868 research outputs found

    Analysis of Fcγ receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B

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    The Fcγ receptors play important roles in the initiation and regulation of many immunological and inflammatory processes, and genetic variants (FCGR) have been associated with numerous autoimmune and infectious diseases. The data in rheumatoid arthritis (RA) are conflicting and we previously demonstrated an association between FCGR3A and RA. In view of the close molecular proximity with FCGR2A, FCGR2B and FCGR3B, additional polymorphisms within these genes and FCGR haplotypes were examined to refine the extent of association with RA. Biallelic polymorphisms in FCGR2A, FCGR2B and FCGR3B were examined for association with RA in two well characterized UK Caucasian and North Indian/Pakistani cohorts, in which FCGR3A genotyping had previously been undertaken. Haplotype frequencies and linkage disequilibrium were estimated across the FCGR locus and a model-free analysis was performed to determine association with RA. This was followed by regression analysis, allowing for phase uncertainty, to identify the particular haplotype(s) that influences disease risk. Our results reveal that FCGR2A, FCGR2B and FCGR3B were not associated with RA. The haplotype with the strongest association with RA susceptibility was the FCGR3A–FCGR3B 158V-NA2 haplotype (odds ratio 3.18, 95% confidence interval 1.13–8.92 [P = 0.03] for homozygotes compared with all genotypes). The association was stronger in the presence of nodules (odds ratio 5.03, 95% confidence interval 1.44–17.56; P = 0.01). This haplotype was also more common in North Indian/Pakistani RA patients than in control individuals, but not significantly so. Logistic regression analyses suggested that FCGR3A remained the most significant gene at this locus. The increased association with an FCGR3A–FCGR3B haplotype suggests that other polymorphic variants within FCGR3A or FCGR3B, or in linkage disequilibrium with this haplotype, may additionally contribute to disease pathogenesis

    Proteome Profiling of Breast Tumors by Gel Electrophoresis and Nanoscale Electrospray Ionization Mass Spectrometry

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    We have conducted proteome-wide analysis of fresh surgery specimens derived from breast cancer patients, using an approach that integrates size-based intact protein fractionation, nanoscale liquid separation of peptides, electrospray ion trap mass spectrometry, and bioinformatics. Through this approach, we have acquired a large amount of peptide fragmentation spectra from size-resolved fractions of the proteomes of several breast tumors, tissue peripheral to the tumor, and samples from patients undergoing noncancer surgery. Label-free quantitation was used to generate protein abundance maps for each proteome and perform comparative analyses. The mass spectrometry data revealed distinct qualitative and quantitative patterns distinguishing the tumors from healthy tissue as well as differences between metastatic and non-metastatic human breast cancers including many established and potential novel candidate protein biomarkers. Selected proteins were evaluated by Western blotting using tumors grouped according to histological grade, size, and receptor expression but differing in nodal status. Immunohistochemical analysis of a wide panel of breast tumors was conducted to assess expression in different types of breast cancers and the cellular distribution of the candidate proteins. These experiments provided further insights and an independent validation of the data obtained by mass spectrometry and revealed the potential of this approach for establishing multimodal markers for early metastasis, therapy outcomes, prognosis, and diagnosis in the future. © 2008 American Chemical Society

    How to Be Unfaithful to Eurocentrism: A Spanglish Decolonial Critique to Knowledge Gentrification, Captivity and Storycide in Qualitative Research

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    From a position of academic activism, we critique the longstanding dominance del production of knowledge that solely implicates fidelity to Eurocentric methodological technologies en qualitative research. Influenced by an Andean decolonial perspective, en Spanglish we problematize métodos of analysis as the dominant research practice, whereby las stories o relatos result en su appropriation, captivity and gentrification, first by researchers’ authorship and later by the publishing industry copyrights. We highlight the racializing and capitalist colonial/modern Eurocentric agenda del current market of knowledge production that displaces to la periphery all knowledge o relatos that do not subscribe to Euro-US American methodological parameters of what counts as knowledge. Therefore, we intend to heighten the readers’ audibility of another possibility of knowing that does not come from Eurocentric methodologically produced stories. At the forefront of our critique, and as an introduction to a decolonial option, we include our written, uttered, and painted stories, with the political intent of social transformation of coloniality. These seek to denounce power structures that have had incarnated effects on our lives y comunidades. We intend to invite researchers to serve as witnesses of our experiences rather than as critics of methodological rigor. We include final commentaries on a decolonial project to rethink the unquestionable fidelity and dependency toward the current research order of things of el center and la periphery. This is so as to render European technologies of knowledge as only one alternative among many other possible means of legitimate knowledge making in qualitative research. We discuss our hope for epistemological coexistence by which fair and reciprocal intercultural translations of knowledge making could take place, not in the name of equality, but difference

    Factors regulating Hb F synthesis in thalassemic diseases

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    BACKGROUND: The thalassemic syndromes originate from mutations of the globin genes that cause, besides the characteristic clinical picture, also an increased Hb F amount. It is not yet clear if there are more factors, besides the beta globin genotype, determining the Hb F production. We have tried to find out if there are relations between total Hb and Hb F, between erythropoietin (Epo) and Hb F, between Hb F and point mutations of the gamma gene promoters. MATERIALS AND METHODS: Hematologic parameters, iron status, alpha/non-alpha globin ratio, Epo level, and thalassemic defects of the alpha-, beta-, and gamma-globin genes were explored using standard methods in patients affected by thalassemic diseases. Ninety-five non thalassemic individuals have been examined as controls. RESULTS: Two clinical variants of beta-thalassemia intermedia referred to as beta-thal int sub-silent and evident are associated with distinct sets of mutations of the beta-globin gene. Silent beta thal mutations are invariably associated with sub-silent beta thal int; beta° or severe beta(+) thal mutations are associated with evident beta thal int (88%) and almost invariably (98%) with thalassemia major. A positive correlation was observed between the severity of the disease and the Hb F level, but no correlation was found between the Hb F and erythropoietin (Epo) level. The mutation Ggamma -158 C→T was detected in 26.9% of patients affected by beta-thal int sub-silent and evident, respectively, but only in 2% of patients with thalassemia major. CONCLUSIONS: The severity of beta-thal int and the increased Hb F level are strictly dependent from the type of beta-globin gene mutations. No relation is found between Hb F synthesis and Epo secretion. The mutation Ggamma -158 C→T, common among patients affected by beta-thal int and very rare in thal major patients, does not seem, in this study, to influence the Hb F content in beta thal int patients

    Choral Classics Concert

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    Sololists: Ivin Bellamy, bass, will perform the Benedictus. He is a junior who participates in basketball, volleyball, track and field, orchestra and chorus. He plans to at-tend the University of North Carolina majoring in music. Kiyah Bracy, soprano, performs as soloist on the Kyrie. She is a senior who par-ticipates in theatre and chorus. She plans on attending Georgia State University with a major in human biology, aspiring to be a pediatric surgeon. Taniyah Colter, soprano, sings as soloist on the Gloria. She is a senior and is the vice president of the choral program. She hopes to attend college to major in psychology and minor in vocal music. Her goal is to become a psychologist. Alona Fransis, soprano, is heard today as soloist on the piece Benedictus. She is a junior who participates in the marching band, and chorus. In the future, she plans to attend Regent University and major in criminal justice. Christopher Freeman, bass, is heard as soloist on the Gloria. He is a senior who participates in volleyball, chorus, enjoys writing and plans to attend Norfolk State University for psychology. Markle Juste, tenor, will perform the Benedictus. Markle is a senior who partici-pates in the theatre program and chorus. After high school, he would like to be a merchant seaman. Sidney Mapp, soprano, will solo on the Gloria. As a sophomore, she is in volley-ball, chorus, and enjoys reading. She plans to attend the University of Virginia to become a nurse. Savion White, bass, is a soloist on the Agnus Dei. Savion is a senior who partici-pates in volleyball and the Teens With a Purpose poetry club. After high school, he hopes to attend The American Musical and Dramatic Academy for music performance and production. Jordan Wright, soprano, will perform as soloist on the Agnus Dei. Jordan is a junior who participates in chorus and enjoys drawing and writing. She plans is to attend Old Dominion University and major in graphic design

    BEYOND THE BORN APPROXIMATION: A PRECISE COMPARISON OF e + p AND e − p ELASTIC SCATTERING IN THE CEBAF LARGE ACCEPTANCE

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    How well we know the structure of the proton depends on our knowledge of the form factors of the proton. The ratio of the electromagnetic form factors of the proton measured by the Rosenbluth and the polarization transfer methods differ by a factor of 3 at four momentum transfer squared (Q 2)=5.6 GeV 2. The two photon exchange (TPE) effect is the leading candidate to explain this discrepancy. The theoretical estimates of the TPE effect are model dependent so precise measurement is required to resolve this problem. The TPE effect can be measured in a model independent way by measuring the ratio of positron-proton to electron-proton elastic scattering cross-sections. We produced a simultaneously mixed electron-positron beam in the engineering test run conducted in October 2006 and measured the e + p/e − p ratio using the CEBAF large acceptance spectrometer (CLAS). Due to the luminosity constraint our kinematic coverage is limited to low Q2 and high ε (longitudinal polarization of the virtual photon). We continued our background study through GEANT4 simulation developed for the test run design in order to find more background sources and to design required shielding. The simulation is validated by using the test run data and is used further to optimize the luminosity for the final experiment. We are able to increase the luninosity by an order of magnitude for the upcoming final run. The final experiment will extend the data in high Q2 and low ε region where TPE effec

    Satellite data for the offshore renewable energy sector: Synergies and innovation opportunities

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    Can satellite data be used to address challenges currently faced by the Offshore Renewable Energy (ORE) sector? What benefit can satellite observations bring to resource assessment and maintenance of ORE farms? Can satellite observations be used to assess the environmental impact of offshore renewables leading towards a more sustainable ORE sector? This review paper faces these questions presenting a holistic view of the current interactions between satellite and ORE sectors, and future needs to make this partnership grow. The aim of the work is to start the conversation between these sectors by establishing a common ground. We present offshore needs and satellite technology limitations, as well as potential opportunities and areas of growth. To better understand this, the reader is guided through the history, current developments, challenges and future of offshore wind, tidal and wave energy technologies. Then, an overview on satellite observations for ocean applications is given, covering types of instruments and how they are used to provide different metocean variables, satellite performance, and data processing and integration. Past, present and future satellite missions are also discussed. Finally, the paper focuses on innovation opportunities and the potential of synergies between the ORE and satellite sectors. Specifically, we pay attention to improvements that satellite observations could bring to standard measurement techniques: assessing uncertainty, wind, tidal and wave conditions forecast, as well as environmental monitoring from space. Satellite–enabled measurement of ocean physical processes and applications for fisheries, mammals and birds, and habitat change, are also discussed in depth
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