increased ROS and/or decreased glutamate buffering, but together failed to show any interaction with morphine. Our findings indicate that HIV-1 strain-specific differences in gp120 are critical determinants in shaping both the timing and pattern of neurotoxic interactions with opioid drugs. PMID:22101471

  5. GP3 is a structural component of the PRRSV type II (US) virion

    SciTech Connect

    Lima, M. de; Ansari, I.H.; Das, P.B.; Ku, B.J.; Martinez-Lobo, F.J.; Pattnaik, A.K.; Osorio, F.A.

    2009-07-20

    Glycoprotein 3 (GP3) is a highly glycosylated PRRSV envelope protein which has been reported as being present in the virions of PRRSV type I, while missing in the type II PRRSV (US) virions. We herein present evidence that GP3 is indeed incorporated in the virus particles of a North American strain of PRRSV (FL12), at a density that is consistent with the minor structural role assigned to GP3 in members of the Arterivirus genus. Two 15aa peptides corresponding to two different immunodominant linear epitopes of GP3 derived from the North American strain of PRRSV (FL12) were used as antigen to generate a rabbit monospecific antiserum to this protein. The specificity of this anti-GP3 antiserum was confirmed by radioimmunoprecipitation (RIP) assay using BHK-21 cells transfected with GP3 expressing plasmid, MARC-145 cells infected with FL12 PRRSV, as well as by confocal microscopy on PRRSV-infected MARC-145 cells. To test if GP3 is a structural component of the virion, {sup 35}S-labelled PRRSV virions were pelleted through a 30% sucrose cushion, followed by a second round of purification on a sucrose gradient (20-60%). Virions were detected in specific gradient fractions by radioactive counts and further confirmed by viral infectivity assay in MARC 145 cells. The GP3 was detected in gradient fractions containing purified virions by RIP using anti-GP3 antiserum. Predictably, the GP3 was less abundant in purified virions than other major structural envelope proteins such as GP5 and M. Further evidence of the presence of GP3 at the level of PRRSV FL12 envelope was obtained by immunogold staining of purified virions from the supernatant of infected cells with anti-GP3 antiserum. Taken together, these results indicate that GP3 is a minor structural component of the PRRSV type II (FL12 strain) virion, as had been previously described for PRRSV type I.

  6. A new member of the GP138 multigene family implicated in cell interactions in Dictyostelium discoideum.

    PubMed

    Hata, T; Yamaguchi, N; Tanaka, Y; Urushihara, H

    1999-06-01

    The cellular slime mold Dictyostelium discoideum reproduces sexually under submerged and dark conditions. Its mating system is polymorphic and particularly interesting with respect to mechanisms of cell recognition. The cell-surface glycoprotein gp138 has been implicated in sexual cell interactions, as it was identified as a target molecule for the antibodies that block sexual cell fusion in D. discoideum. Two mutually homologous genes, GP138A and GP138B, have been cloned, but gene disruption experiments to clarify their functional relationships suggested that there is at least one more gene for gp138. Further protein analysis including peptide mapping also revealed that gp138 exists as three isoforms, DdFRP1, DdFRP2, and DdFRP3. GP138A encodes DdFRP2 and GP138B, DdFRP3, and the presence of a third gp138 gene encoding DdFRP1 was suggested. Here, we isolated and characterized a third GP138 gene, GP138C. Although the deduced amino acid sequences of GP138C matched completely with those of peptide fragments of DdFRP1 in the N-terminal half, the rest did not give complete matches. Overexpression of GP138C caused an increase in the intensity of DdFRP1, but disruption of this gene did not diminish DdFRP1. Our results indicate that GP138C encodes a protein very similar to but distinct from DdFRP1. The GP138 multigene family is thus composed of more members than previously expected, and their functional relationships are of special interest. PMID:10462174

  7. 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

  8. 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.

  9. Antibody to gp41 MPER Alters Functional Properties of HIV-1 Env without Complete Neutralization

    PubMed Central

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

    2014-01-01

    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. PMID:25058619

  10. New Methods of Particle Collimation in Colliders

    SciTech Connect

    Stancari, Giulio; /Fermilab

    2011-10-01

    The collimation system is an essential part of the design of any high-power accelerator. Its functions include protection of components from accidental and intentional energy deposition, reduction of backgrounds, and beam diagnostics. Conventional multi-stage systems based on scatterers and absorbers offer robust shielding and efficient collection of losses. Two complementary concepts have been proposed to address some of the limitations of conventional systems: channeling and volume reflection in bent crystals and collimation with hollow electron beams. The main focus of this paper is the hollow electron beam collimator, a novel concept based on the interaction of the circulating beam with a 5-keV, magnetically confined, pulsed hollow electron beam in a 2-m-long section of the ring. The electrons enclose the circulating beam, kicking halo particles transversely and leaving the beam core unperturbed. By acting as a tunable diffusion enhancer and not as a hard aperture limitation, the hollow electron beam collimator extends conventional collimation systems beyond the intensity limits imposed by tolerable losses. The concept was tested experimentally at the Fermilab Tevatron proton-antiproton collider. Results on the collimation of 980-GeV antiprotons are presented, together with prospects for the future.

  11. 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.

  12. 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.

  13. Method study of parameter choice for a circular proton-proton collider

    NASA Astrophysics Data System (ADS)

    Su, Feng; Gao, Jie; Xiao, Ming; Wang, Dou; Wang, Yi-Wei; Bai, Sha; Bian, Tian-Jian

    2016-01-01

    In this paper we show a systematic method of appropriate parameter choice for a circular proton-proton collider by using an analytical expression for the beam-beam tune shift limit, starting from a given design goal and technical limitations. A suitable parameter space has been explored. Based on the parameter scan, sets of appropriate parameters designed for a 50 km and 100 km circular proton-proton collider are proposed. Supported by National Natural Science Foundation of China (11175192)

  14. Quantum suppression of beamstrahlung for future e+e- linear colliders

    SciTech Connect

    Xie, Ming

    1998-05-01

    Beamstrahlung at interaction point may present severe limitations on linear collider performance. The approach to reduce this effect adopted for all current designs at a center-of-mass energy of 0.5 TeV will become more difficult and less effective at higher energy. We discuss the feasibility of an alternative approach, based on an effect known as quantum suppression of beamstrahlung, for future linear colliders at multi-TeV energy.

  15. 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

  16. 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

  17. 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.

    PubMed

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

    2012-05-25

    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. 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).

  18. 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).

  19. 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

  20. 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. PMID:27558714

  1. Molecular mechanism of transcription inhibition by phage T7 gp2 protein.

    PubMed

    Mekler, Vladimir; Minakhin, Leonid; Sheppard, Carol; Wigneshweraraj, Sivaramesh; Severinov, Konstantin

    2011-11-11

    Escherichia coli T7 bacteriophage gp2 protein is a potent inhibitor of host RNA polymerase (RNAP). gp2 inhibits formation of open promoter complex by binding to the β' jaw, an RNAP domain that interacts with downstream promoter DNA. Here, we used an engineered promoter with an optimized sequence to obtain and characterize a specific promoter complex containing RNAP and gp2. In this complex, localized melting of promoter DNA is initiated but does not propagate to include the point of the transcription start. As a result, the complex is transcriptionally inactive. Using a highly sensitive RNAP beacon assay, we performed quantitative real-time measurements of specific binding of the RNAP-gp2 complex to promoter DNA and various promoter fragments. In this way, the effect of gp2 on RNAP interaction with promoters was dissected. As expected, gp2 greatly decreased RNAP affinity to downstream promoter duplex. However, gp2 also inhibited RNAP binding to promoter fragments that lacked downstream promoter DNA that interacts with the β' jaw. The inhibition was caused by gp2-mediated decrease of the RNAP binding affinity to template and non-template strand segments of the transcription bubble downstream of the -10 promoter element. The inhibition of RNAP interactions with single-stranded segments of the transcription bubble by gp2 is a novel effect, which may occur via allosteric mechanism that is set in motion by the gp2 binding to the β' jaw.

  2. The next linear collider damping ring complex

    SciTech Connect

    Corlett,J.; Atkinson,D.; De Santis,S.; Hartman, N.; Kennedy, K.; Li, D.; Marks, S.; Minamihara, Y.; Nishimura, H.; Pivi, M.; Reavill, D.; Rimmer, R.; Schlueter, R.; Wolski, A.; Anderson,S.; McKee,B.; Raubenheimer, T.; Ross, M.; Sheppard, J.C.

    2001-06-12

    We report progress on the design of the Next Linear Collider (NLC) Damping Rings complexes. The purpose of the damping rings is to provide low emittance electron and positron bunch trains to the NLC linacs, at a rate of 120 Hz. As an option to operate at the higher rate of 180 Hz, two 1.98 GeV main damping rings per beam are proposed, and one positron pre-damping ring. The main damping rings store up to 0.8 amp in 3 trains of 190 bunches each and have normalized extracted beam emittances {gamma}{var_epsilon}x = 3 mm-mrad and {gamma}{var_epsilon}y = 0.02 mm-mrad. The optical designs, based on a theoretical minimum emittance lattice (TME), are described, with an analysis of dynamic aperture and non-linear effects. Key subsystems and components are described, including the wiggler, the vacuum systems and photon stop design, and the higher-order-mode damped RF cavities. Impedance and instabilities are discussed.

  3. Status of the Future Circular Collider Study

    NASA Astrophysics Data System (ADS)

    Benedikt, Michael

    2016-03-01

    Following the 2013 update of the European Strategy for Particle Physics, the international Future Circular Collider (FCC) Study has been launched by CERN as host institute, to design an energy frontier hadron collider (FCC-hh) in a new 80-100 km tunnel with a centre-of-mass energy of about 100 TeV, an order of magnitude beyond the LHC's, as a long-term goal. The FCC study also includes the design of a 90-350 GeV high-luminosity lepton collider (FCC-ee) installed in the same tunnel, serving as Higgs, top and Z factory, as a potential intermediate step, as well as an electron-proton collider option (FCC-he). The physics cases for such machines will be assessed and concepts for experiments will be developed in time for the next update of the European Strategy for Particle Physics by the end of 2018. The presentation will summarize the status of machine designs and parameters and discuss the essential technical components to be developed in the frame of the FCC study. Key elements are superconducting accelerator-dipole magnets with a field of 16 T for the hadron collider and high-power, high-efficiency RF systems for the lepton collider. In addition the unprecedented beam power presents special challenges for the hadron collider for all aspects of beam handling and machine protection. First conclusions of geological investigations and implementation studies will be presented. The status of the FCC collaboration and the further planning for the study will be outlined.

  4. Design of High Luminosity Ring-Ring Electron- Light Ion Collider at CEBAF

    SciTech Connect

    Slawomir Bogacz; Antje Bruell; Jean Delayen; Yaroslav Derbenev; Rolf Ent; Joseph Grames; Andrew Hutton; Geoffrey Krafft; Rui Li; Nikolitsa Merminga; Benard Poelker; Bogdan Wojtsekhowski; Byung Yunn; Yuhong Zhang; C Montag

    2007-06-25

    Experimental studies of fundamental structure of nucleons require an electron-ion collider of a center-of-mass energy up to 90 GeV at luminosity up to 1035 cm-2s-1 with both beams polarized. A CEBAF-based collider of 9 GeV electrons/positrons and 225 GeV ions is envisioned to meet this science need and as a next step for CEBAF after the planned 12 GeV energy upgrade of the fixed target program. A ring-ring scheme of this collider developed recently takes advantage of the existing polarized electron CW beam from the CEBAF and a green-field design of an ion complex with electron cooling. We present a conceptual design and report design studies of this high-luminosity collider.

  5. 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.

  6. Cargoing P-gp inhibitors via nanoparticle sensitizes tumor cells against doxorubicin.

    PubMed

    Singh, Manu Smriti; Lamprecht, Alf

    2015-01-30

    Inhibitors against multidrug resistance (MDR) efflux transporters have failed in most clinical settings due to unfavorable pharmacokinetic interactions with co-administered anti-cancer drug and their inherent toxicities. Nanoparticles (NPs) have shown potential to overcome drug efflux by delivering and localizing therapeutic molecules within tumor mass. In this work, we investigated effect of nanocarrier surface charge and formulation parameters for a hydrophilic and lipophilic MDR inhibitor on their ability to reverse drug resistance. Active inhibition of efflux pumps was achieved by encapsulating first and third generation P-gp inhibitors- verapamil and elacridar respectively in non-ionic, anionic and cationic surfactant-based NPs. The ability of NPs to reverse P-glycoprotein (P-gp)-mediated MDR efflux was evaluated in sensitive (A2780) and resistant (A2780Adr) ovarian cancer cell lines by various in vitro accumulation and cytotoxicity assays. Uptake mechanism for NP appears to be caveolae-dependent with 20%-higher internalization in A2780Adr than A2780 cell lines which can be co-related to the biophysical membrane composition. Cationic- CTAB NPs showed highest reversal efficacy followed by PVA and SDS-NP (P+S NP) and PVA-NPs. As compared to doxorubicin treated drug resistant cells lines, blank-, verapamil- and elacridar-CTAB-NPs showed 2.6-, 20- and 193-fold lower IC50 values. This work highlights the importance of inhibitor-loaded charged particles to overcome cancer drug resistance.

  7. Physics of leptoquarks in precision experiments and at particle colliders

    NASA Astrophysics Data System (ADS)

    Doršner, I.; Fajfer, S.; Greljo, A.; Kamenik, J. F.; Košnik, N.

    2016-06-01

    We present a comprehensive review of physics effects generated by leptoquarks (LQs), i.e., hypothetical particles that can turn quarks into leptons and vice versa, of either scalar or vector nature. These considerations include discussion of possible completions of the Standard Model that contain LQ fields. The main focus of the review is on those LQ scenarios that are not problematic with regard to proton stability. We accordingly concentrate on the phenomenology of light leptoquarks that is relevant for precision experiments and particle colliders. Important constraints on LQ interactions with matter are derived from precision low-energy observables such as electric dipole moments, (g - 2) of charged leptons, atomic parity violation, neutral meson mixing, Kaon, B, and D meson decays, etc. We provide a general analysis of indirect constraints on the strength of LQ interactions with the quarks and leptons to make statements that are as model independent as possible. We address complementary constraints that originate from electroweak precision measurements, top, and Higgs physics. The Higgs physics analysis we present covers not only the most recent but also expected results from the Large Hadron Collider (LHC). We finally discuss direct LQ searches. Current experimental situation is summarized and self-consistency of assumptions that go into existing accelerator-based searches is discussed. A progress in making next-to-leading order predictions for both pair and single LQ productions at colliders is also outlined.

  8. Future proton and electron colliders: Dreams for the 1990's

    SciTech Connect

    Richter, B.

    1988-10-01

    In this paper I have reviewed the possibilities for new colliders that might be available in the 1990's. One or more new proton should be available in the late-90s based on plans of Europe, the US and the USSR. The two very high energy machines, LHC and SSC, are quite expensive, and their construction will be more decided by the politicians' view on the availability of resources than by the physicists' view of the need for new machines. Certainly something will be built, but the question is when. New electron colliders beyond LEP II could be available in the late 1990's as well. Most of the people who have looked at this problem believe that at a minimum three years of RandD are required before a proposal can be made, two years will be required to convince the authorities to go ahead, and five years will be required to build such a machine. Thus the earliest time a new electron collider at high energy could be available is around 1988. A strong international RandD program will be required to meet that schedule. In the field of B factories, PSI's proposal is the first serious step beyond the capabilities of CESR. There are other promising techniques but these need more RandD. The least RandD would be required for the asymmetric storage ring systems, while the most would be required for high luminosity linear colliders. For the next decade, high energy physics will be doing its work at the high energy frontier with Tevatron I and II, UNK, SLC, LEP I and II, and HERA. The opportunities for science presented by experiments at these facilities are very great, and it is to be hoped that the pressure for funding to construct the next generation facilities will not badly affect the operating budgets of the ones we now have or which will soon be turning on. 9 refs., 12 figs., 6 tabs.

  9. Application of artificial neural networks (ANNs) and genetic programming (GP) for prediction of drug release from solid lipid matrices.

    PubMed

    Güres, Sinan; Mendyk, Aleksander; Jachowicz, Renata; Dorożyński, Przemysław; Kleinebudde, Peter

    2012-10-15

    The aim of the present study was to develop a semi-empirical mathematical model, which is able to predict the release profiles of solid lipid extrudates of different dimensions. The development of the model was based on the application of ANNs and GP. ANNs' abilities to deal with multidimensional data were exploited. GP programming was used to determine the constants of the model function, a modified Weibull equation. Differently dimensioned extrudates consisting of diprophylline, tristearin and polyethylene glycol were produced by the use of a twin-screw extruder and their dissolution behaviour was studied. Experimentally obtained dissolution curves were compared to the calculated release profiles, derived from the semi-empirical mathematical model.

  10. Exacerbated inflammatory arthritis in response to hyperactive gp130 signalling is independent of IL-17A

    PubMed Central

    Jones, G W; Greenhill, C J; Williams, J O; Nowell, M A; Williams, A S; Jenkins, B J; Jones, S A

    2013-01-01

    Objective Interleukin (IL)-17A producing CD4 T-cells (TH-17 cells) are implicated in rheumatoid arthritis (RA). IL-6/STAT3 signalling drives TH-17 cell differentiation, and hyperactive gp130/STAT3 signalling in the gp130F/F mouse promotes exacerbated pathology. Conversely, STAT1-activating cytokines (eg, IL-27, IFN-γ) inhibit TH-17 commitment. Here, we evaluate the impact of STAT1 ablation on TH-17 cells during experimental arthritis and relate this to IL-17A-associated pathology. Methods Antigen-induced arthritis (AIA) was established in wild type (WT), gp130F/F mice displaying hyperactive gp130-mediated STAT signalling and the compound mutants gp130F/F:Stat1−/− and gp130F/F:Il17a−/− mice. Joint pathology and associated peripheral TH-17 responses were compared. Results Augmented gp130/STAT3 signalling enhanced TH-17 commitment in vitro and exacerbated joint pathology. Ablation of STAT1 in gp130F/F mice (gp130F/F:Stat1−/−) promoted the hyperexpansion of TH-17 cells in vitro and in vivo during AIA. Despite this heightened peripheral TH-17 cell response, disease severity and the number of joint-infiltrating T-cells were comparable with that of WT mice. Thus, gp130-mediated STAT1 activity within the inflamed synovium controls T-cell trafficking and retention. To determine the contribution of IL-17A, we generated gp130F/F:IL-17a−/− mice. Here, loss of IL-17A had no impact on arthritis severity. Conclusions Exacerbated gp130/STAT-driven disease in AIA is associated with an increase in joint infiltrating T-cells but synovial pathology is IL-17A independent. PMID:23894061

  11. Signaling Pathway of GP88 (Progranulin) in Breast Cancer Cells: Upregulation and Phosphorylation of c-myc by GP88/Progranulin in Her2-Overexpressing Breast Cancer Cells

    PubMed Central

    Kim, Wes E.; Yue, Binbin; Serrero, Ginette

    2015-01-01

    Her2 is a receptor tyrosine kinase overexpressed in 25% of breast tumors. We have shown that the 88 kDa autocrine growth and survival factor GP88 (progranulin) stimulated Her2 phosphorylation and proliferation and conferred Herceptin resistance in Her2-overexpressing cells. Herein, we report that GP88 stimulates c-myc phosphorylation and upregulates c-myc levels in Her2-overexpressing cells. c-myc phosphorylation and upregulation by GP88 were not observed in non-Her2-overexpressing breast cancer cells. c-myc activation was inhibited upon treatment with ERK, PI3 kinase, and c-src pathway inhibitors, U0126, LY294002, and PP2. GP88 also stimulated c-src phosphorylation, a known upstream regulator of c-myc. Thus, we describe here a signaling pathway for GP88 in Her2-overexpressing cells, with GP88 stimulating Src phosphorylation, followed by phosphorylation and upregulation of c-myc. These data would suggest that targeting GP88 could provide a novel treatment approach in breast cancer. PMID:27168723

  12. Protection against 17D yellow fever encephalitis in mice by passive transfer of monoclonal antibodies to the nonstructural glycoprotein gp48 and by active immunization with gp48.

    PubMed

    Schlesinger, J J; Brandriss, M W; Walsh, E E

    1985-10-01

    The protective capacity of antiviral antibodies has generally been considered to depend on their interactions with structural components of the virion. Here we report protection against lethal 17D yellow fever virus (YF) encephalitis of mice by passive administration of nonneutralizing monoclonal antibodies to a 17D YF-specified nonstructural glycoprotein, gp48, and by active immunization with purified gp48. Among five anti-gp48 monoclonal antibodies tested, two with high titer complement-fixing (CF) activity were protective, whereas three antibodies with little or no CF activity were not. The ability of antibodies to protect correlated with their ability to promote complement-mediated cytolysis (CMC) of 51Cr-labeled 17D YF-infected mouse neuroblastoma (Neuro 2a) cells. Purified gp48, prepared from lysates of 17D YF-infected Vero cells by immunoaffinity chromatography, was shown to bear both YF type-specific and flavivirus group-reactive determinants in a solid phase radioimmunoassay. Immunization of mice with purified gp48 resulted in solid protection in the absence of detectable anti-virion antibody, measured by neutralization and radioimmunoprecipitation assays. The results are consistent with plasma membrane expression of gp48 and susceptibility of 17D YF-infected neural cells to CMC, a possible mechanism of host defense in 17D YF encephalitis. Protection provided by immunization with gp48, which bears a group-reactive determinant and is highly conserved among flaviviruses, may have implications in regard to flavivirus vaccine design.

  13. 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.

  14. 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.

  15. The Superconducting Super Collider: A status report

    SciTech Connect

    Schwitters, R.F.

    1993-04-01

    The design of the Superconducting Super Collider (SSC) is briefly reviewed, including its key machine parameters. The scientific objectives are twofold: (1) investigation of high-mass, low-rate, rare phenomena beyond the standard model; and (2) investigation of processes within the domain of the standard model. Machine luminosity, a key parameter, is a function of beam brightness and current, and it must be preserved through the injector chain. Features of the various injectors are discussed. The superconducting magnet system is reviewed in terms of model magnet performance, including the highly successful Accelerator System String Test Various magnet design modifications are noted, reflecting minor changes in the collider arcs and improved installation procedures. The paper concludes with construction scenarios and priority issues for ensuring the earliest collider commissioning.

  16. 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.

  17. 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.

  18. Progress report on the SLAC Linear Collider

    SciTech Connect

    Kozanecki, W.

    1987-11-01

    In this paper we report on the status of the SLAC Linear Collider (SLC), the prototype of a new generation of colliding beam accelerators. This novel type of machine holds the potential of extending electron-positron colliding beam studies to center-of-mass (c.m.) energies far in excess of what is economically achievable with colliding beam storage rings. If the technical challenges posed by linear colliders are solvable at a reasonable cost, this new approach would provide an attractive alternative to electron-positron rings, where, because of rapidly rising synchrotron radiation losses, the cost and size of the ring increases with the square of the c.m. energy. In addition to its role as a test vehicle for the linear collider principle, the SLC aims at providing an abundant source of Z/sup 0/ decays to high energy physics experiments. Accordingly, two major detectors, the upgraded Mark II, now installed on the SLC beam line, and the state-of-the-art SLD, currently under construction, are preparing to probe the Standard Model at the Z/sup 0/ pole. The SLC project was originally funded in 1983. Since the completion of construction, we have been commissioning the machine to bring it up to a performance level adequate for starting the high energy physics program. In the remainder of this paper, we will discuss the status, problems and performance of the major subsystems of the SLC. We will conclude with a brief outline of the physics program, and of the planned enhancements to the capabilities of the machine. 26 refs., 7 figs.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Pharmacophore determination of a gp120 C terminal-derived anti-HIV peptide construct interfering with membrane fusion suggesting that processing of the gp120 C terminus is a prelude to fusion.

    PubMed

    Barbouche, R; Feyfant, E; Belhaj, B; Fenouillet, E

    2002-02-10

    A multiple antigen peptide [CLIV; (PTKAKRR1VVQREKR2)4-K2-K-betaA] from the C terminus of the gp120 subunit of HIV Env inhibits Env-mediated cell-to-cell fusion through direct interference with the process (Virology 2000;273:169). We have examined various CLIV analogs using a cell-to-cell fusion assay, receptor binding assays, and molecular modeling to further address the characteristics of the peptide responsible for its anti-HIV activity. We show that (1) CLIV does not interfere with Env binding to CD4 and does not interact with the binding site of Env on CXCR4; (2) CLIV does not inhibit protease activities already reported to play a role in fusion; and (3) the pharmacophore is composed of cleavage site1 with amino acid residues at its C terminal end. Based on our data and on the literature, we propose that CLIV interferes with processing of the gp120 C terminus at site1 by the lymphocyte surface after CD4 binding. Our hypothesis implies that the cleavage region of Env is submitted to a stepwise processing including the known intracellular cleavage of gp160 at site2 in order to set the activation of the fusion peptide and a yet unexplored cleavage at site1 by the target cell surface that triggers fusion.

  4. Top quark studies at hadron colliders

    SciTech Connect

    Sinervo, P.K.; CDF Collaboration

    1996-08-01

    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 {ital b} quark jets in candidate events. The most recent measurements of top quark properties by the CDF and D{null} 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.

  5. 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.

  6. 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.

  7. FFAG Designs for Muon Collider Acceleration

    SciTech Connect

    Berg, J. Scott

    2014-01-13

    I estimate FFAG parameters for a muon collider with a 70mm longitudinal emittance. I do not discuss the lower emittance beam for a Higgs factory. I produce some example designs, giving only parameters relevant to estimating cost and performance. The designs would not track well, but the parameters of a good design will be close to those described. I compare these cost estimates to those for a fast-ramping synchrotron and a recirculating linear accelerator. I conclude that FFAGs do not appear to be cost-effective for the large longitudinal emittance in a high-energy muon collider.

  8. 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.

  9. A study into the effectiveness of unqualified GP assistants.

    PubMed

    Philip, Marilyn; Turnbull, Betty

    This article aims to address the potential shortfall in care provision offered by general practitioners (GPs) resulting from pending retirement and the retention and recruitment crisis. An educational module was developed that offered both theory and practise to unqualified general practice assistants. The module content was determined following discussion with local GPs. A small qualitative study of six students was carried out to review efficacy of participants in their new role. Using a grounded theory approach, participant and supervisor views of course content and delivery, role preparation diversity were analysed and compared. Tape-recorded interviews were conducted and analysis carried out employing the constant comparative method. Data were coded and emergent themes categorized. Overall, participants agreed that the module had strengthened their knowledge, added new skills, heightened their job satisfaction, added significant diversity to their role and enhanced their employability potential. Five participants communicated that they were more confident in performing clinical skills and advising health improvement techniques. Supervisors also reported that participants displayed a more competent and professional approach to health care, which was complementary to the role of the GP and practice nurse. Ultimately this allowed both GP and practice nurse to focus on dealing with chronic illness targets, as required in the new directive (Scottish Executive, 2004).

  10. Crystallization of the carboxy-terminal region of the bacteriophage T4 proximal long tail fibre protein gp34.

    PubMed

    Granell, Meritxell; Namura, Mikiyoshi; Alvira, Sara; Garcia-Doval, Carmela; Singh, Abhimanyu K; Gutsche, Irina; van Raaij, Mark J; Kanamaru, Shuji

    2014-07-01

    The phage-proximal part of the long tail fibres of bacteriophage T4 consists of a trimer of the 1289 amino-acid gene product 34 (gp34). Different carboxy-terminal parts of gp34 have been produced and crystallized. Crystals of gp34(726-1289) diffracting X-rays to 2.9 Å resolution, crystals of gp34(781-1289) diffracting to 1.9 Å resolution and crystals of gp34(894-1289) diffracting to 3.0 and 2.0 Å resolution and belonging to different crystal forms were obtained. Native data were collected for gp34(726-1289) and gp34(894-1289), while single-wavelength anomalous diffraction data were collected for selenomethionine-containing gp34(781-1289) and gp34(894-1289). For the latter, high-quality anomalous signal was obtained.

  11. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies

    PubMed Central

    Sanders, Rogier W.; Derking, Ronald; Cupo, Albert; Julien, Jean-Philippe; Yasmeen, Anila; de Val, Natalia; Kim, Helen J.; Blattner, Claudia; de la Peña, Alba Torrents; Korzun, Jacob; Golabek, Michael; de los Reyes, Kevin; Ketas, Thomas J.; van Gils, Marit J.; King, C. Richter; Wilson, Ian A.; Ward, Andrew B.; Klasse, P. J.; Moore, John P.

    2013-01-01

    A desirable but as yet unachieved property of a human immunodeficiency virus type 1 (HIV-1) vaccine candidate is the ability to induce broadly neutralizing antibodies (bNAbs). One approach to the problem is to create trimeric mimics of the native envelope glycoprotein (Env) spike that expose as many bNAb epitopes as possible, while occluding those for non-neutralizing antibodies (non-NAbs). Here, we describe the design and properties of soluble, cleaved SOSIP.664 gp140 trimers based on the subtype A transmitted/founder strain, BG505. These trimers are highly stable, more so even than the corresponding gp120 monomer, as judged by differential scanning calorimetry. They are also homogenous and closely resemble native virus spikes when visualized by negative stain electron microscopy (EM). We used several techniques, including ELISA and surface plasmon resonance (SPR), to determine the relationship between the ability of monoclonal antibodies (MAbs) to bind the soluble trimers and neutralize the corresponding virus. In general, the concordance was excellent, in that virtually all bNAbs against multiple neutralizing epitopes on HIV-1 Env were highly reactive with the BG505 SOSIP.664 gp140 trimers, including quaternary epitopes (CH01, PG9, PG16 and PGT145). Conversely, non-NAbs to the CD4-binding site, CD4-induced epitopes or gp41ECTO did not react with the trimers, even when their epitopes were present on simpler forms of Env (e.g. gp120 monomers or dissociated gp41 subunits). Three non-neutralizing MAbs to V3 epitopes did, however, react strongly with the trimers but only by ELISA, and not at all by SPR and to only a limited extent by EM. These new soluble trimers are useful for structural studies and are being assessed for their performance as immunogens. PMID:24068931

  12. HIV-1 gp41 Core with Exposed Membrane-Proximal External Region Inducing Broad HIV-1 Neutralizing Antibodies

    PubMed Central

    Zhou, Leilei; Xu, Liling; Jiang, Shibo; Chen, Ying-hua

    2011-01-01

    The membrane-proximal external region (MPER) of the HIV-1 gp41 consists of epitopes for the broadly cross-neutralizing monoclonal antibodies 2F5 and 4E10. However, antigens containing the linear sequence of these epitopes are unable to elicit potent and broad neutralizing antibody responses in vaccinated hosts, possibly because of inappropriate conformation of these epitopes. Here we designed a recombinant antigen, designated NCM, which comprises the N- and C-terminal heptad repeats that can form a six-helix bundle (6HB) core and the MPER domain of gp41. Two mutations (T569A and I675V) previously reported to expose the neutralization epitopes were introduced into NCM to generate mutants named NCM(TA), NCM(IV), and NCM(TAIV). Our results showed that NCM and its mutants could react with antibodies specific for 6HB and MPER of gp41, suggesting that these antigens are in the form of a trimer of heterodimer (i.e., 6HB) with three exposed MPER tails. Antigen with double mutations, NCM(TAIV), elicited much stronger antibody response in rabbits than immunogens with single mutation, NCM(TA) and NCM(IV), or no mutation, NCM. The purified MPER-specific antibodies induced by NCM(TAIV) exhibited broad neutralizing activity, while the purified 6HB-specific antibodies showed no detectable neutralizing activity. Our recombinant antigen design supported by an investigation of its underlying molecular mechanisms provides a strong scientific platform for the discovery of a gp41 MPER-based AIDS vaccine. PMID:21483871

  13. 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

  14. Delegation of GP-home visits to qualified practice assistants: assessment of economic effects in an ambulatory healthcare centre

    PubMed Central

    2010-01-01

    Background Against the background of a decreasing number of general practitioners (GPs) in rural regions in Germany, the AGnES-concept (AGnES = GP-supporting, community-based, e-health-assisted, systemic intervention) supports the delegation of regular GP-home visits to qualified practice assistants. The concept was implemented and evaluated in different model projects in Germany. To explore the economic effects of this concept, the development of the number of home visits in an ambulatory healthcare centre was analysed and compared with the number of home visits in the surrounding county. Methods Information about GP-home visits was derived from reimbursement data of the ambulatory healthcare centre and a statutory health insurance. Information about home visits conducted by AGnES-practice assistants was collected from the project documentation over a time period of 12 consecutive quarter years, four quarter years before the beginning of the project and 8 quarter years while the project was implemented, considering background temporal trends on the population level in the study region. Results Within the ambulatory healthcare centre, the home visits by the GPs significantly decreased, especially the number of medically urgent home visits. However, the overall rate of home visits (conducted by the GPs and the AGnES-practice assistants together) did not change significantly after implementation of the AGnES-concept. In the surrounding county, the home visit rates of the GPs were continuous; the temporal patterns were approximately equal for both usual and urgent home visits. Conclusion The results of the analyses show that the support by AGnES-practice assistants led to a decrease of GP-home visits rather than an induction of additional home visits by the AGnES-practice assistants. The most extended effect is related to the medically urgent home visits rather than to the usual home visits. PMID:20529307

  15. 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.

  16. Mammalian production of an isotopically enriched outer domain of the HIV-1 gp120 glycoprotein for NMR spectroscopy.

    PubMed

    Sastry, Mallika; Xu, Ling; Georgiev, Ivelin S; Bewley, Carole A; Nabel, Gary J; Kwong, Peter D

    2011-07-01

    NMR spectroscopic characterization of the structure or the dynamics of proteins generally requires the production of samples isotopically enriched in (15)N, (13)C, or (2)H. The bacterial expression systems currently in use to obtain isotopic enrichment, however, cannot produce a number of eukaryotic proteins, especially those that require post-translational modifications such as N-linked glycosylation for proper folding or activity. Here, we report the use of an adenovirus vector-based mammalian expression system to produce isotopically enriched (15)N or (15)N/(13)C samples of an outer domain variant of the HIV-1 gp120 envelope glycoprotein with 15 sites of N-linked glycosylation. Yields for the (15)N- and (15)N/(13)C-labeled gp120s after affinity chromatography were 45 and 44 mg/l, respectively, with an average of over 80% isotope incorporation. Recognition of the labeled gp120 by cognate antibodies that recognize complex epitopes showed affinities comparable to the unlabeled protein. NMR spectra, including (1)H-(15)N and (1)H-(13)C HSQCs, (15)N-edited NOESY-HSQC, and 3D HNCO, were of high quality, with signal-to-noise consistent with an efficient level of isotope incorporation, and with chemical shift dispersion indicative of a well-folded protein. The exceptional protein yields, good isotope incorporation, and ability to obtain well-folded post-translationally modified proteins make this mammalian system attractive for the production of isotopically enriched eukaryotic proteins for NMR spectroscopy.

  17. Targeted gene deletion of Leishmania major genes encoding developmental stage-specific leishmanolysin (GP63).

    PubMed

    Joshi, P B; Sacks, D L; Modi, G; McMaster, W R

    1998-02-01

    The major surface glycoprotein of Leishmania major is a zinc metalloproteinase of 63 kDa referred to as leishmanolysin or GP63, which is encoded by a family of seven genes. Targeted gene replacement was used to delete gp63 genes 1-6 encoding the highly expressed promastigote and constitutively expressed GP63. In the L. major homozygous mutants deficient in gp63 genes 1-6, there was no expression of GP63 as detected by reverse transcription-polymerase chain reaction (RT-PCR) or fluorescent staining in promastigotes from the procyclic stage (logarithmic growth phase). The remaining L. major gP63 gene 7 was shown to be developmentally regulated, as it was expressed exclusively in infectious metacyclic stage (late stationary growth phase) promastigotes and in lesion amastigotes. The gp63 genes 1-6-deficient mutants showed increased sensitivity to complement-mediated lysis. The sensitivity to lysis was greater in procyclics than in metacyclics when compared with the equivalent wild-type stages. Increased resistance of the mutant metacyclic promastigotes correlated with the expression of gp63 gene 7 and was restored to the same levels as wild-type promastigotes by transfection with gp63 gene 1. Thus, expression of GP63 is clearly involved in conferring resistance to complement-mediated lysis. The L. major GP63 1-6 mutants were capable of infecting mouse macrophages and differentiating into amastigotes. Similar levels of infection and subsequent intracellular survival were observed when mouse macrophages were infected in vitro with wild type, GP63 1-6 mutants and mutants transfected with gp63 gene 1. The GP63 1-6 mutants were capable of lesion formation in BALB/c mice and, thus, gp63 genes 1-6 do not play a role in the survival of the parasite within mouse macrophages. The role of gp63 genes 1-6 in parasite development within the sandfly vector was studied. GP63 1-6 mutants grew normally in the blood-engorged midgut of both Phlebotomus argentipes and P. papatasi However

  18. Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Human Monoclonal Antibody That Recognizes a Novel Conformational Epitope on gp41 and Lacks Reactivity against Self-Antigens ▿

    PubMed Central

    Zhang, Mei-Yun; Vu, Bang K.; Choudhary, Anil; Lu, Hong; Humbert, Michael; Ong, Helena; Alam, Munir; Ruprecht, Ruth M.; Quinnan, Gerald; Jiang, Shibo; Montefiori, David C.; Mascola, John R.; Broder, Christopher C.; Haynes, Barton F.; Dimitrov, Dimiter S.

    2008-01-01

    Broadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear epitopes in the membrane-proximal external region (MPER) and bind to cardiolipin and several other autoantigens. It has been hypothesized that, because of such reactivity to self-antigens, elicitation of 2F5 and 4E10 and similar antibodies by vaccine immunogens based on the MPER could be affected by tolerance mechanisms. Here, we report the identification and characterization of a novel anti-gp41 monoclonal antibody, designated m44, which neutralized most of the 22 HIV type 1 (HIV-1) primary isolates from different clades tested in assays based on infection of peripheral blood mononuclear cells by replication-competent virus but did not bind to cardiolipin and phosphatidylserine in an enzyme-linked immunosorbent assay and a Biacore assay nor to any protein or DNA autoantigens tested in Luminex assays. m44 bound to membrane-associated HIV-1 envelope glycoproteins (Envs), to recombinant Envs lacking the transmembrane domain and cytoplasmic tail (gp140s), and to gp41 structures containing five-helix bundles and six-helix bundles, but not to N-heptad repeat trimers, suggesting that the C-heptad repeat is involved in m44 binding. In contrast to 2F5, 4E10, and Z13, m44 did not bind to any significant degree to denatured gp140 and linear peptides derived from gp41, suggesting a conformational nature of the epitope. This is the first report of a gp41-specific cross-reactive HIV-1-neutralizing human antibody that does not have detectable reactivity to autoantigens. Its novel conserved conformational epitope on gp41 could be helpful in the design of vaccine immunogens and as a target for therapeutics. PMID:18480433

  19. Selective Interactions of Polyanions with Basic Surfaces on Human Immunodeficiency Virus Type 1 gp120

    PubMed Central

    Moulard, Maxime; Lortat-Jacob, Hugues; Mondor, Isabelle; Roca, Guillaume; Wyatt, Richard; Sodroski, Joseph; Zhao, Lu; Olson, William; Kwong, Peter D.; Sattentau, Quentin J.

    2000-01-01

    It is well established that the gp120 V3 loop of T-cell-line-adapted human immunodeficiency virus type 1 (HIV-1) binds both cell-associated and soluble polyanions. Virus infectivity is increased by interactions between HIV-1 and heparan sulfate proteoglycans on some cell types, and soluble polyanions such as heparin and dextran sulfate neutralize HIV-1 in vitro. However, the analysis of gp120-polyanion interactions has been limited to T-cell-line-adapted, CXCR4-using virus and virus-derived gp120, and the polyanion binding ability of gp120 regions other than the V3 loop has not been addressed. Here we demonstrate by monoclonal-antibody inhibition, labeled heparin binding, and surface plasmon resonance studies that a second site, most probably corresponding to the newly defined, highly conserved coreceptor binding region on gp120, forms part of the polyanion binding surface. Consistent with the binding of polyanions to the coreceptor binding surface, dextran sulfate interfered with the gp120-CXCR4 association while having no detectable effect on the gp120-CD4 interaction. The interaction between polyanions and X4 or R5X4 gp120 was readily detectable, whereas weak or undetectable binding was observed with R5 gp120. Analysis of mutated forms of X4 gp120 demonstrated that the V3 loop is the major determinant for polyanion binding whereas other regions, including the V1/V2 loop structure and the NH2 and COOH termini, exert a more subtle influence. A molecular model of the electrostatic potential of the conserved coreceptor binding region confirmed that it is basic but that the overall charge on this surface is dominated by the V3 loop. These results demonstrate a selective interaction of gp120 with polyanions and suggest that the conserved coreceptor binding surface may present a novel and conserved target for therapeutic intervention. PMID:10644368

  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. 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…

  2. From the LHC to future colliders

    SciTech Connect

    De Roeck, A.; Assamagan, K.; Ellis, J.; Grojean, C.; Heinemeyer, S.; Jakobs, K.; Weiglien, G.; Well, J.; Azuelos, G.; Dawson, S.; Gripaios, B.; Han, T.; Hewett, J.; Lancaster, M.; Mariotti, C.; Moortgat, F.; Moortgat-Pick, G.; Polesello, G.; Riemann, S.; Schumacher, M.; Bechtle, P.; Carena, M.; Chachamis, G.; Chen, K.F.; De Curtis, S.; Desch, K.; Dittmar, M.; Dreiner, H.; Duhrssen, M.; Foster, B.; Frandsen, M.T.; Giammanco, A.; Godbole, R.; Gopalakrishna, S.; Govoni, P.; Gunion, J.; Hollik, W.; Hou, W.S.; Isidori, G.; Juste, A.; Kalinowski, J.; Korytov, A.; Kou, E.; Kraml, S.; Krawczyk, M.; Martin, A.; Milstead, D.; Morton-Thurtle, V.; Moenig, K.; Mele, B.; Ozcan, E.; Pieri, M.; Plehn, T.; Reina, L.; Richter-Was, E.; Rizzo, T.; Rolbiecki, K.; Sannino, F.; Schram, M.; Smillie, J.; Sultansoy, S.; Tattersall, J.; Uwer, P., Webber, B.; and Wienemann, P.

    2010-03-02

    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, the Working 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.

  3. Recent results from proton-antiproton colliders

    SciTech Connect

    Geer, S. . High Energy Physics Lab.)

    1990-03-01

    New results from the CERN and Fermilab proton-antiproton colliders are summarised. The areas covered are jet physics, direct photon production, W and Z production and decay, heavy flavor production, the search for the top quark, and the search for more exotic phenomena. 46 refs., 20 figs., 4 tabs.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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…

  10. Tau physics at p{bar p} colliders

    SciTech Connect

    Konigsberg, J.

    1993-01-01

    Tau detection techniques in hadron colliders are discussed together with the measurements and searches performed so far. We also underline the importance tau physics has in present and future collider experiments.

  11. 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

  12. Identification of two T-cell epitopes on the candidate Epstein-Barr virus vaccine glycoprotein gp340 recognized by CD4+ T-cell clones.

    PubMed Central

    Wallace, L E; Wright, J; Ulaeto, D O; Morgan, A J; Rickinson, A B

    1991-01-01

    Current efforts to develop an Epstein-Barr virus subunit vaccine are based on the major envelope glycoprotein gp340. Given the central role of CD4+ T cells in regulating immune responses to subunit vaccine antigens, the present study has begun the work of identifying linear epitopes which are recognized by human CD4+ T cells within the 907-amino-acid sequence of gp340. A panel of gp340-specific CD4+ T-cell clones from an Epstein-Barr virus-immune donor were first assayed for their proliferative responses to a series of truncated gp340 molecules expressed from recombinant DNA vectors in rat GH3 cells, by using an autologous B lymphoblastoid cell line as a source of antigen-presenting cells. The first four T-cell clones analyzed all responded to a truncated form of gp340 which contained only the first 260 N-terminal amino acids. These clones were subsequently screened for responses to each of a panel of overlapping synthetic peptides (15-mers) corresponding to the primary amino acid sequence of the first 260 N-terminal amino acids of gp340. One clone (CG2.7) responded specifically to peptides from the region spanning amino acids 61 to 81, while three other clones (CG5.15, CG5.24, and CG5.36) responded specifically to peptides from the region spanning amino acids 163 to 183. Work with individual peptides from these regions allowed finer mapping of the T-cell epitopes and also revealed the highly dose-dependent nature of peptide-induced responses, with inhibitory effects apparent when the most antigenic peptides were present at supraoptimal concentrations. Experiments using homozygous typing B lymphoblastoid cell lines as antigen-presenting cells showed that the T-cell clones with different epitope specificities were restricted through different HLA class II antigens; clone CG2.7 recognized epitope 61-81 in the context of HLA DRw15, whereas clones CG5.15, CG5.24, and CG5.36 recognized epitope 163-183 in the context of HLA DRw11. The present protocol therefore makes a

  13. Towards a Future Linear Collider and The Linear Collider Studies at CERN

    ScienceCinema

    None

    2016-07-12

    During the week 18-22 October, more than 400 physicists will meet at CERN and in the CICG (International Conference Centre Geneva) to review the global progress towards a future linear collider. The 2010 International Workshop on Linear Colliders will study the physics, detectors and accelerator complex of a linear collider covering both the CLIC and ILC options. Among the topics presented and discussed will be the progress towards the CLIC Conceptual Design Report in 2011, the ILC Technical Design Report in 2012, physics and detector studies linked to these reports, and an increasing numbers of common working group activities. The seminar will give an overview of these topics and also CERN’s linear collider studies, focusing on current activities and initial plans for the period 2011-16. n.b: The Council Chamber is also reserved for this colloquium with a live transmission from the Main Auditorium.

  14. Multimerized HIV-gp41-derived peptides as fusion inhibitors and vaccines.

    PubMed

    Nomura, Wataru; Mizuguchi, Takaaki; Tamamura, Hirokazu

    2016-11-01

    To date, several antigens based on the amino-terminal leucine/isoleucine heptad repeat (NHR) region of an HIV-1 envelope protein gp41 and fusion inhibitors based on the carboxy-terminal leucine/isoleucine heptad repeat (CHR) region of gp41 have been reported. We have developed a synthetic antigen targeting the membrane-fusion mechanism of HIV-1. This uses a template designed with C3-symmetric linkers and mimics the trimeric form of the NHR-derived peptide N36. The antiserum obtained by immunization of the N36 trimeric antigen binds preferentially to the N36 trimer and blocks HIV-1 infection effectively, compared with the antiserum obtained by immunization of the N36 monomer. Using another template designed with different C3-symmetric linkers, we have also developed a synthetic peptide mimicking the trimeric form of the CHR-derived peptide C34, with ∼100 times the inhibitory activity against the HIV-1 fusion mechanism than that of the monomer C34 peptide. A dimeric derivative of C34 has potent inhibitory activity at almost the same levels as this C34 trimer mimic, suggesting that presence of a dimeric form of C34 is structurally critical for fusion inhibitors. As examples of rising mid-size drugs, this review describes an effective strategy for the design of HIV vaccines and fusion inhibitors based on a relationship with the native structure of proteins involved in HIV fusion mechanisms. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 622-628, 2016.

  15. High-brightness injectors for hadron colliders

    SciTech Connect

    Wangler, T.P.

    1990-01-01

    The counterrotating beams in collider rings consist of trains of beam bunches with N{sub B} particles per bunch, spaced a distance S{sub B} apart. When the bunches collide, the interaction rate is determined by the luminosity, which is defined as the interaction rate per unit cross section. For head-on collisions between cylindrical Gaussian beams moving at speed {beta}c, the luminosity is given by L = N{sub B}{sup 2}{beta}c/4{pi}{sigma}{sup 2}S{sub B}, where {sigma} is the rms beam size projected onto a transverse plane (the two transverse planes are assumed identical) at the interaction point. This beam size depends on the rms emittance of the beam and the focusing strength, which is a measure of the 2-D phase-space area in each transverse plane, and is defined in terms of the second moments of the beam distribution. Our convention is to use the rms normalized emittance, without factors of 4 or 6 that are sometimes used. The quantity {tilde {beta}} is the Courant-Synder betatron amplitude function at the interaction point, a characteristic of the focusing lattice and {gamma} is the relativistic Lorentz factor. Achieving high luminosity at a given energy, and at practical values of {tilde {beta}} and S{sub B}, requires a large value for the ratio N{sub B}{sup 2}/{var epsilon}{sub n}, which implies high intensity and small emittance. Thus, specification of the luminosity sets the requirements for beam intensity and emittance, and establishes the requirements on the performance of the injector to the collider ring. In general, for fixed N{sub B}, the luminosity can be increased if {var epsilon}{sub n} can be reduced. The minimum emittance of the collider is limited by the performance of the injector; consequently the design of the injector is of great importance for the ultimate performance of the collider.

  16. Muon capture for the front end of a muon collider

    SciTech Connect

    Neuffer, D.; Yoshikawa, C.; /MUONS Inc., Batavia

    2011-03-01

    We discuss the design of the muon capture front end for a {mu}{sup +}-{mu}{sup -} Collider. In the front end, a proton bunch on a target creates secondary pions that drift into a capture transport channel, decaying into muons. A sequence of rf cavities forms the resulting muon beams into strings of bunches of differing energies, aligns the bunches to (nearly) equal central energies, and initiates ionization cooling. The muons are then cooled and accelerated to high energy into a storage ring for high-energy high luminosity collisions. Our initial design is based on the somewhat similar front end of the International Design Study (IDS) neutrino factory.

  17. Approaches to Beam Stabilization in X-Band Linear Colliders

    SciTech Connect

    Frisch, Josef; Hendrickson, Linda; Himel, Thomas; Markiewicz, Thomas; Raubenheimer, Tor; Seryi, Andrei; Burrow, Philip; Molloy, Stephen; White, Glen; /Queen Mary U. of London

    2006-09-05

    In order to stabilize the beams at the interaction point, the X-band linear collider proposes to use a combination of techniques: inter-train and intra-train beam-beam feedback, passive vibration isolation, and active vibration stabilization based on either accelerometers or laser interferometers. These systems operate in a technologically redundant fashion: simulations indicate that if one technique proves unusable in the final machine, the others will still support adequate luminosity. Experiments underway for all of these technologies have already demonstrated adequate performance.

  18. Double diffraction dissociation at the Fermilab Tevatron collider.

    PubMed

    Affolder, T; Akimoto, H; Akopian, A; Albrow, M G; Amaral, P; Amidei, D; Anikeev, K; Antos, J; Apollinari, G; Arisawa, T; Asakawa, T; Ashmanskas, W; Azfar, F; Azzi-Bacchetta, P; Bacchetta, N; Bailey, M W; Bailey, S; de Barbaro, P; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Barone, M; Bauer, G; Bedeschi, F; Belforte, S; Bell, W H; Bellettini, G; Bellinger, J; Benjamin, D; Bensinger, J; Beretvas, A; Berge, J P; Berryhill, J; Bhatti, A; Binkley, M; Bisello, D; Bishai, M; Blair, R E; Blocker, C; Bloom, K; Blumenfeld, B; Blusk, S R; Bocci, A; Bodek, A; Bokhari, W; Bolla, G; Bonushkin, Y; Borras, K; Bortoletto, D; Boudreau, J; Brandl, A; van Den Brink, S; Bromberg, C; Brozovic, M; Bruner, N; Buckley-Geer, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Byon-Wagner, A; Byrum, K L; Cabrera, S; Calafiura, P; Campbell, M; Carithers, W; Carlson, J; Carlsmith, D; Caskey, W; Castro, A; Cauz, D; Cerri, A; Chan, A W; Chang, P S; Chang, P T; Chapman, J; Chen, C; Chen, Y C; Cheng, M T; Chertok, M; Chiarelli, G; Chirikov-Zorin, I; Chlachidze, G; Chlebana, F; Christofek, L; Chu, M L; Chung, Y S; Ciobanu, C I; Clark, A G; Connolly, A; Convery, M; Conway, J; Cordelli, M; Cranshaw, J; Cropp, R; Culbertson, R; Dagenhart, D; D'Auria, S; DeJongh, F; Dell'Agnello, S; Dell'Orso, M; Demortier, L; Deninno, M; Derwent, P F; Devlin, T; Dittmann, J R; Dominguez, A; Donati, S; Done, J; D'Onofrio, M; Dorigo, T; Eddy, N; Einsweiler, K; Elias, J E; Engels, E; Erbacher, R; Errede, D; Errede, S; Fan, Q; Feild, R G; Fernandez, J P; Ferretti, C; Field, R D; Fiori, I; Flaugher, B; Foster, G W; Franklin, M; Freeman, J; Friedman, J; Fukui, Y; Furic, I; Galeotti, S; Gallas, A; Gallinaro, M; Gao, T; Garcia-Sciveres, M; Garfinkel, A F; Gatti, P; Gay, C; Gerdes, D W; Giannetti, P; Glagolev, V; Glenzinski, D; Gold, M; Goldstein, J; Gorelov, I; Goshaw, A T; Gotra, Y; Goulianos, K; Green, C; Grim, G; Gris, P; Groer, L; Grosso-Pilcher, C; Guenther, M; Guillian, G; Guimaraes Da Costa, J; Haas, R M; Haber, C; Hahn, S R; Hall, C; Handa, T; Handler, R; Hao, W; Happacher, F; Hara, K; Hardman, A D; Harris, R M; Hartmann, F; Hatakeyama, K; Hauser, J; Heinrich, J; Heiss, A; Herndon, M; Hill, C; Hoffman, K D; Holck, C; Hollebeek, R; Holloway, L; Hughes, R; Huston, J; Huth, J; Ikeda, H; Incandela, J; Introzzi, G; Iwai, J; Iwata, Y; James, E; Jones, M; Joshi, U; Kambara, H; Kamon, T; Kaneko, T; Karr, K; Kasha, H; Kato, Y; Keaffaber, T A; Kelley, K; Kelly, M; Kennedy, R D; Kephart, R; Khazins, D; Kikuchi, T; Kilminster, B; Kim, B J; Kim, D H; Kim, H S; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kirby, M; Kirk, M; Kirsch, L; Klimenko, S; Koehn, P; Kondo, K; Konigsberg, J; Korn, A; Korytov, A; Kovacs, E; Kroll, J; Kruse, M; Kuhlmann, S E; Kurino, K; Kuwabara, T; Laasanen, A T; Lai, N; Lami, S; Lammel, S; Lancaster, J; Lancaster, M; Lander, R; Latino, G; LeCompte, T; Lee, A M; Lee, K; Leone, S; Lewis, J D; Lindgren, M; Liss, T M; Liu, J B; Liu, Y C; Litvintsev, D O; Lobban, O; Lockyer, N; Loken, J; Loreti, M; Lucchesi, D; Lukens, P; Lusin, S; Lyons, L; Lys, J; Madrak, R; Maeshima, K; Maksimovic, P; Malferrari, L; Mangano, M; Mariotti, M; Martignon, G; Martin, A; Matthews, J A; Mayer, J; Mazzanti, P; McFarland, K S; McIntyre, P; McKigney, E; Menguzzato, M; Menzione, A; Mesropian, C; Meyer, A; Miao, T; Miller, R; Miller, J S; Minato, H; Miscetti, S; Mishina, M; Mitselmakher, G; Moggi, N; Moore, E; Moore, R; Morita, Y; Moulik, T; Mulhearn, M; Mukherjee, A; Muller, T; Munar, A; Murat, P; Murgia, S; Nachtman, J; Nagaslaev, V; Nahn, S; Nakada, H; Nakano, I; Nelson, C; Nelson, T; Neu, C; Neuberger, D; Newman-Holmes, C; Ngan, C Y; Niu, H; Nodulman, L; Nomerotski, A; Oh, S H; Oh, Y D; Ohmoto, T; Ohsugi, T; Oishi, R; Okusawa, T; Olsen, J; Orejudos, W; Pagliarone, C; Palmonari, F; Paoletti, R; Papadimitriou, V; Partos, D; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pescara, L; Phillips, T J; Piacentino, G; Pitts, K T; Pompos, A; Pondrom, L; Pope, G; Popovic, M; Prokoshin, F; Proudfoot, J; Ptohos, F; Pukhov, O; Punzi, G; Rakitine, A; Reher, D; Reichold, A; Ribon, A; Riegler, W; Rimondi, F; Ristori, L; Riveline, M; Robertson, W J; Robinson, A; Rodrigo, T; Rolli, S; Rosenson, L; Roser, R; Rossin, R; Roy, A; Ruiz, A; Safonov, A; St Denis, R; Sakumoto, W K; Saltzberg, D; Sanchez, C; Sansoni, A; Santi, L; Sato, H; Savard, P; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Scodellaro, L; Scott, A; Scribano, A; Segler, S; Seidel, S; Seiya, Y; Semenov, A; Semeria, F; Shah, T; Shapiro, M D; Shepard, P F; Shibayama, T; Shimojima, M; Shochet, M; Sidoti, A; Siegrist, J; Sill, A; Sinervo, P; Singh, P; Slaughter, A J; Sliwa, K; Smith, C; Snider, F D; Solodsky, A; Spalding, J; Speer, T; Sphicas, P; Spinella, F; Spiropulu, M; Spiegel, L; Steele, J; Stefanini, A; Strologas, J; Strumia, F; Stuart, D; Sumorok, K; Suzuki, T; Takano, T; Takashima, R; Takikawa, K; Tamburello, P; Tanaka, M; Tannenbaum, B; Tecchio, M; Tesarek, R; Teng, P K; Terashi, K; Tether, S; Thompson, A S; Thurman-Keup, R; Tipton, P; Tkaczyk, S; Toback, D; Tollefson, K; Tollestrup, A; Tonelli, D; Toyoda, H; Trischuk, W; de Troconiz, J F; Tseng, J; Turini, N; Ukegawa, F; Vaiciulis, T; Valls, J; Vejcik, S; Velev, G; Vidal, R; Vila, I; Vilar, R; Volobouev, I; Vucinic, D; Wagner, R G; Wagner, R L; Wallace, N B; Wang, C; Wang, M J; Ward, B; Waschke, S; Watanabe, T; Waters, D; Watts, T; Webb, R; Wenzel, H; Wester, W C; Wicklund, A B; Wicklund, E; Wilkes, T; Williams, H H; Wilson, P; Winer, B L; Winn, D; Wolbers, S; Wolinski, D; Wolinski, J; Wolinski, S; Worm, S; Wu, X; Wyss, J; Yagil, A; Yao, W; Yeh, G P; Yeh, P; Yoh, J; Yosef, C; Yoshida, T; Yu, I; Yu, S; Yu, Z; Zanetti, A; Zetti, F; Zucchelli, S

    2001-10-01

    We present results from a measurement of double diffraction dissociation in pp collisions at the Fermilab Tevatron collider. The production cross section for events with a central pseudorapidity gap of width Deltaeta(0)>3 (overlapping eta = 0) is found to be 4.43+/-0.02(stat)+/-1.18(syst) mb [ 3.42+/-0.01(stat)+/-1.09(syst) mb] at square root of (s) = 1800[630] GeV. Our results are compared with previous measurements and with predictions based on Regge theory and factorization.

  19. 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.

  20. Neutrino Factory and Muon Collider Collaboration R and D Program

    SciTech Connect

    Zisman, M.S.

    2000-07-01

    The Neutrino Factory and Muon Collider Collaboration (MC) comprises some 140 scientists and engineers located at U.S. National Laboratories and Universities, and at a number of non-U.S. research institutions. In the past year, the MC R and D program has shifted its focus mainly toward the design issues related to the development of a Neutrino Factory based on a muon storage ring. In this paper the status of the various R and D activities is described, and future plans are outlined.

  1. Double diffraction dissociation at the Fermilab Tevatron collider.

    PubMed

    Affolder, T; Akimoto, H; Akopian, A; Albrow, M G; Amaral, P; Amidei, D; Anikeev, K; Antos, J; Apollinari, G; Arisawa, T; Asakawa, T; Ashmanskas, W; Azfar, F; Azzi-Bacchetta, P; Bacchetta, N; Bailey, M W; Bailey, S; de Barbaro, P; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Barone, M; Bauer, G; Bedeschi, F; Belforte, S; Bell, W H; Bellettini, G; Bellinger, J; Benjamin, D; Bensinger, J; Beretvas, A; Berge, J P; Berryhill, J; Bhatti, A; Binkley, M; Bisello, D; Bishai, M; Blair, R E; Blocker, C; Bloom, K; Blumenfeld, B; Blusk, S R; Bocci, A; Bodek, A; Bokhari, W; Bolla, G; Bonushkin, Y; Borras, K; Bortoletto, D; Boudreau, J; Brandl, A; van Den Brink, S; Bromberg, C; Brozovic, M; Bruner, N; Buckley-Geer, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Byon-Wagner, A; Byrum, K L; Cabrera, S; Calafiura, P; Campbell, M; Carithers, W; Carlson, J; Carlsmith, D; Caskey, W; Castro, A; Cauz, D; Cerri, A; Chan, A W; Chang, P S; Chang, P T; Chapman, J; Chen, C; Chen, Y C; Cheng, M T; Chertok, M; Chiarelli, G; Chirikov-Zorin, I; Chlachidze, G; Chlebana, F; Christofek, L; Chu, M L; Chung, Y S; Ciobanu, C I; Clark, A G; Connolly, A; Convery, M; Conway, J; Cordelli, M; Cranshaw, J; Cropp, R; Culbertson, R; Dagenhart, D; D'Auria, S; DeJongh, F; Dell'Agnello, S; Dell'Orso, M; Demortier, L; Deninno, M; Derwent, P F; Devlin, T; Dittmann, J R; Dominguez, A; Donati, S; Done, J; D'Onofrio, M; Dorigo, T; Eddy, N; Einsweiler, K; Elias, J E; Engels, E; Erbacher, R; Errede, D; Errede, S; Fan, Q; Feild, R G; Fernandez, J P; Ferretti, C; Field, R D; Fiori, I; Flaugher, B; Foster, G W; Franklin, M; Freeman, J; Friedman, J; Fukui, Y; Furic, I; Galeotti, S; Gallas, A; Gallinaro, M; Gao, T; Garcia-Sciveres, M; Garfinkel, A F; Gatti, P; Gay, C; Gerdes, D W; Giannetti, P; Glagolev, V; Glenzinski, D; Gold, M; Goldstein, J; Gorelov, I; Goshaw, A T; Gotra, Y; Goulianos, K; Green, C; Grim, G; Gris, P; Groer, L; Grosso-Pilcher, C; Guenther, M; Guillian, G; Guimaraes Da Costa, J; Haas, R M; Haber, C; Hahn, S R; Hall, C; Handa, T; Handler, R; Hao, W; Happacher, F; Hara, K; Hardman, A D; Harris, R M; Hartmann, F; Hatakeyama, K; Hauser, J; Heinrich, J; Heiss, A; Herndon, M; Hill, C; Hoffman, K D; Holck, C; Hollebeek, R; Holloway, L; Hughes, R; Huston, J; Huth, J; Ikeda, H; Incandela, J; Introzzi, G; Iwai, J; Iwata, Y; James, E; Jones, M; Joshi, U; Kambara, H; Kamon, T; Kaneko, T; Karr, K; Kasha, H; Kato, Y; Keaffaber, T A; Kelley, K; Kelly, M; Kennedy, R D; Kephart, R; Khazins, D; Kikuchi, T; Kilminster, B; Kim, B J; Kim, D H; Kim, H S; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kirby, M; Kirk, M; Kirsch, L; Klimenko, S; Koehn, P; Kondo, K; Konigsberg, J; Korn, A; Korytov, A; Kovacs, E; Kroll, J; Kruse, M; Kuhlmann, S E; Kurino, K; Kuwabara, T; Laasanen, A T; Lai, N; Lami, S; Lammel, S; Lancaster, J; Lancaster, M; Lander, R; Latino, G; LeCompte, T; Lee, A M; Lee, K; Leone, S; Lewis, J D; Lindgren, M; Liss, T M; Liu, J B; Liu, Y C; Litvintsev, D O; Lobban, O; Lockyer, N; Loken, J; Loreti, M; Lucchesi, D; Lukens, P; Lusin, S; Lyons, L; Lys, J; Madrak, R; Maeshima, K; Maksimovic, P; Malferrari, L; Mangano, M; Mariotti, M; Martignon, G; Martin, A; Matthews, J A; Mayer, J; Mazzanti, P; McFarland, K S; McIntyre, P; McKigney, E; Menguzzato, M; Menzione, A; Mesropian, C; Meyer, A; Miao, T; Miller, R; Miller, J S; Minato, H; Miscetti, S; Mishina, M; Mitselmakher, G; Moggi, N; Moore, E; Moore, R; Morita, Y; Moulik, T; Mulhearn, M; Mukherjee, A; Muller, T; Munar, A; Murat, P; Murgia, S; Nachtman, J; Nagaslaev, V; Nahn, S; Nakada, H; Nakano, I; Nelson, C; Nelson, T; Neu, C; Neuberger, D; Newman-Holmes, C; Ngan, C Y; Niu, H; Nodulman, L; Nomerotski, A; Oh, S H; Oh, Y D; Ohmoto, T; Ohsugi, T; Oishi, R; Okusawa, T; Olsen, J; Orejudos, W; Pagliarone, C; Palmonari, F; Paoletti, R; Papadimitriou, V; Partos, D; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pescara, L; Phillips, T J; Piacentino, G; Pitts, K T; Pompos, A; Pondrom, L; Pope, G; Popovic, M; Prokoshin, F; Proudfoot, J; Ptohos, F; Pukhov, O; Punzi, G; Rakitine, A; Reher, D; Reichold, A; Ribon, A; Riegler, W; Rimondi, F; Ristori, L; Riveline, M; Robertson, W J; Robinson, A; Rodrigo, T; Rolli, S; Rosenson, L; Roser, R; Rossin, R; Roy, A; Ruiz, A; Safonov, A; St Denis, R; Sakumoto, W K; Saltzberg, D; Sanchez, C; Sansoni, A; Santi, L; Sato, H; Savard, P; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Scodellaro, L; Scott, A; Scribano, A; Segler, S; Seidel, S; Seiya, Y; Semenov, A; Semeria, F; Shah, T; Shapiro, M D; Shepard, P F; Shibayama, T; Shimojima, M; Shochet, M; Sidoti, A; Siegrist, J; Sill, A; Sinervo, P; Singh, P; Slaughter, A J; Sliwa, K; Smith, C; Snider, F D; Solodsky, A; Spalding, J; Speer, T; Sphicas, P; Spinella, F; Spiropulu, M; Spiegel, L; Steele, J; Stefanini, A; Strologas, J; Strumia, F; Stuart, D; Sumorok, K; Suzuki, T; Takano, T; Takashima, R; Takikawa, K; Tamburello, P; Tanaka, M

    2001-10-01

    We present results from a measurement of double diffraction dissociation in pp collisions at the Fermilab Tevatron collider. The production cross section for events with a central pseudorapidity gap of width Deltaeta(0)>3 (overlapping eta = 0) is found to be 4.43+/-0.02(stat)+/-1.18(syst) mb [ 3.42+/-0.01(stat)+/-1.09(syst) mb] at square root of (s) = 1800[630] GeV. Our results are compared with previous measurements and with predictions based on Regge theory and factorization. PMID:11580642

  2. Spectroscopic Classification of ASASSN-16gp as a Type Ia SN

    NASA Astrophysics Data System (ADS)

    Strader, Jay; Chomiuk, Laura; Prieto, Jose L.

    2016-07-01

    We obtained an optical spectrum of ASASSN-16gp (ATel #9199) on UT July 6.96 with the Goodman Spectrograph on the SOAR telescope. Classification with SNID (Blondin and Tonry 2007, ApJ, 666, 1024) indicates ASASSN-16gp is a normal Type Ia SN observed at 20-30 days after peak.

  3. Generalized immunological recognition of the major merozoite surface antigen (gp195) of Plasmodium falciparum

    SciTech Connect

    Chang, S.P.; Hui, G.S.N.; Kato, A.; Siddiqui, W.A. )

    1989-08-01

    The antibody response to the Plasmodium falciparum major merozoite surface antigen (gp195) of congenic mouse strains differing in H-2 haplotype has been examined. All seven strains of mice were capable of producing gp195-specific antibodies. Generalized immune recognition of gp195 by mice of diverse H-2 haplotypes distinguished gp195 from the P. falciparum circumsporozoite protein and the 230-kDa and 48/45-kDa gamete surface antigens. However, the H-2 genetic locus appeared to influence the specificity of gp105-specific antibodies. Immunoblot patterns of mouse sera with parasite antigens revealed a complex pattern of reactivity with terminal and intermediate processing fragments of gp195. The majority of immunoblot bands observed were similar for all of the mouse strains; however, there were several strains that additionally recognized a few unique fragments or displayed more intense reactivities with specific processing fragments. These results suggest that while individuals of diverse major histocompatibility complex makeup are capable of recognizing the gp195 antigen, the recognition of specific gp195 B-cell and T-cell epitopes may be under control of the major histocompatibility complex.

  4. 78 FR 16540 - AIP Series Trust and Morgan Stanley AIP GP LP; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-15

    ... COMMISSION AIP Series Trust and Morgan Stanley AIP GP LP; Notice of Application March 11, 2013. AGENCY...: AIP Series Trust (the ``Trust'') and Morgan Stanley AIP GP LP (the ``Adviser''). DATES: Filing Dates...., Washington, DC 20549-1090. Applicants, c/ o Stefanie V. Chang Yu, Morgan Stanley Investment Management...

  5. Identification of a gp130 cytokine receptor critical site involved in oncostatin M response.

    PubMed

    Olivier, C; Auguste, P; Chabbert, M; Lelièvre, E; Chevalier, S; Gascan, H

    2000-02-25

    Gp130 cytokine receptor is involved in the formation of multimeric functional receptors for interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor, and cardiotrophin-1. Cloning of the epitope recognized by an OSM-neutralizing anti-gp130 monoclonal antibody identified a portion of gp130 receptor localized in the EF loop of the cytokine binding domain. Site-directed mutagenesis of the corresponding region was carried out by alanine substitution of residues 186-198. To generate type 1 or type 2 OSM receptors, gp130 mutants were expressed together with either LIF receptor beta or OSM receptor beta. When positions Val-189/Tyr-190 and Phe-191/Val-192 were alanine-substituted, Scatchard analyses indicated a complete abrogation of OSM binding to both type receptors. Interestingly, binding of LIF to type 1 receptor was not affected, corroborating the notion that in this case gp130 mostly behaves as a converter protein rather than a binding receptor. The present study demonstrates that positions 189-192 of gp130 cytokine binding domain are essential for OSM binding to both gp130/LIF receptor beta and gp130/OSM receptor beta heterocomplexes. PMID:10681548

  6. The neurotrophin receptor p75 mediates gp120-induced loss of synaptic spines in aging mice.

    PubMed

    Bachis, Alessia; Wenzel, Erin; Boelk, Allyssia; Becker, Jodi; Mocchetti, Italo

    2016-10-01

    Human immunodeficiency virus 1 and its envelope protein gp120 reduce synaptodendritic complexity. However, the mechanisms contributing to this pathological feature are still not understood. The proneurotrophin brain-derived neurotrophic factor promotes synaptic simplification through the activation of the p75 neurotrophin receptor (p75NTR). Here, we have used gp120 transgenic (gp120tg) mice to investigate whether p75NTR has a role in gp120-mediated neurotoxicity. Old (∼10 months) gp120tg mice exhibited an increase in proneurotrophin brain-derived neurotrophic factor levels in the hippocampus as well as a decrease in the number of dendritic spines when compared to age-matched wild type. These effects were not observed in 3- or 6-month-old mice. To test if the reduction in spine density and morphology is caused by the activation of p75NTR, we crossed gp120tg mice with p75NTR null mice. We found that deletion of only 1 copy of the p75NTR gene in gp120tg mice is sufficient to normalize the number of hippocampal spines, strongly suggesting that the neurotoxic effect of gp120 is mediated by p75NTR. These data indicate that p75NTR antagonists could provide an adjunct therapy against synaptic simplification caused by human immunodeficiency virus 1. PMID:27498053

  7. Immunogenicity and Protective Efficacy of Oligomeric Human Immunodeficiency Virus Type 1 gp140

    PubMed Central

    Earl, Patricia L.; Sugiura, Wataru; Montefiori, David C.; Broder, Christopher C.; Lee, Susan A.; Wild, Carl; Lifson, Jeffrey; Moss, Bernard

    2001-01-01

    The biologically active form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein is oligomeric. We previously described a soluble HIV-1 IIIB Env protein, gp140, with a stable oligomeric structure composed of uncleaved gp120 linked to the ectodomain of gp41 (P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss, J. Virol. 68:3015–3026, 1994). Here we compared the antibody responses of rabbits to gp120 and gp140 that had been produced and purified in an identical manner. The gp140 antisera exhibited enhanced cross-reactivity with heterologous Env proteins as well as greater neutralization of HIV-1 compared to the gp120 antisera. To examine both immunogenicity and protective efficacy, we immunized rhesus macaques with oligomeric gp140. Strong neutralizing antibodies against a homologous virus and modest neutralization of heterologous laboratory-adapted isolates were elicited. No neutralization of primary isolates was observed. However, a substantial fraction of the neutralizing activity could not be blocked by a V3 loop peptide. After intravenous challenge with simian-HIV virus SHIV-HXB2, three of the four vaccinated macaques exhibited no evidence of virus replication. PMID:11134278

  8. Antiviral activity of glycoprotein GP-1 isolated from Streptomyces kanasensis ZX01.

    PubMed

    Zhang, Guoqiang; Feng, Juntao; Han, Lirong; Zhang, Xing

    2016-07-01

    Plant virus diseases have seriously damaged global food security. However, current antiviral agents are not efficient enough for the requirement of agriculture production. So, developing new efficient and nontoxic antiviral agents is imperative. GP-1, from Streptomyces kanasensis ZX01, is a new antiviral glycoprotein, of which the antiviral activity and the mode of action against Tobacco mosaic virus (TMV) were investigated in this study. The results showed that GP-1 could fracture TMV particles, and the infection and accumulation of TMV in host plants were inhibited. Moreover, GP-1 could induce systematic resistance against TMV in the host, according to the results of activities of defensive enzymes increasing, MDA decreasing and overexpression of pathogenesis-related proteins. Furthermore, GP-1 could promote growth of the host plant. In conclusion, GP-1 showed the ability to be developed as an efficient antiviral agent and a fertilizer for agriculture. PMID:27091231

  9. 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.

  10. 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.

  11. 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.

  12. The C-terminal tail of the gp41 transmembrane envelope glycoprotein of HIV-1 clades A, B, C, and D may exist in two conformations: an analysis of sequence, structure, and function

    SciTech Connect

    Hollier, Mark J.; Dimmock, Nigel J. . E-mail: n.j.dimmock@warwick.ac.uk

    2005-07-05

    In addition to the major ectodomain, the gp41 transmembrane glycoprotein of HIV-1 is now known to have a minor ectodomain that is part of the long C-terminal tail. Both ectodomains are highly antigenic, carry neutralizing and non-neutralizing epitopes, and are involved in virus-mediated fusion activity. However, data have so far been biologically based, and derived solely from T cell line-adapted (TCLA), B clade viruses. Here we have carried out sequence and theoretically based structural analyses of 357 gp41 C-terminal sequences of mainly primary isolates of HIV-1 clades A, B, C, and D. Data show that all these viruses have the potential to form a tail loop structure (the minor ectodomain) supported by three, {beta}-sheet, membrane-spanning domains (MSDs). This means that the first (N-terminal) tyrosine-based sorting signal of the gp41 tail is situated outside the cell membrane and is non-functional, and that gp41 that reaches the cell surface may be recycled back into the cytoplasm through the activity of the second tyrosine-sorting signal. However, we suggest that only a minority of cell-associated gp41 molecules - those destined for incorporation into virions - has 3 MSDs and the minor ectodomain. Most intracellular gp41 has the conventional single MSD, no minor ectodomain, a functional first tyrosine-based sorting signal, and in line with current thinking is degraded intracellularly. The gp41 structural diversity suggested here can be viewed as an evolutionary strategy to minimize HIV-1 envelope glycoprotein expression on the cell surface, and hence possible cytotoxicity and immune attack on the infected cell.

  13. An essential role for gp39, the ligand for CD40, in thymic selection.

    PubMed

    Foy, T M; Page, D M; Waldschmidt, T J; Schoneveld, A; Laman, J D; Masters, S R; Tygrett, L; Ledbetter, J A; Aruffo, A; Claassen, E; Xu, J C; Flavell, R A; Oehen, S; Hedrick, S M; Noelle, R J

    1995-11-01

    The interactions between CD40 on B cells and its ligand gp39 on activated T helper cells are known to be essential for the development of thymus-dependent humoral immunity. However, CD40 is also functionally expressed on thymic epithelial cells and dendritic cells, suggesting that gp39-CD40 interactions may also play a role in thymic education, the process by which self-reactive cells are deleted from the T cell repertoire. Six systems of negative selection were studied for their reliance on gp39-CD40 interactions to mediate negative selection. In all cases, when the antigen/superantigen was endogenously expressed (in contrast to exogenously administered), negative selection was blocked by loss of gp39 function. Specifically, blockade of gp39-CD40 interactions prevented the deletion of thymocytes expressing V beta 3, V beta 11, and V beta 12, specificities normally deleted in BALB/c mice because of the endogenous expression of minor lymphocyte-stimulating determinants. Independent verification of a role of gp39 in negative selection was provided by studies in gp39-deficient mice where alterations in T cell receptor (TCR) V beta expression were also observed. Studies were also performed in the AND TCR transgenic (Tg) mice, which bear the V alpha 11, V beta 3 TCR and recognize both pigeon cytochrome c (PCC)/IEk and H-2As. Neonatal administration of anti-gp39 to AND TCR Tg mice that endogenously express H-2As or endogenously produce PCC prevented the deletion of TCR Tg T cells. In contrast, deletion mediated by high-dose PCC peptide antigen (administered exogenously) in AND TCR mice was unaltered by administration of anti-gp39. In addition, deletion by Staphylococcus enterotoxin B in conventional mice was also unaffected by anti-gp39 administration. gp39 expression was induced on thymocytes by mitogens or by antigen on TCR Tg thymocytes. Immunohistochemical analysis of B7-2 expression in the thymus indicated that, in the absence of gp39, B7-2 expression was

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Fangchinoline Inhibits Human Immunodeficiency Virus Type 1 Replication by Interfering with gp160 Proteolytic Processing

    PubMed Central

    Wan, Zhitao; Lu, Yimei; Liao, Qingjiao; Wu, Yang; Chen, Xulin

    2012-01-01

    The introduction of highly active antiretroviral therapy has led to a significant reduction in the morbidity and mortality of acquired immunodeficiency syndrome patients. However, the emergence of drug resistance has resulted in the failure of treatments in large numbers of patients and thus necessitates the development of new classes of anti-HIV drugs. In this study, more than 200 plant-derived small-molecule compounds were evaluated in a cell-based HIV-1 antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (fangchinoline). Fangchinoline, a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae, exhibited antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 µM. Mechanism-of-action studies showed that fangchinoline did not exhibit measurable antiviral activity in TZM-b1 cells but did inhibit the production of infectious virions in HIV-1 cDNA transfected 293T cells, which suggests that the compound targets a late event in infection cycle. Furthermore, the antiviral effect of fangchinoline seems to be HIV-1 enve1ope-dependent, as the production of infectious HIV-1 particles packaged with a heterologous envelope, the vesicular stomatitis virus G glycoprotein, was unaffected by fangchinoline. Western blot analysis of HIV envelope proteins expressed in transfected 293T cells and in isolated virions showed that fangchinoline inhibited HIV-1 gp160 processing, resulting in reduced envelope glycoprotein incorporation into nascent virions. Collectively, our results demonstrate that fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing. Fangchinoline may serve as a starting point for developing a new HIV-1 therapeutic approach. PMID:22720080

  19. Fangchinoline inhibits human immunodeficiency virus type 1 replication by interfering with gp160 proteolytic processing.

    PubMed

    Wan, Zhitao; Lu, Yimei; Liao, Qingjiao; Wu, Yang; Chen, Xulin

    2012-01-01

    The introduction of highly active antiretroviral therapy has led to a significant reduction in the morbidity and mortality of acquired immunodeficiency syndrome patients. However, the emergence of drug resistance has resulted in the failure of treatments in large numbers of patients and thus necessitates the development of new classes of anti-HIV drugs. In this study, more than 200 plant-derived small-molecule compounds were evaluated in a cell-based HIV-1 antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (fangchinoline). Fangchinoline, a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae, exhibited antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 µM. Mechanism-of-action studies showed that fangchinoline did not exhibit measurable antiviral activity in TZM-b1 cells but did inhibit the production of infectious virions in HIV-1 cDNA transfected 293T cells, which suggests that the compound targets a late event in infection cycle. Furthermore, the antiviral effect of fangchinoline seems to be HIV-1 envelope-dependent, as the production of infectious HIV-1 particles packaged with a heterologous envelope, the vesicular stomatitis virus G glycoprotein, was unaffected by fangchinoline. Western blot analysis of HIV envelope proteins expressed in transfected 293T cells and in isolated virions showed that fangchinoline inhibited HIV-1 gp160 processing, resulting in reduced envelope glycoprotein incorporation into nascent virions. Collectively, our results demonstrate that fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing. Fangchinoline may serve as a starting point for developing a new HIV-1 therapeutic approach. PMID:22720080

  20. Multidrug resistance protein P-gp interaction with nanoparticles (fullerenes and carbon nanotube) to assess their drug delivery potential: a theoretical molecular docking study.

    PubMed

    Shityakov, Sergey; Förster, Carola

    2013-01-01

    P-glycoprotein (P-gp)-mediated efflux system plays an important role to maintain chemical balance in mammalian cells for endogenous and exogenous chemical compounds. However, despite the extensive characterisation of P-gp potential interaction with drug-like molecules, the interaction of carbon nanoparticles with this type of protein molecule is poorly understood. Thus, carbon nanoparticles were analysed, such as buckminsterfullerenes (C20, C60, C70), capped armchair single-walled carbon nanotube (SWCNT or C168), and P-gp interactions using different molecular docking techniques, such as gradient optimisation algorithm (ADVina), Lamarckian genetic algorithm (FastDock), and shape-based approach (PatchDock) to estimate the binding affinities between these structures. The theoretical results represented in this work show that fullerenes might be P-gp binders because of low levels of Gibbs free energy of binding (ΔG) and potential of mean force (PMF) values. Furthermore, the SWCNT binding is energetically unfavourable, leading to a total decrease in binding affinity by elevation of the residual area (Ares), which also affects the π-π stacking mechanisms. Further, the obtained data could potentially call experimental studies using carbon nanostructures, such as SWCNT for development of drug delivery vehicles, to administer and assess drug-like chemical compounds to the target cells since organisms probably did not develop molecular sensing elements to detect these types of carbon molecules.

  1. Mass Spectrometry Approach and ELISA Reveal the Effect of Codon Optimization on N-Linked Glycosylation of HIV-1 gp120

    PubMed Central

    2015-01-01

    The genes encoding many viral proteins such as HIV-1 envelope glycoprotein gp120 have a tendency for codons that are poorly used by the human genome. Why these codons are frequently present in the HIV genome is not known. The presence of these codons limits expression of HIV-1 gp120 for biochemical studies. The poor codons are replaced by synonymous codons that are frequently present in the highly expressed human genes to overexpress this protein. Whether this codon optimization affects functional properties of gp120 such as its N-linked glycosylation is unknown. We applied a bottom-up mass-spectrometry-based workflow for the direct measurement of deglycosylated and unglycosylated peptides with putative N-linked glycosylation sites, that is, NxS/T motifs. Using this mass-spectrometry approach in combination with ELISA, it is found that codon optimization significantly reduces the frequency with which the dolichol pyrophosphate-linked oligosaccharide is added by the catalytic subunits of oligosaccharide transferase complex to the glycosylation sites. This reduction affects binding of glycan-dependent broadly neutralizing antibodies. These data are essential for biochemical studies of gp120 and successful development of a vaccine against HIV-1. Furthermore, they demonstrate a mass-spectrometry approach for studying the site-specific N-linked glycosylation efficiency of glycoproteins. PMID:25285362

  2. COMMISSIONING OF THE RELATIVISTIC HEAVY ION COLLIDER.

    SciTech Connect

    TRBOJEVIC,D.; AHRENS,L.; BLASKIEWICZ,M.; BRENNAN,M.; BAI,M.; CAMERON,P.; CARDONA,J.; CONNOLLY,R.; ET AL; TSOUPAS,N.; VAN ZEIJTS,J.

    2001-06-18

    This report describes in detail steps performed in bringing the Relativistic Heavy Ion Collider (RHIC) from the commissioning into the operational stage when collisions between 60 bunches of fully striped gold ions, were routinely provided. Corrections of the few power supplies connections by the beam measurements are described. Beam lifetime improvements at injection, along the acceleration are shown. The beam diagnostic results; like Schottky detector, beam profile monitor, beam position monitors, tune meter and others, are shown [1].

  3. Electroweak results from the Tevatron Collider

    SciTech Connect

    Dorage, T., Padova University and I.N.F.N.

    1998-08-01

    We present the latest results on electroweak physics obtained from the analysis of p{anti p} collisions at {radical}s=1.8 TeV. The large data samples collected with the CDF and D0 detectors at the Tevatron collider allow measurements of the top quark mass to a 3% accuracy and of the W boson to a 0.1% accuracy. Many precision measurements that test the Standard Model and probe its possible extensions are also described.

  4. 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.

  5. 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.

  6. Large Hadron Collider commissioning and first operation.

    PubMed

    Myers, S

    2012-02-28

    A history of the commissioning and the very successful early operation of the Large Hadron Collider (LHC) is described. The accident that interrupted the first commissioning, its repair and the enhanced protection system put in place are fully described. The LHC beam commissioning and operational performance are reviewed for the period from 2010 to mid-2011. Preliminary plans for operation and future upgrades for the LHC are given for the short and medium term.

  7. 1987 DOE review: First collider run operation

    SciTech Connect

    Childress, S.; Crawford, J.; Dugan, G.; Edwards, H.; Finley, D.A.; Fowler, W.B.; Harrison, M.; Holmes, S.; Makara, J.N.; Malamud, E.

    1987-05-01

    This review covers the operations of the first run of the 1.8 TeV superconducting super collider. The papers enclosed cover: PBAR source status, fixed target operation, Tevatron cryogenic reliability and capacity upgrade, Tevatron Energy upgrade progress and plans, status of the D0 low beta insertion, 1.8 K and 4.7 K refrigeration for low-..beta.. quadrupoles, progress and plans for the LINAC and booster, near term and long term and long term performance improvements.

  8. 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)

  9. 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.

  10. CDF (Collider Detector at Fermilab) calorimetry

    SciTech Connect

    Jensen, H.B.

    1987-03-01

    The Collider Detector at Fermilab (CDF) is a large detector built to study 2 TeV anti p p collisions at the Fermilab Tevatron. The calorimetry, which has polar angle coverage from 2 to 178, and complete azimuthal coverage within this region, forms the subject of this paper. It consists of both electromagnetic shower counters (EM calorimeters) and hadron calorimeters, and is segmented into about 5000 ''towers'' or solid angle elements.

  11. 77 FR 123 - Final Reissuance of General NPDES Permits (GP) for Facilities Related to Oil and Gas Extraction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-03

    ... AGENCY Final Reissuance of General NPDES Permits (GP) for Facilities Related to Oil and Gas Extraction... permit. SUMMARY: A GP regulating the activities of facilities related to oil and gas extraction on the... reissue the GP expanding the coverage area to the TransAlaska Pipeline Corridor along with other...

  12. Structure and Dynamics of Colliding Plasma Jets

    NASA Astrophysics Data System (ADS)

    Li, C. K.; Ryutov, D. D.; Hu, S. X.; Rosenberg, M. J.; Zylstra, A. B.; Séguin, F. H.; Frenje, J. A.; Casey, D. T.; Gatu Johnson, M.; Manuel, M. J.-E.; Rinderknecht, H. G.; Petrasso, R. D.; Amendt, P. A.; Park, H. S.; Remington, B. A.; Wilks, S. C.; Betti, R.; Froula, D. H.; Knauer, J. P.; Meyerhofer, D. D.; Drake, R. P.; Kuranz, C. 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 ReM˜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.

  13. 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.

  14. 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.

  15. Structure and Dynamics of Colliding Plasma Jets

    DOE PAGES

    Li, C.; Ryutov, D.; Hu, S.; Rosenberg, M.; Zylstra, A.; Seguin, F.; Frenje, J.; Casey, D.; Gatu Johnson, M.; Manuel, M.; et al

    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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Interpenetration and stagnation in colliding laser plasmas

    SciTech Connect

    Al-Shboul, K. F.; Harilal, S. S. Hassan, S. M.; Hassanein, A.; Costello, J. T.; Yabuuchi, T.; Tanaka, K. A.; Hirooka, Y.

    2014-01-15

    We have investigated plasma stagnation and interaction effects in colliding laser-produced plasmas. For generating colliding plasmas, two split laser beams were line-focused onto a hemi-circular target and the seed plasmas so produced were allowed to expand in mutually orthogonal directions. This experimental setup forced the expanding seed plasmas to come to a focus at the center of the chamber. The interpenetration and stagnation of plasmas of candidate fusion wall materials, viz., carbon and tungsten, and other materials, viz., aluminum, and molybdenum were investigated in this study. Fast-gated imaging, Faraday cup ion analysis, and optical emission spectroscopy were used for diagnosing seed and colliding plasma plumes. Our results show that high-Z target (W, Mo) plasma ions interpenetrate each other, while low-Z (C, Al) plasmas stagnate at the collision plane. For carbon seed plasmas, an intense stagnation was observed resulting in longer plasma lifetime; in addition, the stagnation layer was found to be rich with C{sub 2} dimers.

  1. Enhanced Dynamics of HIV gp120 Glycoprotein by Small Molecule Binding

    PubMed Central

    Shrivastava, Indira; LaLonde, Judith M.

    2011-01-01

    HIV cell entry and infection are driven by binding events to the CD4 and Chemokine receptors with associated conformational change of the viral glycoprotein, gp120. Scyllatoxin mini-protein CD4 mimetics and a small molecule inhibitor of CD4 binding, NBD-556, also effectively induce gp120 conformational change. In this study we examine the fluctuation profile of gp120 in context of CD4, a mini-protein mimetic and NBD-556 with the aim of understanding the effect of ligand binding on gp120 conformational dynamics. Analysis of Molecular Dynamics trajectories indicate that NBD-556 binding in the Phe 43 cavity enhances the overall mobility of gp120 especially in the outer-domain in comparison to CD4 or mini-protein bound complex. Interactions with the more flexible bridging sheet strengthen upon NBD-556 binding and may contribute to gp120 restructuring. The enhanced mobility of D368, E370 and I371 with NBD-556 bound in the Phe 43 cavity suggests that interactions with α3-helix in the outer-domain are not optimal, providing further insights into gp120-small molecule interactions that may impact small molecule designs. PMID:21488663

  2. The membranotropic regions of the endo and ecto domains of HIV gp41 envelope glycoprotein.

    PubMed

    Moreno, Miguel R; Giudici, Marcela; Villalaín, José

    2006-01-01

    We have identified the membranotropic regions of the full sequence of the HIV gp41 envelope glycoprotein by performing an exhaustive study of membrane rupture, phospholipid-mixing and fusion induced by two 15-mer gp41-derived peptide libraries from HIV strains HIV_MN and HIV_consensus_B on model membranes having different phospholipid compositions. The data obtained for the two strains and its comparison have led us to identify different gp41 membranotropic segments in both ecto- and endodomains which might be implicated in viral membrane fusion and/or membrane interaction. The membranotropic segments corresponding to the gp41 ectodomain were the fusion domain, a stretch located on the N-heptad repeat region adjacent to the fusion domain, part of the immunodominant loop, the pre-transmembrane domain and the transmembrane domain. The membranotropic segments corresponding to the gp41 endodomain were mainly located at some specific parts of the previously described lentivirus lytic sequences. Significantly, the C-heptad repeat region and the Kennedy sequence located in the ectodomain and in the endodomain, respectively, presented no membranotropic activity in any model membrane assayed. The identification of these gp41 segments as well as their membranotropic propensity sustain the notion that different segments of gp41 provide the driving force for the merging of the viral and target cell membranes as well as they help us to define those segments as attractive targets for further development of new anti-viral compounds. PMID:16483537

  3. Structural and Functional Studies on the Marburg Virus GP2 Fusion Loop.

    PubMed

    Liu, Nina; Tao, Yisong; Brenowitz, Michael D; Girvin, Mark E; Lai, Jonathan R

    2015-10-01

    Marburg virus (MARV) and the ebolaviruses belong to the family Filoviridae (the members of which are filoviruses) that cause severe hemorrhagic fever. Infection requires fusion of the host and viral membranes, a process that occurs in the host cell endosomal compartment and is facilitated by the envelope glycoprotein fusion subunit, GP2. The N-terminal fusion loop (FL) of GP2 is a hydrophobic disulfide-bonded loop that is postulated to insert and disrupt the host endosomal membrane during fusion. Here, we describe the first structural and functional studies of a protein corresponding to the MARV GP2 FL. We found that this protein undergoes a pH-dependent conformational change, as monitored by circular dichroism and nuclear magnetic resonance. Furthermore, we report that, under low pH conditions, the MARV GP2 FL can induce content leakage from liposomes. The general aspects of this pH-dependent structure and lipid-perturbing behavior are consistent with previous reports on Ebola virus GP2 FL. However, nuclear magnetic resonance studies in lipid bicelles and mutational analysis indicate differences in structure exist between MARV and Ebola virus GP2 FL. These results provide new insight into the mechanism of MARV GP2-mediated cell entry.

  4. TssA forms a gp6-like ring attached to the type VI secretion sheath.

    PubMed

    Planamente, Sara; Salih, Osman; Manoli, Eleni; Albesa-Jové, David; Freemont, Paul S; Filloux, Alain

    2016-08-01

    The type VI secretion system (T6SS) is a supra-molecular bacterial complex that resembles phage tails. It is a killing machine which fires toxins into target cells upon contraction of its TssBC sheath. Here, we show that TssA1 is a T6SS component forming dodecameric ring structures whose dimensions match those of the TssBC sheath and which can accommodate the inner Hcp tube. The TssA1 ring complex binds the T6SS sheath and impacts its behaviour in vivo In the phage, the first disc of the gp18 sheath sits on a baseplate wherein gp6 is a dodecameric ring. We found remarkable sequence and structural similarities between TssA1 and gp6 C-termini, and propose that TssA1 could be a baseplate component of the T6SS Furthermore, we identified similarities between TssK1 and gp8, the former interacting with TssA1 while the latter is found in the outer radius of the gp6 ring. These observations, combined with similarities between TssF and gp6N-terminus or TssG and gp53, lead us to propose a comparative model between the phage baseplate and the T6SS. PMID:27288401

  5. VHEeP: a very high energy electron-proton collider

    NASA Astrophysics Data System (ADS)

    Caldwell, A.; Wing, M.

    2016-08-01

    Based on current CERN infrastructure, an electron-proton collider is proposed at a centre-of-mass energy of about 9 TeV. A 7 TeV LHC bunch is used as the proton driver to create a plasma wakefield which then accelerates electrons to 3 TeV, these then colliding with the other 7 TeV LHC proton beam. Although of very high energy, the collider has a modest projected integrated luminosity of 10-100 pb^{-1}. For such a collider, with a centre-of-mass energy 30 times greater than HERA, parton momentum fractions, x, down to about 10^{-8} are accessible for photon virtualities, Q^2, of 1 GeV^2. The energy dependence of hadronic cross sections at high energies, such as the total photon-proton cross section, which has synergy with cosmic-ray physics, can be measured and QCD and the structure of matter better understood in a region where the effects are completely unknown. Searches at high Q^2 for physics beyond the Standard Model will be possible, in particular the significantly increased sensitivity to the production of leptoquarks. These and other physics highlights of a very high energy electron-proton collider are outlined.

  6. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers

    PubMed Central

    Blattner, Claudia; Lee, Jeong Hyun; Sliepen, Kwinten; Derking, Ronald; Falkowska, Emilia; de la Peña, Alba Torrents; Cupo, Albert; Julien, Jean-Philippe; van Gils, Marit; Lee, Peter S.; Peng, Wenjie; Paulson, James C.; Poignard, Pascal; Burton, Dennis R.; Moore, John P.; Sanders, Rogier W.

    2014-01-01

    Summary All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. As PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer. PMID:24768348

  7. Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope

    SciTech Connect

    Penn-Nicholson, Adam; Han, Dong P.; Kim, Soon J.; Park, Hanna; Ansari, Rais; Montefiori, David C.; Cho, Michael W.

    2008-03-15

    Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 is targeted by broadly-reactive neutralizing antibodies 2F5 and 4E10, making it an attractive target for vaccine development. To better assess immunogenic properties of gp41, we generated five soluble glutathione S-transferase fusion proteins encompassing C-terminal 30, 64, 100, 142, or 172 (full-length) amino acids of gp41 ectodomain from M group consensus envelope sequence. Antibody responses in HIV-1-infected patients were evaluated using these proteins and overlapping peptides. We found (i) antibody responses against different regions of gp41 varied tremendously among individual patients, (ii) patients with stronger antibody responses against membrane-proximal external region exhibit broader and more potent neutralizing activity, and (iii) several patients mounted antibodies against epitopes that are near, or overlap with, those targeted by 2F5 or 4E10. These soluble gp41 fusion proteins could be an important source of antigens for future vaccine development efforts.

  8. HIV-1 viral envelope protein gp41: An NMR investigation of dodecyl phosphocholine embedded gp41 reveals a dynamic pre-fusion intermediate conformation

    PubMed Central

    Lakomek, Nils-Alexander; Kaufman, Joshua D.; Stahl, Stephen J.; Wingfield, Paul T.

    2014-01-01

    Summary Human immunodeficiency viral (HIV-1) fusion is mediated by the viral envelope gp120/gp41 complex (ENVelope glycoprotein). After gp120 shedding, gp41 is exposed and elicits membrane fusion via a cascade of conformational changes. In contrast to pre-fusion and post-fusion conformation, little is known about any intermediate conformation. We report on a solution NMR investigation of homotrimeric HIV-1 gp4127–194, comprising the transmembrane region and reconstituted in dodecyl phosphocholine (DPC) micelles. The protein is mainly α-helical but experiences internal dynamics on the nanosecond and micro-to millisecond time scale and transient α-helical behavior for certain residues in the N-terminal heptad repeat (NHR). Strong lipid interactions are observed, in particular for C-terminal residues of the NHR and imunodominant loop region connecting NHR and C-terminal heptad repeat (CHR). Our data indicate an extended conformation with features anticipated for a pre-fusion intermediate, presumably in exchange with a lowly populated post-fusion six-helical bundle conformation. PMID:25132083

  9. Investigation of clade B New World arenavirus tropism by using chimeric GP1 proteins.

    PubMed

    Martin, Vanessa K; Droniou-Bonzom, Magali E; Reignier, Therese; Oldenburg, Jill E; Cox, Alex U; Cannon, Paula M

    2010-01-01

    Clade B of the New World arenaviruses contains both pathogenic and nonpathogenic members, whose surface glycoproteins (GPs) are characterized by different abilities to use the human transferrin receptor type 1 (hTfR1) protein as a receptor. Using closely related pairs of pathogenic and nonpathogenic viruses, we investigated the determinants of the GP1 subunit that confer these different characteristics. We identified a central region (residues 85 to 221) in the Guanarito virus GP1 that was sufficient to interact with hTfR1, with residues 159 to 221 being essential. The recently solved structure of part of the Machupo virus GP1 suggests an explanation for these requirements.

  10. 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.

  11. 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.

  12. Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function

    SciTech Connect

    Bellamy-McIntyre, Anna K.; Baer, Severine; Ludlow, Louise; Drummer, Heidi E.; Poumbourios, Pantelis

    2010-04-16

    The conserved disulfide-bonded region (DSR) of the human immunodeficiency virus type 1 (HIV-1) fusion glycoprotein, gp41, mediates association with the receptor-binding glycoprotein, gp120. Interactions between gp120, CD4 and chemokine receptors activate the fusion activity of gp41. The introduction of W596L and W610F mutations to the DSR of HIV-1{sub QH1549.13} blocked viral entry and hemifusion without affecting gp120-gp41 association. The fusion defect correlated with inhibition of CD4-triggered gp41 pre-hairpin formation, consistent with the DSR mutations having decoupled receptor-induced conformational changes in gp120 from gp41 activation. Our data implicate the DSR in sensing conformational changes in the gp120-gp41 complex that lead to fusion activation.

  13. Systematic review: new serological markers (anti-glycan, anti-GP2, anti-GM-CSF Ab) in the prediction of IBD patient outcomes.

    PubMed

    Bonneau, J; Dumestre-Perard, C; Rinaudo-Gaujous, M; Genin, C; Sparrow, M; Roblin, X; Paul, S

    2015-03-01

    Traditionally, IBD diagnosis is based on clinical, radiological, endoscopic, and histological criteria. Biomarkers are needed in cases of uncertain diagnosis, or to predict disease course and therapeutic response. No guideline recommends the detection of antibodies (including ASCA and ANCA) for diagnosis or prognosis of IBD to date. However, many recent data suggest the potential role of new serological markers (anti-glycan (ACCA, ALCA, AMCA, anti-L and anti-C), anti-GP2 and anti-GM-CSF Ab). This review focuses on clinical utility of these new serological markers in diagnosis, prognosis and therapeutic monitoring of IBD. Literature review of anti-glycan, anti-GP2 and anti-GM-CSF Ab and their impact on diagnosis, prognosis and prediction of therapeutic response was performed in PubMed/MEDLINE up to June 2014. Anti-glycan, anti-GP2 and anti-GM-CSF Ab are especially associated with CD and seem to be correlated with complicated disease phenotypes even if results differ between studies. Although anti-glycan Ab and anti-GP2 Ab have low sensitivity in diagnosis of IBD, they could identify a small number of CD patients not detected by other tests such as ASCA. Anti-glycan Abs are associated with a progression to a more severe disease course and a higher risk for IBD-related surgery. Anti-GP2 Ab could particularly contribute to better stratify cases of pouchitis. Anti-GM-CSF Ab seems to be correlated with disease activity and could help predict relapses. These new promising biomarkers could particularly be useful in stratification of patients according to disease phenotype and risk of complications. They could be a valuable aid in prediction of disease course and therapeutic response but more prospective studies are needed.

  14. The use of aqueous two-phase systems to concentrate and purify bovine leukemia virus outer envelope protein gp51.

    PubMed

    Hammar, L; Merza, M; Malm, K; Eriksson, S; Morein, B

    1989-06-01

    Enzootic bovine leucosis is a chronic lymphoproliferative disease of cattle. The causative agent, bovine leukemia virus (BLV), is related to the human retroviruses HTLV-I and -II. The external env-protein of BLV, a glycoprotein of 51 kDa, carries neutralizing epitopes and should be an essential component in a vaccine against the virus. Problems have been encountered with the concentration and purification of intact virions of BLV and other retroviruses. During centrifugation procedures the external env-proteins are to a great extent detached and consequently poorly recovered with the virion particles. Therefore, other methods are sought to obtain a high yield of the external glycoproteins. The use of two-phase systems based on water soluble polymers is described for the extraction of BLV-gp51 from culture medium. Several polymer systems were tested and the results showed that some were attractive for large scale application. The classical combination dextran-polyethylene glycol gave promising results; a partition coefficient of about 0.02 was obtained for the distribution of the gp51 between the top and combined inter- and bottom phases. In a single extraction step it was possible to obtain 45% of the glycoprotein in a small volume bottom phase and at the same time about 15-fold purified. That should be compared with a recovery of less than 20% with the conventional centrifugation procedures. It is concluded that extraction in phase systems based on water soluble polymers is a methodology well suited for the concentration and purification of BLV-gp51. PMID:2474306

  15. Top Quark Anomalous Couplings at the International Linear Collider

    SciTech Connect

    Devetak, Erik; Nomerotski, Andrei; Peskin, Michael; /SLAC

    2011-08-15

    We present a study of the experimental determination of the forward-backward asymmetry in the process e{sup +}e{sup -} {yields} t{bar t} and in the subsequent t {yields} Wb decay, studied in the context of the International Linear Collider. This process probes the elementary couplings of the top quark to the photon, the Z and the W bosons at a level of precision that is difficult to achieve at hadron colliders. Measurement of the forward-backward asymmetry requires excellent b quark identification and determination of the quark charge. The study reported here is performed in the most challenging all-hadronic channel e{sup +}e{sup -} {yields} b{bar b}q{bar q}q{bar q}. It includes realistic details of the experimental environment, a full Monte Carlo simulation of the detector, based on the Silicon Detector concept, and realistic event reconstruction. The forward-backward asymmetries are determined to a precision of approximately 1% for each of two choices of beam polarization. We analyze the implications for the determination of the t{bar t}Z and Wt{bar b} couplings.

  16. Present optics options for TeV colliders

    SciTech Connect

    Spencer, J.E.

    1986-05-01

    A practical approach for implementing TeV collider optics with high luminosities pounds approx. = 10/sup 33/ (cm/sup 2/ s)/sup -1/ but without large pinch effects is given using current alternatives. Characteristics are considered that constrain the optics and the types and orders of magnets required. A modified linac FoDo cell based on permanent magnet hybrid quadrupoles is discussed. Similarly, a demagnifying, permanent magnet telescopic system that allows variation of beta, eta and energy is suggested for the final focus. The basic cell for low emittance damping rings can also be constructed solely from permanent magnets. Small diameter, low permeability, high field permanent magnets have proven useful for injection and extraction lines and are also compatible with the large particle near the interaction regions as well as with exotic experiments for production and use of secondary beams or for multi-bunch coalescing schemes for control of longitudinal bunch distribution. An 8-10 GeV prototype cell and final focus experiment is proposed to verify and study such systems as well as do some interesting physics tests. One example, which could be used with the PEP storage ring, would convert an external electron beam into a photon beam to avoid beamstrahlung effects - a major problem for high energy e+- colliders.

  17. Invisible Higgs decay at the Large Hadron-Electron Collider

    NASA Astrophysics Data System (ADS)

    Tang, Yi-Lei; Zhang, Chen; Zhu, Shou-hua

    2016-07-01

    The possibility that the 125 GeV Higgs boson may decay into invisible non-standard-model (non-SM) particles is theoretically and phenomenologically intriguing. In this paper, we investigate the sensitivity of the Large Hadron Electron Collider (LHeC) to an invisibly decaying Higgs, in its proposed high-luminosity running mode. We focus on the neutral current Higgs production channel which offers more kinematical handles than its charged current counterpart. The signal contains one electron, one jet, and large missing energy. With a cut-based parton-level analysis, we estimate that if the h Z Z coupling is at its standard model (SM) value, then assuming an integrated luminosity of 1 ab-1 , the LHeC with the proposed 60 GeV electron beam (with -0.9 polarization) and 7 TeV proton beam is capable of probing Br (h →TE)=6 % at 2 σ level. Good lepton veto performance (especially hadronic τ veto) in the forward region is crucial to the suppression of the dominant W j e background. We also explicitly point out the important role that may be played by the LHeC in probing a wide class of exotic Higgs decay processes and emphasize the general function of lepton-hadron colliders in the precision study of new resonances after their discovery in hadron-hadron collisions.

  18. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

    SciTech Connect

    Costantini, Lindsey M.; Irvin, Susan C.; Kennedy, Steven C.; Guo, Feng; Goldstein, Harris; Herold, Betsy C.; Snapp, Erik L.

    2015-02-15

    The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells.

  19. Unorthodox method of calculating the activation of groundwater by routine SSC (Superconducting Super Collider) operations

    SciTech Connect

    Cossairt, J.D.

    1987-04-01

    A novel method for estimating the groundwater activation in the environs of the SSC collider ring tunnel is developed. This method, based on the Moyer model, may provide a simpler approach to such estimates and also a check for existing methods. One such method is compared. (LSP)

  20. A surface-associated retinol- and fatty acid-binding protein (Gp-FAR-1) from the potato cyst nematode Globodera pallida: lipid binding activities, structural analysis and expression pattern.

    PubMed Central

    Prior, A; Jones, J T; Blok, V C; Beauchamp, J; McDermott, L; Cooper, A; Kennedy, M W

    2001-01-01

    Parasitic nematodes produce at least two structurally novel classes of small helix-rich retinol- and fatty-acid-binding proteins that have no counterparts in their plant or animal hosts and thus represent potential targets for new nematicides. Here we describe a protein (Gp-FAR-1) from the plant-parasitic nematode Globodera pallida, which is a member of the nematode-specific fatty-acid- and retinol-binding (FAR) family of proteins but localizes to the surface of this species, placing it in a strategic position for interaction with the host. Recombinant Gp-FAR-1 was found to bind retinol, cis-parinaric acid and the fluorophore-tagged lipids 11-(dansylamino)undecanoic acid and dansyl-D,L-alpha-amino-octanoic acid. The fluorescence emission characteristics of the dansylated analogues indicated that the entire ligand enters the binding cavity. Fluorescence competition experiments showed that Gp-FAR-1 binds fatty acids in the range C(11) to C(24), with optimal binding at C(15). Intrinsic fluorescence analysis of a mutant protein into which a tryptophan residue had been inserted supported computer-based predictions of the position of this residue at the protein's interior and possibly also at the binding site. Of direct relevance to plant defence systems was the observation that Gp-FAR-1 binds two lipids (linolenic and linoleic acids) that are precursors of plant defence compounds and the jasmonic acid signalling pathway. Moreover, Gp-FAR-1 was found to inhibit the lipoxygenase-mediated modification of these substrates in vitro. Thus not only does Gp-FAR-1 function as a broad-spectrum retinol- and fatty-acid-binding protein, the results are consistent with the idea that Gp-FAR-1 is involved in the evasion of primary host plant defence systems. PMID:11368765

  1. The human fibroblast receptor for gp86 of human cytomegalovirus is a phosphorylated glycoprotein.

    PubMed Central

    Keay, S; Baldwin, B

    1992-01-01

    A human embryonic lung (HEL) cell receptor for gp86 of human cytomegalovirus that functions in virus-cell fusion was further characterized. Anti-idiotype antibodies that mimic gp86 were used to immunoprecipitate the 92.5-kDa fibroblast membrane receptor for gp86, which was preincubated with various endoglycosidases. The receptor, which has a pI ranging from 5.3 to 5.6, appears to be a glycoprotein with primarily N-linked sugar residues, some of which have high concentrations of mannose and some of which are complex oligosaccharides. Western blots (immunoblots) of electrophoretically transferred receptor incubated with various biotinylated lectins confirmed the presence of sugar moieties, including N-acetylglucosamine, glucose or mannose, and galactose, but not fucose or N-acetylgalactosamine. This gp86 receptor from uninfected HEL cells also incorporated radiolabeled phosphate from orthophosphoric acid, indicating that it is a constitutively phosphorylated receptor. Images PMID:1321272

  2. Membrane skeleton orchestrates the platelet glycoprotein (GP) Ib-IX complex clustering and signaling.

    PubMed

    Shang, Dan; Zhang, Zuping; Wang, Qian; Ran, Yali; Shaw, Tanner S; Van, John N; Peng, Yuandong

    2016-10-01

    Platelet glycoprotein Ib-IX complex is affixed to the membrane skeleton through interaction with actin binding protein 280 (ABP-280). We find that removal of the ABP-280 binding sites in GP Ibα cytoplasmic tail has little impact on the complex clustering induced by antibody crosslinking. However, large truncation of the GP Ibα cytoplasmic tail allows the formation of larger patches of the complex, suggesting that an ABP-280 independent force may exist. Besides, we observe that the signaling upon GP Ib-IX clustering is elicited in both membrane lipid domain dependent and independent manner, a choice that relies on how the membrane skeleton interacts with the complex. Our findings suggest a more complex mechanism for how the membrane skeleton regulates the GP Ib-IX function. © 2016 IUBMB Life, 68(10):823-829, 2016. PMID:27634617

  3. Characterization of a Novel Neutralizing Monoclonal Antibody Against Ebola Virus GP.

    PubMed

    Reynard, Olivier; Volchkov, Viktor E

    2015-10-01

    Ebola virus is the etiological agent of a severe hemorrhagic fever with a high mortality rate. As the only protein exposed on the surface of viral particles, the spike glycoprotein GP is the unique target for neutralizing monoclonal antibodies. In this study, we demonstrate the strong neutralization capacity of the monoclonal antibody #3327 and characterize its activity. GP residues that are required for recognition and neutralization were found to be located both in the internal fusion loop and in the receptor-binding domain. Analysis of Ebola virus entry in the presence of #3327 allows us to hypothesize that this antibody binds to the virus particle before internalization and endosomal processing of GP and likely prevents the final viral fusion step. Importantly, #3327 is able to block entry of virions bearing GP that contain the Q508 escape mutation common to a number of virus-neutralizing antibodies, and therefore provides future perspectives for treatment strategies against Ebola virus infection.

  4. GP73 N-glycosylation at Asn144 reduces hepatocellular carcinoma cell motility and invasiveness

    PubMed Central

    Jiang, Kai; Li, Wei; Zhang, Qinle; Yan, Guoquan; Guo, Kun; Zhang, Shu; Liu, Yinkun

    2016-01-01

    Golgi Protein 73 (GP73) is a potential liver disease glycobiomarker warranting comprehensive analyses of its glycan structure and glycosylation function. In this study, we used mass spectrometry to identify glycosylation sites and the glycan structure, high-throughput lectin microarray to provide rapid and sensitive profiling of glycoconjugates, and site-directed mutagenesis to clarify the impact of glycans on target glycoproteins in vivo. We identified three GP73 N-glycosylation sites: Asn109, Asn144 and Asn398. We found five glycoforms on Asn144, including biantennary, triantennary and fucosylated glycans. Removal of N-glycans at Asn144 enhanced the motility and invasiveness of hepatocellular carcinoma cells, possibly due to inhibition of cell adhesion related to the changes of cell membrane glycosylation. This study increases our understanding of the functional relevance of GP73 glycosylation and suggests that Asn144-deleted GP73 can influence the progression and metastasis of hepatocellular carcinoma. PMID:26993603

  5. 76 FR 28764 - Northwest Pipeline, GP; Notice of Availability of the Environmental Assessment for the Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ... Energy Regulatory Commission Northwest Pipeline, GP; Notice of Availability of the Environmental Assessment for the Proposed Molalla Capacity Replacement Project The staff of the Federal Energy Regulatory Commission (FERC or Commission) has prepared an environmental assessment (EA) for the Molalla...

  6. Membrane skeleton orchestrates the platelet glycoprotein (GP) Ib-IX complex clustering and signaling.

    PubMed

    Shang, Dan; Zhang, Zuping; Wang, Qian; Ran, Yali; Shaw, Tanner S; Van, John N; Peng, Yuandong

    2016-10-01

    Platelet glycoprotein Ib-IX complex is affixed to the membrane skeleton through interaction with actin binding protein 280 (ABP-280). We find that removal of the ABP-280 binding sites in GP Ibα cytoplasmic tail has little impact on the complex clustering induced by antibody crosslinking. However, large truncation of the GP Ibα cytoplasmic tail allows the formation of larger patches of the complex, suggesting that an ABP-280 independent force may exist. Besides, we observe that the signaling upon GP Ib-IX clustering is elicited in both membrane lipid domain dependent and independent manner, a choice that relies on how the membrane skeleton interacts with the complex. Our findings suggest a more complex mechanism for how the membrane skeleton regulates the GP Ib-IX function. © 2016 IUBMB Life, 68(10):823-829, 2016.

  7. Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

    PubMed Central

    Shen, Ling-ling; Jiang, Ming-liang; Liu, Si-si; Cai, Min-chun; Hong, Zhong-qiu; Lin, Li-qing; Xing, Yan-yan; Chen, Gui-lin; Pan, Rui; Yang, Li-juan; Xu, Ying; Dong, Jun

    2015-01-01

    Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug. PMID:26199609

  8. 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.

  9. 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.

  10. Accelerator R&D toward Muon Collider and Neutrino Factory

    NASA Astrophysics Data System (ADS)

    Shiltsev, V.

    2010-12-01

    Over the last decade there has been significant progress in developing the concepts and technologies needed to produce, capture, accelerate and collide high intensity beams of muons. At present, a high-luminosity multi-TeV muon collider presents a viable option for the next generation lepton-lepton collider, which is believed to be needed to fully explore high energy physics in the era following LHC discoveries. Such a collider can offer superb energy resolution, smaller size, and potentially cost and power consumption compared to multi-TeV e + e - linear colliders. This article briefly reviews the motivation, design and status of accelerator R&D for Muon Collider and Neutrino Factory.

  11. Accelerator R&D toward Muon Collider and Neutrino Factory

    SciTech Connect

    Shiltsev, Vladimir; /Fermilab

    2009-10-01

    Over the last decade there has been significant progress in developing the concepts and technologies needed to produce, capture, accelerate and collide high intensity beams of muons. At present, a high-luminosity multi-TeV muon collider presents a viable option for the next generation lepton-lepton collider, which is believed to be needed to fully explore high energy physics in the era following LHC discoveries. Such a collider can offer superb energy resolution, smaller size, and potentially cost and power consumption compared to multi-TeV e{sup +}e{sup -} linear colliders. This article briefly reviews the motivation, design and status of accelerator R&D for Muon Collider and Neutrino Factory.

  12. 120-mm supercondcting quadrupole for interaction regions of hadron colliders

    SciTech Connect

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

    2010-05-01

    Magnetic and mechanical designs of a Nb{sub 3}Sn quadrupole magnet with 120-mm aperture suitable for interaction regions of hadron colliders are presented. The magnet is based on a two-layer shell-type coil and a cold iron yoke. Special spacers made of a low-Z material are implemented in the coil mid-planes to reduce the level of radiation heat deposition and radiation dose in the coil. The quadrupole mechanical structure is based on aluminum collars supported by an iron yoke and a stainless steel skin. Magnet parameters including maximum field gradient and field harmonics, Nb3Sn coil pre-stress and protection at the operating temperatures of 4.5 and 1.9 K are reported. The level and distribution of radiation heat deposition in the coil and other magnet components are discussed.

  13. HIV type 1 Env precursor cleavage state affects recognition by both neutralizing and nonneutralizing gp41 antibodies.

    PubMed

    Chakrabarti, Bimal K; Pancera, Marie; Phogat, Sanjay; O'Dell, Sijy; McKee, Krisha; Guenaga, Javier; Robinson, James; Mascola, John; Wyatt, Richard T

    2011-08-01

    HIV-1 is relatively resistant to antibody-mediated neutralization; however, rare antibodies to the exterior envelope glycoprotein, gp120, and the transmembrane glycoprotein, gp41, can neutralize a broad array of isolates. Two antibodies, 2F5 and 4E10, are directed against the gp41 membrane proximal external region (MPER); however, the kinetic neutralization signature of these antibodies remains unresolved. Previously, we reported that the fully cleaved, cell surface envelope glycoproteins (Env) derived from the primary isolate, JR-FL, are well recognized exclusively by gp120-directed neutralizing ligands and not by nonneutralizing gp120 antibodies. However, the gp120 nonneutralizing antibodies can recognize HIV spikes that are rendered fully cleavage defective by site-directed mutagenesis. Here, we extended such analysis to gp41 neutralizing and nonneutralizing antibodies and, relative to the rules of gp120-specific antibody recognition, we observed marked contrasts. Similar to gp120 recognition, the nonneutralizing gp41 cluster 1 or cluster 2 antibodies bound much more efficiently to cleavage-defective spikes when compared to their recognition of cleaved spikes. In contrast to gp120 neutralizing antibody recognition, the broadly neutralizing gp41 antibodies 2F5 and 4E10, like the nonneutralizing gp41 antibodies, did not efficiently recognize the predominantly cleaved, primary isolate JR-FL spikes. However, if the spikes were rendered cleavage defective, recognition by both the neutralizing and nonneutralizing ligand markedly increased. CD4 interaction with the cleaved spikes markedly increased recognition by most nonneutralizing gp41 antibodies, whereas such treatment had a minimal increase of 2F5 and 4E10 recognition. These data indicate again the profound influence that cleavage imposes on the quaternary packing of primary isolate spikes and have important implications for soluble trimer candidate immunogens. PMID:21158699

  14. HIV type 1 Env precursor cleavage state affects recognition by both neutralizing and nonneutralizing gp41 antibodies.

    PubMed

    Chakrabarti, Bimal K; Pancera, Marie; Phogat, Sanjay; O'Dell, Sijy; McKee, Krisha; Guenaga, Javier; Robinson, James; Mascola, John; Wyatt, Richard T

    2011-08-01

    HIV-1 is relatively resistant to antibody-mediated neutralization; however, rare antibodies to the exterior envelope glycoprotein, gp120, and the transmembrane glycoprotein, gp41, can neutralize a broad array of isolates. Two antibodies, 2F5 and 4E10, are directed against the gp41 membrane proximal external region (MPER); however, the kinetic neutralization signature of these antibodies remains unresolved. Previously, we reported that the fully cleaved, cell surface envelope glycoproteins (Env) derived from the primary isolate, JR-FL, are well recognized exclusively by gp120-directed neutralizing ligands and not by nonneutralizing gp120 antibodies. However, the gp120 nonneutralizing antibodies can recognize HIV spikes that are rendered fully cleavage defective by site-directed mutagenesis. Here, we extended such analysis to gp41 neutralizing and nonneutralizing antibodies and, relative to the rules of gp120-specific antibody recognition, we observed marked contrasts. Similar to gp120 recognition, the nonneutralizing gp41 cluster 1 or cluster 2 antibodies bound much more efficiently to cleavage-defective spikes when compared to their recognition of cleaved spikes. In contrast to gp120 neutralizing antibody recognition, the broadly neutralizing gp41 antibodies 2F5 and 4E10, like the nonneutralizing gp41 antibodies, did not efficiently recognize the predominantly cleaved, primary isolate JR-FL spikes. However, if the spikes were rendered cleavage defective, recognition by both the neutralizing and nonneutralizing ligand markedly increased. CD4 interaction with the cleaved spikes markedly increased recognition by most nonneutralizing gp41 antibodies, whereas such treatment had a minimal increase of 2F5 and 4E10 recognition. These data indicate again the profound influence that cleavage imposes on the quaternary packing of primary isolate spikes and have important implications for soluble trimer candidate immunogens.

  15. N-alkylated isatins evade P-gp mediated efflux and retain potency in MDR cancer cell lines.

    PubMed

    Vine, Kara L; Belfiore, Lisa; Jones, Luke; Locke, Julie M; Wade, Samantha; Minaei, Elahe; Ranson, Marie

    2016-01-01

    The search for novel anticancer therapeutics with the ability to overcome multi-drug resistance (MDR) mechanisms is of high priority. A class of molecules that show potential in overcoming MDR are the N-alkylated isatins. In particular 5,7-dibromo-N-alkylisatins are potent microtubule destabilizing agents that act to depolymerize microtubules, induce apoptosis and inhibit primary tumor growth in vivo. In this study we evaluated the ability of four dibrominated N-alkylisatin derivatives and the parent compound, 5,7-dibromoisatin, to circumvent MDR. All of the isatin-based compounds examined retained potency against the MDR cell lines; U937VbR and MES-SA/Dx5 and displayed bioequivalent dose-dependent cytotoxicity to that of the parental control cell lines. We show that one mechanism by which the isatin-based compounds overcome MDR is by circumventing P-glycoprotein (P-gp) mediated drug efflux. Thus, as the isatin-based compounds are not susceptible to extrusion from P-gp overexpressing tumor cells, they represent a promising alternative strategy as a stand-alone or combination therapy for treating MDR cancer. PMID:27441242

  16. 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.

  17. Depolarization in the SLC Collider Arcs

    SciTech Connect

    Emma, P.; Limberg, T.; Rossmanith, R.

    1994-06-01

    In the 1993 running cycle of the Stanford Linear Collider, electron spin polarization measurements with a Moller polarimeter at the end of the linac and a Compton polarimeter near the interaction point (IP) indicated a relative polarization loss of up to 20% across the arc. The authors present calculations of the depolarizing effects where variations in energy, energy spread and transverse emittance as well as changes in orbit and initial spin orientation are taken into account. They compare their results with measurements and conclude that, in standard operating conditions, the relative polarization loss is only 3{+-}2%.

  18. 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.

  19. Nonlinear resonant collimation for future linear colliders

    NASA Astrophysics Data System (ADS)

    Emma, P.; Helm, R.; Nosochkov, Y.; Pitthan, R.; Raubenheimer, T.; Thompson, K.; Zimmermann, F.

    1999-04-01

    We present a scheme for collimating large amplitude particles in the main linacs of a linear collider, by adding octupoles to the FODO lattice of the linac. With this scheme the requirements on downstream collimation can be greatly reduced or perhaps even eliminated. An analytic estimate of the amplitude at which particles are lost is made by calculating the separatrix of the fourth order resonance, and is in good agreement with the results of simulations. Simulations of particle distributions in the beam core and halo are presented, as well as alignment tolerances for the octupoles.

  20. 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.