7,056 research outputs found

    Neutron spectroscopic factors of Ni isotopes from transfer reactions

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    177 neutron spectroscopic factors for nickel isotopes have been extracted by performing a systematic analysis of the angular distributions measured from (d,p) transfer reactions. A subset of the extracted spectroscopic factors are compared to predictions of large-basis shell models in the full pf model space using the GXPF1A effective interaction, and the (f5/2, p3/2, p1/2, g9/2) model space using the JJ4PNA interaction. For ground states, the predicted spectroscopic factors using the GXPF1A effective interaction in the full pf model space agree very well with the experimental values, while predictions based on several other effective interactions and model spaces are about 30% higher than the experimental values. For low-energy excited states (<3.5 MeV), the agreement between the extracted spectroscopic factors and shell model calculations is not better than a factor of two.Comment: 18 pages, 4 figures, 2 tables. accepted for publication in PR

    CD4+ T-cell responses to Epstein-Barr virus nuclear antigen EBNA1 in Chinese populations are highly focused on novel C-terminal domain-derived epitopes

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    Epstein-Barr virus nuclear antigen EBNA1, the one viral protein uniformly expressed in nasopharyngeal carcinoma (NPC), represents a prime target for T-cell-based immunotherapy. However, little is known about the EBNA1 epitopes, particularly CD4 epitopes, presented by HLA alleles in Chinese people, the group at highest risk for NPC. We analyzed the CD4+^+ T-cell responses to EBNA1 in 78 healthy Chinese donors and found marked focusing on a small number of epitopes in the EBNA1 C-terminal region, including a DP5- restricted epitope that was recognized by almost half of the donors tested and elicited responses able to recognize EBNA1-expressing, DP5-positive target cells

    CD4+ T-cell responses to Epstein-Barr virus (EBV) latent-cycle antigens and the recognition of EBV-transformed lymphoblastoid cell lines

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    There is considerable interest in the potential of Epstein-Barr virus (EBV) latent antigen-specific CD4+^+ T cells to act as direct effectors controlling EBV-induced B lymphoproliferations. Such activity would require direct CD4+^+ T-cell recognition of latently infected cells through epitopes derived from endogenously expressed viral proteins and presented on the target cell surface in association with HLA class II molecules. It is therefore important to know how often these conditions are met. Here we provide CD4+^+ epitope maps for four EBV nuclear antigens, EBNA1, -2, -3A, and -3C, and establish CD4+^+ T-cell clones against 12 representative epitopes. For each epitope we identify the relevant HLA class II restricting allele and determine the efficiency with which epitope-specific effectors recognize the autologous EBV-transformed B-lymphoblastoid cell line (LCL). The level of recognition measured by gamma interferon release was consistent among clones to the same epitope but varied between epitopes, with values ranging from 0 to 35% of the maximum seen against the epitope peptide-loaded LCL. These epitope-specific differences, also apparent in short-term cytotoxicity and longer-term outgrowth assays on LCL targets, did not relate to the identity of the source antigen and could not be explained by the different functional avidities of the CD4+^+ clones; rather, they appeared to reflect different levels of epitope display at the LCL surface. Thus, while CD4+^+ T-cell responses are detectable against many epitopes in EBV latent proteins, only a minority of these responses are likely to have therapeutic potential as effectors directly recognizing latently infected target cells

    Negotiating sexuality and masculinity in school sport: An autoethnography

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    This autoethnography explores challenging and ethically sensitive issues around sexual orientation, sexual identity and masculinity in the context of school sport. Through storytelling, I aim to show how sometimes ambiguous encounters with heterosexism, homophobia and hegemonic masculinity through sport problematise identity development for young same-sex attracted males. By foregrounding personal embodied experience, I respond to an absence of stories of gay and bisexual experiences among males in physical education and school sport, in an effort to reduce a continuing sense of Otherness and difference regarding same-sex attracted males. I rely on the story itself to express the embodied forms of knowing that inhabit the experiences I describe, and resist a finalising interpretation of the story. Instead, I offer personal reflections on particular theoretical and methodological issues which relate to both the form and content of the story

    MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

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    AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p
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