487 research outputs found

    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

    The galactic population of white dwarfs

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    Original paper can be found at: http://www.iop.org/EJ/conf DOI: 10.1088/1742-6596/172/1/012004 [16th European White Dwarfs Workshop]The contribution of white dwarfs of the different Galactic populations to the stellar content of our Galaxy is only poorly known. Some authors claim a vast population of halo white dwarfs, which would be in accordance with some investigations of the early phases of Galaxy formation claiming a top-heavy initial– mass– function. Here, I present a model of the population of white dwarfs in the Milky Way based on observations of the local white dwarf sample and a standard model of Galactic structure. This model will be used to estimate the space densities of thin disc, thick disc and halo white dwarfs and their contribution to the baryonic mass budget of the Milky Way. One result of this investigation is that white dwarfs of the halo population contribute a large fraction of the Galactic white dwarf number count, but they are not responsible for the lion's share of stellar mass in the Milky Way. Another important result is the substantial contribution of the – often neglected – population of thick disc white dwarfs. Misclassification of thick disc white dwarfs is responsible for overestimates of the halo population in previous investigations.Peer reviewe

    The pirate in the pump: children's views of objects as imaginary friends at the start of school

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    The main aim of this paper is to use a phenomenological approach (Merleau-Ponty, 1962. Phenomenology of Perception. Evanston: Northwestern University Press; Merleau-Ponty. 1968. The Visible and the Invisible: Followed by Working Notes. Evanston: Northern University Press) to contribute a new theoretical understanding of what imaginary friends mean for children in the context of starting school. The paper addresses the specific area of ‘object-friends’ and draws on examples from an empirical and consultative study of a small sample of five and six-year-old children’s everyday experiences of friendship in school. The paper argues that if practitioners consider embodiment approaches and listen attentively to the knowledge and information that children share about their imaginary friends, this could be used to nurture children’s early learnin

    Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

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    Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

    Treatment of Older Patients with Mantle-Cell Lymphoma

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    BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphom

    On the problem of the justification of river rights

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    This article aims to work out the social conditions that determine whether the communication of river rights finds success in society. Employing the context of hydropower development in the Mekong region, the article finds that an essentialist strategy which claims that river rights have unlimited ‘moral’ validity regardless of any of the decision consequences is unlikely to succeed. Instead, it is proposed that moral conflicts over river rights may ultimately only be resolvable ‘unmorally’, that is, by procedural legitimacy – and this is best captured by employing a methodological framework composed of thematic, social and temporal dimension

    Bcl-2 expression in rituximab refractory cutaneous B-cell lymphoma

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    Rituximab has been established as an effective and safe therapy for cutaneous B-cell lymphoma (CBCL). Different survival pathways, that is the Raf/MEK/Erk- or the p38MAPK cascade, have been suggested as downstream mediators of rituximab and may be involved in treatment failure. Biopsies from four patients, suffering from different subtypes of CBCL, which were obtained at various time points of relapse during or after therapy with 375 mg rituximab per m2 of body surface area, were analysed for the expression of CD20, CD3, Ki-67, Raf-kinase inhibitory protein (RKIP) and bcl-2 by immunohistochemistry. No CD20-loss variants, that is the suggested main tumour escape mechanism to rituximab therapy, were observed in any specimen of relapsing CBCL. Notably, the expression of proapoptotic RKIP remained increased in these tumour samples. This was concomitated by a constant to slightly reduced proliferation status as demonstrated by Ki-67 staining. However, relapsing CBCL exhibited a strong upregulation of the antiapoptotic molecule bcl-2 in comparison to pretherapeutic levels. The immunohistochemical analyses of this case series of rituximab refractory CBCL suggest that upregulation of bcl-2 may play a major role in therapy resistance

    Profiles of Parental Burnout Around the Globe: Similarities and Differences Across 36 Countries

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    Parental burnout (PB) is a pervasive phenomenon. Parenting is embedded in cultural values, and previous research has shown the role of individualism in PB. In this paper, we reanalyze previously collected data to identify profiles based on the four dimensions of PB, and explore whether these profiles vary across countries' levels of collectivistic-individualistic (COL-IND) values. Our sample comprised 16,885 individuals from 36 countries (73% women; 27% men), and we used a latent profile approach to uncover PB profiles. The findings showed five profiles: Fulfilled, Not in PB, Low risk of PB, High risk of PB and Burned out. The profiles pointed to climbing levels of PB in the total sample and in each of the three country groups (High COL/Low IND, Medium COL-IND, Low COL/High IND). Exploratory analyses revealed that distinct dimensions of PB had the most prominent roles in the climbing pattern, depending on the countries' levels of COL/IND. In particular, we found contrast to be a hallmark dimension and an indicator of severe burnout for individualistic countries. Contrary to our predictions, emotional distance and saturation did not allow a clear differentiation across collectivistic countries. Our findings support several research avenues regarding PB measurement and intervention
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