229 research outputs found

    Renin-Angiotensin System and Genetic Factors in Aneurysms

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    Curves and laminations on the five-times punctured sphere

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    We study laminations on the five-times punctured sphere Σ0;5. The discussion is divided into two parts. The results obtained in the two parts are not directly linked. In particular, each part can be read independently. Firstly, we analyse the inclusion of the curve graph of Σ0;5 into PML(Σ0;5). We completely characterise the image of the induced subgraph on a pentagon and the associated decagon. This enables us to describe explicit loops in the curve graph whose images in PML(Σ0;5) form a Hopf link and a trefoil knot. Secondly, we investigate the topology of superconvergence Ts on the set of boundary laminations BL. Here a boundary lamination is a minimal lamination on Σ0;5 with more than one leaf. We show that (BL;Ts) is path connected. Gabai proved that the space of ending laminations is locally path connected [Gab1]. Using Gabai's theorem, we prove that (BL;Ts) is locally path connected. Combined with work of Brock and Masur [BrocM], this implies that the Gromov boundary of the pants graph of _0;5 is path connected and locally path connected

    Hypertension: Renin-Angiotensin-Aldosterone System Alterations

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    Blockers of the renin-angiotensin-aldosterone system (RAAS), that is, renin inhibitors, angiotensin (Ang)-converting enzyme (ACE) inhibitors, Ang II type 1 receptor antagonists, and mineralocorticoid receptor antagonists, are a cornerstone in the treatment of hypertension. How exactly they exert their effect, in particular in patients with low circulating RAAS activity, also taking into consideration the so-called Ang II/aldosterone escape that often occurs after initial blockade, is still incompletely understood. Multiple studies have tried to find parameters that predict the response to RAAS blockade, allowing a personalized treatment approach. Consequently, the question should now be answered on what basis (eg, sex, ethnicity, age, salt intake, baseline renin, ACE or aldosterone, and genetic variance) a RAAS blocker can be chosen to treat an individual patient. Are all blockers equal? Does optimal blockade imply maximum RAAS blockade, for example, by combining ≥2 RAAS blockers or by simply increasing the dose of 1 blocker? Exciting recent investigations reveal a range of unanticipated extrarenal effects of aldosterone, as well as a detailed insight in the genetic causes of primary aldosteronism, and mineralocorticoid receptor blockers have now become an important treatment option for resistant hypertension. Finally, apart from the deleterious ACE-Ang II-Ang II type 1 receptor arm, animal studies support the existence of protective aminopeptidase A-Ang III-Ang II type 2 receptor and ACE2-Ang-(1 to 7)-Mas receptor arms, paving the way for multiple new treatment options. This review provides an update about all these aspects, critically discussing the many controversies and allowing the reader to obtain a full understanding of what we currently know about RAAS alterations in hypertension

    Cell migration through 3D confining pores: speed accelerations by deformation and recoil of the nucleus

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    Directional cell migration in dense three-dimensional (3D) environments critically depends upon shape adaptation and is impeded depending on the size and rigidity of the nucleus. Accordingly, the nucleus is primarily understood as a physical obstacle, however, its pro-migratory functions by step-wise deformation and reshaping remain unclear. Using atomic force spectroscopy, timelapse fluorescence microscopy and shape change analysis tools, we determined nuclear size, deformability, morphology and shape change of HT1080 fibrosarcoma cells expressing the Fucci cell cycle indicator or being pre-treated with chromatin-decondensating agent TSA. We show oscillating peak accelerations during migration through 3D collagen matrices and microdevices that occur during shape reversion of deformed nuclei (recoil), and increase with confinement. During G1 cell cycle phase, nucleus stiffness was increased and yielded further increased speed fluctuations together with sustained cell migration rates in confinement as compared to interphase populations, or to periods of intrinsic nuclear softening in the S/G2 cell cycle phase. Likewise, nuclear softening by pharmacological chromatin decondensation or after lamin A/C depletion reduced peak oscillations in confinement. In conclusion, deformation and recoil of the stiff nucleus contributes to saltatory locomotion in dense tissues

    ‘The war is a money making show’: Working-Class Attitudes to World War II and Australian Nationalism

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    This paper will address the conference themes of ‘class, power and social structure’ through examining industrial and ideological conflict during World War II. The paper will also address the theme of ‘class and culture’ through an examination of working-class cultural expression as a means of resistance to the government’s wartime offensive. What is overlooked in most histories of World War II is the working-class experience of the war and their understanding of nationalism, particularly as nationalism was cynically exploited by the government to undermine working-class identity and solidarity. The paper will investigate the experience of one of the most militant sections of the Australian working class: the Miners. Primary source material such as the Miners’ journal Common Cause and union records reveal opposition to the war and a much more ambiguous attitude to the national sentiment used to justify Australia’s involvement. The Miners provide an interesting case study as the union was led by the Communist Party. Therefore the union leadership initially opposed to the war then became enthusiastic supporters when Russia entered the war on the allied side. It is clear that the Miners’ union leadership found it difficult to convince the rank and file to support the war. The paper will focus upon rank and file attitudes to the war and Australian nationalism particularly during times of industrial unrest.The symposium is organised on behalf of AAHANZBS by the Business and Labour History Group, The University of Sydney, with the financial support of the University’s Faculty of Economics and Business

    A systematic review and meta-analysis of F-18-fluoro-D-deoxyglucose positron emission tomography interpretation methods in vascular graft and endograft infection

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    OBJECTIVE: Vascular graft and endograft infection (VGEI) has high morbidity and mortality rates. Diagnosis is complicated since symptoms vary and can be non-specific. A recent meta-analysis identified the use of 18F-fluoro-D-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET(/CT)) as the most valuable tool for diagnosing VGEI and favorable to computed tomography as the current standard. However, the availability and varied use of several interpretation methods, without consensus on which interpretation method is best, complicates clinical use. The aim of this study was to evaluate the diagnostic performance of different interpretation methods of 18F-FDG PET(/CT) in diagnosing VGEI. METHODS: A systematic review was performed according to the PRISMA guidelines. Data sources included PubMed/Medline, Embase, and Cochrane. A meta-analysis was conducted on the different interpretation methods for 18F-FDG PET(/CT) in diagnosing VGEI, including visual FDG uptake intensity, visual FDG uptake pattern, and quantitative SUVmax. RESULTS: Out of 613 articles, 13 were included-10 prospective and 3 retrospective articles. The FDG uptake pattern method (I2 26.2%) showed negligible heterogeneity, while the FDG uptake intensity (I2 42.2%) and SUVmax (I2 42.1%) methods both showed moderate heterogeneity. The pooled sensitivity for FDG uptake intensity was 0.90 (95% CI: 0.79-0.96), for uptake pattern 0.94 (95% CI: 0.89-0.97), and for the SUVmax method 0.95 (95% CI: 0.76-0.99). The pooled specificity for FDG uptake intensity was 0.59 (95% CI: 0.38-0.78), whereas for FDG uptake pattern it was 0.81 (95% CI: 0.71-0.88) and for SUVmax it was 0.77 (95% CI: 0.63-0.87). The uptake pattern interpretation method demonstrated the best positive and negative post-test probability-82% and 10%, respectively. CONCLUSION: This meta-analysis identified the FDG uptake pattern as the most accurate assessment method of 18F-FDG PET(/CT) for diagnosing VGEI. The optimal SUVmax cutoff, depending on the vendor, demonstrated strong sensitivity and moderate specificity

    Biophysical Characterization of CD6—TCR/CD3 Interplay in T Cells

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    Activation of the T cell receptor (TCR) on the T cell through ligation with antigen-MHC complex of an antigen-presenting cell (APC) is an essential process in the activation of T cells and induction of the subsequent adaptive immune response. Upon activation, the TCR, together with its associated co-receptor CD3 complex, assembles in signaling microclusters that are transported to the center of the organizational structure at the T cell-APC interface termed the immunological synapse (IS). During IS formation, local cell surface receptors and associated intracellular molecules are reorganized, ultimately creating the typical bull's eye-shaped pattern of the IS. CD6 is a surface glycoprotein receptor, which has been previously shown to associate with CD3 and co-localize to the center of the IS in static conditions or stable T cell-APC contacts. In this study, we report the use of different experimental set-ups analyzed with microscopy techniques to study the dynamics and stability of CD6-TCR/CD3 interaction dynamics and stability during IS formation in more detail. We exploited antibody spots, created with microcontact printing, and antibody-coated beads, and could demonstrate that CD6 and the TCR/CD3 complex co-localize and are recruited into a stimulatory cluster on the cell surface of T cells. Furthermore, we demonstrate, for the first time, that CD6 forms microclusters co-localizing with TCR/CD3 microclusters during IS formation on supported lipid bilayers. These co-localizing CD6 and TCR/CD3 microclusters are both radially transported toward the center of the IS formed in T cells, in an actin polymerization-dependent manner. Overall, our findings further substantiate the role of CD6 during IS formation and provide novel insight into the dynamic properties of this CD6-TCR/CD3 complex interplay. From a methodological point of view, the biophysical approaches used to characterize these receptors are complementary and amenable for investigation of the dynamic interactions of other membrane receptors

    Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling.

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    addresses: Department of Public Health and Epidemiology, University of Birmingham, UK.types: Journal Article; ReviewPublished version. Copyright © 2008 NIHR Health Technology Assessment ProgrammeTo investigate the accuracy of predictive tests for pre-eclampsia and the effectiveness of preventative interventions for pre-eclampsia. Also to assess the cost-effectiveness of strategies (test-intervention combinations) to predict and prevent pre-eclampsia
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