17,698 research outputs found

    Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity.

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    Heart of Glass (HEG1), a transmembrane receptor, and Rasip1, an endothelial-specific Rap1-binding protein, are both essential for cardiovascular development. Here we performed a proteomic screen for novel HEG1 interactors and report that HEG1 binds directly to Rasip1. Rasip1 localizes to forming endothelial cell (EC) cell-cell junctions and silencing HEG1 prevents this localization. Conversely, mitochondria-targeted HEG1 relocalizes Rasip1 to mitochondria in cells. The Rasip1-binding site in HEG1 contains a 9 residue sequence, deletion of which abrogates HEG1's ability to recruit Rasip1. HEG1 binds to a central region of Rasip1 and deletion of this domain eliminates Rasip1's ability to bind HEG1, to translocate to EC junctions, to inhibit ROCK activity, and to maintain EC junctional integrity. These studies establish that the binding of HEG1 to Rasip1 mediates Rap1-dependent recruitment of Rasip1 to and stabilization of EC cell-cell junctions

    Penalty-based heuristic direct method for constrained global optimization

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    This paper is concerned with an extension of the heuristic DIRECT method, presented in[8], to solve nonlinear constrained global optimization (CGO) problems. Using a penalty strategy based on a penalty auxiliary function, the CGO problem is transformed into a bound constrained problem. We have analyzed the performance of the proposed algorithm using fixed values of the penalty parameter, and we may conclude that the algorithm competes favourably with other DIRECT-type algorithms in the literature.The authors wish to thank two anonymous referees for their comments and suggestions to improve the paper. This work has been supported by FCT – Fundação para a Ciência e Tecnologia within the R&D Units Project Scope: UIDB/00319/2020, UIDB/00013/2020 and UIDP/00013/2020 of CMAT-UM

    Whole Atmosphere Climate Change: Dependence on Solar Activity

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    We conducted global simulations of temperature change due to anthropogenic trace gas emissions, which extended from the surface, through the thermosphere and ionosphere, to the exobase. These simulations were done under solar maximum conditions, in order to compare the effect of the solar cycle on global change to previous work using solar minimum conditions. The Whole Atmosphere Community Climate Model‐eXtended was employed in this study. As in previous work, lower atmosphere warming, due to increasing anthropogenic gases, is accompanied by upper atmosphere cooling, starting in the lower stratosphere, and becoming dramatic, almost 2 K per decade for the global mean annual mean, in the thermosphere. This thermospheric cooling, and consequent reduction in density, is less than the almost 3 K per decade for solar minimum conditions calculated in previous simulations. This dependence of global change on solar activity conditions is due to solar‐driven increases in radiationally active gases other than carbon dioxide, such as nitric oxide. An ancillary result of these and previous simulations is an estimate of the solar cycle effect on temperatures as a function of altitude. These simulations used modest, five‐member, ensembles, and measured sea surface temperatures rather than a fully coupled ocean model, so any solar cycle effects were not statistically significant in the lower troposphere. Temperature change from solar minimum to maximum increased from near zero at the tropopause to about 1 K at the stratopause, to approximately 500 K in the upper thermosphere, commensurate with the empirical evidence, and previous numerical models

    Law Libraries and Laboratories: The Legacies of Langdell and His Metaphor

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    Law Librarians and others have often referred to Harvard Law School Dean C.C. Langdell’s statements that the law library is the lawyer’s laboratory. Professor Danner examines the context of what Langdell through his other writings, the educational environment at Harvard in the late nineteenth century, and the changing perceptions of university libraries generally. He then considers how the “laboratory metaphor” has been applied by librarians and legal scholars during the twentieth century and into the twenty-first. The article closes with thoughts on Langdell’s legacy for law librarians and the usefulness of the laboratory metaphor

    Low-Energy Theorems from Holography

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    In the context of gauge/gravity duality, we verify two types of gauge theory low-energy theorems, the dilation Ward identities and the decoupling of heavy flavor. First, we provide an analytic proof of non-trivial dilation Ward identities for a theory holographically dual to a background with gluon condensate (the self-dual Liu--Tseytlin background). In this way an important class of low-energy theorems for correlators of different operators with the trace of the energy-momentum tensor is established, which so far has been studied in field theory only. Another low-energy relationship, the so-called decoupling theorem, is numerically shown to hold universally in three holographic models involving both the quark and the gluon condensate. We show this by comparing the ratio of the quark and gluon condensates in three different examples of gravity backgrounds with non-trivial dilaton flow. As a by-product of our study, we also obtain gauge field condensate contributions to meson transport coefficients.Comment: 32 pages, 4 figures, two references added, typos remove

    Objective and violation upper bounds on a DIRECT-filter method for global optimization

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    This paper addresses the problem of solving a constrained global optimization problem using a modification of the DIRECT method that incorporates the filter methodology to simultaneously minimize the objective function and the constraints violation. Thus, in the “Selection” step of the herein proposed DIRECT-filter algorithm, the hyperrectangles are classified in four categories and subsequently handled separately. The new algorithm also imposes upper bounds on the objective function and constraints violation aiming to discard some hyperrectangles from the process of identifying the potentially optimal ones. A heuristic to avoid the exploration of the hyperrectangles that have been mostly divided is also implemented. Preliminary numerical experiments are carried out to show the effectiveness of the imposed upper bounds on the objective and violation as well as the goodness of the heuristic.The authors wish to thank two anonymous referees for theircomments and suggestions to improve the paper. This work has been supported by FCT{ Fundação para a Ciência e Tecnologia within the Projects Scope: UID/CEC/00319/2019 and UID/MAT/00013/2013
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