Channeling and Volume Reflection Based Crystal Collimation of Tevatron Circulating Beam Halo (T-980)

The T980 crystal collimation experiment is underway at the Tevatron to determine if this technique could increase 980 GeV beam-halo collimation efficiency at high-energy hadron colliders such as the Tevatron and the LHC. T980 also studies various crystal types and parameters. The setup has been substantially enhanced during the Summer 2009 shutdown by installing a new O-shaped crystal in the horizontal goniometer, as well as adding a vertical goniometer with two alternating crystals (O-shaped and multi-strip) and additional beam diagnostics. First measurements with the new system are quite encouraging, with channeled and volume-reflected beams observed on the secondary collimators as predicted. Investigation of crystal collimation efficiencies with crystals in volume reflection and channeling modes are described in comparison with an amorphous primary collimator. Results on the system performance are presented for the end-of-store studies and for entire collider stores. The first investigation of colliding beam collimation simultaneously using crystals in both the vertical and horizontal plane has been made in the regime with horizontally channeled and vertically volume-reflected beams. Planning is underway for significant hardware improvements during the FY10 summer shutdown and for dedicated studies during the final year of Tevatron operation and also for a "post-collider beam physics running" period.Comment: 3 pp. 1st International Particle Accelerator Conference: IPAC'10, 23-28 May 2010: Kyoto, Japa

Class I major histocompatibility complexes loaded by a periodate trigger

Class I major histocompatibility complexes (MHCs) present peptide ligands on the cell surface for recognition by appropriate cytotoxic T cells. The unstable nature of unliganded MHC necessitates the production of recombinant class I complexes through in vitro refolding reactions in the presence of an added excess of peptides. This strategy is not amenable to high-throughput production of vast collections of class I complexes. To address this issue, we recently designed photocaged MHC ligands that can be cleaved by a UV light trigger in the MHC bound state under conditions that do not affect the integrity of the MHC structure. The results obtained with photocaged MHC ligands demonstrate that conditional MHC ligands can form a generally applicable concept for the creation of defined peptide−MHCs. However, the use of UV exposure to mediate ligand exchange is unsuited for a number of applications, due to the lack of UV penetration through cell culture systems and due to the transfer of heat upon UV irradiation, which can induce evaporation. To overcome these limitations, here, we provide proof-of-concept for the generation of defined peptide−MHCs by chemical trigger-induced ligand exchange. The crystal structure of the MHC with the novel chemosensitive ligand showcases that the ligand occupies the expected binding site, in a conformation where the hydroxyl groups should be reactive to periodate. We proceed to validate this technology by producing peptide−MHCs that can be used for T cell detection. The methodology that we describe here should allow loading of MHCs with defined peptides in cell culture devices, thereby permitting antigen-specific T cell expansion and purification for cell therapy. In addition, this technology will be useful to develop miniaturized assay systems for performing high-throughput screens for natural and unnatural MHC ligands

Uncoupled excitons in semiconductor microcavities detected in resonant Raman scattering

We present an outgoing resonant Raman-scattering study of a GaAs/AlGaAs based microcavity embedded in a p-i-n junction. The p-i-n junction allows the vertical electric field to be varied, permitting control of exciton-photon detuning and quenching of photoluminescence which otherwise obscures the inelastic light scattering signals. Peaks corresponding to the upper and lower polariton branches are observed in the resonant Raman cross sections, along with a third peak at the energy of uncoupled excitons. This third peak, attributed to disorder activated Raman scattering, provides clear evidence for the existence of uncoupled exciton reservoir states in microcavities in the strong-coupling regime

A Very Intense Neutrino Super Beam Experiment for Leptonic CP Violation Discovery based on the European Spallation Source Linac: A Snowmass 2013 White Paper

Very intense neutrino beams and large neutrino detectors will be needed in order to enable the discovery of CP violation in the leptonic sector. We propose to use the proton linac of the European Spallation Source currently under construction in Lund, Sweden to deliver, in parallel with the spallation neutron production, a very intense, cost effective and high performance neutrino beam. The baseline program for the European Spallation Source linac is that it will be fully operational at 5 MW average power by 2022, producing 2 GeV 2.86 ms long proton pulses at a rate of 14 Hz. Our proposal is to upgrade the linac to 10 MW average power and 28 Hz, producing 14 pulses/s for neutron production and 14 pulses/s for neutrino production. Furthermore, because of the high current required in the pulsed neutrino horn, the length of the pulses used for neutrino production needs to be compressed to a few $\mu$s with the aid of an accumulator ring. A long baseline experiment using this Super Beam and a megaton underground Water Cherenkov detector located in existing mines 300-600 km from Lund will make it possible to discover leptonic CP violation at 5 $\sigma$ significance level in up to 50% of the leptonic Dirac CP-violating phase range. This experiment could also determine the neutrino mass hierarchy at a significance level of more than 3 $\sigma$ if this issue will not already have been settled by other experiments by then. The mass hierarchy performance could be increased by combining the neutrino beam results with those obtained from atmospheric neutrinos detected by the same large volume detector. This detector will also be used to measure the proton lifetime, detect cosmological neutrinos and neutrinos from supernova explosions. Results on the sensitivity to leptonic CP violation and the neutrino mass hierarchy are presented.Comment: 28 page

Nb3Sn quadrupoles in the LHC IR Phase I upgrade

After a number of years of operation at nominal parameters, the LHC will be upgraded to a higher luminosity. This paper discusses the possibility of using a limited number of Nb{sub 3}Sn quadrupoles for hybrid optics layouts for the LHC Phase I luminosity upgrades with both NbTi and Nb{sub 3}Sn quadrupoles. Magnet parameters and issues related to using Nb{sub 3}Sn quadrupoles including aperture, gradient, magnetic length, field quality, operation margin, et cetera are discussed

Combination CTLA-4 Blockade and 4-1BB Activation Enhances Tumor Rejection by Increasing T-Cell Infiltration, Proliferation, and Cytokine Production

BACKGROUND: The co-inhibitory receptor Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) attenuates immune responses and prevent autoimmunity, however, tumors exploit this pathway to evade the host T-cell response. The T-cell co-stimulatory receptor 4-1BB is transiently upregulated on T-cells following activation and increases their proliferation and inflammatory cytokine production when engaged. Antibodies which block CTLA-4 or which activate 4-1BB can promote the rejection of some murine tumors, but fail to cure poorly immunogenic tumors like B16 melanoma as single agents.METHODOLOGY/PRINCIPAL FINDINGS: We find that combining ?CTLA-4 and ?4-1BB antibodies in the context of a Flt3-ligand, but not a GM-CSF, based B16 melanoma vaccine promoted synergistic levels of tumor rejection. 4-1BB activation elicited strong infiltration of CD8+ T-cells into the tumor and drove the proliferation of these cells, while CTLA-4 blockade did the same for CD4+ effector T-cells. Anti-4-1BB also depressed regulatory T-cell infiltration of tumors. 4-1BB activation strongly stimulated inflammatory cytokine production in the vaccine and tumor draining lymph nodes and in the tumor itself. The addition of CTLA-4 blockade further increased IFN-? production from CD4+ effector T-cells in the vaccine draining node and the tumor. Anti 4-1BB treatment, with or without CTLA-4 blockade, induced approximately 75% of CD8+ and 45% of CD4+ effector T-cells in the tumor to express the killer cell lectin-like receptor G1 (KLRG1). Tumors treated with combination antibody therapy showed 1.7-fold greater infiltration by these KLRG1+CD4+ effector T-cells than did those treated with ?4-1BB alone.CONCLUSIONS/SIGNIFICANCE: This study shows that combining T-cell co-inhibitory blockade with ?CTLA-4 and active co-stimulation with ?4-1BB promotes rejection of B16 melanoma in the context of a suitable vaccine. In addition, we identify KLRG1 as a useful marker for monitoring the anti-tumor immune response elicited by this therapy. These findings should aid in the design of future trials for the immunotherapy of melanoma