45,339 research outputs found

    Early growth response gene-2 (Egr-2) regulates the development of B and T cells

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    The study was supported by Arthritis Research UK. Copyright @ 2011 Li et al.BACKGROUND: Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development. METHODS AND FINDINGS: The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2+ lymphocytes resulted in a severe reduction of CD4+CD8+ (DP) cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP) T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow. CONCLUSIONS: Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.This article is provided by the Brunel Open Access publishing fund

    Forest plots comparing the MAE between Barrett II and Haigis (a), Barrett II and SRK/T (b), EVO and Hill-RBF (c), EVO and Kane (d), EVO and SRK/T (e), Kane and SRK/T (f), Kane and Haigis (g), Hill-RBF and SRK/T (h), Hill-RBF and Holladay 1 (i).

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    Forest plots comparing the MAE between Barrett II and Haigis (a), Barrett II and SRK/T (b), EVO and Hill-RBF (c), EVO and Kane (d), EVO and SRK/T (e), Kane and SRK/T (f), Kane and Haigis (g), Hill-RBF and SRK/T (h), Hill-RBF and Holladay 1 (i).</p

    Measurement of the ratio of branching fractions B(B0→K∗0γ )/B(B0s→φγ ) and the directCP asymmetry inB 0→K∗0γ

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    The ratio of branching fractions of the radiative B decays B0→K⁎0γ and B0s→ϕγ has been measured using an integrated luminosity of 1.0 fb−1 of pp collision data collected by the LHCb experiment at a centre-of-mass energy of s√=7TeV. The value obtained is B(B0→K⁎0γ)B(B0s→ϕγ)=1.23±0.06(stat.)±0.04(syst.)±0.10(fs/fd), where the first uncertainty is statistical, the second is the experimental systematic uncertainty and the third is associated with the ratio of fragmentation fractions fs/fd. Using the world average value for B(B0→K⁎0γ), the branching fraction B(B0s→ϕγ) is measured to be (3.5±0.4)×10−5. The direct CP asymmetry in B0→K⁎0γ decays has also been measured with the same data and found to be ACP(B0→K⁎0γ)=(0.8±1.7(stat.)±0.9(syst.))%. Both measurements are the most precise to date and are in agreement with the previous experimental results and theoretical expectations

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    The construction of Karen Karnak: The multi-author-function

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    This thesis is situated within the comparatively recent developments of Web 2.0 and the emergence of interactive WikiMedia, and explores the mode of authorship within a Read/Write culture compared to that of a Read/Only tradition. The hypothesis of this study is that the role of the audience has become merged with the author, and as such, represents new functions and attributes, distinct from a more conventional concept of authorship, in which the roles of audience and author are more separate. Read/Write and participatory culture, as defined by this study, is focused on collaboration, and includes the influences of D.I.Y. culture, Open-Source practices and the production of text by multiple authors. Multi-authorship presents a re-thinking of several concepts which support the notion of the individual author, since the focus of multi-authorship is not on attribution and ownership of a finished text, but on the continued malleability of a text. Modes of multi-authorship, demonstrated in the use of the pseudonyms Alan Smithee and Karen Eliot, represent declarative authors whose names signify multiple origins, whilst concurrently indicating a distinct body of work. The function of these names form an important context to this study, since primary research involves the construction of an experimental mode of multi-authorship utilising WikiMedia technology and the interaction of thirty nine participants, who are invited to create a body of work under the collective pseudonym Karen Karnak. The data generated by this experiment is analysed using aspects of Michel Foucault's author-function to identify and determine power structures inherent in the WikiMedia context. The interplay of power structures, including concepts such as identity, ownership and the body of work, affect the resulting mode of authorship and contribute to the construction of Karen Karnak, suggesting further areas of research into the emerging multi-author

    Barrett esophagus frequency and predictors of dysplasia or cancer in Barrett esophagus

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    OBJECTIVE: Identificating factors associated with an increased risk for dysplasia and cancer development among patients with Barrett esophagus would aid better patient care and improve risk stratification approaches. This study aimed at examining the frequency of Barrett esophagus and factors predicting the presence of dysplasia and cancer among patients with Barrett esophagus. PATIENTS AND METHODS: Adult patients that underwent upper gastrointestinal endoscopic ex-amination for gastroesophageal complaints were screened in this retrospective, cross-sectional study; and patients diagnosed with Barrett esophagus were included in the analysis. Frequency of dysplasia/cancer and its predictors were examined. RESULTS: Among 10,404 endoscopic examinations performed during the study period, 143 patients (1.4%) were diagnosed with Barrett esophagus. Among patients with Barrett esophagus, the frequency for high-grade dysplasia, low grade dysplasia, and adenocarcinoma was 2.8%, 2.1%, and 1.4%, respectively. On multivariate analysis, age >= 55 years (OR, 11.1 [95%CI: 2.0-61.4], p=0.006) and long segment Barrett esophagus (OR, 5.7 [95%CI: 1.2-27.8], p=0.031) emerged as significant independent predictors for dysplasia/cancer. CONCLUSIONS: Frequency of Barrett esophagus in our population seems to be different than figures reported from different geographical regions. Advanced age and long Barrett segment on endoscopic examination are associated with the presence of concomitant dysplasia/cancer on pathological examination. Larger studies with prospective methodology are warranted

    Measurement of the CKM angle gamma from a combination of B->Dh analyses

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    A combination of three LHCb measurements of the CKM angle gamma is presented. The decays B->DK and B->Dpi are used, where D denotes an admixture of D0 and D0-bar mesons, decaying into K+K-, pi+pi-, K+-pi-+, K+-pi-+pi+-pi-+, KSpi+pi-, or KSK+K- final states. All measurements use a dataset corresponding to 1.0 fb-1 of integrated luminosity. Combining results from B->DK decays alone a best-fit value of gamma = 72.0 deg is found, and confidence intervals are set gamma in [56.4,86.7] deg at 68% CL, gamma in [42.6,99.6] deg at 95% CL. The best-fit value of gamma found from a combination of results from B->Dpi decays alone, is gamma = 18.9 deg, and the confidence intervals gamma in [7.4,99.2] deg or [167.9,176.4] deg at 68% CL, are set, without constraint at 95% CL. The combination of results from B->DK and B->Dpi decays gives a best-fit value of gamma = 72.6 deg and the confidence intervals gamma in [55.4,82.3] deg at 68% CL, gamma in [40.2,92.7] deg at 95% CL are set. All values are expressed modulo 180 deg, and are obtained taking into account the effect of D0-D0bar mixing

    Measurements of t(t)over-bar cross sections in association with b jets and inclusive jets and their ratio using dilepton final states in pp collisions at root s=13 TeV

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    The cross sections for the production of t (t) over bar b (b) over bar and t (t) over bar jj events and their ratio sigma(t (t) over bar b (b) over bar)/sigma(t (t) over bar jj) are measured using data corresponding to an integrated luminosity of 2.3 fb(-1) collected in pp collisions at root s = 13 TeV with the CMS detector at the LHC. Events with two leptons (e or mu) and at least four reconstructed jets, including at least two identified as b quark jets, in the final state are selected. In the full phase space, the measured ratio is 0.022 +/- 0.003 (stat) +/- 0.006 (syst), the cross section sigma(t (t) over bar b (b) over bar) bis 4.0 +/- 0.6 (stat)+/- 1.3 (syst) pb and sigma(t (t) over bar jj) is 184 +/- 6 (stat)+/- 33 (syst) pb. The measurements are compared with the standard model expectations obtained from a POWHEG simulation at next-to-leading-order interfaced with PYTHIA. (c) 2017 The Author. Published by Elsevier B.V

    Impact of HER2 copy number in IHC2+/FISH-amplified breast cancer on outcome of adjuvant trastuzumab treatment in a large UK cancer network

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    Background:Adjuvant trastuzumab with chemotherapy is standard treatment for HER2-positive breast cancer, defined as either HER2 IHC3+ or IHC2+ and FISH amplified. The aim of this study was to investigate the degree to which HER2 amplification in terms of HER2 gene copy numbers in HER2+IHC2+ cancers affected the outcome in a community setting.Methods:Case records of 311 consecutive patients with early breast cancer presenting between 1st January 2005 and 31st December 2008 were reviewed. Progression-free survival and overall survival were calculated with the Kaplan-Meier method using STATA 13.Results:Among 3+ cases (n=230) 163 received T vs 67 no-T. Among 2+ cases (n=81) 59 received T vs 22 no-T. Among 59 IHC2+-treated cases n=28 had an average of >12, n=13 had >6 to 2 to 12) appears to be associated with consistently better response compared with patients with intermediate HER2 copy numbers (6-12). In light of emerging data of patients showing insensivity to trastuzumab therapy, we propose that the HER2 gene copy number value should be included as an additional indicator for stratifying both the management and the follow-up of breast cancer patients

    Quantifying the effect of biopsy lateral decubitus patient positioning compared to supine prostate MRI scanning on prostate translocation and distortion

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    Introduction: More than a quarter of tumors are missed by magnetic resonance imaging/ultrasound (MRI/US) fusion-guided biopsy, the majority due to software-based misregistration. Transrectal approaches to biopsy are typically performed in the lateral decubitus position; conversely, diagnostic MRI is performed with the patient lying supine. Any positionrelated difference in prostate location or gland deformation could potentially exacerbate misregistration at subsequent biopsy. Methods: Fifteen healthy male volunteers (mean age 35.9 years, range 27-53) were included in this prospective, institutional review board-approved study. Each volunteer had an MRI performed in the supine position, followed by the second in the lateral decubitus position (mimicking a typical biopsy position). MRI images were co-registered and analyzed in order to assess prostate translocation and distortion. Results: Whole prostate translocation of ≥5 mm was observed in 20% of patients and ≥3 mm in 60% of patients. When dividing the prostate into prostatic sectors, the prostatic base demonstrated the largest positional difference. When plotting the translocation directions with relative volume difference, there was a moderate negative correlation trend in the latero-lateral direction. Only minimal distortion was observed, with similar distortion among all prostatic sectors. Conclusions: Positional change affects the prostate translocation, however, the effect on prostate distortion appears to be negligible. Prostate translocation in latero-lateral direction can be minimized with larger bladder volumes. Thereby, prostate translocation needs to be considered alongside software misregistration error; however, positional change should not affect software registration of MRI/US fusion-guided prostate biopsy
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