15,234 research outputs found

    Pulmonary surfactant and neutrophil function in cystic fibrosis

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    SIGLEAvailable from British Library Document Supply Centre-DSC:DXN032545 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    Short fiction set in Maine by author Ann Hood.

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    Short fiction set in Maine by author Ann Hood

    Knock-down of LAR protein tyrosine phosphatase induces insulin resistance

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    To test the role of the leukocyte common antigen-related protein tyrosine phosphatase (LAR) as a regulator of insulin receptor (IR) signalling, an siRNA probe against LAR was developed. Knock-down of LAR induced post-receptor insulin resistance with the insulin-induced activation of PKB/Akt and MAP kinases markedly inhibited. The phosphorylation and dephosphorylation of the IR and insulin receptor substrate (IRS) proteins were unaffected by LAR knock-down. These results identify LAR as a crucial regulator of the sensitivity of two key insulin signalling pathways to insulin. Moreover, the siRNA probe provides a molecular tool of general applicability for further dissecting the precise targets and roles of LAR

    Ann Arbor, Michigan: An Historical Analysis Of Board Of Education Decisions On School Desegregation Issues.

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    Purpose of the Study. This study focused on the history of the Ann Arbor Public School System's desegregation and school attendance decisions, from the Brown decision to the present. The purpose was to write an historical analysis of Board of Education decisions regarding racial balance and imbalance in Ann Arbor Public Schools. Specifically, the Board of Education, the administration, and the community were studied concerning four historically relevant decisions: (1) The closing of Jones School in 1965; (2) New building sites in the years 1965-1976; (A) Bryant/Clinton; (B) Logan/Northside; (3) Employment practices; i.e., hiring of and placement of minority staff, 1969-1978; and (4) The busing of North Campus children, 1970-1978. Methodology. Background information on school desegregation in three perspectives was first presented. This included historical information, research findings on methods and results of school desegregation, and a study of local Michigan districts which have undergone court-enforced desegregation. Four questions were developed to provide a focus for historical analysis of the Ann Arbor Board of Education's decisions: (1) What was the situational environment in which each decision was made by the Board of Education? (2) How did the community react to the Board of Education's decision? (3) Was the effect of each decision more or less segregation in the Ann Arbor Public Schools? (4) Did choices or options exist to the Board of Education at the time of the decision which would have possibly resulted in a less segregated situation? Findings. In all instances of new school openings, more rather than less segregation followed the Board's decision. The Jones School closing was found to be the last major decision that led to purposeful desegregation. Placement of academic staff, in particular, added to the inbalance in several elementary schools. In the 1977-78 school year, the Michigan State Board of Education categorized Ann Arbor's school system as racially imbalanced, and requested action on the part of local authorities to rectify this situation within 90 days. The Ann Arbor Board's progress toward the achievement of voluntary desegregation has included the appointment of a citizens' committee. The author concludes that the Board's voluntary commitment to take action to improve racial balance is a wise and proper course of action, since possible implications of past actions could be used in a court case against the system.PhDBilingual educationEducationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/127544/2/8025652.pd

    How does fair trade, as practised by Trade Aid and MINKA, contribute to the aspirations of Quechua producers in Peru?

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    As part of a Master of Indigenous Studies from the University of Otago, Trade Aid staff member, Michelia Ward, conducted research throughout 2011 and 2012 on whether fair trade is able to contribute to the aspirations of indigenous producers. The research focused on fair trade as practiced by Trade Aid, New Zealand and one of its Peruvian partners, MINKA.Fair trade is a development mechanism that aims to support food and craft producers around the world to improve their lives through trade. Many indigenous communities are producers of craft or food products such as woven textiles and coffee, and have engaged in fair trade relationships selling mainly to Western consumers. Fair trade organisations have universal principles that provide guarantees to consumers about working conditions, fair payment and trading relations with producer groups. This research project focuses on whether a universal framework designed to bring development to disadvantaged and marginalized producers can work for unique indigenous cultures across multiple continents. This research focuses on Trade Aid in New Zealand and their partnership with a Peruvian fair trade organisation, MINKA, who works with Quechua producers in the Andes. Indigenous theorists place large value on local epistemes (knowledge systems) and local solutions to local problems. Is fair trade one of these local solutions, or just another solution imposed from the outside upon indigenous producers

    DNA fusion vaccines enter the clinic

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    Induction of effective immune attack on cancer cells in patients requires conversion of weak tumor antigens into strong immunogens. Our strategy employs genetic technology to create DNA vaccines containing tumor antigen sequences fused to microbial genes. The fused microbial protein engages local CD4+ T cells to provide help for anti-tumor immunity, and to reverse potential regulation. In this review, we focus on induction of CD8+ T cells able to kill target tumor cells. The DNA vaccines incorporate tumor-derived peptide sequences fused to an engineered domain of tetanus toxin. In multiple models, this design induces strong CD8+ T-cell responses, able to suppress tumor growth. For clinical relevance, we have used "humanized" mice expressing HLA-A2, successfully inducing cytolytic T-cell responses against a range of candidate human peptides. To overcome physical restriction in translating to patients, we have used electroporation. Clinical trials of patients with cancer are showing induction of responses, with preliminary indications of suppression of tumor growth and evidence for clinically manageable concomitant autoimmunity

    Identification of 80K-H as a protein involved in GLUT4 vesicle trafficking

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    PKC? (protein kinase C? ) is a serine/threonine protein kinase controlled by insulin, various growth factors and phosphoinositide 3-kinase. It has been implicated in controlling glucose transport in response to insulin by the translocation of GLUT4-(glucose transporter 4) containing vesicles to the plasma membrane instimulated cells. How PKC? modulates GLUT4 vesicle trafficking remains unknown. A yeast two-hybrid screen using full-length humanPKC? identified80K-Hprotein as an interactor withPKC? . GST (glutathione S-transferase) pull-down assays with GSTtagged 80K-H constructs confirmed the interaction and showed that the N-terminal portion of 80K-H was not required for the interaction. Immunoprecipitates of endogenous PKC? from Cho cells, 3T3-L1 adipocytes or L6 myotubes contained endogenous 80K-H, demonstrating a physiological interaction. Insulin stimulation enhanced the association 3–5-fold. Immunoprecipitates of endogenous 80K-H contained endogenous munc18c and immunoprecipitates of endogenous munc18c contained endogenous PKC? , with insulin markedly increasing the amount of co-immunoprecipitated protein in each case. These results show that insulin triggers interactions in vivo between PKC? , 80K-H and munc18c. Overexpression of 80K-H constructs mimicked the action of insulin in stimulating both glucose uptake and translocation of Myc-tagged GLUT4 in Cho cells, with the level of effect proportional to the ability of the constructs to associate with munc18c. These results identify 80K-H as a new player involved in GLUT4 vesicle transport and identify a link between a kinase involved in the insulin signalling cascade, PKC?, and a known component of the GLUT4 vesicle trafficking pathway, munc18c. The results suggest amodelwhereby insulin triggers the formation of a PKC?–80K-H–munc18c complex that enhances GLUT4 translocation to the plasma membrane

    Fit for purpose? A case study: validation of immunological endpoint assays for the detection of cellular and humoral responses to anti-tumour DNA fusion vaccines.

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    Clinical trials are governed by an increasingly stringent regulatory framework, which applies to all levels of trial conduct. Study critical immunological endpoints, which define success or failure in early phase clinical immunological trials, require formal pre-trial validation. In this case study, we describe the assay validation process, during which the sensitivity, and precision of immunological endpoint assays were defined. The purpose was the evaluation of two multicentre phase I/II clinical trials from our unit in Southampton, UK, which assess the effects of DNA fusion vaccines on immune responses in HLA-A2+ patients with carcinoembryonic antigen (CEA)-expressing malignancies and prostate cancer. Validated immunomonitoring is being performed using ELISA and IFNgamma ELISPOTs to assess humoral and cellular responses to the vaccines over time. The validated primary endpoint assay, a peptide-specific CD8+ IFNgamma ELISPOT, was tested in a pre-trial study and found to be suitable for the detection of low frequency naturally occurring CEA- and prostate-derived tumour-antigen-specific T cells in patients with CEA-expressing malignancies and prostate cancer

    I remember living at Seabrook, 1945-1953

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    In this "I remember" memoir, Ann Mariko Lowe recalls life at Seabrook, which introduced her to many new experiences, including Halloween traditions. She remembers the living conditions in the dorms at Seabrook, where there was little privacy, and poor facilities. Afterwards, her family moved to the apartments, where they were able to form close bonds with other Japanese families. This was especially helpful with expenses. Ann also played basketball at the Community Center, attended Bible study classes, and was a student at Seabrook School. The Seabrook Educational and Cultural Center has been soliciting current and past residents of Seabrook Farms for an "I remember" project. Residents are asked to create narratives regarding their experiences at Seabrook Farms. These memories help preserve the history and multi-cultural heritage of Seabrook Farms
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