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The use of gateway proxies is one important approach to facilitating adaptation across wireless and mobile environments. Importantly, augmented service entities deployed within the gateway proxy residing on the wired network can be composed and deployed to shield mobile clients from the effects of poor network characteristics. The usual approach to the static composition of service entities on the gateway proxy is to have these service entities interact with each other by explicitly invoking procedures on the named interface, but such a tight coupling of interfaces inhibits the flexible composition and adaptation of the service entities to the dynamic operating characteristics of wireless networks. In this paper, we present a Mobile gateway for the Active deployment of Transport Entities or, for short, MobiGATE (pronounced Mobi-Gate). MobiGATE is a mobile middleware framework that supports the robust and flexible composition of transport entities, known as streamlets. The flow of data traffic is subjected to processing by a chain of streamlets. Each streamlet encapsulates a service entity that adapts the flow of traffic across the wireless network. To facilitate the dynamic reconfiguration of the streamlets, we advocate applying the concept of coordination as the unifying approach to composing these transport service entities. Importantly, MobiGATE delineates a clear separation of interdependent parts from the service-specific computational codes of those service entities. It does this by using a separate coordination language, called MobiGATE Coordination Language (MCL), to describe the coordination among streamlet service entities. The complete design, implementation, and evaluation of the MobiGATE system are presented in this paper. Initial experimental results validate the flexibility of the coordination approach in promoting separation-of-concern in the reconfiguration of services, while achieving low computation and delay overheads. [ABSTRACT FROM AUTHOR]

WEBGOP is a programming architecture for collaborative Web services using graph-oriented programming. The motivation for the project comes from the realization that the integration of collaborative Web services lacks support. The aim of WEBGOP is to extend the Web from a client-server system to a structured multipoint system. A graph abstraction of the network provides the structure for the integration of Web services and facilitates their configuration and programming. Using WEBGOP, a logical graph representing a virtual-overlay network over the Internet is created to link up collaborative Web services. Web services are individually or jointly invoked through either unicast or multicast messages within the overlay network. All messages are based on the simple-object access protocol (SOAP). This forms an extension of the hypertext transfer protocol (HTTP) to support the distributed invocation of Web services. The Web services on different servers work collaboratively for a multipoint network application. This project provides a structured integration of Web services by extending the support of intermediary processing in a multipoint service. It also provides a rich network-programming interface for a new class of integrated Web applications while retaining the use of the Internet protocol and HTTP. [ABSTRACT FROM AUTHOR]

Abstract: We recently identified six neuroblastoma patients with constitutional or tumor-specific mutations in the homeobox gene Phox2B. Phox2B controls part of the differentiation program of the sympathetic nervous system (SNS). Mice with a homozygous inactivation of Phox2B fail in the proper differentiation of the chromaffin lineage of the SNS. Phox2B regulates HASH1 which can control expression of genes of the Delta–Notch pathway. We previously showed that a subset of neuroblastoma cell lines highly expresses Delta-like 1 (Dlk1), which is a marker for the chromaffin lineage of the SNS. Notch3 is expressed in another subset of neuroblastoma cell lines and marks tumors from an alternative differentiation lineage. Phox2B is also related to the TrkA differentiation pathway in neuroblastoma. Here we will review the role of Phox2B in differentiation programs of the SNS and in neuroblastoma pathogenesis. [Copyright &y& Elsevier]

Neuroblastomas are embryonal tumours of the sympatho-adrenal lineage with a clinical course ranging from spontaneous regression to fatal progression. The Phox2B homeobox transcription factor functions in the differentiation of the sympatho-adrenal lineage. Targets of Phox2B are, for example, genes of the (nor)adrenalin synthesis route, like Dopamine Beta Hydroxylase (DBH). Congenital Central Hypoventilation Syndrome was recently found to result from Phox2B mutations and two such patients in addition developed neuroblastoma. A germline mutation in Phox2B was identified in a family with hereditary neuroblastoma. Here, we report the first analysis of Phox2B in a series of 237 sporadic neuroblastomas and 22 cell lines. Six frameshift mutations were found in exons 2 and 3; including one in cell line SK-N-SH. Two patients showed de novo constitutional mutations. One of them was diagnosed with Haddad syndrome. All analysed cases expressed the mutated and wild-type Phox2B alleles. Ectopic expression of TrkA, the Nerve Growth Factor receptor, strongly downregulated Phox2B and DBH expression in cell line SH-SY5Y. However, TrkA and Phox2B showed a positive correlation in a panel of 66 neuroblastoma tumours. Although Phox2B mutations are infrequent (2.3%), they implicate a role for the Phox2B pathway in oncogenesis.Oncogene (2004) 23, 9280-9288. doi:10.1038/sj.onc.1208157 Published online 25 October 2004 [ABSTRACT FROM AUTHOR]

XML (eXtensible Markup Language) has been developed and deployed by domain-specific standardization bodies and commercial companies. Studies have been conducted on a wide variety of issues encompassing XML. In the use of XML for wireless computing, the focus has been on investigating ways to efficiently represent XML data for transmission over a wireless environment. We propose a middleware, Xstrearn (XML Streaming), for efficiently streaming XML contents over a wireless environment by leveraging the rich semantics and structural characteristics of XML documents and by flexibly managing units containing fragments of data into autonomous units, known as XDU (Xstream Data Unit) fragments. The concept of an XDU is fundamental to the operation of Xstream. It provides for the efficient transfer of documents across a wireless link and allows other issues and challenges pertaining to wireless transmission to be addressed. By fragmenting and organizing an XML document into XDU fragments, we are able to incrementally send fragments across a wireless link, while the receiver is able to perform look-ahead processing of the document without having to wait for the entire document to be downloaded. In this paper, we propose a fragmenting strategy based on the value of the wireless link's Maximum Transfer Units (MTUs). In addition, we present and evaluate several packetizing strategies, i.e., strategies wherein a collection of XDU5 are grouped into a packet to optimize packet delivery and processing. At the receiving end of this process, a reassembly strategy incrementally reconstructs the XML document as XDU fragments are being received, thereby facilitating client application implementation of look-ahead processing. [ABSTRACT FROM AUTHOR]

The formulation of a context-aware middleware requires researchers to devise suitable control mechanisms that allow applications to directly participate in resource adaptation in response to dynamic operating environments. This paper describes the design and implementation of an event model for a highly adaptive mobile middleware, Web Proxy for Actively Deployable Services (WebPADS) platform. The event model provides a highly composable event notification framework that uses multiple levels of environment monitors to provide a complex setup of composite events. Based on the event model and the dynamic reconfiguration feature WebPADS supports context awareness and a high level of adaptation to contextual changes through reconfiguration and migration of services. [ABSTRACT FROM AUTHOR]

The virtual programming lab (VPL) project described in this paper is designed to facilitate Internet access to application software. It emulates a real computing laboratory environment that promotes group learning and project management. The laboratory resources are situated at the university and are centrally controlled. Users of the virtual programming laboratory include students, tutors and administrators of the system. Users can be located at different geographical locations to remotely access applications through the Internet. The virtual programming lab design is based on a distance education concept. This paper focuses on the design and development of the runtime modules within the VPL framework. These runtime modules provide underlying services that drive the launching of applications, file management and communications services. In addition, this paper presents an evaluation of the performance of the system. [ABSTRACT FROM AUTHOR]

The proliferation of mobile devices in wireless environments has put special requirements on the ability to access the Web seamlessly. To address the impact of varying contextual characteristics on mobile access, the authors developed the WebPADS framework, which can actively deploy new mobile services. Moreover, WebPADS can dynamically reconfigure its services and migrate them to adapt to the vigorous changes in the wireless environment. [ABSTRACT FROM AUTHOR]

Traditionally, middleware technologies, such as CORBA, Java RMI, and Microsoft's DCOM, have provided a set of distributed computing services that essentially abstract the underlying network services to a monolithic "black box." In a mobile operating environment, the fundamental assumption of middleware abstracting a unified distributed service for all types of applications operating over a static network infrastructure is no longer valid. In particular, mobile applications are not able to leverage the benefits of adaptive computing to optimize its computation based on current contextual situations. In this paper, we introduce the Mobile Platform for Actively Deployable Service (MobiPADS) system. MobIPADS is designed to support context-aware processing by providing an executing platform to enable active service deployment and reconfiguration of the service composition in response to environments of varying contexts. Unlike most mobile middleware, MobiPADS supports dynamic adaptation at both the middleware and application layers to provide flexible óonfiguration of resources to optimize the operations of mobile applications. Within the MobIPADS system, services (known as mobilets) are configured as chained service objects to provide augmented services to the underlying mobile applications so as to alleviate the adverse conditions of a wireless environment. [ABSTRACT FROM AUTHOR]

Discusses the application of common object request broker architecture wrapper technology by the OrbCard framework to extend smart card services to a distributed computing environment. Role of smart card technology in providing security and access control mechanisms for processing online transactions; Development of various smart card applications; Implementation of a simple distributed client-server application that shows the complex interactions between objects within the framework. INSET: Related Work in Distributed Smart Card Applications.

Discusses various issues that XML poses with respect to information retrieval and database research. Techniques for indexing XML documents; Integration between database and information retrieval system; Classes of database structures.

Examines the biological role of vitamin E in treating atherosclerosis. Role of low density lipoprotein oxidation on atherogenesis; Effects on endothelial arachidonic acid and metabolism; Factors affecting vitamin E status.

FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lipidomic analyses, we show that FXR activation in mice or humans specifically reduces hepatic levels of mono- and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1 , Dgat2 , and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption. Replenishing bile acids in the diet prevented decreased lipid absorption in GSK2324-treated mice, suggesting that FXR reduces absorption via decreased bile acids. We used tissue-specific FXR KO mice to show that hepatic FXR controls lipogenic genes, whereas intestinal FXR controls lipid absorption. Together, our studies establish two distinct pathways by which FXR regulates hepatic lipids. [Display omitted] • Non-steroidal agonists of FXR significantly decrease intestinal lipid absorption • FXR decreases hepatic triglycerides independently of SHP and SREBP1C • FXR activation reduces expression of three key lipogenic genes, Scd1, Lpin1, and Dgat2 • Intestinal and hepatic FXR are both required to decrease hepatic triglycerides The nuclear receptor FXR lowers hepatic triglycerides to protect against the onset of NAFLD. Clifford et al. demonstrate that activation of FXR decreases hepatic triglycerides through two distinct mechanisms. First, via bile-acid-dependent decreases in intestinal lipid absorption and second, through selective changes in lipogenesis. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is the physiological clustering of hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, and insulin resistance. The MetS-related chronic illnesses encompass obesity, the cardiovascular system, renal operation, hepatic function, oncology, and mortality. To perform pre-clinical research, it is imperative that these symptoms be successfully induced and optimized in lower taxonomy. Therefore, novel and future applications for a disease model, if proven valid, can be extrapolated to humans. MetS model establishment is evaluated based on the significance of selected test parameters, paradigm shifts from new discoveries, and the accessibility of the latest technology or advanced methodologies. Ultimately, the outcome of animal studies should be advantageous for human clinical trials and solidify their position in advanced medicine for clinicians to treat and adapt to serious or specific medical situations. Rodents (Rattus norvegicus and Mus musculus) have been ideal models for mammalian studies since the 18th century and have been mapped extensively. This review compiles and compares studies published in the past five years between the multitude of rodent comparative models. The response factors, niche parameters, and replicability of diet protocols are also compiled and analyzed to offer insight into MetS-related disease-specific modelling. [ABSTRACT FROM AUTHOR]

The release of arachidonic acid is the rate limiting step in eicosanoid synthesis. In mammalian cells, the release of arachidonic acid is catalyzed by several enzymes. The 85 kDa cytosolic phospholipase A2 (cPLA2) is the key enzyme for the release reaction because of its specific acyl selectivity in phospholipid substrates. We have previously reported that vitamin E enrichment potentiates the arachidonic acid release as well as the spontaneous prostacyclin release in human endothelial cells. In contrast, similar enrichment of diets caused a dose-dependent suppression of platelet thromboxane synthesis. Therefore, the present study was undertaken to determine the effect of vitamin E on arachidonate release and phospholipase A2 activity in a platelet precursor cell, the MEG-01 megakaryocyte cell line. When these cells were incubated with different concentrations of vitamin E, cellular incorporation was linear with the dosages of this vitamin. Determination of arachidonate release after labeling cells with [3H]-arachidonate showed that vitamin E enrichment caused a dose-dependent increase in ionophore A23187-induced [3H]-arachidonic acid release. Analysis of PLA2 activity showed that activity was detected in the cytosol and this activity was completely abolished by the addition of anti-cPLA2, antibody. Determination of cPLA2 activity demonstrated that vitamin E enrichment caused an increase in enzyme activity. Analysis of cPLA2 protein by Western blot revealed that vitamin E caused an increase in enzyme protein. These data showed that the potentiation of arachidonic acid release and cPLA2, activity by vitamin E was mediated by the enhanced expression of cPLA2 protein. [ABSTRACT FROM AUTHOR]

Highlights the efficacy of vitamin E for the treatment of atherosclerosis. Relationship between vitamin E and coronary heart diseases; Physiologic effects of vitamin E; Factors affecting vitamin E status; Protective effects of vitamin E on lipoproteins and different cell types involved in atherogenesis.

Human platelet lipooxygenase converts arachidonic acid to 12-hydroperoxy-eicosatetraenoic acid (12-HPETE), which is rapidly reduced by peroxidases to 12-hydroxy-eicosa-tetraenoic acid (12-HETE). This study was conducted to examine the effect of vitamin E supplementation on platelet 12-lipooxygenase activity. Sixteen healthy subjects were supplemented with 400 IU/day of either D-α-tocopherol (268 mg) or DL-α-tocopherol (364 mg) for 4 wk. Supplements elicited a transitory increase of lipooxygenase activity but a suppression of peroxidase activity, as indicated by increased 12-HETE production and 12-HPETE accumulation. Plasma-tocopherol concentration was double the presupplement value and remained stable during supplementation. Neither age, sex, nor isomeric form of tocopherol supplement significantly influenced the pattern of response. Results show that vitamin E exerts a differential effect on platelet lipooxygenase and peroxidase activities. [ABSTRACT FROM AUTHOR]

The intake of γ-tocopherol by North Americans is generally higher than that of α-tocopherol. However, the levels of α-tocopherol in human blood have consistently been shown to be higher than those of γ-tocopherol suggesting differential cellular retention of the two tocopherol forms. We sought to resolve this question by studying tocopherol metabolism by human endothelial cells in culture. The time- and dose-dependent uptake of γ-tocopherol by endothelial cells was similar to that of α-tocopherol. To determine the comparative uptake between α- and γ-tocopherol, we adopted two approaches in which cells were enriched with either increasing concentrations of an equimolar mixture of α- and γ-tocopherol; or cells were enriched with a fixed concentration of tocopherols in which the α to γ ratio was varied. Our results indicated that there was a preferential uptake of γ-tocopherol by the cells. When cells were enriched with either α- or γ-tocopherol and the disappearance of individual tocopherols was monitored over time, γ-tocopherol exhibited a faster rate of disappearance. The faster turnover of γ-tocopherol can explain the discrepancy between high intake and low retention of γ-tocopherol in man. [ABSTRACT FROM AUTHOR]

We present a deep recurrent convolutional neural network (CNN) approach to solve the problem of hockey player identification in NHL broadcast videos. Player identification is a difficult computer vision problem mainly because of the players' similar appearance, occlusion, and blurry facial and physical features. However, we can observe players' jersey numbers over time by processing variable length image sequences of players (aka 'tracklets'). We propose an end-to-end trainable ResNet+LSTM network, with a residual network (ResNet) base and a long short-term memory (LSTM) layer, to discover spatio-temporal features of jersey numbers over time and learn long-term dependencies. Additionally, we employ a secondary 1-dimensional convolutional neural network classifier as a late score-level fusion method to classify the output of the ResNet+LSTM network. For this work, we created a new hockey player tracklet dataset that contains sequences of hockey player bounding boxes. This achieves an overall player identification accuracy score over 87% on the test split of our new dataset. • Recurrent convolutional neural network proposed for hockey player identification. • Variable length image sequences of player bounding boxes (tracklets) are classified. • Spatial–temporal information across video frames improves jersey number predictions. • A secondary classifier added as a late score-level fusion method increases accuracy. [ABSTRACT FROM AUTHOR]

Objective: Summarize the current evidence on efficacy and tolerability of vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) through a systematic review and meta‐analysis. Methods: We followed the Preferred Reporting Items of Systematic reviews and Meta‐Analyses reporting standards and searched Ovid Medline, Ovid Embase, and the Cochrane Central Register of Controlled Trials. We included published randomized controlled trials (RCTs) and their corresponding open‐label extension studies, as well as prospective case series, with ≥20 participants (excluding studies limited to children). Our primary outcome was the mean (or median, when unavailable) percentage decrease in frequency, as compared to baseline, of all epileptic seizures at last follow‐up. Secondary outcomes included the proportion of treatment responders and proportion with seizure freedom. Results: We identified 30 eligible studies, six of which were RCTs. At long‐term follow‐up (mean 1.3 years), five observational studies for VNS reported a pooled mean percentage decrease in seizure frequency of 34.7% (95% confidence interval [CI]: −5.1, 74.5). In the open‐label extension studies for RNS, the median seizure reduction was 53%, 66%, and 75% at 2, 5, and 9 years of follow‐up, respectively. For DBS, the median reduction was 56%, 65%, and 75% at 2, 5, and 7 years, respectively. The proportion of individuals with seizure freedom at last follow‐up increased significantly over time for DBS and RNS, whereas a positive trend was observed for VNS. Quality of life was improved in all modalities. The most common complications included hoarseness, and cough and throat pain for VNS and implant site pain, headache, and dysesthesia for DBS and RNS. Significance: Neurostimulation modalities are an effective treatment option for drug‐resistant epilepsy, with improving outcomes over time and few major complications. Seizure‐reduction rates among the three therapies were similar during the initial blinded phase. Recent long‐term follow‐up studies are encouraging for RNS and DBS but are lacking for VNS. [ABSTRACT FROM AUTHOR]

Transition between differentiation states in development occurs swift but the mechanisms leading to epigenetic and transcriptional reprogramming are poorly understood. The pediatric cancer neuroblastoma includes adrenergic (ADRN) and mesenchymal (MES) tumor cell types, which differ in phenotype, super-enhancers (SEs) and core regulatory circuitries. These cell types can spontaneously interconvert, but the mechanism remains largely unknown. Here, we unravel how a NOTCH3 intracellular domain reprogrammed the ADRN transcriptional landscape towards a MES state. A transcriptional feed-forward circuitry of NOTCH-family transcription factors amplifies the NOTCH signaling levels, explaining the swift transition between two semi-stable cellular states. This transition induces genome-wide remodeling of the H3K27ac landscape and a switch from ADRN SEs to MES SEs. Once established, the NOTCH feed-forward loop maintains the induced MES state. In vivo reprogramming of ADRN cells shows that MES and ADRN cells are equally oncogenic. Our results elucidate a swift transdifferentiation between two semi-stable epigenetic cellular states. Neuroblastoma includes adrenergic and mesenchymal cell types that can interconvert. Here, the authors show that this transdifferentiation is driven by a NOTCH feedforward loop that allows a swift transition between two semi-stable cellular states. [ABSTRACT FROM AUTHOR]