Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.

Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine

Test-beam and laboratory characterisation of the TORCH prototype detector

The TORCH time-of-flight (TOF) detector is being developed to provide particle identification up to a momentum of 10 GeV/c over a flight distance of 10 m. It has a DIRC-like construction with View the MathML source10mm thick synthetic amorphous fused-silica plates as a Cherenkov radiator. Photons propagate by total internal reflection to the plate periphery where they are focused onto an array of customised position-sensitive micro-channel plate (MCP) detectors. The goal is to achieve a 15 ps time-of-flight resolution per incident particle by combining arrival times from multiple photons. The MCPs have pixels of effective size 0.4 mm×6.6 mm2 in the vertical and horizontal directions, respectively, by incorporating a novel charge-sharing technique to improve the spatial resolution to better than the pitch of the readout anodes. Prototype photon detectors and readout electronics have been tested and calibrated in the laboratory. Preliminary results from testbeam measurements of a prototype TORCH detector are also presented

Neutron skin of 208^{208}Pb from Coherent Pion Photoproduction

Information on the size and shape of the neutron skin on $^{208}$Pb has been extracted from coherent pion photoproduction cross sections measured using the Crystal Ball together with the Glasgow tagger at the MAMI electron beam facility. On exploitation of an interpolated fit of a theoretical model to the measured cross sections the half-height radius and diffuseness of the neutron distribution are found to be 6.70$\pm 0.03(stat)$ fm and 0.55$\pm 0.01(stat)$$^{+0.02}_{-0.03}(sys)$ fm respectively, corresponding to a neutron skin thickness $\Delta r_{np}$=0.15$\pm 0.03(stat)$$^{+0.01}_{-0.03}(sys)$ fm. The results give the first successful extraction of a neutron skin with an electromagnetic probe and indicate the skin of $^{208}$Pb has a halo character. The measurement provides valuable new constraints on both the structure of nuclei and the equation of state for neutron-rich matter.Comment: 4 figures 5 pages. Version submitted to journal. Includes additional studies of systematic effects in the extracted diffuseness, which led to a small increase in the quoted systematic error. These additional studies are discussed in the revised manuscript. Also includes minor editorial improvements to the tex

Search for eta-mesic 4He in the dd->3He n pi0 and dd->3He p pi- reactions with the WASA-at-COSY facility

The search for 4He-eta bound states was performed with the WASA-at-COSY facility via the measurement of the excitation function for the dd->3He n pi0 and dd->3He p pi- processes. The beam momentum was varied continuously between 2.127 GeV/c and 2.422 GeV/c, corresponding to the excess energy for the dd->4He eta reaction ranging from Q=-70 MeV to Q=30 MeV. The luminosity was determined based on the dd->3He n reaction and quasi-free proton-proton scattering via dd->pp n_spectator n_spectator reactions. The excitation functions determined independently for the measured reactions do not reveal a structure which could be interpreted as a narrow mesic nucleus. Therefore, the upper limits of the total cross sections for the bound state production and decay in dd->(4He-eta)_bound->3He n pi0 and dd->(4He-eta)_bound->3He p pi- processes were determined taking into account the isospin relation between both the channels considered. The results of the analysis depend on the assumptions of the N* momentum distribution in the anticipated mesic-4He. Assuming as in the previous works, that this is identical with the distribution of nucleons bound with 20 MeV in 4He, we determined that (for the mesic bound state width in the range from 5 MeV to 50 MeV) the upper limits at 90% confidence level are about 3 nb and about 6 nb for npi0 and ppi- channels, respectively. However, based on the recent theoretical findings of the N*(1535) momentum distribution in the N*-3He nucleus bound by 3.6 MeV, we find that the WASA-at-COSY detector acceptance decreases and hence the corresponding upper limits are 5 nb and 10 nb for npi0 and ppi- channels respectively.Comment: This article will be submitted to JHE

Search for the eta-mesic 4He with WASA-at-COSY detector

An exclusive measurement of the excitation function for the dd->3Heppi- reaction was performed at the Cooler Synchrotron COSY-Juelich with the WASA-at-COSY detection system. The data were taken during a slow acceleration of the beam from 2.185 GeV/c to 2.400 GeV/c crossing the kinematic threshold for the eta meson production in the dd->4He-eta reaction at 2.336 GeV/c. The corresponding excess energy with respect to the 4He-eta system varied from -51.4MeV to 22MeV. The integrated luminosity in the experiment was determined using the dd->3Hen reaction. The shape of the excitation function for the dd->3Heppi- was examined. No signal of the 4He-eta bound state was observed. An upper limit for the cross-section for the bound state formation and decay in the process dd->(4He-eta)bound->3Heppi- was determined on the 90% confidence level and it varies from 20nb to 27nb for the bound state width ranging from 5MeV to 35MeV, respectively.Comment: 8 pages, 9 figure

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

Technical Design Report for the: PANDA Micro Vertex Detector

This document illustrates the technical layout and the expected performance of the Micro Vertex Detector (MVD) of the PANDA experiment. The MVD will detect charged particles as close as possible to the interaction zone. Design criteria and the optimisation process as well as the technical solutions chosen are discussed and the results of this process are subjected to extensive Monte Carlo physics studies. The route towards realisation of the detector is outlined.Comment: 189 pages, 225 figures, 41 table

Physics Performance Report for PANDA: Strong Interaction Studies with Antiprotons

To study fundamental questions of hadron and nuclear physics in interactions of antiprotons with nucleons and nuclei, the universal PANDA detector will be built. Gluonic excitations, the physics of strange and charm quarks and nucleon structure studies will be performed with unprecedented accuracy thereby allowing high-precision tests of the strong interaction. The proposed PANDA detector is a state-of-the art internal target detector at the HESR at FAIR allowing the detection and identification of neutral and charged particles generated within the relevant angular and energy range. This report presents a summary of the physics accessible at PANDA and what performance can be expected.Comment: 216 page

Verbundvorhaben 'Abrasivverschleiss von Bau- und Baustoffmaschinen' Abrasivitaet mineralischer Stoffe. Abschlussbericht

SIGLETIB: FR 4919 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman