178 research outputs found

    Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation

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    After birth cardiomyocytes undergo terminal differentiation, characterized by binucleation and centrosome disassembly, rendering the heart unable to regenerate. Yet, it has been suggested that newborn mammals regenerate their hearts after apical resection by cardiomyocyte proliferation. Thus, we tested the hypothesis that apical resection either inhibits, delays, or reverses cardiomyocyte centrosome disassembly and binucleation. Our data show that apical resection rather transiently accelerates centrosome disassembly as well as the rate of binucleation. Consistent with the nearly 2-fold increased rate of binucleation there was a nearly 2-fold increase in the number of cardiomyocytes in mitosis indicating that the majority of injury-induced cardiomyocyte cell cycle activity results in binucleation, not proliferation. Concurrently, cardiomyocytes undergoing cytokinesis from embryonic hearts exhibited midbody formation consistent with successful abscission, whereas those from 3 day-old cardiomyocytes after apical resection exhibited midbody formation consistent with abscission failure. Lastly, injured hearts failed to fully regenerate as evidenced by persistent scarring and reduced wall motion. Collectively, these data suggest that should a regenerative program exist in the newborn mammalian heart, it is quickly curtailed by developmental mechanisms that render cardiomyocytes post-mitotic

    Resilience beyond neoliberalism? Mystique of complexity, financial crises, and the reproduction of neoliberal life

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    The burgeoning debate on resilience in international relations has seen the emergence of two polarized views: resilience as a manifestation of neoliberal governmentality and resilience as the expression of a post-neoliberal shift. This article explores whether a post-neoliberal resilience may be possible by reflecting upon the ontology of complexity as unknowability at the heart of this view. It argues that this approach neglects how the discourse of complexity as unknowability is a neoliberal technology of government that is instrumental to advance neoliberal forms of resilience. The second half of the article discusses this argument with reference to the 2008 financial crisis. It shows how a resilience-as-post-neoliberal approach resonates with those dominant narratives which have shrouded the causes and mechanics of the crisis in a mystique of complexity, thus encouraging forms of cognitive and political disengagement. The article concludes that by celebrating local knowledge at the expense of an understanding of global dynamics, post-neoliberal resilience offers an impoverished notion of resistance compliant with the dictates of the neoliberal order

    Capturing protest in urban environments:The ‘police kettle’ as a territorial strategy

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    ‘Kettling’ has emerged in recent decades as an established, if controversial, tactic of public order policing. Departing from a historical emphasis on dispersal, kettling instead acts to contain protesters within a police cordon for sustained periods of time. This article elaborates upon the spatial and temporal logics of kettling by investigating the conditions of is historical emergence. We argue that kettling should be understood as a territorial strategy that co-evolved in relation to forms of disruptive protest. Whereas techniques of crowd dispersal serve to diffuse a unified collective, ‘kettling’ aims to capture the volatile intensities of public dissent and exhaust its political energies. Drawing on police manuals, media coverage, accounts from activists and expert interviews, we show how the ‘kettle’ re-territorializes protest by acting on its spatio-temporal and affective constitution. By fabricating an inner outside of the urban milieu, freezing the time of collective mobilization and inducing debilitating affects such as fear and boredom, kettling intervenes into the scene of political subjectification that each congregation of protesting bodies seeks to fashion

    Ascites induces modulation of α6ÎČ1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma

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    Interactions between cancer cells and the surrounding medium are not fully understood. In this study, we demonstrate that ascites induces selective changes in the expression of integrins and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) in ovarian cancer cells. We hypothesise that this change of integrin and uPA/uPAR expression triggers signalling pathways responsible for modulating phenotype-dependent functional changes in ovarian cancer cells. Human ovarian surface epithelial (HOSE) cell lines and epithelial ovarian cancer cell lines were treated with ascites for 48 h. Ascites induced upregulation of α6 integrin, without any change in the expression of αv, ÎČ1 and ÎČ4 integrin subunits. Out of the four ovarian cancer cell lines studied, ascites induced enhancement in the expression of uPA/uPAR in the more invasive OVCA 433 and HEY cell lines without any change in the noninvasive OVHS1 and moderately invasive PEO.36 cell lines. On the other hand, no change in the expression of α6 integrin or uPAR, in response to ascites, was observed in HOSE cells. In response to ascites, enhancement in proliferation and in adhesion was observed in all four ovarian cancer cell lines studied. In contrast, no significant increase in proliferation or adhesion by ascites was observed in HOSE cells. Ascites-induced expression of uPA/uPAR correlated with the increased invasiveness of HEY and OVCA 433 cell lines but was not seen in OVHS1, PEO.36 and HOSE cell lines. Upregulation of α6 integrin and uPA/uPAR correlated with the activation of Ras and downstream Erk pathways. Ascites-induced activation of Ras and downstream Erk can be inhibited by using inhibitory antibodies against α6 and ÎČ1 integrin and uPAR, consistent with the inhibition of proliferation, adhesion and invasive functions of ovarian cancer cell lines. Based on these findings, we conclude that ascites can induce selective upregulation of integrin and uPA/uPAR in ovarian cancer cells and these changes may modulate the functions of ovarian carcinomas

    Angiopoietin-1 inhibits tumour growth and ascites formation in a murine model of peritoneal carcinomatosis

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    Angiopoietin-1 is an important regulator of endothelial cell survival. Angiopoietin-1 also reduces vascular permeability mediated by vascular endothelial growth factor. The effects of angiopoietin-1 on tumour growth and angiogenesis are controversial. We hypothesised that angiopoietin-1 would decrease tumour growth and ascites formation in peritoneal carcinomatosis. Human colon cancer cells (KM12L4) were transfected with vector (pcDNA) alone (control) or vector containing angiopoietin-1 and injected into the peritoneal cavities of mice. After 30 days, the following parameters were measured: number of peritoneal nodules, ascites volume, and diameter of the largest tumour. Effects of angiopoietin-1 on vascular permeability were investigated using an intradermal Miles assay with conditioned media from transfected cells. Seven of the nine mice in the pcDNA group developed ascites (1.3±0.5 ml (mean±s.e.m.)), whereas no ascites was detectable in the angiopoietin-1 group (0 out of 10) (P<0.01). Number of peritoneal metastases (P<0.05), tumour volume, (P<0.05), vessel counts (P<0.01), and tumour cell proliferation (P<0.01) were significantly reduced in angiopoietin-1-expressing tumours. Conditioned medium from angiopoietin-1-transfected cells decreased vascular permeability more than did conditioned medium from control cells (P<0.05). Our results suggest that angiopoietin-1 is an important mediator of angiogenesis and vascular permeability and thus could theoretically serve as an anti-neoplastic agent for patients with carcinomatosis from colorectal cancer

    The Einstein Toolkit: A Community Computational Infrastructure for Relativistic Astrophysics

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    We describe the Einstein Toolkit, a community-driven, freely accessible computational infrastructure intended for use in numerical relativity, relativistic astrophysics, and other applications. The Toolkit, developed by a collaboration involving researchers from multiple institutions around the world, combines a core set of components needed to simulate astrophysical objects such as black holes, compact objects, and collapsing stars, as well as a full suite of analysis tools. The Einstein Toolkit is currently based on the Cactus Framework for high-performance computing and the Carpet adaptive mesh refinement driver. It implements spacetime evolution via the BSSN evolution system and general-relativistic hydrodynamics in a finite-volume discretization. The toolkit is under continuous development and contains many new code components that have been publicly released for the first time and are described in this article. We discuss the motivation behind the release of the toolkit, the philosophy underlying its development, and the goals of the project. A summary of the implemented numerical techniques is included, as are results of numerical test covering a variety of sample astrophysical problems.Comment: 62 pages, 20 figure

    Factors Affecting Disaster Resilience in Oman: Integrating Stakeholder Analysis and Fuzzy Cognitive Mapping

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    Planning for community resilience to disasters is a process that involves co‐ordinated action within and between relevant organizations and stakeholders, with the goal of reducing disaster risk. The effectiveness of this process is influenced by a range of factors, both positively and negatively, that need to be identified and understood so as to develop organizational capacity to build community resilience to disaster. This study investigates disaster planning and management in Oman, a country facing significant natural hazards, and with a relatively new system of institutional disaster management. Fuzzy cognitive mapping integrated with stakeholder analysis is used to identify relevant factors and their inter‐relationships, and hence provides an improved understanding of disaster governance. Developing an improved understanding of the complexity of this institutional behavior allows identification of opportunities to build greater resilience to disaster through improved planning and emergency response. We make recommendations for improved disaster management in Oman relating to governance (including improved plan dissemination and closer working with community organizations), risk assessment, public education, built environment development, and financing for disaster resilience

    A Measurement of Gravitational Lensing of the Cosmic Microwave Background Using SPT-3G 2018 Data

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    We present a measurement of gravitational lensing over 1500 deg2^2 of the Southern sky using SPT-3G temperature data at 95 and 150 GHz taken in 2018. The lensing amplitude relative to a fiducial Planck 2018 Λ\LambdaCDM cosmology is found to be 1.020±0.0601.020\pm0.060, excluding instrumental and astrophysical systematic uncertainties. We conduct extensive systematic and null tests to check the robustness of the lensing measurements, and report a minimum-variance combined lensing power spectrum over angular multipoles of 50<L<200050<L<2000, which we use to constrain cosmological models. When analyzed alone and jointly with primary cosmic microwave background (CMB) spectra within the Λ\LambdaCDM model, our lensing amplitude measurements are consistent with measurements from SPT-SZ, SPTpol, ACT, and Planck. Incorporating loose priors on the baryon density and other parameters including uncertainties on a foreground bias template, we obtain a 1σ1\sigma constraint on σ8Ωm0.25=0.595±0.026\sigma_8 \Omega_{\rm m}^{0.25}=0.595 \pm 0.026 using the SPT-3G 2018 lensing data alone, where σ8\sigma_8 is a common measure of the amplitude of structure today and Ωm\Omega_{\rm m} is the matter density parameter. Combining SPT-3G 2018 lensing measurements with baryon acoustic oscillation (BAO) data, we derive parameter constraints of σ8=0.810±0.033\sigma_8 = 0.810 \pm 0.033, S8â‰ĄÏƒ8(Ωm/0.3)0.5=0.836±0.039S_8 \equiv \sigma_8(\Omega_{\rm m}/0.3)^{0.5}= 0.836 \pm 0.039, and Hubble constant H0=68.8−1.6+1.3H_0 =68.8^{+1.3}_{-1.6} km s−1^{-1} Mpc−1^{-1}. Using CMB anisotropy and lensing measurements from SPT-3G only, we provide independent constraints on the spatial curvature of ΩK=0.014−0.026+0.023\Omega_{K} = 0.014^{+0.023}_{-0.026} (95% C.L.) and the dark energy density of ΩΛ=0.722−0.026+0.031\Omega_\Lambda = 0.722^{+0.031}_{-0.026} (68% C.L.). When combining SPT-3G lensing data with SPT-3G CMB anisotropy and BAO data, we find an upper limit on the sum of the neutrino masses of ∑mÎœ<0.30\sum m_{\nu}< 0.30 eV (95% C.L.)
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