307 research outputs found

    Cohomology of bundles on homological Hopf manifold

    Full text link
    We discuss the properties of complex manifolds having rational homology of S1×S2n1S^1 \times S^{2n-1} including those constructed by Hopf, Kodaira and Brieskorn-van de Ven. We extend certain previously known vanishing properties of cohomology of bundles on such manifolds.As an application we consider degeneration of Hodge-deRham spectral sequence in this non Kahler setting.Comment: To appear in Proceedings of 2007 conference on Several complex variables and Complex Geometry. Xiamen. Chin

    SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1

    Get PDF
    BACKGROUND We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown. METHODS A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer. RESULTS Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53. CONCLUSION Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity

    Anorgasmia in women

    Full text link
    This article reports on the etiology and treatment of anorgasmia. Etiological factors include childhood and adolescent experiences, current individual attitudes, and lifestyle factors, as well as the quality and dynamics of past and present committed relationships. It is important to assess the nature of each of the previously mentioned factors in determining the nature of the orgasmic dysfunction as well as assisting in the development of a treatment plan. Treatment approaches for anorgasmia need to address individual factors (e.g., performance anxiety, poor body image) as well as interpersonal problems. A systemic treatment framework would appear to be the most useful approach to treat this sexual dysfunction, as this type of strategy identifies and treats the difficulties experienced by the anorgasmic woman within the total context of her life. Of course, this approach necessitates the involvement of the partner in therapy, and treatment is unlikely to be effective unless the problems experienced by both the woman and her partner are addressed. Limitations of past research in terms of inadequate evaluation of treatment, low sample sizes, and poorly defined interventions are discussed. Finally, directions for future research to advance our understanding of the most effective treatments for anorgasmia are considered. <br /

    A study of patent thickets

    Get PDF
    Report analysing whether entry of UK enterprises into patenting in a technology area is affected by patent thickets in the technology area

    Variation in Recent Onset Parkinson's Disease : Implications for Prodromal Detection

    Get PDF
    The research was funded by Parkinson’s UK and supported by the National Institute for Health Research (NIHR) DeNDRoN network, the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the NIHR funded Biomedical Research Centre in Cambridge.Peer reviewedPublisher PD

    Higher Plasma Levels of Advanced Glycation End Products Are Associated With Incident Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes: A 12-year follow-up study

    Get PDF
    OBJECTIVE - To investigate the associations of plasma levels of advanced glycation end products (AGEs) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunction, low-grade inflammation, and arterial stiffness. RESEARCH DESIGN AND METHODS - We prospectively followed 169 individuals with diabetic nephropathy and 170 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of N ε -(carboxymethyl)lysine, N ε -(carboxyethyl) lysine, pentosidine and other biomarkers were measured at baseline. The median follow-up duration was 12.3 (interquartile range 7.6-12.5) years. RESULTS - During the course of follow-up, 82 individuals (24.2%) died; 85 (25.1%) suffered a fatal (n = 48) and/or nonfatal (n = 53) CVD event. The incidence of fatal and nonfatal CVD and of all-cause mortality increased with higher baseline levels of AGEs independently of traditional CVD risk factors: hazard ratio (HR) = 1.30 (95% CI = 1.03-1.66) and HR = 1.27 (1.00-1.62), respectively. These associations were not attenuated after further adjustments for markers of renal or endothelial dysfunction, low-grade inflammation, or arterial stiffness. CONCLUSIONS - Higher levels of AGEs are associated with incident fatal and nonfatal CVD as well as all-cause mortality in individuals with type 1 diabetes, independently of other risk factors and of several potential AGEs-related pathophysiological mechanisms. Thus, AGEs may explain, in part, the increased cardiovascular disease andmortality attributable to type 1 diabetes and constitute a specific target for treatment in these patients. 2011 by the American Diabetes Association

    Notes on age determination, size and age structure, longevity, and growth of co-occurring macrourid fishes

    Get PDF
    ACKNOWLEDGEMENTS We are grateful to crew and colleagues who sampled and processed macrourids on the MARECO and ECOMAR cruise, to Ms Hege Ø Hansen for assistance in the otolith laboratory, and to home institutions and the Alfred P Sloan Foundation for financial support. An early version of the results was submitted in partial fulfilment of the requirements for the MSc degree of R.H. Fundings: Data for this paper were collected on cruises funded by Norway and the United Kingdom (Natural Environment Research Council). In addition to institutional funding, the work benefitted from a grant to the ecosystems of the mid-atlantic ridge (MAR-ECO) Programme from the Alfred P. Sloan Foundation, New York, USA.Peer reviewedPublisher PD
    corecore