14,894 research outputs found

    Impacts from initialization techniques – An optimal computational resource allocation problem

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    New tricks for KDEL receptors

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    Gaussian Process Surrogate Models for Neural Networks

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    Not being able to understand and predict the behavior of deep learning systems makes it hard to decide what architecture and algorithm to use for a given problem. In science and engineering, modeling is a methodology used to understand complex systems whose internal processes are opaque. Modeling replaces a complex system with a simpler, more interpretable surrogate. Drawing inspiration from this, we construct a class of surrogate models for neural networks using Gaussian processes. Rather than deriving kernels for infinite neural networks, we learn kernels empirically from the naturalistic behavior of finite neural networks. We demonstrate our approach captures existing phenomena related to the spectral bias of neural networks, and then show that our surrogate models can be used to solve practical problems such as identifying which points most influence the behavior of specific neural networks and predicting which architectures and algorithms will generalize well for specific datasets

    Multiple criteria data envelopment analysis for full ranking units associated to environment impact assessment

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    Author name used in this publication: Chun-Tian ChengAuthor Gang LI, Department of Civil Engineering, Dalian University of Technology, Dalian.2006-2007 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

    Class II ADP-ribosylation factors are required for efficient secretion of Dengue viruses

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    This article is available open access through the publisher’s website.Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins.Research Fund for Control of Infectious Diseases of Hong Kong and BNP Paribas Corporate and Investment Banking

    Improvised bubble continuous positive airway pressure (BCPAP) device at the National Hospital Abuja gives immediate improvement in respiratory rate and oxygenation in neonates with respiratory distress

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    Background: Prematurity accounts for 25% of Neonatal mortality in Nigeria and Respiratory Distress Syndrome is responsible for half of these deaths. Introducing continuous positive airway pressure for the treatment of RDS in Nigeria where health care financing is predominantly out-of-pocket is quite challenging. It was hypothesized that applying the principle of under-water-seal pressure generation could convert a simple oxygen delivery system into an effective Bubble CPAP device.Objectives: To provide evidence in support of the immediate clinical effectiveness of the NHBCPAP device.Design/Methods: At the neonatal unit of the National Hospital Abuja, we assembled a circuit of tubing connecting a gas source (oxygen concentrator or cylinder) through an interface (nasal prongs) to the baby and this was further connected through an expiratory tube to an under-waterseal bottle to generate CPAP. The device is activated by turning on the oxygen source. The device was applied to preterm babies with RDS as well as some term babies with respiratory distress admitted into the neonatal intensive care units. Respiratory rate, SPO2 and other signs of respiratory distress were monitored before and at 1 hour, 6 hours and 12 hours after the application.Results: Forty eight newborn babies with respiratory distress were treated with the device out of whom twenty three (48%) were very low birth weight with respiratory distress syndrome. The mean respiratory rate dropped from 64.5 (19.2)/min before commencement of CPAP to 59.5(11.6)/min, 56.6 (10.5), and 56.6(10.7) at 1, 6 and 12 hours respectively, p<0.05. The corresponding values for SPO2 were 84.5(14) before and 95.9 (5.3), 95.9(6.5) and 96.9(6.4) at 1, 6 and 12 hours respectively, p<0.05. The respiratory changes were however less marked among very low birth weight babies.Conclusion: The simplified customized device produces clinical responses similar to those reported for the conventional CPAP devices

    Tankyrase Inhibitors Target YAP by Stabilizing Angiomotin Family Proteins

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    SummaryAs the key effector in the Hippo pathway, YAP was identified as an oncoprotein whose expression is elevated in various human cancers. However, the development of potentially therapeutic compounds targeting YAP has been slow and limited. Here, we find that tankyrase inhibitors suppress YAP activity. This effect is mediated by anigomotin (AMOT) family proteins. Tankyrases associate with AMOT family proteins and promote their degradation through E3 ligase RNF146. By antagonizing tankyrase activity, tankyrase inhibitors stabilize AMOT family proteins, thereby suppressing YAP oncogenic functions. Together, our studies not only demonstrate the tankyrase-RNF146-AMOT axis as an upstream pathway regulating YAP but also reveal a therapeutic opportunity in targeting YAP for cancer treatment
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