225 research outputs found

    Cloud for Gaming

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    Cloud for Gaming refers to the use of cloud computing technologies to build large-scale gaming infrastructures, with the goal of improving scalability and responsiveness, improve the user's experience and enable new business models.Comment: Encyclopedia of Computer Graphics and Games. Newton Lee (Editor). Springer International Publishing, 2015, ISBN 978-3-319-08234-

    GM-CSF Regulates Alveolar Macrophage Differentiation and Innate Immunity in the Lung through PU.1

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    AbstractGM-CSF gene targeted (GM−/−) mice are susceptible to respiratory infections and develop alveolar proteinosis due to defects in innate immune function and surfactant catabolism in alveolar macrophages (AMs), respectively. Reduced cell adhesion, phagocytosis, pathogen killing, mannose- and Toll-like receptor expression, and LPS- or peptidoglycan-stimulated TNFα release were observed in AMs from GM−/− mice. The transcription factor PU.1 was markedly reduced in AMs of GM−/− mice in vivo and was restored by selective expression of GM-CSF in the lungs of SPC-GM/GM−/− transgenic mice. Retrovirus-mediated expression of PU.1 in AMs from GM−/− mice rescued host defense functions and surfactant catabolism by AMs. We conclude that PU.1 mediates GM-CSF-dependent effects on terminal differentiation of AMs regulating innate immune functions and surfactant catabolism by AMs

    Structural and Functional Determinants of Rodent and Human Surfactant Protein A: A Synthesis of Binding and Computational Data

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    Surfactant protein A (SP-A) provides surfactant stability, first line host defense, and lung homeostasis by binding surfactant phospholipids, pathogens, alveolar macrophages (AMs), and epithelial cells. Non-primates express one SP-A protein whereas humans express two: SP-A1 and SP-A2 with core intra- and inter-species differences in the collagen-like domain. Here, we used macrophages and solid phase binding assays to discern structural correlates of rat (r) and human (h) SP-A function. Binding assays using recombinant rSP-A expressed in insect cells showed that lack of proline hydroxylation, truncations of amino-terminal oligomerization domains, and site-directed serine (S) or alanine (A) mutagenesis of cysteine 6 (C6S), glutamate 195 (E195A), and glutamate 171 (E171A) in the carbohydrate recognition domain (CRD) all impaired SP-A binding. Replacement of arginine 197 with alanine found in hSP-A (R197A), however, restored the binding of hydroxyproline-deficient rSP-A to the SP-A receptor SP-R210 similar to native rat and human SP-A. In silico calculation of Ca++ coordination bond length and solvent accessibility surface area revealed that the “humanized” R197A substitution alters topology and solvent accessibility of the Ca++ coordination residues of the CRD domain. Binding assays in mouse AMs that were exposed to either endogenous SP-A or hSP-A1 (6A2) and hSP-A2 (1A0) isoforms in vivo revealed that mouse SP-A is a functional hybrid of hSP-A1 and hSP-A2 in regulating SP-A receptor occupancy and binding affinity. Binding assays using neonatal and adult human AMs indicates that the interaction of SP-A1 and SP-A2 with AMs is developmentally regulated. Furthermore, our data indicate that the auxiliary ion coordination loop encompassing the conserved E171 residue may comprise a conserved site of interaction with macrophages, and SP-R210 specifically, that merits further investigation to discern conserved and divergent SP-A functions between species. In summary, our findings support the notion that complex structural adaptation of SP-A regulate conserved and species specific AM functions in vertebrates

    Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver

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    The type 2 immune response controls helminth infection and maintains tissue homeostasis but can lead to allergy and fibrosis if not adequately regulated. We have discovered local tissue-specific amplifiers of type 2-mediated macrophage activation. In the lung, surfactant protein A (SP-A) enhanced interleukin-4 (IL-4)-dependent macrophage proliferation and activation, accelerating parasite clearance and reducing pulmonary injury after infection with a lung-migrating helminth. In the peritoneal cavity and liver, C1q enhancement of type 2 macrophage activation was required for liver repair after bacterial infection, but resulted in fibrosis after peritoneal dialysis. IL-4 drives production of these structurally related defense collagens, SP-A and C1q, and the expression of their receptor, myosin 18A. These findings reveal the existence within different tissues of an amplification system needed for local type 2 responses

    Gender Discrimination and Social Identity: Experimental Evidence from Urban Pakistan

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    Gender discrimination in South Asia is a well-documented fact. However, gender is only one of an individual's many identities. This paper investigates how gender discrimination depends on the social identities of interacting parties. We use an experimental approach to identify gender discrimination by randomly matching 2,836 male and female students pursuing bachelor's-equivalent degrees in three different types of institutions - Madrassas (religious seminaries), Islamic universities, and liberal universities - that represent distinct identities within the Pakistani society. Our main finding is that gender discrimination is not uniform in intensity and nature across the educated Pakistani society and varies as a function of the social identity of both individuals who interact. While we find no evidence of higher-socioeconomic-status men discriminating against women, men of lower socioeconomic status and higher religiosity tend to discriminate against women - but only women of lower socioeconomic status who are closest to them in social distance. Moreover, this discrimination is largely taste-based. Our findings suggest that social policies aimed at empowering women need to account for the intersectionality of gender with social identity

    Social Internet of Things and New Generation Computing -- A Survey

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    Social Internet of Things (SIoT) tries to overcome the challenges of Internet of Things (IoT) such as scalability, trust and discovery of resources, by inspiration from social computing. This survey aims to investigate the research done on SIoT from two perspectives including application domain and the integration to the new computing models. For this, a two-dimensional framework is proposed and the projects are investigated, accordingly. The first dimension considers and classifies available research from the application domain perspective and the second dimension performs the same from the integration to new computing models standpoint. The aim is to technically describe SIoT, to classify related research, to foster the dissemination of state-of-the-art, and to discuss open research directions in this field.Comment: IoT, Social computing, Surve

    Fog computing security: a review of current applications and security solutions

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    Fog computing is a new paradigm that extends the Cloud platform model by providing computing resources on the edges of a network. It can be described as a cloud-like platform having similar data, computation, storage and application services, but is fundamentally different in that it is decentralized. In addition, Fog systems are capable of processing large amounts of data locally, operate on-premise, are fully portable, and can be installed on heterogeneous hardware. These features make the Fog platform highly suitable for time and location-sensitive applications. For example, Internet of Things (IoT) devices are required to quickly process a large amount of data. This wide range of functionality driven applications intensifies many security issues regarding data, virtualization, segregation, network, malware and monitoring. This paper surveys existing literature on Fog computing applications to identify common security gaps. Similar technologies like Edge computing, Cloudlets and Micro-data centres have also been included to provide a holistic review process. The majority of Fog applications are motivated by the desire for functionality and end-user requirements, while the security aspects are often ignored or considered as an afterthought. This paper also determines the impact of those security issues and possible solutions, providing future security-relevant directions to those responsible for designing, developing, and maintaining Fog systems

    Human GLI3 Intragenic Conserved Non-Coding Sequences Are Tissue-Specific Enhancers

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    The zinc-finger transcription factor GLI3 is a key regulator of development, acting as a primary transducer of Sonic hedgehog (SHH) signaling in a combinatorial context dependent fashion controlling multiple patterning steps in different tissues/organs. A tight temporal and spatial control of gene expression is indispensable, however, cis-acting sequence elements regulating GLI3 expression have not yet been reported. We show that 11 ancient genomic DNA signatures, conserved from the pufferfish Takifugu (Fugu) rubripes to man, are distributed throughout the introns of human GLI3. They map within larger conserved non-coding elements (CNEs) that are found in the tetrapod lineage. Full length CNEs transiently transfected into human cell cultures acted as cell type specific enhancers of gene transcription. The regulatory potential of these elements is conserved and was exploited to direct tissue specific expression of a reporter gene in zebrafish embryos. Assays of deletion constructs revealed that the human-Fugu conserved sequences within the GLI3 intronic CNEs were essential but not sufficient for full-scale transcriptional activation. The enhancer activity of the CNEs is determined by a combinatorial effect of a core sequence conserved between human and teleosts (Fugu) and flanking tetrapod-specific sequences, suggesting that successive clustering of sequences with regulatory potential around an ancient, highly conserved nucleus might be a possible mechanism for the evolution of cis-acting regulatory elements

    Transient up- and down-regulation of expression of myosin light chain 2 and myostatin mRNA mark the changes from stratified hyperplasia to muscle fiber hypertrophy in larvae of gilthead sea bream (Sparus aurata L.)

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    Hyperplasia and hypertrophy are the two mechanisms by which muscle develops and grows. We study these two mechanisms, during the early development of white muscle in Sparus aurata, by means of histology and the expression of structural and regulatory genes. A clear stage of stratified hyperplasia was identified early in the development of gilthead sea bream but ceased by 35 dph when hypertrophy took over. Mosaic recruitment of new white fibers began as soon as 60 dph. The genes mlc2a and mlc2b were expressed at various levels during the main phases of hyperplasia and hypertrophy. The genes myog and mlc2a were significantly up-regulated during the intensive stratified formation of new fibers and their expression was significantly correlated. Expression of mstn1 and igf1 increased at 35 dph, appeared to regulate the hyperplasia-to-hypertrophy transition, and may have stimulated the expression of mlc2a, mlc2b and col1a1 at the onset of mosaic hyperplasia. The up-regulation of mstn1 at transitional phases in muscle development indicates a dual regulatory role of myostatin in fish larval muscle growth
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