1,883 research outputs found

    Class I major histocompatibility complexes loaded by a periodate trigger

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    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

    Constraints from Solar and Reactor Neutrinos on Unparticle Long-Range Forces

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    We have investigated the impact of long-range forces induced by unparticle operators of scalar, vector and tensor nature coupled to fermions in the interpretation of solar neutrinos and KamLAND data. If the unparticle couplings to the neutrinos are mildly non-universal, such long-range forces will not factorize out in the neutrino flavour evolution. As a consequence large deviations from the observed standard matter-induced oscillation pattern for solar neutrinos would be generated. In this case, severe limits can be set on the infrared fix point scale, Lambda_u, and the new physics scale, M, as a function of the ultraviolet (d_UV) and anomalous (d) dimension of the unparticle operator. For a scalar unparticle, for instance, assuming the non-universality of the lepton couplings to unparticles to be of the order of a few per mil we find that, for d_UV=3 and d=1.1, M is constrained to be M > O(10^9) TeV (M > O(10^10) TeV) if Lambda_u= 1 TeV (10 TeV). For given values of Lambda_u and d, the corresponding bounds on M for vector [tensor] unparticles are approximately 100 [3/Sqrt(Lambda_u/TeV)] times those for the scalar case. Conversely, these results can be translated into severe constraints on universality violation of the fermion couplings to unparticle operators with scales which can be accessible at future colliders.Comment: 13 pages, 3 figures. Minor changes due to precision in numerical factors and correction in figure labels. References added. Conclusions remain unchange

    Measurement of the Negative Muon Anomalous Magnetic Moment to 0.7 ppm

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    The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 parts per million (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement of the negative muon. The result a_mu= 11 659 214(8)(3) \times 10^{-10} (0.7 ppm), where the first uncertainty is statistical and the second is sytematic, is consistend with previous measurements of the anomaly for the positive and negative muon. The average for the muon anomaly a_{mu}(exp) = 11 659 208(6) \times 10^{-10} (0.5ppm).Comment: 4 pages, 4 figures, submitted to Physical Review Letters, revised to reflect referee comments. Text further revised to reflect additional referee comments and a corrected Fig. 3 replaces the older versio

    Les Houches 2015: Physics at TeV colliders - new physics working group report

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    We present the activities of the 'New Physics' working group for the 'Physics at TeV Colliders' workshop (Les Houches, France, 1-19 June, 2015). Our report includes new physics studies connected with the Higgs boson and its properties, direct search strategies, reinterpretation of the LHC results in the building of viable models and new computational tool developments. Important signatures for searches for natural new physics at the LHC and new assessments of the interplay between direct dark matter searches and the LHC are also considered.Comment: Proceedings of the New Physics Working Group of the 2015 Les Houches Workshop, Physics at TeV Colliders, Les Houches 1-19 June 2015. 197 page

    Fast calculation of thermodynamic and structural parameters of solutions using the 3DRISM model and the multi-grid method

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    In the paper a new method to solve the tree-dimensional reference interaction site model (3DRISM) integral equations is proposed. The algorithm uses the multi-grid technique which allows to decrease the computational expanses. 3DRISM calculations for aqueous solutions of four compounds (argon, water, methane, methanol) on the different grids are performed in order to determine a dependence of the computational error on the parameters of the grid. It is shown that calculations on the grid with the step 0.05\Angstr and buffer 8\Angstr give the error of solvation free energy calculations less than 0.3 kcal/mol which is comparable to the accuracy of the experimental measurements. The performance of the algorithm is tested. It is shown that the proposed algorithm is in average more than 12 times faster than the standard Picard direct iteration method.Comment: the information in this preprint is not up to date. Since the first publication of the preprint (9 Nov 2011) the algorithm was modified which allowed to achieve better results. For the new algorithm see the JCTC paper: DOI: 10.1021/ct200815v, http://pubs.acs.org/doi/abs/10.1021/ct200815

    Phytochemicals as antibiotic alternatives to promote growth and enhance host health

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    There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

    The substructure of three repetitive DNA regions of Schistosoma haematobium group species as a potential marker for species recognition and interbreeding detection

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    The file attached is the Published/publisher’s pdf version of the article.© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

    The Anti-Inflammatory and Antibacterial Basis of Human Omental Defense: Selective Expression of Cytokines and Antimicrobial Peptides

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    BACKGROUND: The wound healing properties of the human omentum are well known and have extensively been exploited clinically. However, the underlying mechanisms of these effects are not well understood. We hypothesize that the omentum tissue promotes wound healing via modulation of anti-inflammatory pathways, and because the omentum is rich in adipocytes, the adipocytes may modulate the anti-inflammatory response. Factors released by human omentum may affect healing, inflammation and immune defense. METHODOLOGY: Six human omentum tissues (non obese, free from malignancy, and any other systemic disorder) were obtained during diagnostic laparoscopies having a negative outcome. Healthy oral mucosa (obtained from routine oral biopsies) was used as control. Cultured adipocytes derived from human omentum were exposed to lipopolysaccharide (LPS) (1-50 ng/mL) for 12-72 hours to identify the non-cytotoxic doses. Levels of expression (mRNA and protein) were carried out for genes associated with pro- and anti-inflammatory cytokine responses and antibacterial/antimicrobial activity using qRT-PCR, western blotting, and cell-based ELISA assays. RESULTS: The study shows significant higher levels of expression (mRNA and protein) of several specific cytokines, and antibacterial peptides in the omentum tissues when compared to oral sub-mucosal tissues. In the validation studies, primary cultures of adipocytes, derived from human omentum were exposed to LPS (5 and 10 ng/mL) for 24 and 48 h. The altered expressions were more pronounced in cultured adipocytes cells when exposed to LPS as compared to the omentum tissue. CONCLUSIONS/SIGNIFICANCE: Perhaps, this is the first report that provides evidence of expressional changes in pro- and anti-inflammatory cytokines and antibacterial peptides in the normal human omentum tissue as well as adipocytes cultured from this tissue. The study provides new insights on the molecular and cellular mechanisms of healing and defense by the omentum, and suggests the potential applicability of cultured adipocytes derived from the omentum for future therapeutic applications
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