1,880 research outputs found

    Instability of black hole formation under small pressure perturbations

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    We investigate here the spectrum of gravitational collapse endstates when arbitrarily small perfect fluid pressures are introduced in the classic black hole formation scenario as described by Oppenheimer, Snyder and Datt (OSD) [1]. This extends a previous result on tangential pressures [2] to the more physically realistic scenario of perfect fluid collapse. The existence of classes of pressure perturbations is shown explicitly, which has the property that injecting any smallest pressure changes the final fate of the dynamical collapse from a black hole to a naked singularity. It is therefore seen that any smallest neighborhood of the OSD model, in the space of initial data, contains collapse evolutions that go to a naked singularity outcome. This gives an intriguing insight on the nature of naked singularity formation in gravitational collapse.Comment: 7 pages, 1 figure, several modifications to match published version on GR

    An essential function for the ATR-Activation-Domain (AAD) of TopBP1 in mouse development and cellular senescence

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    ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development

    Organ printing as an information technology

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    Funding Information: This work has been sponsored by the São Paulo Research Foundation (FAPESP), The Brazilian Institute of Biofabrication (INCT-BIOFABRIS) and National Council for Scientific and Technological Development (CNPq). Publisher Copyright: © 2015 Published by Elsevier Ltd.Organ printing is defined as a layer by layer additive robotic computer-aided biofabrication of functional 3D organ constructs with using self-assembling tissue spheroids according to digital model. Information technology and computer-aided design softwares are instrumental in the transformation of virtual 3D bioimaging information about human tissue and organs into living biological reality during 3D bioprinting. Information technology enables design blueprints for bioprinting of human organs as well as predictive computer simulation both printing and post-printing processes. 3D bioprinting is now considered as an emerging information technology and the effective application of existing information technology tools and development of new technological platforms such as human tissue and organ informatics, design automation, virtual human organs, virtual organ biofabrication line, mathematical modeling and predictive computer simulations of bioprinted tissue fusion and maturation is an important technological imperative for advancing organ bioprinting.publishersversionPeer reviewe

    A parallel implementation of sequential minimal optimization on FPGA

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    This paper proposes a parallel FPGA implementation of the training phase of a Support Vector Machine (SVM). The training phase of the SVM is implemented using Sequential Minimal Optimization (SMO), which enables the resolution of a complex convex optimization problem using simple steps. The SMO implementation is also highly parallel and uses some acceleration techniques, such as the error cache. Moreover, the Hardware Friendly Kernel (HFK) is used in order to reduce the kernel’s area, enabling an increase in the number of kernels per area. After the parallel implementation in hardware, the SVM is validated by bit-accurate simulation. Finally, analysis associated with the temporal performance of the proposed structure, as well as analysis associated with FPGAs area usage is performed

    Dust and Ionized Gas Association in E/S0 Galaxies with Dust Lanes: Clues to their Origin

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    We present results from an on-going programme to study the dust and ionized gas in E/S0 galaxies with dust lanes. Our data, together with results from previous studies of E/S0 galaxies, are used to demonstrate the tight relationship between these two components. This relationship is discussed in light of our current understanding of the nature and origin of the interstellar medium (ISM), and in particular in the context of the interplay between the different multi-temperature components. We show that focusing on dust obscured regions as tracers of the ISM, and on their properties, serves as independent evidence for the external origin of the dust and ionized gas.Comment: 11 pages, 5 figures, 3 tables. MNRAS in pres

    Lipid-hydrogel films for sustained drug release

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    We report a hybrid system, fabricated from nanostructured lipid particles and polysaccharide based hydrogel, for sustained release applications. Lipid particles were prepared by kinetically stabilizing self-assembled lipid nanostructures whereas the hydrogel was obtained by dissolving kappa-carrageenan (KC) in water. The drug was incorporated in native as well as lipid particles loaded hydrogels, which upon dehydration formed thin films. The kinetics of drug release from these films was monitored by UV–vis spectroscopy while the films were characterized by Fourier transform infra-red (FTIR) spectroscopy and small angle X-ray scattering techniques. Pre-encapsulation of a drug into lipid particles is demonstrably advantageous in certain ways; for instance, direct interactions between KC and drug molecules are prohibited due to the mediation of hydrophobic forces generated by lipid tails. Rapid diffusion of small drug molecules from porous hydrogel network is interrupted by their encapsulation into rather large sized lipid particles. The drug release from the lipid-hydrogel matrix was sustained by an order of magnitude timescale with respect to the release from native hydrogel films. These studies form a strong platform for the development of combined carrier systems for controlled therapeutic applications

    Regulation of Apoptotic Effects by Erythrocarpine E, a Cytotoxic Limonoid from Chisocheton erythrocarpus in HSC-4 Human Oral Cancer Cells

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    The aim of this study was to determine the cytotoxic and apoptotic effects of erythrocarpine E (CEB4), a limonoid extracted from Chisocheton erythrocarpus on human oral squamous cell carcinoma. Based on preliminary dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, CEB4 treated HSC-4 cells demonstrated a cytotoxic effect and inhibited cell proliferation in a time and dose dependent manner with an IC50 value of 4.0±1.9 µM within 24 h of treatment. CEB4 was also found to have minimal cytotoxic effects on the normal cell line, NHBE with cell viability levels maintained above 80% upon treatment. Annexin V-fluorescein isothiocyanate (FITC), poly-ADP ribose polymerase (PARP) cleavage and DNA fragmentation assay results showed that CEB4 induces apoptosis mediated cell death. Western blotting results demonstrated that the induction of apoptosis by CEB4 appeared to be mediated through regulation of the p53 signalling pathway as there was an increase in p53 phosphorylation levels. CEB4 was also found to up-regulate the pro-apoptotic protein, Bax, while down-regulating the anti-apoptotic protein, Bcl-2, suggesting the involvement of the intrinsic mitochondrial pathway. Reduced levels of initiator procaspase-9 and executioner caspase-3 zymogen were also observed following CEB4 exposure, hence indicating the involvement of cytochrome c mediated apoptosis. These results demonstrate the cytotoxic and apoptotic ability of erythrocarpine E, and suggest its potential development as a cancer chemopreventive agent
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