Beam instrumentation for the RFQ injector at CRYRING

DOI: 10.1017/S000497271600041

Beam Instrumentation for CRYRING@@ESR

BACKGROUND: The disulfide-bonded region (DSR) of HIV-1 gp41 mediates association with gp120 and plays a role in transmission of receptor-induced conformational changes in gp120 to gp41 that activate membrane fusion function. In this study, forced viral evolution of a DSR mutant that sheds gp120 was employed to identify domains within gp120-gp41 that are functionally linked to the glycoprotein association site. RESULTS: The HIV-1AD8 mutant, W596L/K601D, was serially passaged in U87.CD4.CCR5 cells until replication was restored. Whereas the W596L mutation persisted throughout the cultures, a D601H pseudoreversion in the DSR partially restored cell-free virus infectivity and virion gp120-gp41 association, with further improvements to cell-free virus infectivity following a 2nd-site D674E mutation in the membrane-proximal external region (MPER) of gp41. In an independent culture, D601H appeared with a deletion in V4 (Thr-394-Trp-395) and a D674N substitution in the MPER, however this MPER mutation was inhibitory to W596L/K601H cell-free virus infectivity. While cell-free virus infectivity was not fully restored for the revertant genotypes, their cell-to-cell transmission approached the levels observed for WT. Interestingly, the functional boost associated with the addition of D674E to W596L/K601H was not observed for cell-cell fusion where the cell-surface expressed glycoproteins function independently of virion assembly. The W596L/K601H and W596L/K601H/D674E viruses exhibited greater sensitivity to neutralization by the broadly reactive MPER directed monoclonal antibodies, 2F5 and 4E10, indicating that the reverting mutations increase the availability of conserved neutralization epitopes in the MPER. CONCLUSIONS: The data indicate for the first time that functional crosstalk between the DSR and MPER operates in the context of assembled virions, with the Leu-596-His-601-Glu-674 combination optimizing viral spread via the cell-to-cell route. Our data also indicate that changes in the gp120-gp41 association site may increase the exposure of conserved MPER neutralization epitopes in virus

GO-GN conceptual frameworks guide

This collaboratively written book brings together insights from a range of researchers into their use of conceptual frameworks in studying open education. Also included is an overview of different approaches to understanding the role(s) of theories and conceptual frameworks in doctoral research. In addition to discussing the different ways that conceptual frameworks are used we provide a (selective) overview of a range of conceptual frameworks and examples of their use. The GO-GN Conceptual Frameworks Guide is intended for those working in doctoral research but accessible enough to be used by anyone interested in carrying out a research project.Librar

Search for Extended Sources of Neutrino Emission in the Galactic Plane with IceCube

The Galactic plane, harboring a diffuse neutrino flux, is a particularly interesting target to study potential cosmic-ray acceleration sites. Recent gamma-ray observations by HAWC and LHAASO have presented evidence for multiple Galactic sources that exhibit a spatially extended morphology and have energy spectra continuing beyond 100 TeV. A fraction of such emission could be produced by interactions of accelerated hadronic cosmic rays, resulting in an excess of high-energy neutrinos clustered near these regions. Using 10 years of IceCube data comprising track-like events that originate from charged-current muon neutrino interactions, we perform a dedicated search for extended neutrino sources in the Galaxy. We find no evidence for time-integrated neutrino emission from the potential extended sources studied in the Galactic plane. The most significant location, at 2.6$\sigma$ post-trials, is a 1.7$^\circ$ sized region coincident with the unidentified TeV gamma-ray source 3HWC J1951+266. We provide strong constraints on hadronic emission from several regions in the Galaxy.Comment: 13 pages, 4 figures, 5 tables including an appendix. Accepted for publication in Astrophysical Journa

Exploring Predictors of Outcome in the Psychosis Prodrome: Implications for Early Identification and Intervention

Functional disability is a key component of many psychiatric illnesses, particularly schizophrenia. Impairments in social and role functioning are linked to cognitive deficits, a core feature of psychosis. Retrospective analyses demonstrate that substantial functional decline precedes the onset of psychosis. Recent investigations reveal that individuals at clinical-high-risk (CHR) for psychosis show impairments in social relationships, work/school functioning and daily living skills. CHR youth also demonstrate a pattern of impairment across a range of cognitive domains, including social cognition, which is qualitatively similar to that of individuals with schizophrenia. While many studies have sought to elucidate predictors of clinical deterioration, specifically the development of schizophrenia, in such CHR samples, few have investigated factors relevant to psychosocial outcome. This review integrates recent findings regarding cognitive and social-cognitive predictors of outcome in CHR individuals, and proposes potential directions for future research that will contribute to targeted interventions and improved outcome for at-risk youth

Mechanical design of the optical modules intended for IceCube-Gen2

IceCube-Gen2 is an expansion of the IceCube neutrino observatory at the South Pole that aims to increase the sensitivity to high-energy neutrinos by an order of magnitude. To this end, about 10,000 new optical modules will be installed, instrumenting a fiducial volume of about 8 km3. Two newly developed optical module types increase IceCube’s current sensitivity per module by a factor of three by integrating 16 and 18 newly developed four-inch PMTs in specially designed 12.5-inch diameter pressure vessels. Both designs use conical silicone gel pads to optically couple the PMTs to the pressure vessel to increase photon collection efficiency. The outside portion of gel pads are pre-cast onto each PMT prior to integration, while the interiors are filled and cast after the PMT assemblies are installed in the pressure vessel via a pushing mechanism. This paper presents both the mechanical design, as well as the performance of prototype modules at high pressure (70 MPa) and low temperature (−40∘C), characteristic of the environment inside the South Pole ice

The next generation neutrino telescope: IceCube-Gen2

The IceCube Neutrino Observatory, a cubic-kilometer-scale neutrino detector at the geographic South Pole, has reached a number of milestones in the field of neutrino astrophysics: the discovery of a high-energy astrophysical neutrino flux, the temporal and directional correlation of neutrinos with a flaring blazar, and a steady emission of neutrinos from the direction of an active galaxy of a Seyfert II type and the Milky Way. The next generation neutrino telescope, IceCube-Gen2, currently under development, will consist of three essential components: an array of about 10,000 optical sensors, embedded within approximately 8 cubic kilometers of ice, for detecting neutrinos with energies of TeV and above, with a sensitivity five times greater than that of IceCube; a surface array with scintillation panels and radio antennas targeting air showers; and buried radio antennas distributed over an area of more than 400 square kilometers to significantly enhance the sensitivity of detecting neutrino sources beyond EeV. This contribution describes the design and status of IceCube-Gen2 and discusses the expected sensitivity from the simulations of the optical, surface, and radio components