266 research outputs found
US-LHC Magnet Database and conventions
The US-LHC Magnet Database is designed for production-magnet quality assurance, field and alignment error impact analysis, cryostat assembly assistance, and ring installation assistance. The database consists of tables designed to store magnet field and alignment measurements data and quench data. This information will also be essential for future machine operations including local IR corrections. (7 refs)
Multi-species sociology of the body
The human body has become a central focus in sociology. Such work has centred largely on the human body and its significance in social contexts. This article draws on sociological understandings of human embodiment, especially the idea of the âbody as a projectâ, to facilitate a multi-species understanding of bodies and their entanglements. Conceptualising the body as a project has provided sociological insights into the scientific and technological innovations that are designed to improve health and delay death. Nonhuman animals are entangled in these efforts, though their presence is often occluded. By examining notions of body masks, body regimes and body options, which are well established in sociological thinking about the body, this article seeks to prompt consideration of how to utilise theories of the body to examine humanânonhuman animal entanglements in order to establish a multi-species sociology of the body
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 peptideâMHCs. 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 peptideâMHCs 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 peptideâMHCs 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
Societal sentience: constructions of the public in animal research policy and practice
The use of non-human animals as models in research and drug testing is a key route through which contemporary scientific knowledge is certified. Given ethical concerns, regulation of animal research promotes the use of less âsentientâ animals. This paper draws on a documentary analysis of legal documents, and qualitative interviews with Named Veterinary Surgeons and others at a commercial laboratory in the UK. Its key claim is that the concept of animal sentience is entangled with a particular imaginary of how the general public or wider society views animals. We call this imaginary societal sentience. Against a backdrop of increasing ethnographic work on care encounters in the laboratory, this concept helps to stress the wider context within which such encounters take place. We conclude that societal sentience has potential purchase beyond the animal research field, in helping to highlight the affective dimension of public imaginaries (Welsh and Wynne 2013), and their ethical consequences. Researching and critiquing societal sentience, we argue, may ultimately have more impact on the fate of humans and non-humans in the laboratory, than focusing wholly on ethics as situated practice
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 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 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 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
Conceptual design of a nonscaling fixed field alternating gradient accelerator for protons and carbon ions for charged particle therapy
Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articleâs title, journal citation, and DOI.The conceptual design for a nonscaling fixed field alternating gradient accelerator suitable for charged particle therapy (the use of protons and other light ions to treat some forms of cancer) is described.EPSR
Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
PURPOSE
Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with a fast off rate, designed for more physiologic T-cell activation to reduce toxicity and improve engraftment. We describe the multicenter phase I ALLCAR19 (NCT02935257) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r/r) adult B-ALL.
METHODS
Patients age â„ 16 years with r/r B-ALL were eligible. Primary outcomes were toxicity and manufacturing feasibility. Secondary outcomes were depth of response at 1 and 3 months, persistence of CAR-T, incidence and duration of hypogammaglobulinemia and B-cell aplasia, and event-free survival and overall survival at 1 and 2 years.
RESULTS
Twenty-five patients were leukapheresed, 24 products were manufactured, and 20 patients were infused with AUTO1. The median age was 41.5 years; 25% had prior blinatumomab, 50% prior inotuzumab ozogamicin, and 65% prior allogeneic stem-cell transplantation. At the time of preconditioning, 45% had â„ 50% bone marrow blasts. No patients experienced â„ grade 3 cytokine release syndrome; 3 of 20 (15%) experienced grade 3 neurotoxicity that resolved to †grade 1 within 72 hours with steroids. Seventeen of 20 (85%) achieved minimal residual diseaseânegative complete response at month 1, and 3 of 17 underwent allogeneic stem-cell transplantation while in remission. The event-free survival at 6 and 12 months was 68.3% (42.4-84.4) and 48.3% (23.1%-69.7%), respectively. High-level expansion (Cmax 127,152 copies/”g genomic DNA) and durable CAR-T persistence were observed with B-cell aplasia ongoing in 15 of 20 patients at last follow-up.
CONCLUSION
AUTO1 demonstrates a tolerable safety profile, high remission rates, and excellent persistence in r/r adult B-ALL. Preliminary data support further development of AUTO1 as a stand-alone treatment for r/r adult B-ALL
CMV-specific T cell isolation from G-CSF mobilized peripheral blood: depletion of myeloid progenitors eliminates non-specific binding of MHC-multimers
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