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Sample records for controls kshv latency

  1. Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.

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    Grzegorz Sarek

    2010-03-01

    Full Text Available Nucleophosmin (NPM is a multifunctional nuclear phosphoprotein and a histone chaperone implicated in chromatin organization and transcription control. Oncogenic Kaposi's sarcoma herpesvirus (KSHV is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma (PEL and multicentric Castleman disease (MCD. In the infected host cell KSHV displays two modes of infection, the latency and productive viral replication phases, involving extensive viral DNA replication and gene expression. A sustained balance between latency and reactivation to the productive infection state is essential for viral persistence and KSHV pathogenesis. Our study demonstrates that the KSHV v-cyclin and cellular CDK6 kinase phosphorylate NPM on threonine 199 (Thr199 in de novo and naturally KSHV-infected cells and that NPM is phosphorylated to the same site in primary KS tumors. Furthermore, v-cyclin-mediated phosphorylation of NPM engages the interaction between NPM and the latency-associated nuclear antigen LANA, a KSHV-encoded repressor of viral lytic replication. Strikingly, depletion of NPM in PEL cells leads to viral reactivation, and production of new infectious virus particles. Moreover, the phosphorylation of NPM negatively correlates with the level of spontaneous viral reactivation in PEL cells. This work demonstrates that NPM is a critical regulator of KSHV latency via functional interactions with v-cyclin and LANA.

  2. Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Upregulates Survivin Expression in KSHV-Associated B-Lymphoma Cells and Contributes to Their Proliferation▿

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    Lu, Jie; Verma, Subhash C.; Murakami, Masanao; Cai, Qiliang; KUMAR, Pankaj; Xiao, Bingyi; Robertson, Erle S.

    2009-01-01

    Survivin is a master regulator of cell proliferation and cell viability and is highly expressed in most human tumors. The molecular network linked to survivin expression in tumors has not been completely elucidated. In this study, we show that latency-associated nuclear antigen (LANA), a multifunctional protein of Kaposi's sarcoma-associated herpesvirus (KSHV) that is found in Kaposi's sarcoma tumors, upregulates survivin expression and increases the proliferation of KSHV-infected B cells. An...

  3. Influence of ND10 components on epigenetic determinants of early KSHV latency establishment.

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    Thomas Günther

    2014-07-01

    Full Text Available We have previously demonstrated that acquisition of intricate patterns of activating (H3K4me3, H3K9/K14ac and repressive (H3K27me3 histone modifications is a hallmark of KSHV latency establishment. The precise molecular mechanisms that shape the latent histone modification landscape, however, remain unknown. Promyelocytic leukemia nuclear bodies (PML-NB, also called nuclear domain 10 (ND10, have emerged as mediators of innate immune responses that can limit viral gene expression via chromatin based mechanisms. Consequently, although ND10 functions thus far have been almost exclusively investigated in models of productive herpesvirus infection, it has been proposed that they also may contribute to the establishment of viral latency. Here, we report the first systematic study of the role of ND10 during KSHV latency establishment, and link alterations in the subcellular distribution of ND10 components to a temporal analysis of histone modification acquisition and host cell gene expression during the early infection phase. Our study demonstrates that KSHV infection results in a transient interferon response that leads to induction of the ND10 components PML and Sp100, but that repression by ND10 bodies is unlikely to contribute to KSHV latency establishment. Instead, we uncover an unexpected role for soluble Sp100 protein, which is efficiently and permanently relocalized from nucleoplasmic and chromatin-associated fractions into the insoluble matrix. We show that LANA expression is sufficient to induce Sp100 relocalization, likely via mediating SUMOylation of Sp100. Furthermore, we demonstrate that depletion of soluble Sp100 occurs precisely when repressive H3K27me3 marks first accumulate on viral genomes, and that knock-down of Sp100 (but not PML or Daxx facilitates H3K27me3 acquisition. Collectively, our data support a model in which non-ND10 resident Sp100 acts as a negative regulator of polycomb repressive complex-2 (PRC2 recruitment, and

  4. Kaposi Sarcoma Herpesvirus (KSHV Latency-Associated Nuclear Antigen (LANA recruits components of the MRN (Mre11-Rad50-NBS1 repair complex to modulate an innate immune signaling pathway and viral latency.

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    Giuseppe Mariggiò

    2017-04-01

    Full Text Available Kaposi Sarcoma Herpesvirus (KSHV, a γ2-herpesvirus and class 1 carcinogen, is responsible for at least three human malignancies: Kaposi Sarcoma (KS, Primary Effusion Lymphoma (PEL and Multicentric Castleman's Disease (MCD. Its major nuclear latency protein, LANA, is indispensable for the maintenance and replication of latent viral DNA in infected cells. Although LANA is mainly a nuclear protein, cytoplasmic isoforms of LANA exist and can act as antagonists of the cytoplasmic DNA sensor, cGAS. Here, we show that cytosolic LANA also recruits members of the MRN (Mre11-Rad50-NBS1 repair complex in the cytosol and thereby inhibits their recently reported role in the sensing of cytoplasmic DNA and activation of the NF-κB pathway. Inhibition of NF-κB activation by cytoplasmic LANA is accompanied by increased lytic replication in KSHV-infected cells, suggesting that MRN-dependent NF-κB activation contributes to KSHV latency. Cytoplasmic LANA may therefore support the activation of KSHV lytic replication in part by counteracting the activation of NF-κB in response to cytoplasmic DNA. This would complement the recently described role of cytoplasmic LANA in blocking an interferon response triggered by cGAS and thereby promoting lytic reactivation. Our findings highlight a second point at which cytoplasmic LANA interferes with the innate immune response, as well as the importance of the recently discovered role of cytoplasmic MRN complex members as innate sensors of cytoplasmic DNA for the control of KSHV replication.

  5. Regulation of latency to lytic life cycle:multiple tricks by KSHV RTA

    Institute of Scientific and Technical Information of China (English)

    Jiemin Wong

    2010-01-01

    @@ Higher Education Press and Springer-Verlag Berlin Heidelberg 2010The herpesviruses are large enveloped DNA viruses that infect a wide spectrum hosts including human being. A key characteristic of all herpesviruses is their ability to establish life-time latency within the infected host and to periodically reactivate and enter the iytic replication to produce infectious virus progeny. During latency the 120-300 kb double-stranded DNA genomes of these viruses are maintained as multiple copies of circular episomes within the nuclei of the host cells. Lytic replication is marked by an increase in viral gene expression and the production of infectious virus progeny.

  6. Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus Latency and Reactivation

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    Fengchun Ye

    2011-01-01

    Full Text Available The life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV consists of latent and lytic replication phases. During latent infection, only a limited number of KSHV genes are expressed. However, this phase of replication is essential for persistent infection, evasion of host immune response, and induction of KSHV-related malignancies. KSHV reactivation from latency produces a wide range of viral products and infectious virions. The resulting de novo infection and viral lytic products modulate diverse cellular pathways and stromal microenvironment, which promote the development of Kaposi's sarcoma (KS. The mechanisms controlling KSHV latency and reactivation are complex, involving both viral and host factors, and are modulated by diverse environmental factors. Here, we review the cellular and molecular basis of KSHV latency and reactivation with a focus on the most recent advancements in the field.

  7. Resveratrol inhibits KSHV reactivation by lowering the levels of cellular EGR-1.

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    Ossie F Dyson

    Full Text Available In the field of herpesvirus research, the exact molecular mechanism by which such viruses reactivate from latency remains elusive. Kaposi's sarcoma-associated herpesvirus (KSHV primarily exists in a latent state, while only 1-3% of cells support lytic infection at any specific time. KSHV reactivation from latency is an exceedingly intricate process mediated by the integration of viral and cellular factors. Previously, our lab has described early growth response-1 (Egr-1 as an essential component for the KSHV reactivation process via its ability to mediate transcription of KSHV ORF50, the gene encoding for replication and transcription activator (RTA, a viral component known to control the switch from latent to lytic infection. In here, electrophoretic mobility shift assays (EMSA and chromatin immunoprecipitation (ChIP experiments revealed that Egr-1 binds KSHV ORF50 promoter (ORF50P in at least two different GC-rich binding domains. Expression profiles of cellular egr-1 and KSHV-encoded ORF50 follow a similar pattern during de novo KSHV infection. Over-expressing Egr-1, a signaling component downstream of Raf>MEK>ERK1/2, in KSHV-infected cells activates KSHV lytic replication. Through performing more physiologically relevant experiments, we analyzed the effect of a dietary supplement containing resveratrol on KSHV-infected cells. Our results, for the first time, demonstrate resveratrol to act in lowering ERK1/2 activity and expression of Egr-1 in KSHV-infected cells, resulting in the suppression of virus reactivation from latency. Taken together, these findings will undoubtedly contribute to future studies on not only combating KSHV related disease conditions, but also on other herpesviruses-induced pathogenesis.

  8. Piracy of PGE2/EP receptor mediated signaling by Kaposi’s sarcoma associated herpes virus (KSHV/HHV-8) for latency gene expression: Strategy of a successful pathogen

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    Paul, Arun George; Sharma-Walia, Neelam; Kerur, Nagaraj; White, Carl; Chandran, Bala

    2010-01-01

    KSHV is implicated in the pathogenesis of KS, a chronic inflammation associated malignancy. COX-2 and its metabolite PGE2, two pivotal proinflammatory/oncogeneic molecules, are proposed to play roles in the expression of major KSHV latency associated nuclear antigen-1 (LANA-1). Microsomal prostaglandin E2 synthase (mPGES), PGE2 and its receptors (EP1, EP2, EP3, and EP4) were detected in KS lesions with the distinct staining of EP2/EP4 in KS lesions. In latently infected endothelial TIVE-LTC cells, EP receptor antagonists down-regulated LANA-1 expression as well as Ca2+, p-Src, p-PI3K, p-PKCζ/λ, and p-NF-κB, which are also some of the signal molecules proposed to be important in KS pathogenesis. Exogenous PGE2 and EP receptor agonists induced the LANA-1 promoter in 293 cells, and YY1, Sp1, Oct-1, Oct-6, C/EBP and c-Jun transcription factors appear to be involved in this induction. PGE2/EP receptor induced LANA-1 promoter activity was down-regulated significantly by the inhibition of Ca2+, p-Src, p-PI3K, p-PKCζ/λ, and p-NF-κB. These findings implicate the inflammatory PGE2/EP receptors and the associated signal molecules in herpes virus latency and uncover a novel paradigm that demonstrates the evolution of KSHV genome plasticity to utilize inflammatory response for its survival advantage of maintaining latent gene expression. This data also suggests that potential use of anti-COX-2 and anti-EP receptor therapy may not only ameliorate the chronic inflammation associated with KS but could also lead to elimination of the KSHV latent infection and the associated KS lesions. PMID:20388794

  9. Towards Controlling Latency in Wireless Networks

    KAUST Repository

    Bouacida, Nader

    2017-04-24

    Wireless networks are undergoing an unprecedented revolution in the last decade. With the explosion of delay-sensitive applications in the Internet (i.e., online gaming and VoIP), latency becomes a major issue for the development of wireless technology. Taking advantage of the significant decline in memory prices, industrialists equip the network devices with larger buffering capacities to improve the network throughput by limiting packets drops. Over-buffering results in increasing the time that packets spend in the queues and, thus, introducing more latency in networks. This phenomenon is known as “bufferbloat”. While throughput is the dominant performance metric, latency also has a huge impact on user experience not only for real-time applications but also for common applications like web browsing, which is sensitive to latencies in order of hundreds of milliseconds. Concerns have arisen about designing sophisticated queue management schemes to mitigate the effects of such phenomenon. My thesis research aims to solve bufferbloat problem in both traditional half-duplex and cutting-edge full-duplex wireless systems by reducing delay while maximizing wireless links utilization and fairness. Our work shed lights on buffer management algorithms behavior in wireless networks and their ability to reduce latency resulting from excessive queuing delays inside oversized static network buffers without a significant loss in other network metrics. First of all, we address the problem of buffer management in wireless full-duplex networks by using Wireless Queue Management (WQM), which is an active queue management technique for wireless networks. Our solution is based on Relay Full-Duplex MAC (RFD-MAC), an asynchronous media access control protocol designed for relay full-duplexing. Compared to the default case, our solution reduces the end-to-end delay by two orders of magnitude while achieving similar throughput in most of the cases. In the second part of this thesis

  10. CTCF and Rad21 act as host cell restriction factors for Kaposi's sarcoma-associated herpesvirus (KSHV lytic replication by modulating viral gene transcription.

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    Da-Jiang Li

    2014-01-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is a human herpesvirus that causes Kaposi's sarcoma and is associated with the development of lymphoproliferative diseases. KSHV reactivation from latency and virion production is dependent on efficient transcription of over eighty lytic cycle genes and viral DNA replication. CTCF and cohesin, cellular proteins that cooperatively regulate gene expression and mediate long-range DNA interactions, have been shown to bind at specific sites in herpesvirus genomes. CTCF and cohesin regulate KSHV gene expression during latency and may also control lytic reactivation, although their role in lytic gene expression remains incompletely characterized. Here, we analyze the dynamic changes in CTCF and cohesin binding that occur during the process of KSHV viral reactivation and virion production by high resolution chromatin immunoprecipitation and deep sequencing (ChIP-Seq and show that both proteins dissociate from viral genomes in kinetically and spatially distinct patterns. By utilizing siRNAs to specifically deplete CTCF and Rad21, a cohesin component, we demonstrate that both proteins are potent restriction factors for KSHV replication, with cohesin knockdown leading to hundred-fold increases in viral yield. High-throughput RNA sequencing was used to characterize the transcriptional effects of CTCF and cohesin depletion, and demonstrated that both proteins have complex and global effects on KSHV lytic transcription. Specifically, both proteins act as positive factors for viral transcription initially but subsequently inhibit KSHV lytic transcription, such that their net effect is to limit KSHV RNA accumulation. Cohesin is a more potent inhibitor of KSHV transcription than CTCF but both proteins are also required for efficient transcription of a subset of KSHV genes. These data reveal novel effects of CTCF and cohesin on transcription from a relatively small genome that resemble their effects on the cellular

  11. Post-Translational Modifications of Kaposi’s Sarcoma-Associated Herpesvirus (KSHV Regulatory Proteins-SUMO and KSHV

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    Mel eCampbell

    2012-02-01

    Full Text Available Reactivation from a latent state is an important feature of infection and disease caused by many herpesviruses. KSHV latency can be envisioned as an outcome that is balanced between factors that promote viral gene expression and lytic replication against those that facilitate gene silencing and establish or maintain latency. A large body of work has focused on the activities of the key viral regulatory proteins involved in KSHV latent or lytic states. Moreover, recent studies have also begun to document the importance of epigenetic landscape evolution of the KSHV viral genome during latency and reactivation. However, one area of KSHV molecular virology that remains largely unanswered is the precise role of post-translational modifications on the activities of viral factors that function during latency and reactivation. In this review, we will summarize the post-translational modifications associated with three viral factors whose activities contribute to the viral state. The viral proteins discussed are the two major KSHV encoded transcription factors, K-Rta and K-bZIP (KSHV basic leucine zipper and the viral latency-associated nuclear antigen (LANA. A special emphasis will be placed on the role of the sumoylation pathway in the modulation of the KSHV lifecycle. Newly uncovered SUMO-dependent properties of LANA and K-Rta will also be presented, namely LANA histone-targeting SUMO E3 ligase activity and K-Rta SUMO-targeted ubiquitin ligase function.

  12. Epigenetic Control of Cytomegalovirus Latency and Reactivation

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    Mary Hummel

    2013-05-01

    Full Text Available Cytomegalovirus (CMV gene expression is repressed in latency due to heterochromatinization of viral genomes. In murine CMV (MCMV latently infected mice, viral genomes are bound to histones with heterochromatic modifications, to enzymes that mediate these modifications, and to adaptor proteins that may recruit co-repressor complexes. Kinetic analyses of repressor binding show that these repressors are recruited at the earliest time of infection, suggesting that latency may be the default state. Kidney transplantation leads to epigenetic reprogramming of latent viral chromatin and reactivation of immediate early gene expression. Inflammatory signaling pathways, which activate transcription factors that regulate the major immediate early promoter (MIEP, likely mediate the switch in viral chromatin.

  13. Fast control latency uncertainty elimination for the BESIII ETOF upgrade

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    Wang, Yun; Cao, Ping; Liu, Shu-bin; An, Qi

    2016-09-01

    A new fanning topology is proposed to precisely fan out fast control signals in the Beijing Spectrometer (BESIII) end-cap time-of-flight (ETOF) electronics. However, uncertainty in transfer latency is introduced by the new fanning channel, which will degrade the precision of fast control. In this paper, latency uncertainty elimination for the BESIII ETOF upgrade is introduced. The latency uncertainty is determined by a Time-Digital-Converter (TDC) embedded in a Field-Programmable Gate Array (FPGA) and is eliminated by re-capturing at synchronous and determinate time. Compared with the existing method of Barrel-cap TOF (BTOF), it has advantages of flexible structure, easy calibration and good adaptability. Field tests on the BESIII ETOF system show that this method effectively eliminates transfer latency uncertainty. Supported by CAS Maintenance Project for Major Scientific and Technological Infrastructure (IHEP-SW-953/2013)

  14. Kaposi's sarcoma associated herpesvirus (KSHV entry into target cells

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    Sayan eChakraborty

    2012-01-01

    Full Text Available Herpesvirus infection of target cells is a complex process involving multiple host cell surface molecules (receptors and multiple viral envelope glycoproteins. Kaposi’s sarcoma associated herpesvirus (KSHV or HHV-8 infects a variety of in vivo target cells such as endothelial cells, B cells, monocytes, epithelial cells, and keratinocytes. KSHV also infects a diversity of in vitro target cells and establishes in vitro latency in many of these cell types. KSHV interactions with the host cell surface molecules and its mode of entry in the various target cells are critical for the understanding of KSHV pathogenesis. KSHV is the first herpesvirus shown to interact with adherent target cell integrins and this interaction initiates the host cell pre-existing signal pathways that are utilized for successful infection. This chapter discusses the various aspects of the early stage of KSHV infection of target cells, receptors used and issues that need to be clarified and future directions. The various signaling events triggered by KSHV infection and the potential role of signaling events in the different stages of infection are summarized providing the framework and starting point for further detailed studies essential to fully comprehend the pathogenesis of KSHV.

  15. The mTOR Complex Controls HIV Latency.

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    Besnard, Emilie; Hakre, Shweta; Kampmann, Martin; Lim, Hyung W; Hosmane, Nina N; Martin, Alyssa; Bassik, Michael C; Verschueren, Erik; Battivelli, Emilie; Chan, Jonathan; Svensson, J Peter; Gramatica, Andrea; Conrad, Ryan J; Ott, Melanie; Greene, Warner C; Krogan, Nevan J; Siliciano, Robert F; Weissman, Jonathan S; Verdin, Eric

    2016-12-14

    A population of CD4 T lymphocytes harboring latent HIV genomes can persist in patients on antiretroviral therapy, posing a barrier to HIV eradication. To examine cellular complexes controlling HIV latency, we conducted a genome-wide screen with a pooled ultracomplex shRNA library and in vitro system modeling HIV latency and identified the mTOR complex as a modulator of HIV latency. Knockdown of mTOR complex subunits or pharmacological inhibition of mTOR activity suppresses reversal of latency in various HIV-1 latency models and HIV-infected patient cells. mTOR inhibitors suppress HIV transcription both through the viral transactivator Tat and via Tat-independent mechanisms. This inhibition occurs at least in part via blocking the phosphorylation of CDK9, a p-TEFb complex member that serves as a cofactor for Tat-mediated transcription. The control of HIV latency by mTOR signaling identifies a pathway that may have significant therapeutic opportunities. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Fast Control Latency Uncertainty Elimination for BESIII ETOF Upgrade

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    Wang, Yun; Liu, Shubin; An, Qi

    2016-01-01

    Under upgrade program of Beijing Spectrometer (BES III) end-cap time of flight (ETOF), which makes the total electronic channels increasing greatly. To fan out fast control signals precisely to new ETOF electronics, new fanning out scheme based on technique of high serial communication is used for upgraded ETOF and for barrel TOF meanwhile. However, uncertainty of transfer latency is introduced by the SerDes chip, which will degrade the precision of fast control. In this paper, a new method of latency uncertainty elimination is proposed. This method has advantages of flexible structure, easy for calibration, little resource cost and ability of multi-channel application. Field tests on BES III ETOF system shows that this method can eliminate transfer latency uncertainty effectively.

  17. SUMO and KSHV Replication

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    Chang, Pei-Ching [Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan (China); Kung, Hsing-Jien, E-mail: hkung@nhri.org.tw [Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan (China); Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616 (United States); UC Davis Cancer Center, University of California, Davis, CA 95616 (United States); Division of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan (China)

    2014-09-29

    Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi’s sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV’s life cycle and pathogenesis.

  18. Latency and activation in the control of TGF-beta

    Science.gov (United States)

    Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1996-01-01

    The biological activity of the transforming growth factor-beta's (TGF-beta)3 is tightly controlled by their persistence in the extracellular compartment as latent complexes. Each of the three mammalian isoform genes encodes a product that is cleaved intracellularly to form two polypeptides, each of which dimerizes. Mature TGF-beta, a 24 kD homodimer, is noncovalently associated with the 80 kD latency-associated peptide (LAP). LAP is a fundamental component of TGF-beta that is required for its efficient secretion, prevents it from binding to ubiquitous cell surface receptors, and maintains its availability in a large extracellular reservoir that is readily accessed by activation. This latent TGF-beta complex (LTGF-beta) is secreted by all cells and is abundant both in circulating forms and bound to the extracellular matrix. Activation describes the collective events leading to the release of TGF-beta. Despite the importance of TGF-beta regulation of growth and differentiation in physiological and malignant tissue processes, remarkably little is known about the mechanisms of activation in situ. Recent studies of irradiated mammary gland reveal certain features of TGF-beta 1 activation that may shed light on its regulation and potential roles in the normal and neoplastic mammary gland.

  19. Twenty Years of KSHV

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    Yuan Chang

    2014-11-01

    Full Text Available Twenty years ago, Kaposi’s sarcoma (KS was the oncologic counterpart to Winston Churchill’s Russia: a riddle, wrapped in a mystery, inside an enigma. First described by Moritz Kaposi in 1872, who reported it to be an aggressive skin tumor, KS became known over the next century as a slow-growing tumor of elderly men—in fact, most KS patients were expected to die with the tumor rather than from it. Nevertheless, the course and manifestations of the disease varied widely in different clinical contexts. The puzzle of KS came to the forefront as a harbinger of the AIDS epidemic. The articles in this issue of Viruses recount progress made in understanding Kaposi’s sarcoma herpesvirus (KSHV since its initial description in 1994.

  20. Biphasic euchromatin-to-heterochromatin transition on the KSHV genome following de novo infection.

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    Zsolt Toth

    Full Text Available The establishment of latency is an essential step for the life-long persistent infection and pathogenesis of Kaposi's sarcoma-associated herpesvirus (KSHV. While the KSHV genome is chromatin-free in the virions, the viral DNA in latently infected cells has a chromatin structure with activating and repressive histone modifications that promote latent gene expression but suppress lytic gene expression. Here, we report a comprehensive epigenetic study of the recruitment of chromatin regulatory factors onto the KSHV genome during the pre-latency phase of KSHV infection. This demonstrates that the KSHV genome undergoes a biphasic chromatinization following de novo infection. Initially, a transcriptionally active chromatin (euchromatin, characterized by high levels of the H3K4me3 and acetylated H3K27 (H3K27ac activating histone marks, was deposited on the viral episome and accompanied by the transient induction of a limited number of lytic genes. Interestingly, temporary expression of the RTA protein facilitated the increase of H3K4me3 and H3K27ac occupancy on the KSHV episome during de novo infection. Between 24-72 hours post-infection, as the levels of these activating histone marks declined on the KSHV genome, the levels of the repressive H3K27me3 and H2AK119ub histone marks increased concomitantly with the decline of lytic gene expression. Importantly, this transition to heterochromatin was dependent on both Polycomb Repressive Complex 1 and 2. In contrast, upon infection of human gingiva-derived epithelial cells, the KSHV genome underwent a transcription-active euchromatinization, resulting in efficient lytic gene expression. Our data demonstrate that the KSHV genome undergoes a temporally-ordered biphasic euchromatin-to-heterochromatin transition in endothelial cells, leading to latent infection, whereas KSHV preferentially adopts a transcriptionally active euchromatin in oral epithelial cells, resulting in lytic gene expression. Our results

  1. Chromatinization of the KSHV Genome During the KSHV Life Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Uppal, Timsy [Department of Microbiology and Immunology, School of Medicine, University of Nevada, 1664 N Virginia Street, MS 320, Reno, NV 89557 (United States); Jha, Hem C. [Department of Microbiology and the Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States); Verma, Subhash C. [Department of Microbiology and Immunology, School of Medicine, University of Nevada, 1664 N Virginia Street, MS 320, Reno, NV 89557 (United States); Robertson, Erle S., E-mail: erle@mail.med.upenn.edu [Department of Microbiology and the Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States)

    2015-01-14

    Kaposi’s sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpesvirus family and is the causative agent of various lymphoproliferative diseases in humans. KSHV, like other herpesviruses, establishes life-long latent infection with the expression of a limited number of viral genes. Expression of these genes is tightly regulated by both the viral and cellular factors. Recent advancements in identifying the expression profiles of viral transcripts, using tilling arrays and next generation sequencing have identified additional coding and non-coding transcripts in the KSHV genome. Determining the functions of these transcripts will provide a better understanding of the mechanisms utilized by KSHV in altering cellular pathways involved in promoting cell growth and tumorigenesis. Replication of the viral genome is critical in maintaining the existing copies of the viral episomes during both latent and lytic phases of the viral life cycle. The replication of the viral episome is facilitated by viral components responsible for recruiting chromatin modifying enzymes and replication factors for altering the chromatin complexity and replication initiation functions, respectively. Importantly, chromatin modification of the viral genome plays a crucial role in determining whether the viral genome will persist as latent episome or undergo lytic reactivation. Additionally, chromatinization of the incoming virion DNA, which lacks chromatin structure, in the target cells during primary infection, helps in establishing latent infection. Here, we discuss the recent advancements on our understating of KSHV genome chromatinization and the consequences of chromatin modifications on viral life cycle.

  2. Evaluation of DECT for low latency real-time industrial control networks

    NARCIS (Netherlands)

    Das, Kallol; Havinga, Paul J.M.

    2013-01-01

    Wireless sensor networks (WSNs) have revolutionized the industrial networks by enabling wireless sensing and control to the machine parts where wiring is impossible. However, new challenges in terms of communication reliability and latency, appear with the advances in the industrial wireless control

  3. Evaluation of DECT for low latency real-time industrial control networks

    NARCIS (Netherlands)

    Das, Kallol; Havinga, Paul

    2013-01-01

    Wireless sensor networks (WSNs) have revolutionized the industrial networks by enabling wireless sensing and control to the machine parts where wiring is impossible. However, new challenges in terms of communication reliability and latency, appear with the advances in the industrial wireless control

  4. Influence of network latency in a remote control system using haptic media

    Science.gov (United States)

    Asano, Toshio; Ishibashi, Yutaka; Kurokawa, Youichi

    2006-10-01

    This paper deals with a remote control system which controls a haptic interface device with another remote haptic interface device. Applications of the system include a remote drawing instruction system, a remote calligraphy system and a remote medical operation system. This paper examines the influence of network latency on the output quality of haptic media by subjective assessment in the remote drawing instruction system. As a result, we show that the instructor has smaller Mean Opinion Score (MOS) values than the learner, and the MOS value can be estimated with high accuracy from the summation of the network latency from an instructor's terminal to a learner's terminal and that in the opposite direction.

  5. KSHV-Mediated Regulation of Par3 and SNAIL Contributes to B-Cell Proliferation

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    Jha, Hem C.; Sun, Zhiguo; Upadhyay, Santosh K.; El-Naccache, Darine W.; Singh, Rajnish K.; Sahu, Sushil K.; Robertson, Erle S.

    2016-01-01

    Studies have suggested that Epithelial–Mesenchymal Transition (EMT) and transformation is an important step in progression to cancer. Par3 (partitioning-defective protein) is a crucial factor in regulating epithelial cell polarity. However, the mechanism by which the latency associated nuclear antigen (LANA) encoded by Kaposi's Sarcoma associated herpesvirus (KSHV) regulates Par3 and EMTs markers (Epithelial-Mesenchymal Transition) during viral-mediated B-cell oncogenesis has not been fully explored. Moreover, several studies have demonstrated a crucial role for EMT markers during B-cell malignancies. In this study, we demonstrate that Par3 is significantly up-regulated in KSHV-infected primary B-cells. Further, Par3 interacted with LANA in KSHV positive and LANA expressing cells which led to translocation of Par3 from the cell periphery to a predominantly nuclear signal. Par3 knockdown led to reduced cell proliferation and increased apoptotic induction. Levels of SNAIL was elevated, and E-cadherin was reduced in the presence of LANA or Par3. Interestingly, KSHV infection in primary B-cells led to enhancement of SNAIL and down-regulation of E-cadherin in a temporal manner. Importantly, knockdown of SNAIL, a major EMT regulator, in KSHV cells resulted in reduced expression of LANA, Par3, and enhanced E-cadherin. Also, SNAIL bound to the promoter region of p21 and can regulate its activity. Further a SNAIL inhibitor diminished NF-kB signaling through upregulation of Caspase3 in KSHV positive cells in vitro. This was also supported by upregulation of SNAIL and Par3 in BC-3 transplanted NOD-SCID mice which has potential as a therapeutic target for KSHV-associated B-cell lymphomas. PMID:27463802

  6. KSHV-Mediated Regulation of Par3 and SNAIL Contributes to B-Cell Proliferation.

    Directory of Open Access Journals (Sweden)

    Hem C Jha

    2016-07-01

    Full Text Available Studies have suggested that Epithelial-Mesenchymal Transition (EMT and transformation is an important step in progression to cancer. Par3 (partitioning-defective protein is a crucial factor in regulating epithelial cell polarity. However, the mechanism by which the latency associated nuclear antigen (LANA encoded by Kaposi's Sarcoma associated herpesvirus (KSHV regulates Par3 and EMTs markers (Epithelial-Mesenchymal Transition during viral-mediated B-cell oncogenesis has not been fully explored. Moreover, several studies have demonstrated a crucial role for EMT markers during B-cell malignancies. In this study, we demonstrate that Par3 is significantly up-regulated in KSHV-infected primary B-cells. Further, Par3 interacted with LANA in KSHV positive and LANA expressing cells which led to translocation of Par3 from the cell periphery to a predominantly nuclear signal. Par3 knockdown led to reduced cell proliferation and increased apoptotic induction. Levels of SNAIL was elevated, and E-cadherin was reduced in the presence of LANA or Par3. Interestingly, KSHV infection in primary B-cells led to enhancement of SNAIL and down-regulation of E-cadherin in a temporal manner. Importantly, knockdown of SNAIL, a major EMT regulator, in KSHV cells resulted in reduced expression of LANA, Par3, and enhanced E-cadherin. Also, SNAIL bound to the promoter region of p21 and can regulate its activity. Further a SNAIL inhibitor diminished NF-kB signaling through upregulation of Caspase3 in KSHV positive cells in vitro. This was also supported by upregulation of SNAIL and Par3 in BC-3 transplanted NOD-SCID mice which has potential as a therapeutic target for KSHV-associated B-cell lymphomas.

  7. KSHV Induction of Angiogenic and Lymphangiogenic Phenotypes

    Directory of Open Access Journals (Sweden)

    Terri A. DiMiao

    2012-03-01

    Full Text Available Kaposi’s Sarcoma is a highly vascularized tumor supporting large amounts of neo-angiogenesis. The major cell type in KS tumors is the spindle cell, a cell that expresses markers of lymphatic endothelium. KSHV, the etiologic agent of KS, is found in the spindle cells of all KS tumors. Considering the extreme extent of angiogenesis in KS tumors at all stages it has been proposed that KSHV directly induces angiogenesis in a paracrine fashion. In accordance with this theory, KSHV infection of endothelial cells in culture induces a number of host pathways involved in activation of angiogenesis and a number of KSHV genes themselves can induce pathways involved in angiogenesis. Because spindle cells are phenotypically endothelial in nature, activation through the induction of angiogenic and/or lymphangiogenic phenotypes by the virus may also be directly involved in spindle cell growth and tumor induction. Accordingly, KSHV infection of endothelial cells induces cell autonomous angiogenic phenotypes to activate host cells. KSHV infection can also reprogram blood endothelial cells to lymphatic endothelium. However, KSHV induces some blood endothelial specific genes upon infection of lymphatic endothelial cells creating a phenotypic intermediate between blood and lymphatic endothelium. Induction of pathways involved in angiogenesis and lymphangiogenesis are likely to be critical for tumor cell growth and spread. Thus, induction of both cell autonomous and non-autonomous changes in angiogenic and lymphangiogenic pathways by KSHV likely plays a key role in the formation of KS tumors.

  8. Clinical Manifestations of Kaposi Sarcoma Herpesvirus (KSHV Lytic Activation: Multicentric Castleman Disease (KSHV-MCD and the KSHV Inflammatory Cytokine Syndrome (KICS

    Directory of Open Access Journals (Sweden)

    Mark N. Polizzotto

    2012-03-01

    Full Text Available Soon after the discovery of Kaposi sarcoma associated herpesvirus (KSHV, it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD arising in patients infected with human immunodeficiency virus (HIV. It has subsequently been recognized that KSHV-MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV-MCD is dominated by systemic inflammatory symptoms including fevers, cachexia and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV-MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6. Patients with KSHV-MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV-MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS has been described. Its clinical manifestations resemble those of KSHV-MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV-MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, hIL-6 and IL-10 comparable to those seen in KSHV-MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some patients with severe Kaposi

  9. Differences in Kaposi sarcoma-associated herpesvirus-specific and herpesvirus-non-specific immune responses in classic Kaposi sarcoma cases and matched controls in Sicily.

    Science.gov (United States)

    Amodio, Emanuele; Goedert, James J; Barozzi, Patrizia; Riva, Giovanni; Firenze, Alberto; Bonura, Filippa; Viviano, Enza; Romano, Nino; Luppi, Mario

    2011-10-01

    Kaposi sarcoma (KS) might develop because of incompetent immune responses, both non-specifically and specifically against the KS-associated herpesvirus (KSHV). Peripheral blood mononuclear cells from 15 classic (non-AIDS) KS cases, 13 KSHV seropositives (without KS) and 15 KSHV-seronegative controls were tested for interferon-γ T-cell (enzyme-linked immunospot [Elispot]) responses to KSHV-latency-associated nuclear antigen (LANA), KSHV-K8.1 and CMV/Epstein-Barr virus (EBV) peptide pools. The forearm and thigh of each participant was also tested for delayed-type hypersensitivity (DTH) against common recall antigens. Groups were compared with Fisher exact test and multinomial logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). A KSHV Elispot response was detected in 10 (67%) classic KS cases, 11 (85%) KSHV seropositives (without KS) and two (13%) seronegative controls. All four cases with KSHV-LANA responses had current KS lesions, whereas five of six cases with KSHV-K8.1 responses had no lesions (P = 0.048). No case responded to both LANA and K8.1. Compared with the seronegative controls, the risk for classic KS was inversely related to DTH in the thigh (OR 0.71, 95% CI 0.55-0.94, P = 0.01), directly associated with DTH in the forearm (OR 1.35, 95% CI 1.02-1.80, P = 0.04) and tended to be increased fivefold per KSHV Elispot response (OR 5.13, 95% CI 0.86-30.77, P = 0.07). Compared with KSHV seropositives (without KS), the risk for classic KS was reduced fivefold (OR 0.20, CI 0.03-0.77, P = 0.04) per KSHV response. The CMV/EBV Elispot responses were irrelevant. Deficiency of both KSHV-specific and KSHV-non-specific immunity is associated with classic KS. This might clarify why Kaposi sarcoma responds to immune reconstitution.

  10. AKTivation of the PI3K/AKT/mTOR signaling pathway by KSHV

    Directory of Open Access Journals (Sweden)

    Aadra P Bhatt

    2013-01-01

    Full Text Available As an obligate intracellular parasite, the Kaposi sarcoma-associated herpesvirus (KSHV relies on host cell machinery to meet its needs for survival, viral replication, production, and dissemination of progeny virions. KSHV is a ɣ-herpesvirus that is associated with three different malignancies: Kaposi sarcoma (KS, and two B cell lymphoproliferative disorders, primary effusion lymphoma (PEL and multicentric Castleman disease (MCD. KSHV viral proteins modulate cellular phosphatidylinositol-3-kinase (PI3K/AKT/mammalian target of rapamycin (mTOR signaling pathway, which is a ubiquitous pathway that also controls B lymphocyte proliferation and development. We review the mechanisms by which KSHV manipulates the PI3K/AKT/mTOR pathway, with a specific focus on B cells.

  11. Single molecule analysis of replicated DNA reveals the usage of multiple KSHV genome regions for latent replication.

    Directory of Open Access Journals (Sweden)

    Subhash C Verma

    2011-11-01

    Full Text Available Kaposi's sarcoma associated herpesvirus (KSHV, an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA. Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD. Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA

  12. KSHV LANA and EBV LMP1 induce the expression of UCH-L1 following viral transformation

    Energy Technology Data Exchange (ETDEWEB)

    Bentz, Gretchen L.; Bheda-Malge, Anjali; Wang, Ling [Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill (United States); Shackelford, Julia [Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill (United States); Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill (United States); Damania, Blossom [Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill (United States); Departments of Medicine and of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC (United States); Pagano, Joseph S., E-mail: joseph_pagano@med.unc.edu [Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill (United States); Departments of Medicine and of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC (United States)

    2014-01-05

    Ubiquitin C-terminal Hydrolase L1 (UCH-L1) has oncogenic properties and is highly expressed during malignancies. We recently documented that Epstein-Barr virus (EBV) infection induces uch-l1 expression. Here we show that Kaposi's Sarcoma-associated herpesvirus (KSHV) infection induced UCH-L1 expression, via cooperation of KSHV Latency-Associated Nuclear Antigen (LANA) and RBP-Jκ and activation of the uch-l1 promoter. UCH-L1 expression was also increased in Primary Effusion Lymphoma (PEL) cells co-infected with KSHV and EBV compared with PEL cells infected only with KSHV, suggesting EBV augments the effect of LANA on uch-l1. EBV latent membrane protein 1 (LMP1) is one of the few EBV products expressed in PEL cells. Results showed that LMP1 was sufficient to induce uch-l1 expression, and co-expression of LMP1 and LANA had an additive effect on uch-l1 expression. These results indicate that viral latency products of both human γ-herpesviruses contribute to uch-l1 expression, which may contribute to the progression of lymphoid malignancies. - Highlights: • Infection of endothelial cells with KSHV induced UCH-L1 expression. • KSHV LANA is sufficient for the induction of uch-l1. • Co-infection with KSHV and EBV (observed in some PELs) results in the additive induction of uch-l1. • EBV LMP1 also induced UCH-L1 expression. • LANA- and LMP1-mediated activation of the uch-l1 promoter is in part through RBP-Jκ.

  13. Phosphorylation of the chromatin binding domain of KSHV LANA.

    Directory of Open Access Journals (Sweden)

    Crystal Woodard

    Full Text Available The Kaposi sarcoma associated herpesvirus (KSHV latency associated nuclear antigen (LANA is expressed in all KSHV associated malignancies and is essential for maintenance of KSHV genomes in infected cells. To identify kinases that are potentially capable of modifying LANA, in vitro phosphorylation assays were performed using an Epstein Barr virus plus LANA protein microarray and 268 human kinases purified in active form from yeast. Interestingly, of the Epstein-Barr virus proteins on the array, the EBNA1 protein had the most similar kinase profile to LANA. We focused on nuclear kinases and on the N-terminus of LANA (amino acids 1-329 that contains the LANA chromatin binding domain. Sixty-three nuclear kinases phosphorylated the LANA N-terminus. Twenty-four nuclear kinases phosphorylated a peptide covering the LANA chromatin binding domain (amino acids 3-21. Alanine mutations of serine 10 and threonine 14 abolish or severely diminish chromatin and histone binding by LANA. However, conversion of these residues to the phosphomimetic glutamic acid restored histone binding suggesting that phosphorylation of serine 10 and threonine 14 may modulate LANA function. Serine 10 and threonine 14 were validated as substrates of casein kinase 1, PIM1, GSK-3 and RSK3 kinases. Short-term treatment of transfected cells with inhibitors of these kinases found that only RSK inhibition reduced LANA interaction with endogenous histone H2B. Extended treatment of PEL cell cultures with RSK inhibitor caused a decrease in LANA protein levels associated with p21 induction and a loss of PEL cell viability. The data indicate that RSK phosphorylation affects both LANA accumulation and function.

  14. Controlling Unknown Saddle Type Steady States of Dynamical Systems with Latency in the Feedback Loop

    DEFF Research Database (Denmark)

    Tamasevicius, Arunas; Bumeliene, Skaidra; Tamaseviciute, Elena

    2009-01-01

    We suggest an adaptive control technique for stabilizing saddle type unstable steady states of dynamical systems. The controller is composed of an unstable and a stable high-pass filters operating in parallel. The mathematical model is considered analytically and numerically. The conjoint...... controller is sufficiently robust to time latencies in the feedback loop. In addition, it is not sensitive to the damping parameters of the system and is relatively fast. Experiments have been performed using a simplified version of the electronic Young-Silva circuit imitating behavior of the Duffing...

  15. The RBP-Jκ binding sites within the RTA promoter regulate KSHV latent infection and cell proliferation.

    Directory of Open Access Journals (Sweden)

    Jie Lu

    2012-01-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is tightly linked to at least two lymphoproliferative disorders, primary effusion lymphoma (PEL and multicentric Castleman's disease (MCD. However, the development of KSHV-mediated lymphoproliferative disease is not fully understood. Here, we generated two recombinant KSHV viruses deleted for the first RBP-Jκ binding site (RTA(1st and all three RBP-Jκ binding sites (RTA(all within the RTA promoter. Our results showed that RTA(1st and RTA(all recombinant viruses possess increased viral latency and a decreased capability for lytic replication in HEK 293 cells, enhancing colony formation and proliferation of infected cells. Furthermore, recombinant RTA(1st and RTA(all viruses showed greater infectivity in human peripheral blood mononuclear cells (PBMCs relative to wt KSHV. Interestingly, KSHV BAC36 wt, RTA(1st and RTA(all recombinant viruses infected both T and B cells and all three viruses efficiently infected T and B cells in a time-dependent manner early after infection. Also, the capability of both RTA(1st and RTA(all recombinant viruses to infect CD19+ B cells was significantly enhanced. Surprisingly, RTA(1st and RTA(all recombinant viruses showed greater infectivity for CD3+ T cells up to 7 days. Furthermore, studies in Telomerase-immortalized human umbilical vein endothelial (TIVE cells infected with KSHV corroborated our data that RTA(1st and RTA(all recombinant viruses have enhanced ability to persist in latently infected cells with increased proliferation. These recombinant viruses now provide a model to explore early stages of primary infection in human PBMCs and development of KSHV-associated lymphoproliferative diseases.

  16. Traffic Adaptive Energy Efficient and Low Latency Medium Access Control for Wireless Sensor Networks

    Science.gov (United States)

    Yadav, Rajesh; Varma, Shirshu; Malaviya, N.

    2008-05-01

    Medium access control for wireless sensor networks has been a very active research area in the recent years. The traditional wireless medium access control protocol such as IEEE 802.11 is not suitable for the sensor network application because these are battery powered. The recharging of these sensor nodes is expensive and also not possible. The most of the literature in the medium access for the sensor network focuses on the energy efficiency. The proposed MAC protocol solves the energy inefficiency caused by idle listening, control packet overhead and overhearing taking nodes latency into consideration based on the network traffic. Simulation experiments have been performed to demonstrate the effectiveness of the proposed approach. The validation of the simulation results of the proposed MAC has been done by comparing it with the analytical model. This protocol has been simulated in Network Simulator ns-2.

  17. KSHV-Mediated Angiogenesis in Tumor Progression

    Directory of Open Access Journals (Sweden)

    Pravinkumar Purushothaman

    2016-07-01

    Full Text Available Human herpesvirus 8 (HHV-8, also known as Kaposi’s sarcoma-associated herpesvirus (KSHV, is a malignant human oncovirus belonging to the gamma herpesvirus family. HHV-8 is closely linked to the pathogenesis of Kaposi’s sarcoma (KS and two other B-cell lymphoproliferative diseases: primary effusion lymphoma (PEL and a plasmablastic variant of multicentric Castleman’s disease (MCD. KS is an invasive tumor of endothelial cells most commonly found in untreated HIV-AIDS or immuno-compromised individuals. KS tumors are highly vascularized and have abnormal, excessive neo-angiogenesis, inflammation, and proliferation of infected endothelial cells. KSHV directly induces angiogenesis in an autocrine and paracrine fashion through a complex interplay of various viral and cellular pro-angiogenic and inflammatory factors. KS is believed to originate due to a combination of KSHV’s efficient strategies for evading host immune systems and several pro-angiogenic and pro-inflammatory stimuli. In addition, KSHV infection of endothelial cells produces a wide array of viral oncoproteins with transforming capabilities that regulate multiple host-signaling pathways involved in the activation of angiogenesis. It is likely that the cellular-signaling pathways of angiogenesis and lymph-angiogenesis modulate the rate of tumorigenesis induction by KSHV. This review summarizes the current knowledge on regulating KSHV-mediated angiogenesis by integrating the findings reported thus far on the roles of host and viral genes in oncogenesis, recent developments in cell-culture/animal-model systems, and various anti-angiogenic therapies for treating KSHV-related lymphoproliferative disorders.

  18. KSHV-Mediated Angiogenesis in Tumor Progression

    Science.gov (United States)

    Purushothaman, Pravinkumar; Uppal, Timsy; Sarkar, Roni; Verma, Subhash C.

    2016-01-01

    Human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV), is a malignant human oncovirus belonging to the gamma herpesvirus family. HHV-8 is closely linked to the pathogenesis of Kaposi’s sarcoma (KS) and two other B-cell lymphoproliferative diseases: primary effusion lymphoma (PEL) and a plasmablastic variant of multicentric Castleman’s disease (MCD). KS is an invasive tumor of endothelial cells most commonly found in untreated HIV-AIDS or immuno-compromised individuals. KS tumors are highly vascularized and have abnormal, excessive neo-angiogenesis, inflammation, and proliferation of infected endothelial cells. KSHV directly induces angiogenesis in an autocrine and paracrine fashion through a complex interplay of various viral and cellular pro-angiogenic and inflammatory factors. KS is believed to originate due to a combination of KSHV’s efficient strategies for evading host immune systems and several pro-angiogenic and pro-inflammatory stimuli. In addition, KSHV infection of endothelial cells produces a wide array of viral oncoproteins with transforming capabilities that regulate multiple host-signaling pathways involved in the activation of angiogenesis. It is likely that the cellular-signaling pathways of angiogenesis and lymph-angiogenesis modulate the rate of tumorigenesis induction by KSHV. This review summarizes the current knowledge on regulating KSHV-mediated angiogenesis by integrating the findings reported thus far on the roles of host and viral genes in oncogenesis, recent developments in cell-culture/animal-model systems, and various anti-angiogenic therapies for treating KSHV-related lymphoproliferative disorders. PMID:27447661

  19. A role for MALT1 activity in Kaposi's sarcoma-associated herpes virus latency and growth of primary effusion lymphoma.

    Science.gov (United States)

    Bonsignore, L; Passelli, K; Pelzer, C; Perroud, M; Konrad, A; Thurau, M; Stürzl, M; Dai, L; Trillo-Tinoco, J; Del Valle, L; Qin, Z; Thome, M

    2017-03-01

    Primary effusion lymphoma (PEL) is an incurable malignancy that develops in immunodeficient patients as a consequence of latent infection of B-cells with Kaposi's sarcoma-associated herpes virus (KSHV). Malignant growth of KSHV-infected B cells requires the activity of the transcription factor nuclear factor (NF)-κB, which controls maintenance of viral latency and suppression of the viral lytic program. Here we show that the KSHV proteins K13 and K15 promote NF-κB activation via the protease mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1), a key driver of NF-κB activation in lymphocytes. Inhibition of the MALT1 protease activity induced a switch from the latent to the lytic stage of viral infection, and led to reduced growth and survival of PEL cell lines in vitro and in a xenograft model. These results demonstrate a key role for the proteolytic activity of MALT1 in PEL, and provide a rationale for the pharmacological targeting of MALT1 in PEL therapy.

  20. A high-density ERP study reveals latency, amplitude, and topographical differences in multiple sclerosis patients versus controls.

    LENUS (Irish Health Repository)

    Whelan, R

    2012-02-01

    OBJECTIVE: To quantify latency, amplitude and topographical differences in event-related potential (ERP) components between multiple sclerosis (MS) patients and controls and to compare ERP findings with results from the paced auditory serial addition test (PASAT). METHODS: Fifty-four subjects (17 relapsing remitting (RRMS) patients, 16 secondary progressive (SPMS) patients, and 21 controls) completed visual and auditory oddball tasks while data were recorded from 134 EEG channels. Latency and amplitude differences, calculated using composite mean amplitude measures, were tested using an ANOVA. Topographical differences were tested using statistical parametric mapping (SPM). RESULTS: In the visual modality, P2, P3 amplitudes and N2 latency were significantly different across groups. In the auditory modality, P2, N2, and P3 latencies and N1 amplitude were significantly different across groups. There were no significant differences between RRMS and SPMS patients on any ERP component. There were topographical differences between MS patients and controls for both early and late components for the visual modality, but only in the early components for the auditory modality. PASAT score correlated significantly with auditory P3 latency for MS patients. CONCLUSIONS: There were significant ERP differences between MS patients and controls. SIGNIFICANCE: The present study indicated that both early sensory and later cognitive ERP components are impaired in MS patients relative to controls.

  1. Treating KSHV-Associated Multicentric Castleman Disease

    Science.gov (United States)

    In this study, patients with KSHV-associated multicentric Castleman disease will receive IV tocilizumab every other week for up to 12 weeks. Patients who do not benefit may go on to receive high-dose AZT and valganciclovir as well.

  2. GPUbased, Microsecond Latency, HectoChannel MIMO Feedback Control of Magnetically Confined Plasmas

    Science.gov (United States)

    Rath, Nikolaus

    Feedback control has become a crucial tool in the research on magnetic confinement of plasmas for achieving controlled nuclear fusion. This thesis presents a novel plasma feedback control system that, for the first time, employs a Graphics Processing Unit (GPU) for microsecond-latency, real-time control computations. This novel application area for GPU computing is opened up by a new system architecture that is optimized for low-latency computations on less than kilobyte sized data samples as they occur in typical plasma control algorithms. In contrast to traditional GPU computing approaches that target complex, high-throughput computations with massive amounts of data, the architecture presented in this thesis uses the GPU as the primary processing unit rather than as an auxiliary of the CPU, and data is transferred from A-D/D-A converters directly into GPU memory using peer-to-peer PCI Express transfers. The described design has been implemented in a new, GPU-based control system for the High-Beta Tokamak - Extended Pulse (HBT-EP) device. The system is built from commodity hardware and uses an NVIDIA GeForce GPU and D-TACQ A-D/D-A converters providing a total of 96 input and 64 output channels. The system is able to run with sampling periods down to 4 μs and latencies down to 8 μs. The GPU provides a total processing power of 1.5 x 1012 floating point operations per second. To illustrate the performance and versatility of both the general architecture and concrete implementation, a new control algorithm has been developed. The algorithm is designed for the control of multiple rotating magnetic perturbations in situations where the plasma equilibrium is not known exactly and features an adaptive system model: instead of requiring the rotation frequencies and growth rates embedded in the system model to be set a priori, the adaptive algorithm derives these parameters from the evolution of the perturbation amplitudes themselves. This results in non-linear control

  3. KSHV encoded LANA recruits Nucleosome Assembly Protein NAP1L1 for regulating viral DNA replication and transcription

    Science.gov (United States)

    Gupta, Namrata; Thakker, Suhani; Verma, Subhash C.

    2016-09-01

    The establishment of latency is an essential for lifelong persistence and pathogenesis of Kaposi’s sarcoma-associated herpesvirus (KSHV). Latency-associated nuclear antigen (LANA) is the most abundantly expressed protein during latency and is important for viral genome replication and transcription. Replication-coupled nucleosome assembly is a major step in packaging the newly synthesized DNA into chromatin, but the mechanism of KSHV genome chromatinization post-replication is not understood. Here, we show that nucleosome assembly protein 1-like protein 1 (NAP1L1) associates with LANA. Our binding assays revealed an association of LANA with NAP1L1 in KSHV-infected cells, which binds through its amino terminal domain. Association of these proteins confirmed their localization in specific nuclear compartments of the infected cells. Chromatin immunoprecipitation assays from NAP1L1-depleted cells showed LANA-mediated recruitment of NAP1L1 at the terminal repeat (TR) region of the viral genome. Presence of NAP1L1 stimulated LANA-mediated DNA replication and persistence of a TR-containing plasmid. Depletion of NAP1L1 led to a reduced nucleosome positioning on the viral genome. Furthermore, depletion of NAP1L1 increased the transcription of viral lytic genes and overexpression decreased the promoter activities of LANA-regulated genes. These results confirmed that LANA recruitment of NAP1L1 helps in assembling nucleosome for the chromatinization of newly synthesized viral DNA.

  4. Heterogeneity and Breadth of Host Antibody Response to KSHV Infection Demonstrated by Systematic Analysis of the KSHV Proteome

    Science.gov (United States)

    Labo, Nazzarena; Miley, Wendell; Marshall, Vickie; Gillette, William; Esposito, Dominic; Bess, Matthew; Turano, Alexandra; Uldrick, Thomas; Polizzotto, Mark N.; Wyvill, Kathleen M.; Bagni, Rachel; Yarchoan, Robert; Whitby, Denise

    2014-01-01

    The Kaposi sarcoma associated herpesvirus (KSHV) genome encodes more than 85 open reading frames (ORFs). Serological evaluation of KSHV infection now generally relies on reactivity to just one latent and/or one lytic protein (commonly ORF73 and K8.1). Most of the other polypeptides encoded by the virus have unknown antigenic profiles. We have systematically expressed and purified products from 72 KSHV ORFs in recombinant systems and analyzed seroreactivity in US patients with KSHV-associated malignancies, and US blood donors (low KSHV seroprevalence population). We identified several KSHV proteins (ORF38, ORF61, ORF59 and K5) that elicited significant responses in individuals with KSHV-associated diseases. In these patients, patterns of reactivity were heterogeneous; however, HIV infection appeared to be associated with breadth and intensity of serological responses. Improved antigenic characterization of additional ORFs may increase the sensitivity of serologic assays, lead to more rapid progresses in understanding immune responses to KSHV, and allow for better comprehension of the natural history of KSHV infection. To this end, we have developed a bead-based multiplex assay detecting antibodies to six KSHV antigens. PMID:24675986

  5. Heterogeneity and breadth of host antibody response to KSHV infection demonstrated by systematic analysis of the KSHV proteome.

    Directory of Open Access Journals (Sweden)

    Nazzarena Labo

    2014-03-01

    Full Text Available The Kaposi sarcoma associated herpesvirus (KSHV genome encodes more than 85 open reading frames (ORFs. Serological evaluation of KSHV infection now generally relies on reactivity to just one latent and/or one lytic protein (commonly ORF73 and K8.1. Most of the other polypeptides encoded by the virus have unknown antigenic profiles. We have systematically expressed and purified products from 72 KSHV ORFs in recombinant systems and analyzed seroreactivity in US patients with KSHV-associated malignancies, and US blood donors (low KSHV seroprevalence population. We identified several KSHV proteins (ORF38, ORF61, ORF59 and K5 that elicited significant responses in individuals with KSHV-associated diseases. In these patients, patterns of reactivity were heterogeneous; however, HIV infection appeared to be associated with breadth and intensity of serological responses. Improved antigenic characterization of additional ORFs may increase the sensitivity of serologic assays, lead to more rapid progresses in understanding immune responses to KSHV, and allow for better comprehension of the natural history of KSHV infection. To this end, we have developed a bead-based multiplex assay detecting antibodies to six KSHV antigens.

  6. Supraspinal control of a short-latency cutaneous pathway to hindlimb motoneurons.

    Science.gov (United States)

    Fleshman, J W; Rudomin, P; Burke, R E

    1988-01-01

    The effects of two supraspinal systems on transmission through a short latency hindlimb cutaneous reflex pathway were studied in cats anesthetized with pentobarbital or alpha-chloralose. Fleshman et al. (1984) described a mixed excitatory-inhibitory input from low threshold superficial peroneal (SP) afferents to flexor digitorum longus (FDL) motoneurons with central latencies so short as to suggest a disynaptic component in the initial excitatory phase of the PSP. In the present study, conditioning stimulation of either the red nucleus (RN) or the pyramidal tract (PT) caused a marked decrease in latency and increase in amplitude of both the excitatory and inhibitory components of the SP PSP in FDL motoneurons and several other motoneuron species. The minimal central latencies of the conditioned initial excitatory phase of the PSPs were on the order of 1.5 ms, consistent with the possibility of a disynaptic linkage. The facilitatory effects of RN and PT conditioning were observed in both anesthetic conditions, although preparation-specific differences in latency were observed. Lesion experiments suggested that the interneurons involved in this pathway are located caudal to the L5 segment, most likely in segments L6 and L7.

  7. Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

    Directory of Open Access Journals (Sweden)

    Van Lint Carine

    2009-12-01

    Full Text Available Abstract The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway.

  8. A systems approach for data compression and latency reduction in cortically controlled brain machine interfaces.

    Science.gov (United States)

    Oweiss, Karim G

    2006-07-01

    This paper suggests a new approach for data compression during extracutaneous transmission of neural signals recorded by high-density microelectrode array in the cortex. The approach is based on exploiting the temporal and spatial characteristics of the neural recordings in order to strip the redundancy and infer the useful information early in the data stream. The proposed signal processing algorithms augment current filtering and amplification capability and may be a viable replacement to on chip spike detection and sorting currently employed to remedy the bandwidth limitations. Temporal processing is devised by exploiting the sparseness capabilities of the discrete wavelet transform, while spatial processing exploits the reduction in the number of physical channels through quasi-periodic eigendecomposition of the data covariance matrix. Our results demonstrate that substantial improvements are obtained in terms of lower transmission bandwidth, reduced latency and optimized processor utilization. We also demonstrate the improvements qualitatively in terms of superior denoising capabilities and higher fidelity of the obtained signals.

  9. Reactivation of Kaposi's sarcoma-associated herpesvirus from latency requires MEK/ERK, JNK and p38 multiple mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Xie, Jianping; Ajibade, Adetola Olalekan; Ye, Fengchun; Kuhne, Kurt; Gao, Shou-Jiang

    2008-02-05

    Lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV) promotes the progression of Kaposi's sarcoma (KS), a dominant malignancy in patients with AIDS. While 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced KSHV reactivation from latency is mediated by the protein kinase C delta and MEK/ERK mitogen-activated protein kinase (MAPK) pathways, we have recently shown that the MEK/ERK, JNK and p38 MAPK pathways modulate KSHV lytic replication during productive primary infection of human umbilical vein endothelial cells [Pan, H., Xie, J., Ye, F., Gao, S.J., 2006. Modulation of Kaposi's sarcoma-associated herpesvirus infection and replication by MEK/ERK, JNK, and p38 multiple mitogen-activated protein kinase pathways during primary infection. J. Virol. 80 (11), 5371-5382]. Here, we report that, besides the MEK/ERK pathway, the JNK and p38 MAPK pathways also mediate TPA-induced KSHV reactivation from latency. The MEK/ERK, JNK and p38 MAPK pathways were constitutively activated in latent KSHV-infected BCBL-1 cells. TPA treatment enhanced the levels of activated ERK and p38 but not those of activated JNK. Inhibitors of all three MAPK pathways reduced TPA-induced production of KSHV infectious virions in BCBL-1 cells in a dose-dependent fashion. The inhibitors blocked KSHV lytic replication at the early stage(s) of reactivation, and reduced the expression of viral lytic genes including RTA, a key immediate-early transactivator of viral lytic replication. Activation of MAPK pathways was necessary and sufficient for activating the promoter of RTA. Furthermore, we showed that the activation of RTA promoter by MAPK pathways was mediated by their downstream target AP-1. Together, these findings suggest that MAPK pathways might have general roles in regulating the life cycle of KSHV by mediating both viral infection and switch from viral latency to lytic replication.

  10. Influence of the metabolic control on latency values of visual evoked potentials (VEP) in patients with diabetes mellitus type 1.

    Science.gov (United States)

    Matanovic, Dragana; Popovic, Srdjan; Parapid, Biljana; Petronic, Ivana; Cirovic, Dragana; Nikolic, Dejan

    2012-12-01

    The aim of our study was to investigate the relationship between the metabolic control parameters of diabetes mellitus (glycemia and HbA1c) and visual evoked potentials (VEP) latency values. The study included 61 patients with diabetes mellitus type 1 that were hospitalized at the Clinic for Endocrinology, Diabetes and Metabolic Diseases due to the poor metabolic control. All patients were divided into 3 groups. Group 1 consisted of patients on conventional insulin therapy (CT); Group 2 included patients on CT at the moment of hospitalization, with a change towards intensified insulin therapy (IIT); and Group 3 consisted of patients on IIT. Patients with diabetic retinopathy (DR) were excluded from the study. Metabolic control (glycemia and HbA1c) and VEP parameters were compared at the beginning of the study and six months later. After six months of strict glycoregulation, significant improvement in VEP parameters was followed by significant improvement of evaluated parameters of metabolic control. We found statistically significant reduction in frequency of pathological VEP findings, prolonged P100 latency and low amplitude potentials in Group 2, while in Groups 1 and 3 we found that these parameters did not significantly changed but the frequencies were lower. The VEP testing is a noninvasive diagnostic procedure which may help in early diagnosis of DR, prognosis during the metabolic control and treatment. If changes in the retina could be detected before DR is noticed using this noninvasive diagnostic procedure and include patients in a strict glycoregulation, we could be in the position to prevent serious complications that may cause blindness.

  11. Nuclear Localization and Cleavage of STAT6 Is Induced by Kaposi’s Sarcoma-Associated Herpesvirus for Viral Latency

    Science.gov (United States)

    Zhang, Liming; Li, Yuhong; Feng, Yanling; Xu, Jianqing; Wang, Bin; Yuan, Zhenghong; Robertson, Erle S.; Cai, Qiliang

    2017-01-01

    Emerging evidence implies that STAT6 plays an important role in both the adaptive and innate immune responses to virus infection. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus agent associated with several human malignancies, including Kaposi’s sarcoma (KS) and primary effusion lymphomas (PELs). Previously, we demonstrated that KSHV blocks IL-4-induced STAT6 phosphorylation and retains a basal IL-13/STAT6 constitutive activation for cell survival and proliferation. However, the mechanism by which KSHV regulates STAT6 remains largely unknown. Here, we found that KSHV-encoded LANA interacts with STAT6 and promotes nuclear localization of STAT6 independent of the tyrosine 641-phosphorylation state. Moreover, nuclear localization of STAT6 is also dramatically increased in KS tissue. The latent antigen LANA induces serine protease-mediated cleavage of STAT6 in the nucleus, where the cleaved STAT6 lacking transactivation domain functions as a dominant-negative regulator to repress transcription of Replication and Transcription Activator (RTA) and in turn shut off viral lytic replication. Blockade of STAT6 by small interference RNA dramatically enhances expression of RTA, and in turn reduces KSHV-infected endothelial cell growth and colony formation. Taken together, these results suggest that nuclear localization and cleavage of STAT6 is important for modulating the viral latency and pathogenesis of KSHV. PMID:28099521

  12. Molecular basis for oligomeric-DNA binding and episome maintenance by KSHV LANA.

    Directory of Open Access Journals (Sweden)

    John F Domsic

    Full Text Available LANA is the KSHV-encoded terminal repeat binding protein essential for viral replication and episome maintenance during latency. We have determined the X-ray crystal structure of LANA C-terminal DNA binding domain (LANADBD to reveal its capacity to form a decameric ring with an exterior DNA binding surface. The dimeric core is structurally similar to EBV EBNA1 with an N-terminal arm that regulates DNA binding and is required for replication function. The oligomeric interface between LANA dimers is dispensable for single site DNA binding, but is required for cooperative DNA binding, replication function, and episome maintenance. We also identify a basic patch opposite of the DNA binding surface that is responsible for the interaction with BRD proteins and contributes to episome maintenance function. The structural features of LANADBD suggest a novel mechanism of episome maintenance through DNA-binding induced oligomeric assembly.

  13. Using Ecological Momentary Assessment to investigate associations between ejaculatory latency and control in partnered and non-partnered sexual activities.

    Science.gov (United States)

    Jern, Patrick; Gunst, Annika; Sandqvist, Felicia; Sandnabba, N Kenneth; Santtila, Pekka

    2011-07-01

    Ecological Momentary Assessment (EMA) was used to investigate associations between, and variations in, ejaculatory control and ejaculation latency time (ELT) over repeated measurements of sexual activities. Differences between measures recorded in partnered or non-partnered settings were also investigated. The sample consisted of 21 male Finns aged 18 years or above, contributing a total of 158 reports of partnered and non-partnered sexual activities over a six-week period. In the context of non-partnered sexual activities, after controlling for within-subjects dependence, ELTs between events were predictive of one another, but ELT did not predict ejaculatory control when measured simultaneously, nor at subsequent events. Also, ejaculatory control could not predict simultaneously measured ELT or ejaculatory control at subsequent events. During partnered sexual activities, both ejaculatory control and ELT could be accurately predicted by observing ejaculatory control at prior events. In this context, ejaculatory control could also reliably predict simultaneously measured ELT. ELT or ejaculatory control during partnered sexual activity could not be predicted by observing ELT at prior events. Between-event correlations were generally low, indicating considerable variation in ejaculatory functioning over time. EMA is a thrifty assessment method for studying variations in ejaculatory function, and is likely suitable for studying sexual dysfunctions in general.

  14. A human herpesvirus miRNA attenuates interferon signaling and contributes to maintenance of viral latency by targeting IKKε

    Institute of Scientific and Technical Information of China (English)

    Deguang Liang; Yuan Gao; Xianzhi Lin; Zhiheng He; Qinglan Zhao; Qiang Deng; Ke Lan

    2011-01-01

    Type I interferon(IFN)signaling is the principal response mediating antiviral innate immunity. IFN transcription is dependent upon the activation of transcription factors IRF3/IRF7 and NF-KB. Many viral proteins have been shown as being capable of interfering with IFN signaling to facilitate evasion from the host innate immune response.Here, we report that a viral miRNA, miR-K12-11, encoded by Kaposi's sarcoma-associated herpesvirus(KSHV)is critical for the modulation of IFN signaling and acts through targeting 1-kappa-B kinase epsilon(IKKε). Ectopic expression of miR-K12-11 resulted in decreased IKKε expression, while inhibition of miR-K12-11 was found to restore IKKE expression in KSHV-infected cells. Importantly, expression of milk-K12-I1 attenuated IFN signaling by decreasing IKKε-mediated IRF3/IRF7 phosphorylation and by inhibiting the activation of IKKE-dependent IFN stimulating genes(ISGs), allowing miR-K12-11 suppression of antiviral immunity. Our data suggest that IKKE targeting by miR-K12-11 is an important strategy utilized by KSHV to modulate IFN signaling during the KSHV lifecycle, especially in latency. We also demonstrated that IKKE was able to enhance KSHV reactivation synergistically with the treatment of 12-O-tetradecanoylphorbol 13-acetate. Moreover, inhibition of miR-K12-11enhanced KSHV reactivation induced by vesicular stomatitis virus infection. Taken together, our findings also suggest that miR-K12-11 can contribute to maintenance of KSHV latency by targeting IKKE.

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  19. The Role of RNA Polymerase II Elongation Control in HIV-1 Gene Expression, Replication, and Latency

    Directory of Open Access Journals (Sweden)

    Kyle A. Nilson

    2011-01-01

    Full Text Available HIV-1 usurps the RNA polymerase II elongation control machinery to regulate the expression of its genome during lytic and latent viral stages. After integration into the host genome, the HIV promoter within the long terminal repeat (LTR is subject to potent downregulation in a postinitiation step of transcription. Once produced, the viral protein Tat commandeers the positive transcription elongation factor, P-TEFb, and brings it to the engaged RNA polymerase II (Pol II, leading to the production of viral proteins and genomic RNA. HIV can also enter a latent phase during which factors that regulate Pol II elongation may play a role in keeping the virus silent. HIV, the causative agent of AIDS, is a worldwide health concern. It is hoped that knowledge of the mechanisms regulating the expression of the HIV genome will lead to treatments and ultimately a cure.

  20. KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription Factors

    Directory of Open Access Journals (Sweden)

    Karlie Plaisance-Bonstaff

    2014-10-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV microRNAs are encoded in the latency-associated region. Knockdown of KSHV miR-K12-3 and miR-K12-11 increased expression of lytic genes in BC-3 cells, and increased virus production from latently infected BCBL-1 cells. Furthermore, iSLK cells infected with miR-K12-3 and miR-K12-11 deletion mutant viruses displayed increased spontaneous reactivation and were more sensitive to inducers of reactivation than cells infected with wild type KSHV. Predicted binding sites for miR-K12-3 and miR-K12-11 were found in the 3’UTRs of the cellular transcription factors MYB, Ets-1, and C/EBPα, which activate RTA, the KSHV replication and transcription activator. Targeting of MYB by miR-K12-11 was confirmed by cloning the MYB 3’UTR downstream from the luciferase reporter. Knockdown of miR‑K12-11 resulted in increased levels of MYB transcript, and knockdown of miR-K12-3 increased both C/EBPα and Ets-1 transcripts. Thus, miR-K12-11 and miR-K12-3 contribute to maintenance of latency by decreasing RTA expression indirectly, presumably via down‑regulation of MYB, C/EBPα and Ets-1, and possibly other host transcription factors.

  1. [Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8)].

    Science.gov (United States)

    Katano, Harutaka

    2010-12-01

    Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8, HHV-8) are members of gamma-herpes virus family. Both viruses infect to B cells and cause malignancies such as lymphoma. Since EBV and HHV-8 are so-called 'oncovirus', their oncogenecities have been focused in the researches on EBV and KSHV for a long time. EBV was discovered in 1964, whereas KSHV was identified in 1994. However, KSHV was analyzed rapidly in these fifteen years. One of the recent progresses in the research on EBV and KSHV is that virus-encoded small RNAs were identified in their genomes and characterized. EBV is the first human virus in whose genome microRNA was identified. The oncogenecity of EBV and KSHV remains unclear. Here, I discuss the pathogenesis by EBV and KSHV with special reference to recent progress in this field.

  2. 3.8-ms latency correlation tracker for active mirror control based on a reconfigurable interface to a standard workstation

    Science.gov (United States)

    Shand, Mark; Wei, Wang; Scharmer, Goran B.

    1995-09-01

    We describe the use of a reconfigurable interface board based on FPGAs and a UNIX workstation to implement a correlation tracker with 3.8ms latency. The correlation tracker is part of an active mirror system in use at the Swedish Vacuum Solar Telescope, La Palma, Canary Islands. The reconfigurable interface is used to leverage the workstation CPU, relieving it of tasks that it performs poorly such as rapid context switching and low-level bit manipulation. The reconfigurable interface handles control of external devices, high- performance input (16 MB/s) and data preformatting. The workstation CPU, a 64-bit microprocessor, performs the bulk of the computation. For the key computations of the correlation tracker we are able to treat 8 pixels in parallel in the CPU's 64-bit integer datapath. We present the structure of the CCD interface configuration and the implementations of the key algorithms on the workstation CPU. We describe the design trade-offs that arose during the development of the system, and demonstrate the symbiosis between components implemented in software and configurable hardware.

  3. Macaque homologs of EBV and KSHV show uniquely different associations with simian AIDS-related lymphomas.

    Directory of Open Access Journals (Sweden)

    A Gregory Bruce

    Full Text Available Two gammaherpesviruses, Epstein-Barr virus (EBV (Lymphocryptovirus genus and Kaposi's sarcoma-associated herpesvirus (KSHV (Rhadinovirus genus have been implicated in the etiology of AIDS-associated lymphomas. Homologs of these viruses have been identified in macaques and other non-human primates. In order to assess the association of these viruses with non-human primate disease, archived lymphoma samples were screened for the presence of macaque lymphocryptovirus (LCV homologs of EBV, and macaque rhadinoviruses belonging to the RV1 lineage of KSHV homologs or the more distant RV2 lineage of Old World primate rhadinoviruses. Viral loads were determined by QPCR and infected cells were identified by immunolabeling for different viral proteins. The lymphomas segregated into three groups. The first group (n = 6 was associated with SIV/SHIV infections, contained high levels of LCV (1-25 genomes/cell and expressed the B-cell antigens CD20 or BLA.36. A strong EBNA-2 signal was detected in the nuclei of the neoplastic cells in one of the LCV-high lymphomas, indicative of a type III latency stage. None of the lymphomas in this group stained for the LCV viral capsid antigen (VCA lytic marker. The second group (n = 5 was associated with D-type simian retrovirus-2 (SRV-2 infections, contained high levels of RV2 rhadinovirus (9-790 genomes/cell and expressed the CD3 T-cell marker. The third group (n = 3 was associated with SIV/SHIV infections, contained high levels of RV2 rhadinovirus (2-260 genomes/cell and was negative for both CD20 and CD3. In both the CD3-positive and CD3/CD20-negative lymphomas, the neoplastic cells stained strongly for markers of RV2 lytic replication. None of the lymphomas had detectable levels of retroperitoneal fibromatosis herpesvirus (RFHV, the macaque RV1 homolog of KSHV. Our data suggest etiological roles for both lymphocryptoviruses and RV2 rhadinoviruses in the development of simian AIDS-associated lymphomas and indicate that

  4. Kaposi's Sarcoma Associated-Herpes Virus (KSHV Seroprevalence in Pregnant Women in South Africa

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    Malope-Kgokong Babatyi I

    2010-08-01

    Full Text Available Abstract Background Factors previously associated with Kaposi's sarcoma-associated herpesvirus (KSHV transmission in Africa include sexual, familial, and proximity to river water. We measured the seroprevalence of KSHV in relation to HIV, syphilis, and demographic factors among pregnant women attending public antenatal clinics in the Gauteng province of South Africa. Methods We tested for antibodies to KSHV lytic K8.1 and latent Orf73 antigens in 1740 pregnant women attending antenatal clinics who contributed blood to the "National HIV and Syphilis Sero-Prevalence Survey - South Africa, 2001". Information on HIV and syphilis serology, age, education, residential area, gravidity, and parity was anonymously linked to evaluate risk factors for KSHV seropositivity. Clinics were grouped by municipality regions and their proximity to the two main river catchments defined. Results KSHV seropositivity (reactive to either lytic K8.1 and latent Orf73 was nearly twice that of HIV (44.6% vs. 23.1%. HIV and syphilis seropositivity was 12.7% and 14.9% in women without KSHV, and 36.1% and 19.9% respectively in those with KSHV. Women who are KSHV seropositive were 4 times more likely to be HIV positive than those who were KSHV seronegative (AOR 4.1 95%CI: 3.4 - 5.7. Although, women with HIV infection were more likely to be syphilis seropositive (AOR 1.8 95%CI: 1.3 - 2.4, no association between KSHV and syphilis seropositivity was observed. Those with higher levels of education had lower levels of KSHV seropositivity compared to those with lower education levels. KSHV seropositivity showed a heterogeneous pattern of prevalence in some localities. Conclusions The association between KSHV and HIV seropositivity and a lack of common association with syphilis, suggests that KSHV transmission may involve geographical and cultural factors other than sexual transmission.

  5. Online control of reaching and pointing to visual, auditory, and multimodal targets: Effects of target modality and method of determining correction latency.

    Science.gov (United States)

    Holmes, Nicholas P; Dakwar, Azar R

    2015-12-01

    Movements aimed towards objects occasionally have to be adjusted when the object moves. These online adjustments can be very rapid, occurring in as little as 100ms. More is known about the latency and neural basis of online control of movements to visual than to auditory target objects. We examined the latency of online corrections in reaching-to-point movements to visual and auditory targets that could change side and/or modality at movement onset. Visual or auditory targets were presented on the left or right sides, and participants were instructed to reach and point to them as quickly and as accurately as possible. On half of the trials, the targets changed side at movement onset, and participants had to correct their movements to point to the new target location as quickly as possible. Given different published approaches to measuring the latency for initiating movement corrections, we examined several different methods systematically. What we describe here as the optimal methods involved fitting a straight-line model to the velocity of the correction movement, rather than using a statistical criterion to determine correction onset. In the multimodal experiment, these model-fitting methods produced significantly lower latencies for correcting movements away from the auditory targets than away from the visual targets. Our results confirm that rapid online correction is possible for auditory targets, but further work is required to determine whether the underlying control system for reaching and pointing movements is the same for auditory and visual targets.

  6. KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway.

    Science.gov (United States)

    Gao, S J; Boshoff, C; Jayachandra, S; Weiss, R A; Chang, Y; Moore, P S

    1997-10-16

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus linked to the development of Kaposi's sarcoma and a rare B cell lymphoma, primary effusion lymphoma. The KSHV gene ORF K9 encodes vIRF which is a protein with low but significant homology to members of the interferon (IFN) regulatory factor (IRF) family responsible for regulating intracellular interferon signal transduction (Moore PS, Boshoff C, Weiss RA and Chang Y. (1996). Science, 274, 1739-1744). vIRF inhibits IFN-beta signal transduction as measured using an IFN-responsive ISG54 reporter construct co-transfected with ORF K9 into HeLa and 293 cells. vIRF also suppresses genes under IFN regulatory control as shown by inhibition of the IFN-beta inducibility of p21WAF1/CIP1, however, no direct DNA-binding or protein-protein interactions characteristic for IRF repressor proteins were identified. Stable transfectant NIH3T3 clones expressing vIRF grew in soft agar and at low serum concentrations, lost contact inhibition and formed tumors after injection into nude mice indicating that vIRF has the properties of a viral oncogene. Since vIRF is primarily expressed in KSHV-infected B cells, not KS spindle cells, this study suggests that vIRF is a transforming oncogene active in B cell neoplasias that may provide a unique immune escape mechanism for infected cells. This data is consistent with tumor suppressor pathways serving a dual function as host cell antiviral pathways.

  7. KSHV 2.0: a comprehensive annotation of the Kaposi's sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features.

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    Carolina Arias

    2014-01-01

    Full Text Available Productive herpesvirus infection requires a profound, time-controlled remodeling of the viral transcriptome and proteome. To gain insights into the genomic architecture and gene expression control in Kaposi's sarcoma-associated herpesvirus (KSHV, we performed a systematic genome-wide survey of viral transcriptional and translational activity throughout the lytic cycle. Using mRNA-sequencing and ribosome profiling, we found that transcripts encoding lytic genes are promptly bound by ribosomes upon lytic reactivation, suggesting their regulation is mainly transcriptional. Our approach also uncovered new genomic features such as ribosome occupancy of viral non-coding RNAs, numerous upstream and small open reading frames (ORFs, and unusual strategies to expand the virus coding repertoire that include alternative splicing, dynamic viral mRNA editing, and the use of alternative translation initiation codons. Furthermore, we provide a refined and expanded annotation of transcription start sites, polyadenylation sites, splice junctions, and initiation/termination codons of known and new viral features in the KSHV genomic space which we have termed KSHV 2.0. Our results represent a comprehensive genome-scale image of gene regulation during lytic KSHV infection that substantially expands our understanding of the genomic architecture and coding capacity of the virus.

  8. DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

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    Cha, Seho [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Lim, Chunghun [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Lee, Jae Young [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Song, Yoon-Jae [Department of Life Science, Kyungwon University, Seongnam-Si, Kyeonggi-Do 461-701 (Korea, Republic of); Park, Junsoo [Division of Biological Science and Technology, Yonsei University, Wonju 220-100 (Korea, Republic of); Choe, Joonho [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Seo, Taegun, E-mail: tseo@dongguk.edu [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of)

    2010-04-16

    During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

  9. Interaction of KSHV with Host Cell Surface Receptors and Cell Entry

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    Mohanan Valiya Veettil

    2014-10-01

    Full Text Available Virus entry is a complex process characterized by a sequence of events. Since the discovery of KSHV in 1994, tremendous progress has been made in our understanding of KSHV entry into its in vitro target cells. KSHV entry is a complex multistep process involving viral envelope glycoproteins and several cell surface molecules that is utilized by KSHV for its attachment and entry. KSHV has a broad cell tropism and the attachment and receptor engagement on target cells have an important role in determining the cell type-specific mode of entry. KSHV utilizes heparan sulfate, integrins and EphrinA2 molecules as receptors which results in the activation of host cell pre-existing signal pathways that facilitate the subsequent cascade of events resulting in the rapid entry of virus particles, trafficking towards the nucleus followed by viral and host gene expression. KSHV enters human fibroblast cells by dynamin dependant clathrin mediated endocytosis and by dynamin independent macropinocytosis in dermal endothelial cells. Once internalized into endosomes, fusion of the viral envelope with the endosomal membranes in an acidification dependent manner results in the release of capsids which subsequently reaches the nuclear pore vicinity leading to the delivery of viral DNA into the nucleus. In this review, we discuss the principal mechanisms that enable KSHV to interact with the host cell surface receptors as well as the mechanisms that are required to modulate cell signaling machinery for a successful entry.

  10. Sequence Analysis of Kaposi Sarcoma–Associated Herpesvirus (KSHV) MicroRNAs in Patients with Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome

    Science.gov (United States)

    Ray, Alex; Marshall, Vickie; Uldrick, Thomas; Leighty, Robert; Labo, Nazzarena; Wyvill, Kathy; Aleman, Karen; Polizzotto, Mark N.; Little, Richard F.; Yarchoan, Robert; Whitby, Denise

    2012-01-01

    Background Kaposi sarcoma–associated herpesvirus (KSHV) encodes 12 pre-microRNAs that yield 25 mature microRNAs. We previously reported phylogenetic analysis of the microRNA-coding region of KSHV from Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD) patients. We observed a high level of conservation for most sequences but also a divergent cluster of 5 KSHV sequences, including 2 from MCD patients. Methods KSHV microRNA sequences from 23 MCD patients and 7 patients with a newly described KSHV-associated inflammatory cytokine syndrome (KICS) were examined by amplification, cloning, and sequencing of a 646-bp fragment of K12/T0.7 encoding microRNA-K12-10 and microRNA-K12-12 and a 2.8-kbp fragment containing the remaining 10 pre-microRNAs. Results Phylogenetic analysis showed a distinct variant cluster consisting exclusively of MCD and KICS patients in all trees. Pearson χ2 analysis revealed that 40 single-nucleotide polymorphisms (SNPs) at various loci were significantly associated with MCD and KICS risk. Cluster analysis of these SNPs generated several combinations of 3 SNPs as putative indicators of MCD and KICS risk. Conclusions These findings show that MCD and KICS patients frequently have unusual KSHV microRNA sequences and suggest an association between the observed sequence variation and risk of MCD and KICS. PMID:22448005

  11. Abortive lytic reactivation of KSHV in CBF1/CSL deficient human B cell lines.

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    Barbara A Scholz

    Full Text Available Since Kaposi's sarcoma associated herpesvirus (KSHV establishes a persistent infection in human B cells, B cells are a critical compartment for viral pathogenesis. RTA, the replication and transcription activator of KSHV, can either directly bind to DNA or use cellular DNA binding factors including CBF1/CSL as DNA adaptors. In addition, the viral factors LANA1 and vIRF4 are known to bind to CBF1/CSL and modulate RTA activity. To analyze the contribution of CBF1/CSL to reactivation in human B cells, we have successfully infected DG75 and DG75 CBF1/CSL knock-out cell lines with recombinant KSHV.219 and selected for viral maintenance by selective medium. Both lines maintained the virus irrespective of their CBF1/CSL status. Viral reactivation could be initiated in both B cell lines but viral genome replication was attenuated in CBF1/CSL deficient lines, which also failed to produce detectable levels of infectious virus. Induction of immediate early, early and late viral genes was impaired in CBF1/CSL deficient cells at multiple stages of the reactivation process but could be restored to wild-type levels by reintroduction of CBF1/CSL. To identify additional viral RTA target genes, which are directly controlled by CBF1/CSL, we analyzed promoters of a selected subset of viral genes. We show that the induction of the late viral genes ORF29a and ORF65 by RTA is strongly enhanced by CBF1/CSL. Orthologs of ORF29a in other herpesviruses are part of the terminase complex required for viral packaging. ORF65 encodes the small capsid protein essential for capsid shell assembly. Our study demonstrates for the first time that in human B cells viral replication can be initiated in the absence of CBF1/CSL but the reactivation process is severely attenuated at all stages and does not lead to virion production. Thus, CBF1/CSL acts as a global hub which is used by the virus to coordinate the lytic cascade.

  12. Trends in Kaposi's sarcoma-associated Herpesvirus antibodies prior to the development of HIV-associated Kaposi's sarcoma: A nested case-control study

    Science.gov (United States)

    Wakeham, Katie; Johnston, W Thomas; Nalwoga, Angela; Webb, Emily L; Mayanja, Billy N; Miley, Wendell; Elliott, Alison M; Whitby, Denise; Newton, Robert

    2015-01-01

    HIV-associated Kaposi's sarcoma (KS) is a public health challenge in sub-Saharan Africa since both the causative agent, Kaposi's sarcoma associated-herpesvirus (KSHV), and the major risk factor, HIV, are prevalent. In a nested case-control study within a long-standing clinical cohort in rural Uganda, we used stored sera to examine the evolution of antibody titres against the KSHV antigens K8.1 and latency-associated nuclear antigen (LANA) among 30 HIV-infected subjects who subsequently developed HIV-related KS (cases) and among 108 matched HIV/KSHV coinfected controls who did not develop KS. Throughout the 6 years prior to diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases than controls (p < 0.0001), and titres increased prior to diagnosis in the cases. K8.1 titres differed more between KS cases and controls, compared to LANA titres. These differences in titre between cases and controls suggest a role for lytic viral replication in the pathogenesis of HIV-related KS in this setting. PMID:25395177

  13. Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease

    Science.gov (United States)

    Polizzotto, Mark N.; Aleman, Karen; Wyvill, Kathleen M.; Marshall, Vickie; Whitby, Denise; Wang, Victoria; Pittaluga, Stefania; O’Mahony, Deirdre; Steinberg, Seth M.; Little, Richard F.; Yarchoan, Robert

    2014-01-01

    Kaposi sarcoma (KS) herpesvirus–associated multicentric Castleman disease (KSHV-MCD) is a lymphoproliferative disorder, most commonly seen in HIV-infected patients, that has a high mortality if untreated. Concurrent KS is common. Although rituximab has reported activity in KSHV-MCD, its use is often associated with KS progression. Within a natural history study of KSHV-MCD, we prospectively evaluated rituximab 375 mg/m2 combined with liposomal doxorubicin 20 mg/m2 (R-Dox) every 3 weeks in 17 patients. Patients received a median of 4 cycles (range 3-9). All received antiretroviral therapy, 11 received consolidation interferon-α, and 6 received consolidation high-dose zidovudine with valganciclovir. Using NCI KSHV-MCD response criteria, major clinical and biochemical responses were attained in 94% and 88% of patients, respectively. With a median 58 months’ potential follow-up, 3-year event-free survival was 69% and 3-year overall survival was 81%. During R-Dox therapy, cutaneous KS developed in 1 patient, whereas 5 of 6 patients with it had clinical improvement. R-Dox was associated with significant improvement in anemia and hypoalbuminemia. KSHV viral load, KSHV viral interleukin-6, C-reactive protein, human interleukin-6, and serum immunoglobulin free light chains decreased with therapy. R-Dox is effective in symptomatic KSHV-MCD and may be useful in patients with concurrent KS. This trial was registered at www.clinicaltrials.gov as #NCT00092222. PMID:25331113

  14. Treatment of Kaposi sarcoma-associated herpesvirus (KSHV-associated cancers

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    Dirk P Dittmer

    2012-04-01

    Full Text Available Kaposi sarcoma (KS is the most frequent AIDS-defining cancer worldwide. Kaposi sarcoma associated herpesvirus (KSHV is the etiological agent of KS, and the virus is also associated with two lymphoproliferative diseases. Both KS and KSHV-associated lymphomas, are cancers of unique molecular composition. They represent a challenge for cancer treatment and an opportunity to identify new mechanisms of transformation. Here, we review the current clinical insights into KSHV-associated cancers and discuss scientific insights into the pathobiology of KS, primary effusion lymphoma and multicentric Castleman’s disease.

  15. Prevention and Treatment of KSHV-associated Diseases with Antiviral Drugs

    Institute of Scientific and Technical Information of China (English)

    Ren-rong TIAN; Qing-jiao LIAO; Xulin CHEN

    2008-01-01

    s Kaposi's sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi's sarcoma (KS) in 1994.KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD).Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons.The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.

  16. Binding of cellular export factor REF/Aly by Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein is not required for efficient KSHV lytic replication.

    Science.gov (United States)

    Li, Da-Jiang; Verma, Dinesh; Swaminathan, Sankar

    2012-09-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein is expressed early during lytic KSHV replication, enhances expression of many KSHV genes, and is essential for virus production. ORF57 is a member of a family of proteins conserved among all human and many animal herpesviruses that are multifunctional regulators of gene expression and act posttranscriptionally to increase accumulation of their target mRNAs. The mechanism of ORF57 action is complex and may involve effects on mRNA transcription, stability, and export. ORF57 directly binds to REF/Aly, a cellular RNA-binding protein component of the TREX complex that mediates RNA transcription and export. We analyzed the effects of an ORF57 mutation known to abrogate REF/Aly binding and demonstrate that the REF-binding mutant is impaired in activation of viral mRNAs and noncoding RNAs confined to the nucleus. Although the inability to bind REF leads to decreased ORF57 activity in enhancing gene expression, there is no demonstrable effect on nuclear export of viral mRNA or the ability of ORF57 to support KSHV replication and virus production. These data indicate that REF/Aly-ORF57 interaction is not essential for KSHV lytic replication but may contribute to target RNA stability independent of effects on RNA export, suggesting a novel role for REF/Aly in viral RNA metabolism.

  17. Conservation of complex nuclear localization signals utilizing classical and non-classical nuclear import pathways in LANA homologs of KSHV and RFHV.

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    Lidia Cherezova

    Full Text Available ORF73 latency-associated nuclear antigen (LANA of the Kaposi's sarcoma-associated herpesvirus (KSHV is targeted to the nucleus of infected cells where it binds to chromatin and mediates viral episome persistence, interacts with cellular proteins and plays a role in latency and tumorigenesis. A structurally related LANA homolog has been identified in the retroperitoneal fibromatosis herpesvirus (RFHV, the macaque homolog of KSHV. Here, we report the evolutionary and functional conservation of a novel bi-functional nuclear localization signal (NLS in KSHV and RFHV LANA. N-terminal peptides from both proteins were fused to EGFP or double EGFP fusions to examine their ability to induce nuclear transport of a heterologous protein. In addition, GST-pull down experiments were used to analyze the ability of LANA peptides to interact with members of the karyopherin family of nuclear transport receptors. Our studies revealed that both LANA proteins contain an N-terminal arginine/glycine (RG-rich domain spanning a conserved chromatin-binding motif, which binds directly to importin β1 in a RanGTP-sensitive manner and serves as an NLS in the importin β1-mediated non-classical nuclear import pathway. Embedded within this domain is a conserved lysine/arginine-(KR-rich bipartite motif that binds directly to multiple members of the importin α family of nuclear import adaptors in a RanGTP-insensitive manner and serves as an NLS in the classical importin α/β-mediated nuclear import pathway. The positioning of a classical bipartite kr-NLS embedded within a non-classical rg-NLS is a unique arrangement in these viral proteins, whose nuclear localization is critical to their functionality and to the virus life cycle. The ability to interact with multiple import receptors provides alternate pathways for nuclear localization of LANA. Since different import receptors can import cargo to distinct subnuclear compartments, a multifunctional NLS may provide LANA with an

  18. A population-based case-control study of Selective Serotonin Reuptake Inhibitors (SSRIs and breast cancer: The impact of duration of use, cumulative dose and latency

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    Lévesque LE

    2010-12-01

    Full Text Available Abstract Background Selective serotonin reuptake inhibitors (SSRIs, a popular class of antidepressants, may increase breast cancer risk by stimulating the secretion of prolactin, a potential tumour promoter. We evaluated the effects of duration of SSRI use, cumulative dose, and latency on the risk of breast cancer by conducting a population-based case-control study utilizing Saskatchewan health databases. Methods Cases included 1,701 women with primary invasive breast cancer diagnosed from 2003 to 2006, and controls consisted of 17,017 women, randomly selected from the population registry. Use of SSRIs was compiled using the Saskatchewan prescription database. Unconditional logistic regression was conducted to evaluate the impact of duration of combined SSRI use (total number of prescriptions dispensed, cumulative dose (total dosage received and timing of use (two or more years, two to seven years and more than seven years prior to index date on the risk of breast cancer. Results Overall, SSRI use was not associated with an increased risk of breast cancer regardless of our definition of cumulative use (total number of prescriptions dispensed and total dosage. In addition, our results indicate that prolonged SSRI use does not have a latent effect on breast cancer risk. Also, our findings are not suggestive of an increased risk of breast cancer with the use of individual SSRIs. Conclusions Our study improved upon most previous studies by having a longer follow-up period, a larger sample size of long-term SSRI users and consideration of risk during specific exposure time windows that take latency into account. Given the potential health benefits of using SSRIs, our results suggest that the issue of breast cancer risk may no longer be a concern for women requiring long-term SSRIs.

  19. Low Latency High Throughout Circular Asynchronous FIFO

    Institute of Scientific and Technical Information of China (English)

    XIAO Yong; ZHOU Runde

    2008-01-01

    This paper describes a circular first in first out (FIFO) and its protocols which have a very low la-tency while still maintaining high throughput. Unlike the existing serial FIFOs based on asynchronous micro-pipelines, this FIFO's cells communicate directly with the input and output ports through a common bus, which effectively eliminates the data movement from the input port to the output port, thereby reducing the latency and the power consumption. Furthermore, the latency does not increase with the number of FIFO stages. Single-track asynchronous protocols are used to simplify the FIFO controller design, with only three C-gates needed in each cell controller, which substantially reduces the area. Simulations with the TSMC 0.25 Ijm CMOS logic process show that the latency of the 4-stage FIFO is less than 581 ps and the throughput is higher than 2.2 GHz.

  20. Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency

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    Gumez Audrey

    2005-11-01

    viral latency may provide potential new targets to control HIV-1 replication in latent viral reservoirs.

  1. KSHV Targeted Therapy: An Update on Inhibitors of Viral Lytic Replication

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    Natacha Coen

    2014-11-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV is the causative agent of Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. Since the discovery of KSHV 20 years ago, there is still no standard treatment and the management of virus-associated malignancies remains toxic and incompletely efficacious. As the majority of tumor cells are latently infected with KSHV, currently marketed antivirals that target the virus lytic cycle have shown inconsistent results in clinic. Nevertheless, lytic replication plays a major role in disease progression and virus dissemination. Case reports and retrospective studies have pointed out the benefit of antiviral therapy in the treatment and prevention of KSHV-associated diseases. As a consequence, potent and selective antivirals are needed. This review focuses on the anti-KSHV activity, mode of action and current status of antiviral drugs targeting KSHV lytic cycle. Among these drugs, different subclasses of viral DNA polymerase inhibitors and compounds that do not target the viral DNA polymerase are being discussed. We also cover molecules that target cellular kinases, as well as the potential of new drug targets and animal models for antiviral testing.

  2. Phosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication.

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    Denis Avey

    2015-07-01

    Full Text Available Kaposi's Sarcoma-Associated Herpesvirus (KSHV is an oncogenic virus which has adapted unique mechanisms to modulate the cellular microenvironment of its human host. The pathogenesis of KSHV is intimately linked to its manipulation of cellular signaling pathways, including the extracellular signal-regulated kinase (ERK mitogen-activated protein kinase (MAPK pathway. We have previously shown that KSHV ORF45 contributes to the sustained activation of both ERK and p90 ribosomal S6 kinase (RSK, a major functional mediator of ERK/MAPK signaling during KSHV lytic replication. ORF45-activated RSK is required for optimal KSHV lytic gene expression and progeny virion production, though the underlying mechanisms downstream of this activation are still unclear. We hypothesized that the activation of RSK by ORF45 causes differential phosphorylation of cellular and viral substrates, affecting biological processes essential for efficient KSHV lytic replication. Accordingly, we observed widespread and significant differences in protein phosphorylation upon induction of lytic replication. Mass-spectrometry-based phosphoproteomic screening identified putative substrates of ORF45-activated RSK in KSHV-infected cells. Bioinformatic analyses revealed that nuclear proteins, including several transcriptional regulators, were overrepresented among these candidates. We validated the ORF45/RSK-dependent phosphorylation of several putative substrates by employing KSHV BAC mutagenesis, kinase inhibitor treatments, and/or CRISPR-mediated knockout of RSK in KSHV-infected cells. Furthermore, we assessed the consequences of knocking out these substrates on ORF45/RSK-dependent regulation of gene expression and KSHV progeny virion production. Finally, we show data to support that ORF45 regulates the translational efficiency of a subset of viral/cellular genes with complex secondary structure in their 5' UTR. Altogether, these data shed light on the mechanisms by which KSHV ORF45

  3. Signal, Noise, and Variation in Neural and Sensory-Motor Latency.

    Science.gov (United States)

    Lee, Joonyeol; Joshua, Mati; Medina, Javier F; Lisberger, Stephen G

    2016-04-01

    Analysis of the neural code for sensory-motor latency in smooth pursuit eye movements reveals general principles of neural variation and the specific origin of motor latency. The trial-by-trial variation in neural latency in MT comprises a shared component expressed as neuron-neuron latency correlations and an independent component that is local to each neuron. The independent component arises heavily from fluctuations in the underlying probability of spiking, with an unexpectedly small contribution from the stochastic nature of spiking itself. The shared component causes the latency of single-neuron responses in MT to be weakly predictive of the behavioral latency of pursuit. Neural latency deeper in the motor system is more strongly predictive of behavioral latency. A model reproduces both the variance of behavioral latency and the neuron-behavior latency correlations in MT if it includes realistic neural latency variation, neuron-neuron latency correlations in MT, and noisy gain control downstream of MT.

  4. Localization of latency-associated nuclear antigen (LANA) on mitotic chromosomes

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    Rahayu, Retno; Ohsaki, Eriko [Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Omori, Hiroko [Central Instrumentation Laboratory Research Institute for Microbial Diseases (BIKEN), Osaka University, Osaka 565-0871 (Japan); Ueda, Keiji, E-mail: kueda@virus.med.osaka-u.ac.jp [Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2016-09-15

    In latent infection of Kaposi's sarcoma-associated herpesvirus (KSHV), viral gene expression is extremely limited and copy numbers of viral genomes remain constant. Latency-associated nuclear antigen (LANA) is known to have a role in maintaining viral genome copy numbers in growing cells. Several studies have shown that LANA is localized in particular regions on mitotic chromosomes, such as centromeres/pericentromeres. We independently examined the distinct localization of LANA on mitotic chromosomes during mitosis, using super-resolution laser confocal microscopy and correlative fluorescence microscopy–electron microscopy (FM-EM) analyses. We found that the majority of LANA were not localized at particular regions such as telomeres/peritelomeres, centromeres/pericentromeres, and cohesion sites, but at the bodies of condensed chromosomes. Thus, LANA may undergo various interactions with the host factors on the condensed chromosomes in order to tether the viral genome to mitotic chromosomes and realize faithful viral genome segregation during cell division. - Highlights: • This is the first report showing LANA dots on mitotic chromosomes by fluorescent microscopy followed by electron microscopy. • LANA dots localized randomly on condensed chromosomes other than centromere/pericentromere and telomere/peritelomre. • Cellular mitotic checkpoint should not be always involved in the segregation of KSHV genomes in the latency.

  5. Latent KSHV Infected Endothelial Cells Are Glutamine Addicted and Require Glutaminolysis for Survival.

    Directory of Open Access Journals (Sweden)

    Erica L Sanchez

    2015-07-01

    Full Text Available Kaposi's Sarcoma-associated Herpesvirus (KSHV is the etiologic agent of Kaposi's Sarcoma (KS. KSHV establishes a predominantly latent infection in the main KS tumor cell type, the spindle cell, which is of endothelial cell origin. KSHV requires the induction of multiple metabolic pathways, including glycolysis and fatty acid synthesis, for the survival of latently infected endothelial cells. Here we demonstrate that latent KSHV infection leads to increased levels of intracellular glutamine and enhanced glutamine uptake. Depletion of glutamine from the culture media leads to a significant increase in apoptotic cell death in latently infected endothelial cells, but not in their mock-infected counterparts. In cancer cells, glutamine is often required for glutaminolysis to provide intermediates for the tri-carboxylic acid (TCA cycle and support for the production of biosynthetic and bioenergetic precursors. In the absence of glutamine, the TCA cycle intermediates alpha-ketoglutarate (αKG and pyruvate prevent the death of latently infected cells. Targeted drug inhibition of glutaminolysis also induces increased cell death in latently infected cells. KSHV infection of endothelial cells induces protein expression of the glutamine transporter, SLC1A5. Chemical inhibition of SLC1A5, or knockdown by siRNA, leads to similar cell death rates as glutamine deprivation and, similarly, can be rescued by αKG. KSHV also induces expression of the heterodimeric transcription factors c-Myc-Max and related heterodimer MondoA-Mlx. Knockdown of MondoA inhibits expression of both Mlx and SLC1A5 and induces a significant increase in cell death of only cells latently infected with KSHV, again, fully rescued by the supplementation of αKG. Therefore, during latent infection of endothelial cells, KSHV activates and requires the Myc/MondoA-network to upregulate the glutamine transporter, SLC1A5, leading to increased glutamine uptake for glutaminolysis. These findings

  6. Estimating latency from inhibitory input

    DEFF Research Database (Denmark)

    Levakova, Marie; Ditlevsen, Susanne; Lansky, Petr

    2014-01-01

    to the stimulus by an increase in the firing rate. We focus on the estimation of the response latency in the case of inhibitory stimuli. Models used in this paper represent two different descriptions of response latency. We consider either the latency to be constant across trials or to be a random variable......Stimulus response latency is the time period between the presentation of a stimulus and the occurrence of a change in the neural firing evoked by the stimulation. The response latency has been explored and estimation methods proposed mostly for excitatory stimuli, which means that the neuron reacts....... In the case of random latency, special attention is given to models with selective interaction. The aim is to propose methods for estimation of the latency or the parameters of its distribution. Parameters are estimated by four different methods: method of moments, maximum-likelihood method, a method...

  7. KSHV latent protein LANA2 inhibits sumo2 modification of p53

    Science.gov (United States)

    Laura, Marcos-Villar; de la Cruz-Herrera, Carlos F; Ferreirós, Alba; Baz-Martínez, Maite; Lang, Valerie; Vidal, Anxo; Muñoz-Fontela, Cesar; Rodríguez, Manuel S; Collado, Manuel; Rivas, Carmen

    2015-01-01

    Tumor suppressor p53 plays a crucial antiviral role and targeting of p53 by viral proteins is a common mechanism involved in virus oncogenesis. The activity of p53 is tightly regulated at the post-translational levels through a myriad of modifications. Among them, modification of p53 by SUMO has been associated with the onset of cellular senescence. Kaposi´s sarcoma-associated herpesvirus (KSHV) expresses several proteins targeting p53, including the latent protein LANA2 that regulates polyubiquitylation and phosphorylation of p53. Here we show that LANA2 also inhibits the modification of p53 by SUMO2. Furthermore, we show that the reduction of p53-SUMO2 conjugation by LANA2, as well as the p53-LANA2 interaction, both require the SUMOylation of the viral protein and its interaction with SUMO or SUMOylated proteins in a non-covalent manner. Finally, we show that the control of p53-SUMO2 conjugation by LANA2 correlates with its ability to inhibit SUMO2- and type I interferon-induced senescence. These results highlight the importance of p53 SUMOylation in the control of virus infection and suggest that viral oncoproteins could contribute to viral infection and cell transformation by abrogating p53 SUMOylation. PMID:25607652

  8. Contribution of Viral Mimics of Cellular Genes to KSHV Infection and Disease

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    Shuhei Sakakibara

    2014-09-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV, also named Human herpesvirus 8 HHV-8 is the cause of Kaposi sarcoma (KS, the most common malignancy in HIV-infected individuals worldwide, primary effusion lymphoma (PEL and multicentric Castleman disease (MCD. KSHV is a double-stranded DNA virus that encodes several homologues of cellular proteins. The structural similarity between viral and host proteins explains why some viral homologues function as their host counterparts, but sometimes at unusual anatomical sites and inappropriate times. In other cases, structural modification in the viral proteins can suppress or override the function of the host homologue, contributing to KSHV-related diseases. For example, viral IL-6 (vIL-6 is sufficiently different from human IL-6 to activate gp130 signaling independent of the α subunit. As a consequence, vIL-6 can activate many cell types that are unresponsive to cellular IL-6, contributing to MCD disease manifestations. Here, we discuss the molecular biology of KSHV homologues of cellular products as conduits of virus/host interaction with a focus on identifying new strategies for therapy of KS and other KSHV-related diseases.

  9. Regulation and autoregulation of the promoter for the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus.

    Science.gov (United States)

    Jeong, Joseph H; Orvis, Joshua; Kim, Jong Wook; McMurtrey, Curtis P; Renne, Rolf; Dittmer, Dirk P

    2004-04-16

    Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 has been established as the etiological agent of Kaposi's sarcoma and certain AIDS-associated lymphomas. KSHV establishes latent infection in these tumors, invariably expressing high levels of the viral latency-associated nuclear antigen (LANA) protein. LANA is necessary and sufficient to maintain the KSHV episome. It also modulates viral and cellular transcription and has been implicated directly in oncogenesis because of its ability to bind to the p53 and pRb tumor suppressor proteins. Previously, we identified the LANA promoter (LANAp) and showed that it was positively regulated by LANA itself. Here, we present a detailed mutational analysis and define cis-acting elements and trans-acting factors for the core LANAp. We found that a downstream promoter element, TATA box, and GC box/Sp1 site at -29 are all individually required for activity. This architecture places LANAp into the small and unusual group of eukaryotic promoters that contain both the downstream promoter element and TATA element but lack a defined initiation site. Furthermore, we demonstrate that LANA regulates its own promoter via its C-terminal domain and does bind to a defined site within the core promoter.

  10. KSHV MicroRNAs Repress Tropomyosin 1 and Increase Anchorage-Independent Growth and Endothelial Tube Formation.

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    Philippe Kieffer-Kwon

    Full Text Available Kaposi's sarcoma (KS is characterized by highly vascularized spindle-cell tumors induced after infection of endothelial cells by Kaposi's sarcoma-associated herpesvirus (KSHV. In KS tumors, KSHV expresses only a few latent proteins together with 12 pre-microRNAs. Previous microarray and proteomic studies predicted that multiple splice variants of the tumor suppressor protein tropomyosin 1 (TPM1 were targets of KSHV microRNAs. Here we show that at least two microRNAs of KSHV, miR-K2 and miR-K5, repress protein levels of specific isoforms of TPM1. We identified a functional miR-K5 binding site in the 3' untranslated region (UTR of one TPM1 isoform. Furthermore, the inhibition or loss of miR-K2 or miR-K5 restores expression of TPM1 in KSHV-infected cells. TPM1 protein levels were also repressed in KSHV-infected clinical samples compared to uninfected samples. Functionally, miR-K2 increases viability of unanchored human umbilical vein endothelial cells (HUVEC by inhibiting anoikis (apoptosis after cell detachment, enhances tube formation of HUVECs, and enhances VEGFA expression. Taken together, KSHV miR-K2 and miR-K5 may facilitate KSHV pathogenesis.

  11. Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV in Ugandan women

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    Ndibazza Juliet

    2011-09-01

    Full Text Available Abstract Background Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods and antibodies against Kaposi's sarcoma herpesvirus (KSHV, measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda. Results Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01, hookworm (67% vs 56% p = 0.001 and Mansonella perstans (69% vs 59% p = 0.05; seroprevalence increased with increasing intensity of hookworm infection (p Conclusions Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.

  12. Preparation and application of polyclonal antibodiesagainst KSHV v-cyclin.

    Science.gov (United States)

    Xue, Min; Guo, Yuanyuan; Yan, Qin; Qin, Di; Lu, Chun

    2013-09-01

    We prepared rabbit polyclonal antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded v-cyclin (ORF 72) and detected the natural viral protein using these polyclonal antibodies. Three antigenic polypeptides of v-cyclin were designed and synthesized. A fragment of the v-cyclin gene was cloned into a eukaryotic expression vector pEF-MCS-Flag-IRES/Puro to construct a recombinant vector, pEF v-cyclin. Then, pEF v-cyclin was transfected into 293T and EA.hy926 cells to obtain v-cyclin-Flag fusion proteins. Six New Zealand white rabbits were immunized with KLH-conjugated peptides to generate polyclonal antibodies against v-cyclin. The polyclonal antibodies were then characterized by ELISA and Western blotting assays. Finally, the polyclonal antibodies against v-cyclin were used to detect natural viral protein expressed in BCBL-1, BC-3, and JSC-1 cells. The results showed that using the Flag antibody, v-cyclin-Flag fusion protein was detected in 293T and EA.hy926 cells transfected with pEF-v-cyclin. Furthermore, ELISA showed that the titer of the induced polyclonal rabbit anti-v-cyclin antibodies was higher than 1:8,000. In Western blotting assays, the antibodies reacted specifically with the v-cyclin-Flag fusion protein as well as the natural viral protein. The recombinant expression vector pEF-v-cyclin was constructed successfully, and the polyclonal antibodies prepared can be used for various biological tests including ELISA and Western blotting assays.

  13. P300 latency indexes nitrogen narcosis.

    Science.gov (United States)

    Fowler, B; Pogue, J; Porlier, G

    1990-03-01

    This experiment investigated the effects of nitrogen narcosis on reaction time (RT) and P300 latency and amplitude. Ten subjects breathed either air or a non-narcotic 20% oxygen-80% helium (heliox) mixture in a hyperbaric chamber at 6.5, 8.3 and 10 atmospheres absolute (ATA). The subjects responded under controlled accuracy conditions to visually presented male or female names in an oddball paradigm. Single-trial analysis revealed a strong relationship between RT and P300 latency, both of which were slowed in a dose-related manner by hyperbaric air but not by heliox. A clear-cut dose-response relationship could not be established for P300 amplitude. These results indicate that P300 latency indexes nitrogen narcosis and are interpreted as support for the slowed processing model of inert gas narcosis.

  14. Unsupervised, low latency

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    Jayaram Raghuram

    2014-07-01

    Full Text Available We propose a method for detecting anomalous domain names, with focus on algorithmically generated domain names which are frequently associated with malicious activities such as fast flux service networks, particularly for bot networks (or botnets, malware, and phishing. Our method is based on learning a (null hypothesis probability model based on a large set of domain names that have been white listed by some reliable authority. Since these names are mostly assigned by humans, they are pronounceable, and tend to have a distribution of characters, words, word lengths, and number of words that are typical of some language (mostly English, and often consist of words drawn from a known lexicon. On the other hand, in the present day scenario, algorithmically generated domain names typically have distributions that are quite different from that of human-created domain names. We propose a fully generative model for the probability distribution of benign (white listed domain names which can be used in an anomaly detection setting for identifying putative algorithmically generated domain names. Unlike other methods, our approach can make detections without considering any additional (latency producing information sources, often used to detect fast flux activity. Experiments on a publicly available, large data set of domain names associated with fast flux service networks show encouraging results, relative to several baseline methods, with higher detection rates and low false positive rates.

  15. Piracy of prostaglandin E2/EP receptor-mediated signaling by Kaposi's sarcoma-associated herpes virus (HHV-8) for latency gene expression: strategy of a successful pathogen.

    Science.gov (United States)

    George Paul, Arun; Sharma-Walia, Neelam; Kerur, Nagaraj; White, Carl; Chandran, Bala

    2010-05-01

    Kaposi's sarcoma-associated herpes virus (KSHV) is implicated in the pathogenesis of KS, a chronic inflammation-associated malignancy. Cyclooxygenase-2 (COX-2) and its metabolite prostaglandin E2 (PGE2), two pivotal proinflammatory/oncogeneic molecules, are proposed to play roles in the expression of major KSHV latency-associated nuclear antigen-1 (LANA-1). Microsomal PGE2 synthase, PGE2, and its receptors (EP1, EP2, EP3, and EP4) were detected in KS lesions with the distinct staining of EP2/EP4 in KS lesions. In latently infected endothelial TIVE-LTC cells, EP receptor antagonists downregulated LANA-1 expression as well as Ca(2+), p-Src, p-PI3K, p-PKCzeta/lambda, and p-NF-kappaB, which are also some of the signal molecules proposed to be important in KS pathogenesis. Exogenous PGE2 and EP receptor agonists induced the LANA-1 promoter in 293 cells, and YY1, Sp1, Oct-1, Oct-6, C/EBP, and c-Jun transcription factors seem to be involved in this induction. PGE2/EP receptor-induced LANA-1 promoter activity was downregulated significantly by the inhibition of Ca(2+), p-Src, p-PI3K, p-PKCzeta/lambda, and p-NF-kappaB. These findings implicate the inflammatory PGE2/EP receptors and the associated signal molecules in herpes virus latency and uncover a novel paradigm that shows the evolution of KSHV genome plasticity to use inflammatory response for its survival advantage of maintaining latent gene expression. These data also suggest that potential use of anti-COX-2 and anti-EP receptor therapy may not only ameliorate the chronic inflammation associated with KS but could also lead to elimination of the KSHV latent infection and the associated KS lesions.

  16. Crystal structure of a KSHV-SOX-DNA complex: insights into the molecular mechanisms underlying DNase activity and host shutoff.

    Science.gov (United States)

    Bagnéris, Claire; Briggs, Louise C; Savva, Renos; Ebrahimi, Bahram; Barrett, Tracey E

    2011-07-01

    The early lytic phase of Kaposi's sarcoma herpesvirus infection is characterized by viral replication and the global degradation (shutoff) of host mRNA. Key to both activities is the virally encoded alkaline exonuclease KSHV SOX. While the DNase activity of KSHV SOX is required for the resolution of viral genomic DNA as a precursor to encapsidation, its exact involvement in host shutoff remains to be determined. We present the first crystal structure of a KSHV SOX-DNA complex that has illuminated the catalytic mechanism underpinning both its endo and exonuclease activities. We further illustrate that KSHV SOX, similar to its Epstein-Barr virus homologue, has an intrinsic RNase activity in vitro that although an element of host shutoff, cannot solely account for the phenomenon.

  17. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV–MCD and the KSHV Inflammatory Cytokine Syndrome

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    Mark N. Polizzotto

    2012-03-01

    Full Text Available Soon after the discovery of Kaposi sarcoma (KS-associated herpesvirus (KSHV, it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV–MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV–MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV–MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6. Patients with KSHV–MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV–MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS has been described. Its clinical manifestations resemble those of KSHV–MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV–MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV–MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms

  18. Global metabolic profiling of infection by an oncogenic virus: KSHV induces and requires lipogenesis for survival of latent infection.

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    Tracie Delgado

    Full Text Available Like cancer cells, virally infected cells have dramatically altered metabolic requirements. We analyzed global metabolic changes induced by latent infection with an oncogenic virus, Kaposi's Sarcoma-associated herpesvirus (KSHV. KSHV is the etiologic agent of Kaposi's Sarcoma (KS, the most common tumor of AIDS patients. Approximately one-third of the nearly 200 measured metabolites were altered following latent infection of endothelial cells by KSHV, including many metabolites of anabolic pathways common to most cancer cells. KSHV induced pathways that are commonly altered in cancer cells including glycolysis, the pentose phosphate pathway, amino acid production and fatty acid synthesis. Interestingly, over half of the detectable long chain fatty acids detected in our screen were significantly increased by latent KSHV infection. KSHV infection leads to the elevation of metabolites involved in the synthesis of fatty acids, not degradation from phospholipids, and leads to increased lipid droplet organelle formation in the infected cells. Fatty acid synthesis is required for the survival of latently infected endothelial cells, as inhibition of key enzymes in this pathway led to apoptosis of infected cells. Addition of palmitic acid to latently infected cells treated with a fatty acid synthesis inhibitor protected the cells from death indicating that the products of this pathway are essential. Our metabolomic analysis of KSHV-infected cells provides insight as to how oncogenic viruses can induce metabolic alterations common to cancer cells. Furthermore, this analysis raises the possibility that metabolic pathways may provide novel therapeutic targets for the inhibition of latent KSHV infection and ultimately KS tumors.

  19. A viral genome landscape of RNA polyadenylation from KSHV latent to lytic infection.

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    Vladimir Majerciak

    Full Text Available RNA polyadenylation (pA is one of the major steps in regulation of gene expression at the posttranscriptional level. In this report, a genome landscape of pA sites of viral transcripts in B lymphocytes with Kaposi sarcoma-associated herpesvirus (KSHV infection was constructed using a modified PA-seq strategy. We identified 67 unique pA sites, of which 55 could be assigned for expression of annotated ~90 KSHV genes. Among the assigned pA sites, twenty are for expression of individual single genes and the rest for multiple genes (average 2.7 genes per pA site in cluster-gene loci of the genome. A few novel viral pA sites that could not be assigned to any known KSHV genes are often positioned in the antisense strand to ORF8, ORF21, ORF34, K8 and ORF50, and their associated antisense mRNAs to ORF21, ORF34 and K8 could be verified by 3'RACE. The usage of each mapped pA site correlates to its peak size, the larger (broad and wide peak size, the more usage and thus, the higher expression of the pA site-associated gene(s. Similar to mammalian transcripts, KSHV RNA polyadenylation employs two major poly(A signals, AAUAAA and AUUAAA, and is regulated by conservation of cis-elements flanking the mapped pA sites. Moreover, we found two or more alternative pA sites downstream of ORF54, K2 (vIL6, K9 (vIRF1, K10.5 (vIRF3, K11 (vIRF2, K12 (Kaposin A, T1.5, and PAN genes and experimentally validated the alternative polyadenylation for the expression of KSHV ORF54, K11, and T1.5 transcripts. Together, our data provide not only a comprehensive pA site landscape for understanding KSHV genome structure and gene expression, but also the first evidence of alternative polyadenylation as another layer of posttranscriptional regulation in viral gene expression.

  20. The Kaposi Sarcoma Herpesvirus Latency-associated Nuclear Antigen DNA Binding Domain Dorsal Positive Electrostatic Patch Facilitates DNA Replication and Episome Persistence.

    Science.gov (United States)

    Li, Shijun; Tan, Min; Juillard, Franceline; Ponnusamy, Rajesh; Correia, Bruno; Simas, J Pedro; Carrondo, Maria A; McVey, Colin E; Kaye, Kenneth M

    2015-11-20

    Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes.

  1. The Conundrum of Causality in Tumor Virology: The Cases of KSHV and MCV

    Science.gov (United States)

    Moore, Patrick S.; Chang, Yuan

    2014-01-01

    Controversy has plagued tumor virology since the first tumor viruses were described over 100 years ago. Methods to establish cancer causation, such as Koch’s postulates, work poorly or not at all for these viruses. Kaposi’s sarcoma herpesvirus (KSHV/HHV8) and Merkel cell polyomavirus (MCV) were both found using nucleic acid identification methods but they represent opposite poles in the patterns for tumor virus epidemiology. KSHV is uncommon and has specific risk factors that contribute to infection and subsequent cancers. MCV and Merkel cell carcinoma (MCC), in contrast, is an example in which mutations to our normal viral flora contribute to cancer. Given the near-ubiquity of human MCV infection, establishing cancer causality relies on molecular evidence that does not fit comfortably within traditional infectious disease epidemiological models. These two viruses reveal some of the challenges and opportunities for inferring viral cancer causation in the age of molecular biology. PMID:24304907

  2. Epidemiology and genetic variability of HHV-8/KSHV in Pygmy and Bantu populations in Cameroon.

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    Edouard Betsem

    2014-05-01

    Full Text Available BACKGROUND: Kaposi's sarcoma associated herpesvirus (KSHV/HHV-8 is the causal agent of all forms of Kaposi sarcoma. Molecular epidemiology of the variable K1 region identified five major subtypes exhibiting a clear geographical clustering. The present study is designed to gain new insights into the KSHV epidemiology and genetic diversity in Cameroon. METHODOLOGY/PRINCIPAL FINDINGS: Bantu and Pygmy populations from remote rural villages were studied. Antibodies directed against latent nuclear antigens (LANA were detected by indirect immunofluorescence using BC3 cells. Peripheral blood cell DNAs were subjected to a nested PCR amplifying a 737 bp K1 gene fragment. Consensus sequences were phylogenetically analyzed. We studied 2,063 persons (967 females, 1,096 males, mean age 39 years, either Bantus (1,276 or Pygmies (787. The Bantu group was older (42 versus 35 years: P<10(-4. KSHV anti-LANA seroprevalence was of 37.2% (768/2063, with a significant increase with age (P<10(-4 but no difference according to sex. Seroprevalence, as well as the anti-LANA antibodies titres, were higher in Bantus (43.2% than in Pygmies (27.6% (P<10(-4, independently of age. We generated 29 K1 sequences, comprising 24 Bantus and five Pygmies. These sequences belonged to A5 (24 cases or B (five cases subtypes. They exhibited neither geographical nor ethnic aggregation. A5 strains showed a wide genetic diversity while the B strains were more homogenous and belonged to the B1 subgroup. CONCLUSION: These data demonstrate high KSHV seroprevalence in the two major populations living in Southern and Eastern Cameroon with presence of mostly genetically diverse A5 but also B K1 subtypes.

  3. Latency and User Performance in Virtual Environments and Augmented Reality

    Science.gov (United States)

    Ellis, Stephen R.

    2009-01-01

    System rendering latency has been recognized by senior researchers, such as Professor Fredrick Brooks of UNC (Turing Award 1999), as a major factor limiting the realism and utility of head-referenced displays systems. Latency has been shown to reduce the user's sense of immersion within a virtual environment, disturb user interaction with virtual objects, and to contribute to motion sickness during some simulation tasks. Latency, however, is not just an issue for external display systems since finite nerve conduction rates and variation in transduction times in the human body's sensors also pose problems for latency management within the nervous system. Some of the phenomena arising from the brain's handling of sensory asynchrony due to latency will be discussed as a prelude to consideration of the effects of latency in interactive displays. The causes and consequences of the erroneous movement that appears in displays due to latency will be illustrated with examples of the user performance impact provided by several experiments. These experiments will review the generality of user sensitivity to latency when users judge either object or environment stability. Hardware and signal processing countermeasures will also be discussed. In particular the tuning of a simple extrapolative predictive filter not using a dynamic movement model will be presented. Results show that it is possible to adjust this filter so that the appearance of some latencies may be hidden without the introduction of perceptual artifacts such as overshoot. Several examples of the effects of user performance will be illustrated by three-dimensional tracking and tracing tasks executed in virtual environments. These experiments demonstrate classic phenomena known from work on manual control and show the need for very responsive systems if they are indented to support precise manipulation. The practical benefits of removing interfering latencies from interactive systems will be emphasized with some

  4. Response rate, latency, and resistance to change

    Science.gov (United States)

    Fath, Stephen J.; Fields, Lanny; Malott, M. Kay; Grossett, Deborah

    1983-01-01

    Pigeons were trained on a multiple variable-interval/variable-interval schedule with pacing contingencies that generated high response rates in one component and low response rates in the other. Timeout periods separated the schedule components. During resistance-to-change tests, response-independent food was presented during the timeout periods, and the duration of that food presentation was varied among test sessions. Response rates in the schedule components decreased and latencies to the first response increased as a function of the duration of food presentations during the timeout. Both dependent measures changed about the same amount relative to their own baseline levels. The conclusions are that baseline response rates controlled by pacing contingencies are equally resistant to change, given equal reinforcement densities, and latency is a sensitive measure of resistance to change. PMID:16812319

  5. Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma (PEL.

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    Lu Dai

    Full Text Available Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL, which arises preferentially in the setting of infection with human immunodeficiency virus (HIV. Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+ PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+ PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.

  6. Quantitative Determinations of Anti-Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Antibody Levels in Men Who Have Sex with Men

    Science.gov (United States)

    Gogineni, Emile; Marshall, Vickie; Miley, Wendell; Bayat, Ahmad; Whitby, Denise; Kovacs, Joseph A.; Burbelo, Peter D.

    2013-01-01

    Infection with Kaposi’s Sarcoma-Associated Herpesvirus (KSHV/HHV-8) is common among men who have sex with men (MSM). Here quantitative anti-KSHV antibody levels were measured using Luciferase Immunoprecipitation Systems (LIPS) in a MSM cohort with and without HIV from the NIH Clinical Center. Antibodies were detected using a mixture of four KSHV antigens in the MSM cohort and in Kaposi Sarcoma (KS) patients. Along with HIV status, these results were compared with K8.1 and ORF73 ELISA, PCR virus detection, and additional LIPS testing. LIPS revealed that 25% (76/307) of the MSM cohort were KSHV seropositive, including 59 HIV+ and 17 HIV− subjects. The anti-KSHV antibody levels detected by LIPS were not statistically different between the KSHV+/HIV+ and KSHV+/HIV− subgroups, but were lower than the KS patients (P<0.0001). ELISA analysis of the MSM cohort detected a 35.5% frequency of KSHV infection and showed agreement with 81% of the samples evaluated by LIPS. Further LIPS testing with v-cyclin, a second ORF73 fragment and ORF38 reconciled some of the differences observed between LIPS and the ELISA immunoassays and the revised LIPS seroprevalence in the MSM cohort was increased to 31%. Additional quantitative antibody analysis demonstrated statistically lower KSHV antibody levels in MSM compared to KS patients, but no difference was found between KSHV infected with and without HIV coinfection. These findings also suggest that antibodies against v-cyclin and ORF38 are useful for identifying patients with asymptomatic KSHV infection. PMID:23541691

  7. Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription.

    Science.gov (United States)

    Kusano, Shuichi; Eizuru, Yoshito

    2010-06-04

    Kaposi's sarcoma-associated herpes virus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein has been reported to interact with glycogen synthase kinase 3beta (GSK-3beta) and to negatively regulate its activity, leading to stimulation of GSK-3beta-dependent beta-catenin degradation. We show here that the I-mfa domain proteins, HIC (human I-mfa domain-containing protein) and I-mfa (inhibitor of MyoD family a), interacted in vivo with LANA through their C-terminal I-mfa domains. This interaction affected the intracellular localization of HIC, inhibited the LANA-dependent transactivation of a beta-catenin-regulated reporter construct, and decreased the level of the LANA.GSK-3beta complex. These data reveal for the first time that I-mfa domain proteins interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA.GSK-3beta complex.

  8. Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription

    Energy Technology Data Exchange (ETDEWEB)

    Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Eizuru, Yoshito [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2010-06-04

    Kaposi's sarcoma-associated herpes virus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein has been reported to interact with glycogen synthase kinase 3{beta} (GSK-3{beta}) and to negatively regulate its activity, leading to stimulation of GSK-3{beta}-dependent {beta}-catenin degradation. We show here that the I-mfa domain proteins, HIC (human I-mfa domain-containing protein) and I-mfa (inhibitor of MyoD family a), interacted in vivo with LANA through their C-terminal I-mfa domains. This interaction affected the intracellular localization of HIC, inhibited the LANA-dependent transactivation of a {beta}-catenin-regulated reporter construct, and decreased the level of the LANA.GSK-3{beta} complex. These data reveal for the first time that I-mfa domain proteins interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA.GSK-3{beta} complex.

  9. KSHV Entry and Trafficking in Target Cells—Hijacking of Cell Signal Pathways, Actin and Membrane Dynamics

    Directory of Open Access Journals (Sweden)

    Binod Kumar

    2016-11-01

    Full Text Available Kaposi’s sarcoma associated herpesvirus (KSHV is etiologically associated with human endothelial cell hyperplastic Kaposi’s sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS, integrins (α3β1, αVβ3 and αVβ5, and EphA2 receptor tyrosine kinase (EphA2R. This review summarizes the accumulated studies demonstrating that KSHV manipulates the host signal pathways to enter and traffic in the cytoplasm of the target cells, to deliver the viral genome into the nucleus, and initiate viral gene expression. KSHV interactions with the cell surface receptors is the key platform for the manipulations of host signal pathways which results in the simultaneous induction of FAK, Src, PI3-K, Rho-GTPase, ROS, Dia-2, PKC ζ, c-Cbl, CIB1, Crk, p130Cas and GEF-C3G signal and adaptor molecules that play critical roles in the modulation of membrane and actin dynamics, and in the various steps of the early stages of infection such as entry and trafficking towards the nucleus. The Endosomal Sorting Complexes Required for Transport (ESCRT proteins are also recruited to assist in viral entry and trafficking. In addition, KSHV interactions with the cell surface receptors also induces the host transcription factors NF-κB, ERK1/2, and Nrf2 early during infection to initiate and modulate viral and host gene expression. Nuclear delivery of the viral dsDNA genome is immediately followed by the host innate responses such as the DNA damage response (DDR, inflammasome and interferon responses. Overall, these studies form the initial framework for further studies of

  10. KSHV Entry and Trafficking in Target Cells—Hijacking of Cell Signal Pathways, Actin and Membrane Dynamics

    Science.gov (United States)

    Kumar, Binod; Chandran, Bala

    2016-01-01

    Kaposi’s sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi’s sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R). This review summarizes the accumulated studies demonstrating that KSHV manipulates the host signal pathways to enter and traffic in the cytoplasm of the target cells, to deliver the viral genome into the nucleus, and initiate viral gene expression. KSHV interactions with the cell surface receptors is the key platform for the manipulations of host signal pathways which results in the simultaneous induction of FAK, Src, PI3-K, Rho-GTPase, ROS, Dia-2, PKC ζ, c-Cbl, CIB1, Crk, p130Cas and GEF-C3G signal and adaptor molecules that play critical roles in the modulation of membrane and actin dynamics, and in the various steps of the early stages of infection such as entry and trafficking towards the nucleus. The Endosomal Sorting Complexes Required for Transport (ESCRT) proteins are also recruited to assist in viral entry and trafficking. In addition, KSHV interactions with the cell surface receptors also induces the host transcription factors NF-κB, ERK1/2, and Nrf2 early during infection to initiate and modulate viral and host gene expression. Nuclear delivery of the viral dsDNA genome is immediately followed by the host innate responses such as the DNA damage response (DDR), inflammasome and interferon responses. Overall, these studies form the initial framework for further studies of simultaneous targeting of

  11. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    Science.gov (United States)

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  12. Identification of noisy response latency

    DEFF Research Database (Denmark)

    Tamborrino, Massimiliano; Ditlevsen, Susanne; Lansky, Petr

    2012-01-01

    be highly unreliable, unless the background signal is accounted for in the analysis. In fact, if the background signal is ignored, however small it is compared to the response and however large the delay is, the estimate of the time delay will go to zero for any reasonable estimator when increasing...... the number of observations. Here we propose a unified concept of response latency identification in event data corrupted by a background signal. It is done in the context of information transfer within a neural system, more specifically on spike trains from single neurons. The estimators are compared...

  13. Genomic analysis of xCT-regulatory network in KSHV+ primary effusion lymphomas

    Directory of Open Access Journals (Sweden)

    Zhiqiang Qin

    2016-06-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is the etiological agent of primary effusion lymphoma (PEL, a rapidly progressing malignancy mostly arising in HIV-infected patients Chen et al. (2007 [1]. Even under conventional chemotherapy, PEL continues to portend nearly 100% mortality within several months, which urgently requires novel therapeutic strategies. We have previously demonstrated that targeting xCT, an amino acid transporter for cystine/glutamate exchange, induces significant PEL cell apoptosis through regulation of multiple host and viral factors [2]. More importantly, one of xCT selective inhibitors, Sulfasalazine (SASP, effectively prevents PEL tumor progression in an immune-deficient xenograft model [2]. In the current study, we use Illumina microarray to explore the profile of genes altered by SASP treatment within 3 KSHV+ PEL cell-lines, and discover that many genes involved in oxidative stress/antioxidant defense system, apoptosis/anti-apoptosis/cell death, and cellular response to unfolded proteins/topologically incorrect proteins are potentially regulated by xCT Dai et al. (2015 [3]. The microarray original data have been submitted to Gene Expression Omnibus (GEO database (Accession number: GSE65418.

  14. Mono-ubiquitylated ORF45 Mediates Association of KSHV Particles with Internal Lipid Rafts for Viral Assembly and Egress.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2015-12-01

    Full Text Available Herpesviruses acquire their envelope by budding into the lumen of cytoplasmic membrane vesicles. This process is initiated by component(s on viral particles, which recognize the budding site where the viral glycoproteins are present and recruit cellular cargo transport and sorting machinery to the site to complete the budding process. Proteins in the tegument layer, connecting capsid and envelope, are candidates for the recognition of budding sites on vesicle membrane and induction of budding and final envelopment. We examined several outer and matrix tegument proteins of Kaposi's sarcoma-associated herpesvirus (KSHV and found that ORF45 associates with lipid rafts (LRs of cellular membrane. LRs are membrane micro-domains, which have been implicated as relay stations in intracellular signaling and transport including viral entry and virion assembly. The ability of ORF45 to target LR is dependent on the mono-ubiquitylation of ORF45 at Lys297 as the mutation at Lys297 (K297R abolished LR-association of ORF45. The K297R mutation also impairs ORF45 and viral particle co-localization with trans-Golgi network and endosomes, but facilitates ORF45 and viral particles co-localizing with lysosomes. More importantly, the recombinant KSHV carrying ORF45 K297R mutant (BAC-K297R was found severely defective in producing mature and infectious virion particles in comparison to wild type KSHV (BAC16. Taken together, our results reveal a new function of KSHV tegument protein ORF45 in targeting LR of host cell membrane, promoting viral particles co-localization with trans-Golgi and endosome vesicles and facilitating the maturation and release of virion particles, suggesting that ORF45 plays a role in bringing KSHV particles to the budding site on cytoplasmic vesicle membrane and triggering the viral budding process for final envelopment and virion maturation.

  15. [Intravaginal ejaculatory latency time: Advances in studies].

    Science.gov (United States)

    Wang, Wan-rong; Xie, Sheng

    2016-02-01

    Although premature ejaculation (PE) is a common type of male sexual dysfunction, to date we lack a unified definition of PE. The multidimensional definition of PE has been accepted by more and more clinicians. Intravaginal ejaculatory latency time (IELT) is one of the three important dimensions (time to ejaculation, inability to control or delay ejaculation, and negative consequences) for defining PE. Rapid ejaculation is one of the core symptoms of PE and IELT is an objective measurement as well as an important tool for the evaluation of PE. This article reviews estimated IELT, stopwatch-measured IELT, the correlation between estimated and stopwatch-measured IELT, and the factors affecting IELT in the general male population, PE patients, and those complaining of PE.

  16. KSHV METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  17. Oncovirus Kaposi sarcoma herpesvirus (KSHV) represses tumor suppressor PDLIM2 to persistently activate nuclear factor κB (NF-κB) and STAT3 transcription factors for tumorigenesis and tumor maintenance.

    Science.gov (United States)

    Sun, Fan; Xiao, Yadong; Qu, Zhaoxia

    2015-03-20

    Kaposi sarcoma herpesvirus (KSHV) is the most common cause of malignancies among AIDS patients. However, how KSHV induces tumorigenesis remains largely unknown. Here, we demonstrate that one important mechanism underlying the tumorigenesis of KSHV is through transcriptional repression of the tumor suppressor gene PDZ-LIM domain-containing protein 2 (PDLIM2). PDLIM2 expression is repressed in KSHV-transformed human umbilical vascular endothelial cells as well as in KSHV-associated cancer cell lines and primary tumors. Importantly, PDLIM2 repression is essential for KSHV-induced persistent activation of nuclear factor κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) and subsequent tumorigenesis and tumor maintenance. Our mechanistic studies indicate that PDLIM2 repression by KSHV involves DNA methylation. Notably, the epigenetic repression of PDLIM2 can be reversed by 5-aza-2-deoxycytidine and vitamin D to suppress KSHV-associated cancer cell growth. These studies not only improve our understanding of KSHV pathogenesis but also provide immediate therapeutic strategies for KSHV-mediated cancers, particularly those associated with AIDS.

  18. Viral Inhibition of PRR-Mediated Innate Immune Response: Learning from KSHV Evasion Strategies.

    Science.gov (United States)

    Lee, Hye-Ra; Choi, Un Yung; Hwang, Sung-Woo; Kim, Stephanie; Jung, Jae U

    2016-11-30

    The innate immune system has evolved to detect and destroy invading pathogens before they can establish systemic infection. To successfully eradicate pathogens, including viruses, host innate immunity is activated through diverse pattern recognition receptors (PRRs) which detect conserved viral signatures and trigger the production of type I interferon (IFN) and pro-inflammatory cytokines to mediate viral clearance. Viral persistence requires that viruses co-opt cellular pathways and activities for their benefit. In particular, due to the potent antiviral activities of IFN and cytokines, viruses have developed various strategies to meticulously modulate intracellular innate immune sensing mechanisms to facilitate efficient viral replication and persistence. In this review, we highlight recent advances in the study of viral immune evasion strategies with a specific focus on how Kaposi's sarcoma-associated herpesvirus (KSHV) effectively targets host PRR signaling pathways.

  19. Alternative RNA splicing of KSHV ORF57 produces two different RNA isoforms.

    Science.gov (United States)

    Majerciak, Vladimir; Zheng, Zhi-Ming

    2016-01-15

    In lytically infected B cells Kaposi sarcoma-associated herpesvirus (KSHV) ORF57 gene encodes two RNA isoforms by alternative splicing of its pre-mRNA, which contains a small, constitutive intron in its 5' half and a large, suboptimal intron in its 3's half. The RNA1 isoform encodes full-length ORF57 and is a major isoform derived from splicing of the constitutive small intron, but retaining the suboptimal large intron as the coding region. A small fraction (splicing to produce a smaller non-coding RNA2 due to lack of a translational termination codon. Both RNAs are cleaved and polyadenylated at the same cleavage site CS83636. The insertion of ORF57 RNA1 into a restriction cutting site in certain mammalian expression vectors activates splicing of the subopitmal intron and produces a truncated ORF57 protein.

  20. Antiviral activity of tumor-suppressor pathways: clues from molecular piracy by KSHV.

    Science.gov (United States)

    Moore, P S; Chang, Y

    1998-04-01

    A common feature of many tumor viruses is that they possess genes that produce specific proteins to inhibit major cellular tumor-suppressor pathways. Despite intensive studies, the reasons why these diverse and unrelated viruses have independently evolved oncogenes remains obscure. Kaposi-sarcoma-associated herpesvirus (KSHV or HHV8) has pirated a number of recognizable cellular genes that are key to cell survival and proliferation. In this review, we provide an overview of the known activities of these viral genes and show that many of these pirated proteins affect the same cellular pathways targeted by other, unrelated tumor viruses. We speculate that tumor-suppressor pathways are used by the cell as a primary defense against persistent virus infection, in addition to their well-known activity in regulating cell proliferation.

  1. IRF-4-mediated CIITA transcription is blocked by KSHV encoded LANA to inhibit MHC II presentation.

    Directory of Open Access Journals (Sweden)

    Qiliang Cai

    2013-10-01

    Full Text Available Peptides presentation to T cells by MHC class II molecules is of importance in initiation of immune response to a pathogen. The level of MHC II expression directly influences T lymphocyte activation and is often targeted by various viruses. Kaposi's sarcoma-associated herpesvirus (KSHV encoded LANA is known to evade MHC class I peptide processing, however, the effect of LANA on MHC class II remains unclear. Here, we report that LANA down-regulates MHC II expression and presentation by inhibiting the transcription of MHC II transactivator (CIITA promoter pIII and pIV in a dose-dependent manner. Strikingly, although LANA knockdown efficiently disrupts the inhibition of CIITA transcripts from its pIII and pIV promoter region, the expression of HLA-DQβ but no other MHC II molecules was significantly restored. Moreover, we revealed that the presentation of HLA-DQβ enhanced by LANA knockdown did not help LANA-specific CD4+ T cell recognition of PEL cells, and the inhibition of CIITA by LANA is independent of IL-4 or IFN-γ signaling but dependent on the direct interaction of LANA with IRF-4 (an activator of both the pIII and pIV CIITA promoters. This interaction dramatically blocked the DNA-binding ability of IRF-4 on both pIII and pIV promoters. Thus, our data implies that LANA can evade MHC II presentation and suppress CIITA transcription to provide a unique strategy of KSHV escape from immune surveillance by cytotoxic T cells.

  2. CHRONIC DISSEMINATED HISTOPLASMOSIS WITH PROLONGED LATENCY

    Science.gov (United States)

    A case of chronic disseminated histoplasmosis in an ex-serviceman is described. Evidence is presented to support a latency period of over sixty years between acquisition of infection and clinical manifestation. This is the longest latency period for histoplasmosis described in the medical literature...

  3. An Interaction between KSHV ORF57 and UIF Provides mRNA-Adaptor Redundancy in Herpesvirus Intronless mRNA Export

    Science.gov (United States)

    Jackson, Brian R.; Boyne, James R.; Noerenberg, Marko; Taylor, Adam; Hautbergue, Guillaume M.; Walsh, Matthew J.; Wheat, Rachel; Blackbourn, David J.; Wilson, Stuart A.; Whitehouse, Adrian

    2011-01-01

    The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs. PMID:21814512

  4. Interferon alpha induces establishment of alphaherpesvirus latency in sensory neurons in vitro.

    Directory of Open Access Journals (Sweden)

    Nick De Regge

    Full Text Available BACKGROUND: Several alphaherpesviruses, including herpes simplex virus 1 (HSV-1 and pseudorabies virus (PRV, establish lifelong latency in neurons of the trigeminal ganglion (TG. Although it is thought that efficient establishment of alphaherpesvirus latency is based on a subtle interplay between virus, neurons and the immune system, it is not clear which immune components are of major importance for the establishment of latency. METHODOLOGY/PRINCIPAL FINDINGS: Here, using an in vitro model that enables a natural route of infection, we show that interferon alpha (IFNalpha has the previously uncharacterized capacity to induce a quiescent HSV-1 and PRV infection in porcine TG neurons that shows strong similarity to in vivo latency. IFNalpha induced a stably suppressed HSV-1 and PRV infection in TG neurons in vitro. Subsequent treatment of neurons containing stably suppressed virus with forskolin resulted in reactivation of both viruses. HSV and PRV latency in vivo is often accompanied by the expression of latency associated transcripts (LATs. Infection of TG neurons with an HSV-1 mutant expressing LacZ under control of the LAT promoter showed activation of the LAT promoter and RT-PCR analysis confirmed that both HSV-1 and PRV express LATs during latency in vitro. CONCLUSIONS/SIGNIFICANCE: These data represent a unique in vitro model of alphaherpesvirus latency and indicate that IFNalpha may be a driving force in promoting efficient latency establishment.

  5. EBV latency types adopt alternative chromatin conformations.

    Directory of Open Access Journals (Sweden)

    Italo Tempera

    2011-07-01

    Full Text Available Epstein-Barr Virus (EBV can establish latent infections with distinct gene expression patterns referred to as latency types. These different latency types are epigenetically stable and correspond to different promoter utilization. Here we explore the three-dimensional conformations of the EBV genome in different latency types. We employed Chromosome Conformation Capture (3C assay to investigate chromatin loop formation between the OriP enhancer and the promoters that determine type I (Qp or type III (Cp gene expression. We show that OriP is in close physical proximity to Qp in type I latency, and to Cp in type III latency. The cellular chromatin insulator and boundary factor CTCF was implicated in EBV chromatin loop formation. Combining 3C and ChIP assays we found that CTCF is physically associated with OriP-Qp loop formation in type I and OriP-Cp loop formation in type III latency. Mutations in the CTCF binding site located at Qp disrupt loop formation between Qp and OriP, and lead to the activation of Cp transcription. Mutation of the CTCF binding site at Cp, as well as siRNA depletion of CTCF eliminates both OriP-associated loops, indicating that CTCF plays an integral role in loop formation. These data indicate that epigenetically stable EBV latency types adopt distinct chromatin architectures that depend on CTCF and mediate alternative promoter targeting by the OriP enhancer.

  6. Advanced LIGO low-latency searches

    Science.gov (United States)

    Kanner, Jonah; LIGO Scientific Collaboration, Virgo Collaboration

    2016-06-01

    Advanced LIGO recently made the first detection of gravitational waves from merging binary black holes. The signal was first identified by a low-latency analysis, which identifies gravitational-wave transients within a few minutes of data collection. More generally, Advanced LIGO transients are sought with a suite of automated tools, which collectively identify events, evaluate statistical significance, estimate source position, and attempt to characterize source properties. This low-latency effort is enabling a broad multi-messenger approach to the science of compact object mergers and other transients. This talk will give an overview of the low-latency methodology and recent results.

  7. Low latency IP mobility management: protocol and analysis

    Directory of Open Access Journals (Sweden)

    Guo Xiaobing

    2011-01-01

    Full Text Available Abstract Mobile IP is one of the dominating protocols that enable a mobile node to remain reachable while moving around in the Internet. However, it suffers from long handoff latency and route inefficiency. In this article, we present a novel distributed mobility management architecture, ADA (Asymmetric Double-Agents, which introduces double mobility agents to serve one end-to-end communication. One mobility agent is located close to the MN and the other close to the CN. ADA can achieve both low handoff latency and low transmission latency, which is crucial for improvement of user perceived QoS. It also provides an easy-to-use mechanism for MNs to manage and control each traffic session with a different policy and provide specific QoS support. We apply ADA to MIPv6 communications and present a detailed protocol design. Subsequently, we propose an analytical framework for systematic and thorough performance evaluation of mobile IP-based mobility management protocols. Equipped with this model, we analyze the handoff latency, single interaction delay and total time cost under the bidirectional tunneling mode and the route optimization mode for MIPv6, HMIPv6, CNLP, and ADA. Through both quantitative analysis and NS2-based simulations, we show that ADA significantly outperforms the existing mobility management protocols.

  8. Optimizing latency in Xilinx FPGA implementations of the GBT

    CERN Document Server

    Muschter, S; Bohm, C; Cachemiche, J-P; Baron, S

    2010-01-01

    The GigaBit Transceiver (GBT) {[}1] system has been developed to replace the Timing, Trigger and Control (TTC) system {[}2], currently used by LHC, as well as to provide data transmission between on-detector and off-detector components in future sLHC detectors. A VHDL version of the GBT-SERDES, designed for FPGAs, was released in March 2010 as a GBT-FPGA Starter Kit for future GBT users and for off-detector GBT implementation {[}3]. This code was optimized for resource utilization {[}4], as the GBT protocol is very demanding. It was not, however, optimized for latency - which will be a critical parameter when used in the trigger path. The GBT-FPGA Starter Kit firmware was first analyzed in terms of latency by looking at the separate components of the VHDL version. Once the parts which contribute most to the latency were identified and modified, two possible optimizations were chosen, resulting in a latency reduced by a factor of three. The modifications were also analyzed in terms of logic utilization. The la...

  9. Let-7在KSHV原发感染过程中的表达变化%The Relative Expression Changes of Let-7 in the Process of KSHV Primary Infection

    Institute of Scientific and Technical Information of China (English)

    南玉龙; 谭晓华; 高媛; 杨磊

    2012-01-01

    为研究在KSHV原发感染过程中Let-7表达水平的变化情况.采用20ng/mL TPA诱导培养BCBL-1细胞4d,收集并裂解细胞;超速离心制备KSHV病毒颗粒;感染293T细胞,采用实时定量聚合酶链反应(quantitative Real-time polymerase chain reaction,qRT-PCR)检测感染1-66 d内Let-7的表达水平.结果显示,Let-7在KSHV原发感染293T细胞的1-4 d表达水平均下调,感染后1-2 d表达水平最低.7a、7b、7 g、7i均下调为对照细胞的0.01倍以下.之后随感染天数增加Let-7表达水平逐渐增加,其中Let-7c(7d、7D表达水平在第6天分别达到未感染对照细胞的0.9倍,Let-7b、Let-7e、mir-98在第6天的表达水平与对照细胞接近除了Let-7e上调3倍.由此可知,Let-7在KSHV原发感染过程中总体表现为下调趋势.因此推测,Let-7可能在KSHV原发感染过程中产生重要调控作用.%To examine the relative expression levels of Let-7 after infection of KSHV in different days. Methods: BCBL-1 cells were induced by treatment with 20 ng/ml tetradecanoyl phorbol acetate(TPA) for 4 days,then supernatants were transferred to fresh tubes and ultracentrifuged to obtain KSHV infectious virus particles; 293T cells were infected by virus particles; relative expression changes of Let-7 in 1-6 days were detected by quantitative Real-time polymerase chain reaction,qRT-PCR. Results; Let-7 in 293T cells showed varying degrees of down-regulation after KSHV primary infection in 1-4 days,with the lowest level in 1-2 days. 7a,7b,7g,and 7i were down to 0.01 time. Compare with mock control cells,Let-7c(d,f) were down-regulated to 0. 9 times;Let-7b (e) and mir-98 expression in the first 6 days were close to the level of the control cells except for Let-7e(up-regulated 3 times). Then the levels of Let-7 expression gradually restored to its pre-infected state. Conclusions:Let-7a,7d,7e and 7i members showed a downward trend in the process of establishment of KSHV infection in different days, which

  10. Low-Latency Lunar Surface Telerobotics from Earth-Moon Libration Points

    Science.gov (United States)

    Lester, Daniel; Thronson, Harley

    2011-01-01

    Concepts for a long-duration habitat at Earth-Moon LI or L2 have been advanced for a number of purposes. We propose here that such a facility could also have an important role for low-latency telerobotic control of lunar surface equipment, both for lunar science and development. With distances of about 60,000 km from the lunar surface, such sites offer light-time limited two-way control latencies of order 400 ms, making telerobotic control for those sites close to real time as perceived by a human operator. We point out that even for transcontinental teleoperated surgical procedures, which require operational precision and highly dexterous manipulation, control latencies of this order are considered adequate. Terrestrial telerobots that are used routinely for mining and manufacturing also involve control latencies of order several hundred milliseconds. For this reason, an Earth-Moon LI or L2 control node could build on the technology and experience base of commercially proven terrestrial ventures. A lunar libration-point telerobotic node could demonstrate exploration strategies that would eventually be used on Mars, and many other less hospitable destinations in the solar system. Libration-point telepresence for the Moon contrasts with lunar telerobotic control from the Earth, for which two-way control latencies are at least six times longer. For control latencies that long, telerobotic control efforts are of the "move-and-wait" variety, which is cognitively inferior to near real-time control.

  11. Host transcript accumulation during lytic KSHV infection reveals several classes of host responses.

    Directory of Open Access Journals (Sweden)

    Sanjay Chandriani

    Full Text Available Lytic infection by Kaposi's sarcoma-associated herpesvirus (KSHV is associated with an extensive shutoff of host gene expression, mediated chiefly by accelerated mRNA turnover due to expression of the viral SOX protein. We have previously identified a small number of host mRNAs that can escape SOX-mediated degradation. Here we present a detailed, transcriptome-wide analysis of host shutoff, with careful microarray normalization to allow rigorous determination of the magnitude and extent of transcript loss. We find that the extent of transcript reduction represents a continuum of susceptibilities of transcripts to virus-mediated shutoff. Our results affirm that the levels of over 75% of host transcripts are substantially reduced during lytic infection, but also show that another approximately 20% of cellular mRNAs declines only slightly (less than 2-fold during the course of infection. Approximately 2% of examined cellular genes are strongly upregulated during lytic infection, most likely due to transcriptional induction of mRNAs that display intrinsic SOX-resistance.

  12. Latency in Distributed Acquisition and Rendering for Telepresence Systems.

    Science.gov (United States)

    Ohl, Stephan; Willert, Malte; Staadt, Oliver

    2015-12-01

    Telepresence systems use 3D techniques to create a more natural human-centered communication over long distances. This work concentrates on the analysis of latency in telepresence systems where acquisition and rendering are distributed. Keeping latency low is important to immerse users in the virtual environment. To better understand latency problems and to identify the source of such latency, we focus on the decomposition of system latency into sub-latencies. We contribute a model of latency and show how it can be used to estimate latencies in a complex telepresence dataflow network. To compare the estimates with real latencies in our prototype, we modify two common latency measurement methods. This presented methodology enables the developer to optimize the design, find implementation issues and gain deeper knowledge about specific sources of latency.

  13. A Simulation Base Investigation of High Latency Space Systems Operations

    Science.gov (United States)

    Li, Zu Qun; Crues, Edwin Z.; Bielski, Paul; Moore, Michael

    2017-01-01

    NASA's human space program has developed considerable experience with near Earth space operations. Although NASA has experience with deep space robotic missions, NASA has little substantive experience with human deep space operations. Even in the Apollo program, the missions lasted only a few weeks and the communication latencies were on the order of seconds. Human missions beyond the relatively close confines of the Earth-Moon system will involve missions with durations measured in months and communications latencies measured in minutes. To minimize crew risk and to maximize mission success, NASA needs to develop a better understanding of the implications of these types of mission durations and communication latencies on vehicle design, mission design and flight controller interaction with the crew. To begin to address these needs, NASA performed a study using a physics-based subsystem simulation to investigate the interactions between spacecraft crew and a ground-based mission control center for vehicle subsystem operations across long communication delays. The simulation, built with a subsystem modeling tool developed at NASA's Johnson Space Center, models the life support system of a Mars transit vehicle. The simulation contains models of the cabin atmosphere and pressure control system, electrical power system, drinking and waste water systems, internal and external thermal control systems, and crew metabolic functions. The simulation has three interfaces: 1) a real-time crew interface that can be use to monitor and control the vehicle subsystems; 2) a mission control center interface with data transport delays up to 15 minutes each way; 3) a real-time simulation test conductor interface that can be use to insert subsystem malfunctions and observe the interactions between the crew, ground, and simulated vehicle. The study was conducted at the 21st NASA Extreme Environment Mission Operations (NEEMO) mission between July 18th and Aug 3rd of year 2016. The NEEMO

  14. Short REM latency in impotence without depression.

    Science.gov (United States)

    Schmidt, H S; Nofzinger, E A

    1988-05-01

    In a retrospective study, the presence of depression was studied in a group of 14 impotent patients who were selected on the basis of the similarity between their electroencephalographic (EEG) sleep patterns and those of patients with endogenous depression. Specifically, the value of rapid eye movement (REM) latency plus age less than 100 was used as a selection criterion. Sleep continuity disturbances, increased REM time, and increased REM% were noted in the short REM latency impotent group. On the basis of MMPI and psychiatric history and interview, only one of these impotent patients showed major depression. The authors conclude that impotent patients with a short REM latency are not, as a group, depressed and that the incidence of depression in impotent men should be determined irrespective of EEG sleep findings.

  15. Reduced-Latency SC Polar Decoder Architectures

    CERN Document Server

    Zhang, Chuan; Parhi, Keshab K

    2011-01-01

    Polar codes have become one of the most favorable capacity achieving error correction codes (ECC) along with their simple encoding method. However, among the very few prior successive cancellation (SC) polar decoder designs, the required long code length makes the decoding latency high. In this paper, conventional decoding algorithm is transformed with look-ahead techniques. This reduces the decoding latency by 50%. With pipelining and parallel processing schemes, a parallel SC polar decoder is proposed. Sub-structure sharing approach is employed to design the merged processing element (PE). Moreover, inspired by the real FFT architecture, this paper presents a novel input generating circuit (ICG) block that can generate additional input signals for merged PEs on-the-fly. Gate-level analysis has demonstrated that the proposed design shows advantages of 50% decoding latency and twice throughput over the conventional one with similar hardware cost.

  16. MicroRNA-155 Reinforces HIV Latency*

    Science.gov (United States)

    Ruelas, Debbie S.; Chan, Jonathan K.; Oh, Eugene; Heidersbach, Amy J.; Hebbeler, Andrew M.; Chavez, Leonard; Verdin, Eric; Rape, Michael; Greene, Warner C.

    2015-01-01

    The presence of a small number of infected but transcriptionally dormant cells currently thwarts a cure for the more than 35 million individuals infected with HIV. Reactivation of these latently infected cells may result in three fates: 1) cell death due to a viral cytopathic effect, 2) cell death due to immune clearance, or 3) a retreat into latency. Uncovering the dynamics of HIV gene expression and silencing in the latent reservoir will be crucial for developing an HIV-1 cure. Here we identify and characterize an intracellular circuit involving TRIM32, an HIV activator, and miR-155, a microRNA that may promote a return to latency in these transiently activated reservoir cells. Notably, we demonstrate that TRIM32, an E3 ubiquitin ligase, promotes reactivation from latency by directly modifying IκBα, leading to a novel mechanism of NF-κB induction not involving IκB kinase activation. PMID:25873391

  17. A Readout Mechanism for Latency Codes

    Science.gov (United States)

    Zohar, Oran; Shamir, Maoz

    2016-01-01

    Response latency has been suggested as a possible source of information in the central nervous system when fast decisions are required. The accuracy of latency codes was studied in the past using a simplified readout algorithm termed the temporal-winner-take-all (tWTA). The tWTA is a competitive readout algorithm in which populations of neurons with a similar decision preference compete, and the algorithm selects according to the preference of the population that reaches the decision threshold first. It has been shown that this algorithm can account for accurate decisions among a small number of alternatives during short biologically relevant time periods. However, one of the major points of criticism of latency codes has been that it is unclear how can such a readout be implemented by the central nervous system. Here we show that the solution to this long standing puzzle may be rather simple. We suggest a mechanism that is based on reciprocal inhibition architecture, similar to that of the conventional winner-take-all, and show that under a wide range of parameters this mechanism is sufficient to implement the tWTA algorithm. This is done by first analyzing a rate toy model, and demonstrating its ability to discriminate short latency differences between its inputs. We then study the sensitivity of this mechanism to fine-tuning of its initial conditions, and show that it is robust to wide range of noise levels in the initial conditions. These results are then generalized to a Hodgkin-Huxley type of neuron model, using numerical simulations. Latency codes have been criticized for requiring a reliable stimulus-onset detection mechanism as a reference for measuring latency. Here we show that this frequent assumption does not hold, and that, an additional onset estimator is not needed to trigger this simple tWTA mechanism.

  18. Latency and Jitter Analysis for IEEE 802.11e Wireless LANs

    Directory of Open Access Journals (Sweden)

    Sungkwan Youm

    2013-01-01

    Full Text Available This paper presents a numerical analysis of latency and jitter for IEEE 802.11e wireless local area networks (WLANs in a saturation condition, by using a Markov model. We use this model to explicate how the enhanced distributed coordination function (EDCF differentiates classes of service and to characterize the probability distribution of the medium access control (MAC layer packet latency and jitter, on which the quality of the voice over Internet protocol (VoIP calls is dependent. From the proposed analytic model, we can estimate the available number of nodes determining the system performance, in order to satisfy user demands on the latency and jitter.

  19. Antibodies against lytic and latent Kaposi's sarcoma-associated herpes virus antigens and lymphoma in the European EpiLymph case–control study

    Science.gov (United States)

    Benavente, Y; Mbisa, G; Labo, N; Casabonne, D; Becker, N; Maynadie, M; Foretova, L; Cocco, P L; Nieters, A; Staines, A; Bofetta, P; Brennan, P; Whitby, D; de Sanjosé, S

    2011-01-01

    Background: Kaposi's sarcoma-associated herpes virus is associated with primary effusion lymphoma and multicentric Castleman's disease. Methods: Seropositivity to lytic and latent Kaposi's sarcoma herpes virus (KSHV) antigens were examined in 2083 lymphomas and 2013 controls from six European countries. Results: Antibodies against KSHV latent and lytic antigens were detectable in 4.5% and 3.4% of controls, respectively, and 3.6% of cases (P>0.05). The KSHV seropositivity was associated with splenic marginal zone lymphoma (SMZL) (odds ratio (OR)=4.11, 95% confidence interval (CI)=1.57–10.83) and multiple myeloma (OR=0.31, 95% CI=0.11–0.85). Conclusion: The KSHV is unlikely to contribute importantly to lymphomagenesis among immunocompetent subjects. However, the observed association with SMZL may underline a chronic antigen mechanism in its aetiology. PMID:21952625

  20. Long Latency Auditory Evoked Potentials during Meditation.

    Science.gov (United States)

    Telles, Shirley; Deepeshwar, Singh; Naveen, Kalkuni Visweswaraiah; Pailoor, Subramanya

    2015-10-01

    The auditory sensory pathway has been studied in meditators, using midlatency and short latency auditory evoked potentials. The present study evaluated long latency auditory evoked potentials (LLAEPs) during meditation. Sixty male participants, aged between 18 and 31 years (group mean±SD, 20.5±3.8 years), were assessed in 4 mental states based on descriptions in the traditional texts. They were (a) random thinking, (b) nonmeditative focusing, (c) meditative focusing, and (d) meditation. The order of the sessions was randomly assigned. The LLAEP components studied were P1 (40-60 ms), N1 (75-115 ms), P2 (120-180 ms), and N2 (180-280 ms). For each component, the peak amplitude and peak latency were measured from the prestimulus baseline. There was significant decrease in the peak latency of the P2 component during and after meditation (Pmeditation facilitates the processing of information in the auditory association cortex, whereas the number of neurons recruited was smaller in random thinking and non-meditative focused thinking, at the level of the secondary auditory cortex, auditory association cortex and anterior cingulate cortex.

  1. THE PEAK LATENCY OF ORBITAL PRESACCADIC SPIKE POTENTIAL WITH HORIZONTAL EYE MOVEMENTS

    Institute of Scientific and Technical Information of China (English)

    单扬; MarkL.Moster; RichardA.Roemer[

    1996-01-01

    Purpose.To investigate the peak latency of the orbital presaccedic spike potential (SP) with horizontal eyemovement in normals.Methods. Orbital SP was recorded in 28 normal subjects from 8 electrodes around the eyes with Pz as the reference while performing 5°,10°,20°,30° and 40° horizontal saccedes to visual targets. SP peak latencywas measured from SP onset to SP peak on averaged data aligned on SP peak.Re,Its. Significant main effects on SP peak latency are found for saccade size (P0. 05). No significant main effect on SP peak htency is found for eye (P>0. 05). SP peak latency increases with increasing saccade size from 5° to 40°. SP peak latency is longer with saccades back to center than away from center, and with abducting saccades than with adducting saccades. SP peak latency differs at the electrode sites with an order from shorter to longer as follows; innercanth° (IC); inferior orbit (IO); outer canthus (OC); superior orbit (SO).Conclusions. The effects on the peak latency of orbital SP can be explained by the saccade dynamic property, volume conduction as weft as physiologic and anatomic factors of the eyes and orbits. The peak latency of orbital SP can be used to reflect the temporal characteristics of ocular motor units controlling saccedic eye movement.

  2. Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter

    Directory of Open Access Journals (Sweden)

    John Sinclair

    2013-06-01

    Full Text Available Lytic infection of differentiated cell types with human cytomegalovirus (HCMV results in the temporal expression of between 170–200 open reading frames (ORFs. A number of studies have demonstrated the temporal regulation of these ORFs and that this is orchestrated by both viral and cellular mechanisms associated with the co-ordinated recruitment of transcription complexes and, more recently, higher order chromatin structure. Importantly, HCMV, like all herpes viruses, establishes a lifelong latent infection of the host—one major site of latency being the undifferentiated haematopoietic progenitor cells resident in the bone marrow. Crucially, the establishment of latency is concomitant with the recruitment of cellular enzymes that promote extensive methylation of histones bound to the major immediate early promoter. As such, the repressive chromatin structure formed at the major immediate early promoter (MIEP elicits inhibition of IE gene expression and is a major factor involved in maintenance of HCMV latency. However, it is becoming increasingly clear that a distinct subset of viral genes is also expressed during latency. In this review, we will discuss the mechanisms that control the expression of these latency-associated transcripts and illustrate that regulation of these latency-associated promoters is also subject to chromatin mediated regulation and that the instructive observations previously reported regarding the negative regulation of the MIEP during latency are paralleled in the regulation of latent gene expression.

  3. Advanced techniques for the analysis of crisis stability, deterrence, and latency

    Energy Technology Data Exchange (ETDEWEB)

    Canavan, G.H.

    1997-12-01

    Studies on crisis stability, deterrence, and latency are presented in chronological order, which also reflects their logical order of development, captures the main features of stability analysis; relates first strike, crisis, and arms control stability as seen from US and Russian perspective; and addresses questions such as whether uncertainty in damage preference or defense deployment can be destabilizing. It illustrates the problems with alternative metrics, latency and reconstitution, and deep unilateral and proportional force reductions.

  4. Therapeutics for HIV-1 reactivation from latency.

    Science.gov (United States)

    Sgarbanti, Marco; Battistini, Angela

    2013-08-01

    Intensive combined antiretroviral therapy successfully suppresses HIV-1 replication and AIDS disease progression making infection manageable, but it is unable to eradicate the virus that persists in long-lived, drug-insensitive and immune system-insensitive reservoirs thus asking for life-long treatments with problems of compliance, resistance, toxicity and cost. These limitations and recent insights into latency mechanisms have fueled a renewed effort in finding a cure for HIV-1 infection. Proposed eradication strategies involve reactivation of the latent reservoir upon induction of viral transcription followed by the elimination of reactivated virus-producing cells by viral cytopathic effect or host immune response. Several molecules identified by mechanism-directed approaches or in large-scale screenings have been proposed as latency reversing agents. Some of them have already entered clinical testing in humans but with mixed or unsatisfactory results.

  5. Arbitration in crossbar interconnect for low latency

    Energy Technology Data Exchange (ETDEWEB)

    Ohmacht, Martin; Sugavanam, Krishnan

    2013-02-05

    A system and method and computer program product for reducing the latency of signals communicated through a crossbar switch, the method including using at slave arbitration logic devices associated with Slave devices for which access is requested from one or more Master devices, two or more priority vector signals cycled among their use every clock cycle for selecting one of the requesting Master devices and updates the respective priority vector signal used every clock cycle. Similarly, each Master for which access is requested from one or more Slave devices, can have two or more priority vectors and can cycle among their use every clock cycle to further reduce latency and increase throughput performance via the crossbar.

  6. Arbitration in crossbar interconnect for low latency

    Science.gov (United States)

    Ohmacht, Martin; Sugavanam, Krishnan

    2013-02-05

    A system and method and computer program product for reducing the latency of signals communicated through a crossbar switch, the method including using at slave arbitration logic devices associated with Slave devices for which access is requested from one or more Master devices, two or more priority vector signals cycled among their use every clock cycle for selecting one of the requesting Master devices and updates the respective priority vector signal used every clock cycle. Similarly, each Master for which access is requested from one or more Slave devices, can have two or more priority vectors and can cycle among their use every clock cycle to further reduce latency and increase throughput performance via the crossbar.

  7. Neuronal IFN signaling is dispensable for the establishment of HSV-1 latency.

    Science.gov (United States)

    Rosato, Pamela C; Katzenell, Sarah; Pesola, Jean M; North, Brian; Coen, Donald M; Leib, David A

    2016-10-01

    IFN responses control acute HSV infection, but their role in regulating HSV latency is poorly understood. To address this we used mice lacking IFN signaling specifically in neural tissues. These mice supported a higher acute viral load in nervous tissue and delayed establishment of latency. While latent HSV-1 genome copies were equivalent, ganglia from neuronal IFN signaling-deficient mice unexpectedly supported reduced reactivation. IFNβ promoted survival of primary sensory neurons after infection with HSV-1, indicating a role for IFN signaling in sustaining neurons. We observed higher levels of latency associated transcripts (LATs) per HSV genome in mice lacking neuronal IFN signaling, consistent with a role for IFN in regulating LAT expression. These data show that neuronal IFN signaling modulates the expression of LAT and may conserve the pool of neurons available to harbor latent HSV-1 genome. The data also show that neuronal IFN signaling is dispensable for the establishment of latency.

  8. The determination of the link with the smallest end-to-end network latency in ethernet architecture

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Ethernet fundamental and its data transmission model are introduced in brief and end-to-end network latency was analyzed in this paper. On the premise of not considering transmission quality and transmission cost, latency was the function of the rest of network resource parameter (NRP). The relation between the number of nodes and that of end-to-end links was presented. In ethernet architecture, the algorithm to determine the link with the smallest latency is a polynomial issue when the number of network nodes is limited, so it can be solved by way of polynomial equations. Latency measuring is the key issue to determine the link with the smallest network latency. 3-node brigade (regiment) level network centric warfare (NCW) demonstration platform was studied and the latency between the detectors and weapon control stations was taken as an example. The algorithm of end-to-end network latency and link information in NCW was presented. The algorithm program based on Server/Client architecture was developed. The data transmission optimal link is one whose end-to-end latency is the smallest. This paper solves the key issue to determine the link whose end-to-end latency is the smallest in ethernet architecture. The study can be widely applied to determine the optimal link which is in the complex network environment of multiple service provision points.

  9. Detecting Intermediary Hosts by TCP Latency Measurements

    Science.gov (United States)

    Singh, Gurvinder; Eian, Martin; Willassen, Svein Y.; Mjølsnes, Stig Fr.

    Use of intermediary hosts as stepping stones to conceal tracks is common in Internet misuse. It is therefore desirable to find a method to detect whether the originating party is using an intermediary host. Such a detection technique would allow the activation of a number of countermeasures that would neutralize the effects of misuse, and make it easier to trace a perpetrator. This work explores a new approach in determining if a host communicating via TCP is the data originator or if it is acting as a mere TCP proxy. The approach is based on measuring the inter packet arrival time at the receiving end of the connection only, and correlating the observed results with the network latency between the receiver and the proxy. The results presented here indicate that determining the use of a proxy host is possible, if the network latency between the originator and proxy is larger than the network latency between the proxy and the receiver. We show that this technique has potential to be used to detect connections were data is sent through a TCP proxy, such as remote login through TCP proxies, or rejecting spam sent through a bot network.

  10. Glomerular latency coding in artificial olfaction

    Directory of Open Access Journals (Sweden)

    Jaber eAl Yamani

    2012-01-01

    Full Text Available Sensory perception results from the way sensory information is subsequently transformed in the brain. Olfaction is a typical example in which odor representations undergo considerable changes as they pass from olfactory receptor neurons (ORNs to second-order neurons. First, many ORNs expressing the same receptor protein yet presenting heterogeneous dose-response properties converge onto individually identifiable glomeruli. Second, onset latency of glomerular activation is believed to play a role in encoding odor quality and quantity in the context of fast information processing. Taking inspiration from the olfactory pathway, we designed a simple yet robust glomerular latency coding scheme for processing gas sensor data. The proposed bio-inspired approach was evaluated using an in-house Sn02 sensor array. Glomerular convergence was achieved by noting the possible analogy between receptor protein expressed in ORNs and metal catalyst used across the fabricated gas sensor array. Ion implantation was another technique used to account both for sensor heterogeneity and enhanced sensitivity. The response of the gas sensor array was mapped into glomerular latency patterns, whose rank order is concentration-invariant. Gas recognition was achieved by simply looking for a match within a library of spatio-temporal spike fingerprints. Because of its simplicity, this approach enables the integration of sensing and processing onto a single-chip.

  11. HIV-1 Latency in Monocytes/Macrophages

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2014-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

  12. MicroRNA-155 Reinforces HIV Latency.

    Science.gov (United States)

    Ruelas, Debbie S; Chan, Jonathan K; Oh, Eugene; Heidersbach, Amy J; Hebbeler, Andrew M; Chavez, Leonard; Verdin, Eric; Rape, Michael; Greene, Warner C

    2015-05-29

    The presence of a small number of infected but transcriptionally dormant cells currently thwarts a cure for the more than 35 million individuals infected with HIV. Reactivation of these latently infected cells may result in three fates: 1) cell death due to a viral cytopathic effect, 2) cell death due to immune clearance, or 3) a retreat into latency. Uncovering the dynamics of HIV gene expression and silencing in the latent reservoir will be crucial for developing an HIV-1 cure. Here we identify and characterize an intracellular circuit involving TRIM32, an HIV activator, and miR-155, a microRNA that may promote a return to latency in these transiently activated reservoir cells. Notably, we demonstrate that TRIM32, an E3 ubiquitin ligase, promotes reactivation from latency by directly modifying IκBα, leading to a novel mechanism of NF-κB induction not involving IκB kinase activation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Kaposi's Sarcoma-Associated Herpesvirus (KSHV Induces the Oncogenic miR-17-92 Cluster and Down-Regulates TGF-β Signaling.

    Directory of Open Access Journals (Sweden)

    Hong Seok Choi

    Full Text Available KSHV is a DNA tumor virus that causes Kaposi's sarcoma. Upon KSHV infection, only a limited number of latent genes are expressed. We know that KSHV infection regulates host gene expression, and hypothesized that latent genes also modulate the expression of host miRNAs. Aberrant miRNA expression contributes to the development of many types of cancer. Array-based miRNA profiling revealed that all six miRNAs of the oncogenic miR-17-92 cluster are up-regulated in KSHV infected endothelial cells. Among candidate KSHV latent genes, we found that vFLIP and vCyclin were shown to activate the miR-17-92 promoter, using luciferase assay and western blot analysis. The miR-17-92 cluster was previously shown to target TGF-β signaling. We demonstrate that vFLIP and vCyclin induce the expression of the miR-17-92 cluster to strongly inhibit the TGF-β signaling pathway by down-regulating SMAD2. Moreover, TGF-β activity and SMAD2 expression were fully restored when antagomirs (inhibitors of miR-17-92 cluster were transfected into cells expressing either vFLIP or vCyclin. In addition, we utilized viral genetics to produce vFLIP or vCyclin knock-out viruses, and studied the effects in infected TIVE cells. Infection with wildtype KSHV abolished expression of SMAD2 protein in these endothelial cells. While single-knockout mutants still showed a marked reduction in SMAD2 expression, TIVE cells infected by a double-knockout mutant virus were fully restored for SMAD2 expression, compared to non-infected TIVE cells. Expression of either vFLIP or vCycIin was sufficient to downregulate SMAD2. In summary, our data demonstrate that vFLIP and vCyclin induce the oncogenic miR-17-92 cluster in endothelial cells and thereby interfere with the TGF-β signaling pathway. Manipulation of the TGF-β pathway via host miRNAs represents a novel mechanism that may be important for KSHV tumorigenesis and angiogenesis, a hallmark of KS.

  14. Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Induces the Oncogenic miR-17-92 Cluster and Down-Regulates TGF-β Signaling

    Science.gov (United States)

    Choi, Hong Seok; Jain, Vaibhav; Krueger, Brian; Marshall, Vickie; Kim, Chang Hee; Shisler, Joanna L.; Whitby, Denise; Renne, Rolf

    2015-01-01

    KSHV is a DNA tumor virus that causes Kaposi’s sarcoma. Upon KSHV infection, only a limited number of latent genes are expressed. We know that KSHV infection regulates host gene expression, and hypothesized that latent genes also modulate the expression of host miRNAs. Aberrant miRNA expression contributes to the development of many types of cancer. Array-based miRNA profiling revealed that all six miRNAs of the oncogenic miR-17-92 cluster are up-regulated in KSHV infected endothelial cells. Among candidate KSHV latent genes, we found that vFLIP and vCyclin were shown to activate the miR-17-92 promoter, using luciferase assay and western blot analysis. The miR-17-92 cluster was previously shown to target TGF-β signaling. We demonstrate that vFLIP and vCyclin induce the expression of the miR-17-92 cluster to strongly inhibit the TGF-β signaling pathway by down-regulating SMAD2. Moreover, TGF-β activity and SMAD2 expression were fully restored when antagomirs (inhibitors) of miR-17-92 cluster were transfected into cells expressing either vFLIP or vCyclin. In addition, we utilized viral genetics to produce vFLIP or vCyclin knock-out viruses, and studied the effects in infected TIVE cells. Infection with wildtype KSHV abolished expression of SMAD2 protein in these endothelial cells. While single-knockout mutants still showed a marked reduction in SMAD2 expression, TIVE cells infected by a double-knockout mutant virus were fully restored for SMAD2 expression, compared to non-infected TIVE cells. Expression of either vFLIP or vCycIin was sufficient to downregulate SMAD2. In summary, our data demonstrate that vFLIP and vCyclin induce the oncogenic miR-17-92 cluster in endothelial cells and thereby interfere with the TGF-β signaling pathway. Manipulation of the TGF-β pathway via host miRNAs represents a novel mechanism that may be important for KSHV tumorigenesis and angiogenesis, a hallmark of KS. PMID:26545119

  15. Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Induces the Oncogenic miR-17-92 Cluster and Down-Regulates TGF-β Signaling.

    Science.gov (United States)

    Choi, Hong Seok; Jain, Vaibhav; Krueger, Brian; Marshall, Vickie; Kim, Chang Hee; Shisler, Joanna L; Whitby, Denise; Renne, Rolf

    2015-01-01

    KSHV is a DNA tumor virus that causes Kaposi's sarcoma. Upon KSHV infection, only a limited number of latent genes are expressed. We know that KSHV infection regulates host gene expression, and hypothesized that latent genes also modulate the expression of host miRNAs. Aberrant miRNA expression contributes to the development of many types of cancer. Array-based miRNA profiling revealed that all six miRNAs of the oncogenic miR-17-92 cluster are up-regulated in KSHV infected endothelial cells. Among candidate KSHV latent genes, we found that vFLIP and vCyclin were shown to activate the miR-17-92 promoter, using luciferase assay and western blot analysis. The miR-17-92 cluster was previously shown to target TGF-β signaling. We demonstrate that vFLIP and vCyclin induce the expression of the miR-17-92 cluster to strongly inhibit the TGF-β signaling pathway by down-regulating SMAD2. Moreover, TGF-β activity and SMAD2 expression were fully restored when antagomirs (inhibitors) of miR-17-92 cluster were transfected into cells expressing either vFLIP or vCyclin. In addition, we utilized viral genetics to produce vFLIP or vCyclin knock-out viruses, and studied the effects in infected TIVE cells. Infection with wildtype KSHV abolished expression of SMAD2 protein in these endothelial cells. While single-knockout mutants still showed a marked reduction in SMAD2 expression, TIVE cells infected by a double-knockout mutant virus were fully restored for SMAD2 expression, compared to non-infected TIVE cells. Expression of either vFLIP or vCycIin was sufficient to downregulate SMAD2. In summary, our data demonstrate that vFLIP and vCyclin induce the oncogenic miR-17-92 cluster in endothelial cells and thereby interfere with the TGF-β signaling pathway. Manipulation of the TGF-β pathway via host miRNAs represents a novel mechanism that may be important for KSHV tumorigenesis and angiogenesis, a hallmark of KS.

  16. The viral KSHV chemokine vMIP-II inhibits the migration of Naive and activated human NK cells by antagonizing two distinct chemokine receptors.

    Directory of Open Access Journals (Sweden)

    Rachel Yamin

    2013-08-01

    Full Text Available Natural killer (NK cells are innate immune cells able to rapidly kill virus-infected and tumor cells. Two NK cell populations are found in the blood; the majority (90% expresses the CD16 receptor and also express the CD56 protein in intermediate levels (CD56(Dim CD16(Pos while the remaining 10% are CD16 negative and express CD56 in high levels (CD56(Bright CD16(Neg. NK cells also reside in some tissues and traffic to various infected organs through the usage of different chemokines and chemokine receptors. Kaposi's sarcoma-associated herpesvirus (KSHV is a human virus that has developed numerous sophisticated and versatile strategies to escape the attack of immune cells such as NK cells. Here, we investigate whether the KSHV derived cytokine (vIL-6 and chemokines (vMIP-I, vMIP-II, vMIP-III affect NK cell activity. Using transwell migration assays, KSHV infected cells, as well as fusion and recombinant proteins, we show that out of the four cytokine/chemokines encoded by KSHV, vMIP-II is the only one that binds to the majority of NK cells, affecting their migration. We demonstrate that vMIP-II binds to two different receptors, CX3CR1 and CCR5, expressed by naïve CD56(Dim CD16(Pos NK cells and activated NK cells, respectively. Furthermore, we show that the binding of vMIP-II to CX3CR1 and CCR5 blocks the binding of the natural ligands of these receptors, Fractalkine (Fck and RANTES, respectively. Finally, we show that vMIP-II inhibits the migration of naïve and activated NK cells towards Fck and RANTES. Thus, we present here a novel mechanism in which KSHV uses a unique protein that antagonizes the activity of two distinct chemokine receptors to inhibit the migration of naïve and activated NK cells.

  17. Data latency and the user community

    Science.gov (United States)

    Escobar, V. M.; Brown, M. E.; Carroll, M.

    2013-12-01

    The community using NASA Earth science observations in applications has grown significantly, with increasing sophistication to serve national interests. The National Research Council's Earth Science Decadal Survey report stated that the planning for applied and operational considerations in the missions should accompany the acquisition of new knowledge about Earth (NRC, 2007). This directive has made product applications at NASA an integral part of converting the data collected into actionable knowledge that can be used to inform policy. However, successfully bridging scientific research with operational decision making in different application areas requires looking into user data requirements and operational needs. This study was conducted to determine how users are incorporating NASA data into applications and operational processes. The approach included a review of published materials, direct interviews with mission representatives, and an online professional review, which was distributed to over 6000 individuals. We provide a complete description of the findings with definitions and explanations of what goes into measuring latency as well as how users and applications utilize NASA data products. We identified 3 classes of users: operational (need data in 3 hours or less), near real time (need data within a day of acquisition), and scientific users (need highest quality data, time independent). We also determined that most users with applications are interested in specific types of products that may come from multiple missions. These users will take the observations when they are available, however the observations may have additional applications value if they are available either by a certain time of day or within a period of time after acquisition. NASA has supported the need for access to low latency data on an ad-hoc basis and more substantively in stand-alone systems such as the MODIS Rapid Response system and more recently with LANCE. The increased level

  18. Genetic variants in RBFOX3 are associated with sleep latency

    NARCIS (Netherlands)

    Amin, Najaf; Allebrandt, Karla V.; van der Spek, Ashley; Mueller-Myhsok, Bertram; Hek, Karin; Teder-Laving, Maris; Hayward, Caroline; Esko, Tonu; van Mill, Josine G.; Mbarek, Hamdi; Watson, Nathaniel F.; Melville, Scott A.; Del Greco, Fabiola M.; Byrne, Enda M.; Oole, Edwin; Kolcic, Ivana; Chen, Ting-hsu; Evans, Daniel S.; Coresh, Josef; Vogelzangs, Nicole; Karjalainen, Juha; Willemsen, Gonneke; Gharib, Sina A.; Zgaga, Lina; Mihailov, Evelin; Stone, Katie L.; Campbell, Harry; Brouwer, Rutger Ww; Demirkan, Ayse; Isaacs, Aaron; Dogas, Zoran; Marciante, Kristin D.; Campbell, Susan; Borovecki, Fran; Luik, Annemarie I.; Li, Man; Hottenga, Jouke Jan; Huffman, Jennifer E.; van den Hout, Mirjam C. G. N.; Cummings, Steven R.; Aulchenko, Yuru S.; Gehrman, Philip R.; Uitterlinden, Andre G.; Wichmann, Heinz-Erich; Muller-Nurasyid, Martina; Fehrmann, Rudolf S. N.; Montgomery, Grant W.; Hofman, Albert; Kao, Wen Hong Linda; Oostra, Ben A.; Wright, Alan F.; Vink, Jacqueline M.; Wilson, James F.; Pramstaller, Peter P.; Hicks, Andrew A.; Polasek, Ozren; Punjabi, Naresh M.; Redline, Susan; Psaty, Bruce M.; Heath, Andrew C.; Merrow, Martha; Tranah, Gregory J.; Gottlieb, Daniel J.; Boomsma, Dorret I.; Martin, Nicholas G.; Rudan, Igor; Tiemeier, Henning; van IJcken, Wilfred F. J.; Penninx, Brenda W.; Metspalu, Andres; Meitinger, Thomas; Franke, Lude; Roenneberg, Till; van Duijn, Cornelia M.

    2016-01-01

    Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We

  19. Reducing audio stimulus presentation latencies across studies, laboratories, and hardware and operating system configurations.

    Science.gov (United States)

    Babjack, Destiny L; Cernicky, Brandon; Sobotka, Andrew J; Basler, Lee; Struthers, Devon; Kisic, Richard; Barone, Kimberly; Zuccolotto, Anthony P

    2015-09-01

    Using differing computer platforms and audio output devices to deliver audio stimuli often introduces (1) substantial variability across labs and (2) variable time between the intended and actual sound delivery (the sound onset latency). Fast, accurate audio onset latencies are particularly important when audio stimuli need to be delivered precisely as part of studies that depend on accurate timing (e.g., electroencephalographic, event-related potential, or multimodal studies), or in multisite studies in which standardization and strict control over the computer platforms used is not feasible. This research describes the variability introduced by using differing configurations and introduces a novel approach to minimizing audio sound latency and variability. A stimulus presentation and latency assessment approach is presented using E-Prime and Chronos (a new multifunction, USB-based data presentation and collection device). The present approach reliably delivers audio stimuli with low latencies that vary by ≤1 ms, independent of hardware and Windows operating system (OS)/driver combinations. The Chronos audio subsystem adopts a buffering, aborting, querying, and remixing approach to the delivery of audio, to achieve a consistent 1-ms sound onset latency for single-sound delivery, and precise delivery of multiple sounds that achieves standard deviations of 1/10th of a millisecond without the use of advanced scripting. Chronos's sound onset latencies are small, reliable, and consistent across systems. Testing of standard audio delivery devices and configurations highlights the need for careful attention to consistency between labs, experiments, and multiple study sites in their hardware choices, OS selections, and adoption of audio delivery systems designed to sidestep the audio latency variability issue.

  20. Clinical value of ipsi- and contralateral sacral reflex latency measurement: a normative data study in man.

    Science.gov (United States)

    Amarenco, G; Kerdraon, J

    2000-01-01

    The latency of the bulbocavernosus reflex (BCR) evoked by electrical stimulation of the penis provides a measure of the conduction velocity over the sacral reflex arc at the S2-4 level but does not allow evaluation of the side affected since it results from the simultaneous excitation of both dorsal nerves of the penis (DNP) at the penile root. To evaluate the reliability of the side-to-side BCR latency measurement, this study compared the reflex characteristics of the response elicited by both DNP stimulation and unilateral DNP block. After a unilateral selective DNP anesthesic block, we found that the early response of the contralateral BCR is strictly ipsilateral with no differences in terms of latency, morphology, and reflex threshold from controls. This result may indicate that the side-to-side BCR latency measurement allows a comparative study of the respective right and left sacral reflex arcs in men. We found a mean inter-latency difference of 1.8 +/- 0.4 millisecond of the early BCR response after simultaneous recording of the right and left sides in 10 normal men. We established that an inter-latency difference >3 milliseconds may be indicative of a significant alteration in the conduction over the sacral reflex arc.

  1. Long-latency reflexes account for limb biomechanics through several supraspinal pathways

    Directory of Open Access Journals (Sweden)

    Isaac Louis Kurtzer

    2015-01-01

    Full Text Available Accurate control of body posture is enforced by a multitude of corrective actions operating over a range of time scales. The earliest correction is the short-latency reflex which occurs between 20-45 ms following a sudden displacement of the limb and is generated entirely by spinal circuits. In contrast, voluntary reactions are generated by a highly distributed network but at a significantly longer delay after stimulus onset (greater than 100 ms. Between these two epochs is the long-latency reflex (around 50-100 ms which but acts more rapidly than of voluntary reactions but shares some supraspinal pathways and functional capabilities. In particular, the long-latency reflex accounts for the arm’s biomechanical properties rather than only responding to local muscle stretch like the short-latency reflex. This paper will review how the long-latency reflex accounts for the arm’s biomechanical properties and the supraspinal pathways supporting this ability. Relevant experimental paradigms include clinical studies, non-invasive brain stimulation, neural recordings in monkeys, and human behavioral studies. The sum of this effort indicates that primary motor cortex and reticular formation contribute to the the long-latency reflex either by generating or scaling its structured response appropriate for the arm’s biomechanics whereas the cerebellum scales the magnitude of the feedback response. Additional putative pathways are discussed as well as potential research lines.

  2. Low-Latency Science Exploration of Planetary Bodies: How ISS Might Be Used as Part of a Low-Latency Analog Campaign for Human Exploration

    Science.gov (United States)

    Thronson, Harley; Valinia, Azita; Bleacher, Jacob; Eigenbrode, Jennifer; Garvin, Jim; Petro, Noah

    2014-01-01

    We suggest that the International Space Station be used to examine the application and validation of low-latency telepresence for surface exploration from space as an alternative, precursor, or potentially as an adjunct to astronaut "boots on the ground." To this end, controlled experiments that build upon and complement ground-based analog field studies will be critical for assessing the effects of different latencies (0 to 500 milliseconds), task complexity, and alternate forms of feedback to the operator. These experiments serve as an example of a pathfinder for NASA's roadmap of missions to Mars with low-latency telerobotic exploration as a precursor to astronaut's landing on the surface to conduct geological tasks.

  3. Enhancements to the multiple sleep latency test

    Directory of Open Access Journals (Sweden)

    Meza-Vargas S

    2016-05-01

    Full Text Available Sonia Meza-Vargas, Eleni Giannouli, Magdy Younes Sleep Disorders Centre, University of Manitoba, Winnipeg, MB, Canada Introduction: The utility of multiple sleep latency tests (MSLTs is limited to determining sleep onset latency (SOL and rapid eye movement sleep latency. The odds ratio product (ORP is a continuous index of sleep depth with values of 0, 1.0, and 2.5 reflecting very deep sleep, light sleep, and full wakefulness, respectively. We determined the time course of sleep depth during MSLT naps expecting that this would enhance the test's clinical utility. Methods: Thirty MSLTs (150 naps were performed for excessive somnolence. Patients indicated whether they slept (yes/no after each nap. SOL was scored by two experienced technologists. Time course of ORP was determined with a commercial system. We determined ORP at SOL (ORPSOL, times ORP decreased <2.0, <1.5, <1.0 and <0.5 during the entire nap duration, and the integral of decrease in ORP over nap duration (ΔORPINT. Results: SOL occurred almost invariably when ORP was between 1.0 and 2.0. Of 47 naps (21 patients with SOL ,5 minutes, ORP decreased <1.0 (light sleep in <5 minutes in only 13 naps (nine patients and <0.5 (deep sleep in only two naps in one patient. The relation between ORPINT and frequency of sleep perception was well defined, allowing determination of a threshold for sleep perception. This threshold ranged widely (5–50 ΔORP*epoch. Conclusion: As currently identified, SOL reflects transition into a highly unstable state between wakefulness and sleep. Reporting the times of attaining different sleep depths may help better identify patients at high risk of vigilance loss. Furthermore, an ORPSOL outside the range 1.0–2.0 can help identify scoring errors. Keywords: odds ratio product, sleep perception, idiopathic hypersomnia

  4. CTCF prevents the epigenetic drift of EBV latency promoter Qp.

    Directory of Open Access Journals (Sweden)

    Italo Tempera

    Full Text Available The establishment and maintenance of Epstein-Barr Virus (EBV latent infection requires distinct viral gene expression programs. These gene expression programs, termed latency types, are determined largely by promoter selection, and controlled through the interplay between cell-type specific transcription factors, chromatin structure, and epigenetic modifications. We used a genome-wide chromatin-immunoprecipitation (ChIP assay to identify epigenetic modifications that correlate with different latency types. We found that the chromatin insulator protein CTCF binds at several key regulatory nodes in the EBV genome and may compartmentalize epigenetic modifications across the viral genome. Highly enriched CTCF binding sites were identified at the promoter regions upstream of Cp, Wp, EBERs, and Qp. Since Qp is essential for long-term maintenance of viral genomes in type I latency and epithelial cell infections, we focused on the role of CTCF in regulating Qp. Purified CTCF bound approximately 40 bp upstream of the EBNA1 binding sites located at +10 bp relative to the transcriptional initiation site at Qp. Mutagenesis of the CTCF binding site in EBV bacmids resulted in a decrease in the recovery of stable hygromycin-resistant episomes in 293 cells. EBV lacking the Qp CTCF site showed a decrease in Qp transcription initiation and a corresponding increase in Cp and Fp promoter utilization at 8 weeks post-transfection. However, by 16 weeks post-transfection, bacmids lacking CTCF sites had no detectable Qp transcription and showed high levels of histone H3 K9 methylation and CpG DNA methylation at the Qp initiation site. These findings provide direct genetic evidence that CTCF functions as a chromatin insulator that prevents the promiscuous transcription of surrounding genes and blocks the epigenetic silencing of an essential promoter, Qp, during EBV latent infection.

  5. CTCF prevents the epigenetic drift of EBV latency promoter Qp.

    Science.gov (United States)

    Tempera, Italo; Wiedmer, Andreas; Dheekollu, Jayaraju; Lieberman, Paul M

    2010-08-12

    The establishment and maintenance of Epstein-Barr Virus (EBV) latent infection requires distinct viral gene expression programs. These gene expression programs, termed latency types, are determined largely by promoter selection, and controlled through the interplay between cell-type specific transcription factors, chromatin structure, and epigenetic modifications. We used a genome-wide chromatin-immunoprecipitation (ChIP) assay to identify epigenetic modifications that correlate with different latency types. We found that the chromatin insulator protein CTCF binds at several key regulatory nodes in the EBV genome and may compartmentalize epigenetic modifications across the viral genome. Highly enriched CTCF binding sites were identified at the promoter regions upstream of Cp, Wp, EBERs, and Qp. Since Qp is essential for long-term maintenance of viral genomes in type I latency and epithelial cell infections, we focused on the role of CTCF in regulating Qp. Purified CTCF bound approximately 40 bp upstream of the EBNA1 binding sites located at +10 bp relative to the transcriptional initiation site at Qp. Mutagenesis of the CTCF binding site in EBV bacmids resulted in a decrease in the recovery of stable hygromycin-resistant episomes in 293 cells. EBV lacking the Qp CTCF site showed a decrease in Qp transcription initiation and a corresponding increase in Cp and Fp promoter utilization at 8 weeks post-transfection. However, by 16 weeks post-transfection, bacmids lacking CTCF sites had no detectable Qp transcription and showed high levels of histone H3 K9 methylation and CpG DNA methylation at the Qp initiation site. These findings provide direct genetic evidence that CTCF functions as a chromatin insulator that prevents the promiscuous transcription of surrounding genes and blocks the epigenetic silencing of an essential promoter, Qp, during EBV latent infection.

  6. (±)-Japonones A and B, two pairs of new enantiomers with anti-KSHV activities from Hypericum japonicum

    Science.gov (United States)

    Hu, Linzhen; Zhu, Hucheng; Li, Lei; Huang, Jinfeng; Sun, Weiguang; Liu, Junjun; Li, Hua; Luo, Zengwei; Wang, Jianping; Xue, Yongbo; Zhang, Yu; Zhang, Yonghui

    2016-06-01

    Two pairs of new enantiomers with unusual 5,5-spiroketal cores, termed (±)-japonones A and B [(±)-1 and (±)-2], were obtained from Hypericum japonicum Thunb. The absolute configurations of (±)-1 and (±)-2 were characterized by extensive analyses of spectroscopic data and calculated electronic circular dichroism (ECD) spectra, the application of modified Mosher’s methods, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Among these metabolites, (+)-1 exhibited some inhibitory activity on Kaposi’s sarcoma associated herpesvirus (KSHV). Virtual screening of (±)-1 and (±)-2 were conducted using the Surflex-Dock module in the Sybyl software, and (+)-1 exhibited ability to bind with ERK to form key interactions with residues Lys52, Pro56, Ile101, Asp165, Gly167 and Val99.

  7. HIV-1 transcription and latency: an update

    Science.gov (United States)

    2013-01-01

    Combination antiretroviral therapy, despite being potent and life-prolonging, is not curative and does not eradicate HIV-1 infection since interruption of treatment inevitably results in a rapid rebound of viremia. Reactivation of latently infected cells harboring transcriptionally silent but replication-competent proviruses is a potential source of persistent residual viremia in cART-treated patients. Although multiple reservoirs may exist, the persistence of resting CD4+ T cells carrying a latent infection represents a major barrier to eradication. In this review, we will discuss the latest reports on the molecular mechanisms that may regulate HIV-1 latency at the transcriptional level, including transcriptional interference, the role of cellular factors, chromatin organization and epigenetic modifications, the viral Tat trans-activator and its cellular cofactors. Since latency mechanisms may also operate at the post-transcriptional level, we will consider inhibition of nuclear RNA export and inhibition of translation by microRNAs as potential barriers to HIV-1 gene expression. Finally, we will review the therapeutic approaches and clinical studies aimed at achieving either a sterilizing cure or a functional cure of HIV-1 infection, with a special emphasis on the most recent pharmacological strategies to reactivate the latent viruses and decrease the pool of viral reservoirs. PMID:23803414

  8. High-speed, fixed-latency serial links with Xilinx FPGAs

    Institute of Scientific and Technical Information of China (English)

    Xue LIU; Qing-xu DENG; Bo-ning HOU; Ze-ke WANG

    2014-01-01

    High-speed, fixed-latency serial links find application in distributed data acquisition and control systems, such as the timing trigger and control (TTC) system for high energy physics experiments. However, most high-speed serial transceivers do not keep the same chip latency after each power-up or reset, as there is no deterministic phase relationship between the transmitted and received clocks after each power-up. In this paper, we propose a fixed-latency serial link based on high-speed transceivers embedded in Xilinx field programmable gate arrays (FPGAs). First, we modify the configuration and clock distribution of the transceiver to eliminate the phase difference between the clock domains in the transmitter/receiver. Second, we use the internal alignment circuit of the transceiver and a digital clock manager (DCM)/phase-locked loop (PLL) based clock generator to eliminate the phase difference between the clock domains in the transmitter and receiver. The test results of the link latency are shown. Compared with existing solutions, our design not only implements fixed chip latency, but also reduces the average system lock time.

  9. A new latency-reducing and energy-efficient protocol for the wireless sensor network

    Institute of Scientific and Technical Information of China (English)

    XIONG Junjie; QU Yugui; LIN Huahui; PAN Quanke; ZHAO Baohua

    2007-01-01

    This paper introduces a new protocol routing medium access control (RMAC) that integrates the routing and medium access control (MAC) layer protocol.They can both reduce latency and save energy in the wireless sensor network (WSN) while most others propose protocols that sacrifice latency for energy.To make RMAC fit WSN better,we designed an easy and efficient routing protocol base station flooding (BSF) and then integrated it with a MAC protocol timing out MAC (TMAC) [1],while traditionally BSF and TMAC work separately at two layers.We call this two-layer protocol (TLP).We theoretically proved the advantages of RMAC over TLP and evaluated RMAC over NS-2.The simulation results show that RMAC spends half the latency of TLP,as well as consumes less energy than TLE

  10. Molecular Understanding of HIV-1 Latency

    Directory of Open Access Journals (Sweden)

    W. Abbas

    2012-01-01

    Full Text Available The introduction of highly active antiretroviral therapy (HAART has been an important breakthrough in the treatment of HIV-1 infection and has also a powerful tool to upset the equilibrium of viral production and HIV-1 pathogenesis. Despite the advent of potent combinations of this therapy, the long-lived HIV-1 reservoirs like cells from monocyte-macrophage lineage and resting memory CD4+ T cells which are established early during primary infection constitute a major obstacle to virus eradication. Further HAART interruption leads to immediate rebound viremia from latent reservoirs. This paper focuses on the essentials of the molecular mechanisms for the establishment of HIV-1 latency with special concern to present and future possible treatment strategies to completely purge and target viral persistence in the reservoirs.

  11. Effects of ankle joint cooling on peroneal short latency response.

    Science.gov (United States)

    Hopkins, J Ty; Hunter, Iain; McLoda, Todd

    2006-01-01

    While cryotherapy has direct physiological effects on contractile tissues, the extent to which joint cooling affects the neuromuscular system is not well understood. The purpose of the study was to detect changes in ankle dynamic restraint (peroneal short latency response and muscle activity amplitude) during inversion perturbation following ankle joint cryotherapy. A 2x3 factorial design was used to compare reaction time and EMG amplitude data of treatment conditions (cryotherapy and control) across time (pre-treatment, post-treatment, and 30 min post-treatment). Thirteen healthy volunteers (age 23 ± 4 yrs, ht 1.76 ± 0.09 m, mass 78.8 ± 16.6 kg), with no history of lower extremity joint injury participated in this study. Surface EMG was collected from the peroneus longus (PL) of the dominant leg during an ankle inversion perturbation triggered while walking. Subjects walked the length of a 6.1 m runway 30 times. A trap door mechanism, inducing inversion perturbation, was released at heel contact during six randomly selected trials for each leg. Following baseline measurements, a 1.5 L bag of crushed ice was applied to the lateral ankle of subjects in the treatment group with an elastic wrap. A bag similar in weight and consistency was applied to the lateral ankle of subjects in the control group. A repeated measures ANOVA was used to compare treatment conditions across time (p 0.05) for PL reaction time. Average RMS EMG, normalized to an isometric reference position, increased in the cryotherapy group at the 30 min post-treatment interval relative to the control group (p movement is unknown.Short latency response should be measured during functional movement instead of during stance to take into consideration alterations in motor drive.Joint cooling has no effect on peroneal short latency response, and joint cooling may result in increased short term peroneal activation.Joint cooling has no effect on the peroneus longus as a dynamic stabilizer during walking.

  12. A new insight into viral proteins as Immunomodulatory therapeutic agents. KSHV vOX2 a homolog of human CD200 as a potent anti-inflammatory protein

    Directory of Open Access Journals (Sweden)

    Maryam Mousavinezhad-Moghaddam

    2016-01-01

    Full Text Available The physiologic function of the immune system is defense against infectious microbes and internal tumour cells, Therefore, need to have precise modulatory mechanisms to maintain the body homeostasis. The mammalian cellular CD200 (OX2/CD200R interaction is one of such modulatory mechanisms in which myeloid and lymphoid cells are regulated. CD200 and CD200R molecules are membrane proteins that their immunomodulatory effects are able to suppress inflammatory responses, particularly in the privilege sites such as CNS and eyes. Kaposi’s sarcoma-associated herpesvirus (KSHV, encodes a wide variety of immunoregulatory proteins which play central roles in modulating inflammatory and anti-inflammatory responses in favour of virus dissemination. One such protein is a homologue of the, encoded by open reading frame (ORF K14 and therefore called vOX2. Based on its gene expression profile during the KSHV life cycle, it is hypothesised that vOX2 modulates host inflammatory responses. Moreover, it seems that vOX2 involves in cell adhesion and modulates innate immunity and promotes Th2 immune responses. In this review the activities of mammalian CD200 and KSHV CD200 in cell adhesion and immune system modulation are reviewed in the context of potential therapeutic agents.

  13. Kinesiology taping does not change fibularis longus latency time and postural sway.

    Science.gov (United States)

    Correia, Christophe; Lopes, Susana; Gonçalves, Rafael; Torres, Rui; Pinho, Francisco; Gonçalves, Pedro; Rodrigues, Mário; Costa, Rui; Lopes, Mário; Ribeiro, Fernando

    2016-01-01

    Kinesiology tape seems to improve muscle force, although little is known regarding its effect on latency time and postural sway. To examine the effects of kinesiology taping on fibularis longus latency time and postural sway in healthy subjects. Thirty participants were equally randomized into three groups, two experimental groups receiving kinesiology tape (EG1, from origin to insertion; EG2, from insertion to origin) and a control group. Before and 20-min after the intervention, postural sway was assessed on a force platform and fibularis longus latency time was recorded with surface electromyography during a sudden inversion perturbation. At baseline, no differences were found between groups regarding age, anthropometrics variables, postural sway and fibularis longus latency time. In both experimental groups, the application of tape did not change postural sway and fibularis longus latency time (EG1: 93.7 ± 15.0 to 89.9 ± 15.6 ms; EG2, 81.24 ± 14.21 to 81.57 ± 16.64, p Kinesiology tape seems not to enhance fibularis longus reaction time and postural sway in young healthy subjects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Minimization of Handoff Latency by Distance Measurement Method

    Directory of Open Access Journals (Sweden)

    Debabrata Sarddar

    2011-03-01

    Full Text Available Now a day, IEEE 802.11 based wireless local area networks (WLAN have been widely deployed for business and personal applications. The main issue regarding wireless network technology is handoff or hand over management. Quality of service (QoS demanding applications like Voice over IP (VoIP and multimedia require seamless handover. But handoff delay (time required to perform hand off provides a serious barrier for such services to be made available to mobile platforms. Throughout the last few years so many researches had been done to reduce the hand off delay. Here we propose a new scanning method in which we determine the distance of nearest access points from the mobile node to bypass the main processes involved in increasing Medium Access Control (MAC layer handoff latency.

  15. Advanced techniques for the analysis of crisis stability, deterrence, and latency

    Energy Technology Data Exchange (ETDEWEB)

    Canavan, G.H.

    1998-12-31

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The principal results of studies on crisis stability, deterrence, and latency are presented in their order of development. They capture the main features of stability analysis; relate first strike, crisis, and arms control stability as seen from US and Russian perspective; and address whether different metrics, uncertain damage preferences, or the deployment of defenses can be destabilizing. The report explores differences between unilateral and proportional force reductions in the region of deep reductions where concern shifts from stability to latency.

  16. Parametric inference of neuronal response latency in presence of a background signal

    DEFF Research Database (Denmark)

    Tamborrino, Massimiliano; Ditlevsen, Susanne; Lansky, Petr

    2013-01-01

    Neurons are commonly characterized by spontaneous generation of action potentials (spikes), which appear without any apparent or controlled stimulation. When a stimulus is applied, the spontaneous firing may prevail and hamper identification of the effect of the stimulus. Therefore, for any...... will persist even when sample size is increasing. The first question is: what is the response latency to the stimulus? Answering this question becomes even more difficult if the latency is of a complex nature, for example composed of a physically implied deterministic part and a stochastic part. This scenario...

  17. Model emulates human smooth pursuit system producing zero-latency target tracking.

    Science.gov (United States)

    Bahill, A T; McDonald, J D

    1983-01-01

    Humans can overcome the 150 ms time delay of the smooth pursuit eye movement system and track smoothly moving visual targets with zero-latency. Our target-selective adaptive control model can also overcome an inherent time delay and produce zero-latency tracking. No other model or man-made system can do this. Our model is physically realizable and physiologically realistic. The technique used in our model should be useful for analyzing other time-delay systems, such as man-machine systems and robots.

  18. Measurement and analysis of workload effects on fault latency in real-time systems

    Science.gov (United States)

    Woodbury, Michael H.; Shin, Kang G.

    1990-01-01

    The authors demonstrate the need to address fault latency in highly reliable real-time control computer systems. It is noted that the effectiveness of all known recovery mechanisms is greatly reduced in the presence of multiple latent faults. The presence of multiple latent faults increases the possibility of multiple errors, which could result in coverage failure. The authors present experimental evidence indicating that the duration of fault latency is dependent on workload. A synthetic workload generator is used to vary the workload, and a hardware fault injector is applied to inject transient faults of varying durations. This method makes it possible to derive the distribution of fault latency duration. Experimental results obtained from the fault-tolerant multiprocessor at the NASA Airlab are presented and discussed.

  19. Energy latency tradeoffs for medium access and sleep scheduling in wireless sensor networks

    Science.gov (United States)

    Gang, Lu

    energy-latency-throughput tradeoffs with joint scheduling and power control and present both exponential and polynomial complexity solutions. Then we investigate the problem of minimizing total transmission energy while satisfying transmission requests within a latency bound, and present an iterative approach which converges rapidly to the optimal parameter settings.

  20. 短潜伏期体感诱发电位量化得气:随机交叉对照试验方案%Quantification of Deqi (arrival of qi) by Short-latency Somatosensory Evoked Potentials:A Randomized Crossover Controlled Trial Plan

    Institute of Scientific and Technical Information of China (English)

    林驰; 王亚峰; 张露芬; 朱江; 王培; 吴桂雯; 胡妮娟; 郝杰; 胡尚卿; 齐丹丹; 赵珉一; 孙俊俊

    2015-01-01

    目的:探索运用短潜伏期体感诱发电位(SLSEP)客观量化得气的可行性。方法采用随机对照交叉试验,纳入健康受试者,分为得气组(粗针、深刺、行手法促使得气)和不得气组(细针、浅刺、不行手法避免得气),记录针刺前、中、后体感诱发电位,量表测评受试者得气情况,观察三阴交穴得气与否对电位的影响。结果通过预试验进行可行性初探,发现得气对于SLSEP的影响具有一定规律性,值得观察。结论该方案具有可行性,可以展开正式试验。%Objective To explore the feasibility of using short-latency somatosensory evoked potentials (SLSEP) to quantitate Deqi.Methods A randomized crossover controlled trial was carried out. Healthy subjects were enrolled and allocated to treatment (thick needle, deep insertion and manipulation for Deqi) and control (thin needle, shallow insertion and no manipulation without Deqi) groups. Somatosensory evoked potentials were recorded before, during and after acupuncture. Deqi was assessed using the score scale in the subjets. The effects of Deqi and no Deqi at point Sanyinjiao (SP 6) on the potentials were observed.Results The preliminary exploration of the feasibility by the trial test showed that the effect of Deqi on short-latency somatosensory evoked potentials had certain regularity. It was worthy to be observed.Conclusion The plan is feasible. The formal test can be conducted.

  1. HSV-1作用于KSHV ORF50启动子区中特异性应答位点序列的初寻%The detection of the specific sequence of the promoter region of the KSHV ORF50 acted by HSV-1

    Institute of Scientific and Technical Information of China (English)

    程伟; 郝婷婷; 王子盾; 朱小飞; 冯宁翰; 华立新; 秦娣; 卢春

    2011-01-01

    Objective:To construct the recombinant luciferase reporter plasmids containing series of truncated sequences of Kaposi' s sarcoma-associated herpesvirus(KSHV) ORF50 promoter and seek the specific response sites sequences of ORF50 promoter acted by HSV-1. Methods:Series of truncated sequences of KSHV ORF50 promoter were amplified using PCR from KSHV genome. The PCR products were further cloned into pGL3 basic vector to construct the recombinant luciferase reporter plasmids. The recombinant plasmids were confirmed by restriction enzymes digestion and sequence analysis. After infected with HSV-1, Vero cells were transfected with the ORF50 promoter-driven luciferase constructs to induce luciferase gene expression. Relative luciferase activity unit (RLU) was calculated and compared. Results:Series of truncated sequences of KSHV ORF50 promoter were isolated and cloned successfully. The promoter-driven luciferase expression of pGL3-95, pGL3-46 and pGL3-17 were declined significantly in Vero cells infected with HSV-1 when compared with pGL3-1500, pGL3-750, pGL3-375 and pGL3-185. Conclusion:The recombinant luciferase reporter plasmids containing series of truncated sequences of KSHV ORF50 promoter were constructed successfully. The specific response sites sequences of ORF50 promoter acted by HSV-1 are between -185 bp and -95 bp.%目的:构建卡波济肉瘤相关疱疹病毒(Kaposi's sarcoma-associated herpesvirus,KSHV)ORF50启动子系列截短序列克隆,初步寻找HSV-1作用于KSHV ORF50启动子区中特异性应答位点序列.方法:以KSHV基因组为模板,PCR扩增KSHVORF50启动子系列截短序列,克隆至含有虫荧光素酶(Luciferase)报告基因的基本载体pGL-3中,构建含ORF50启动子系列截短序列的重组Lueiferase报告质粒.系列重组报告质粒经酶切鉴定和序列测定分析后,分别转染单纯疱疹病毒1型(HSV-1)感染后的非洲绿猴肾细胞(Vero细胞),进行Luciferase活性检测,计算

  2. Latency represents sound frequency in mouse IC

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Frequency is one of the fundamental parameters of sound.The frequency of an acoustic stimulus can be represented by a neural response such as spike rate,and/or first spike latency(FSL)of a given neuron.The spike rates/frequency function of most neurons changes with different acoustic ampli-tudes,whereas FSL/frequency function is highly stable.This implies that FSL might represent the fre-quency of a sound stimulus more efficiently than spike rate.This study involved representations of acoustic frequency by spike rate and FSL of central inferior colliculus(IC)neurons responding to free-field pure-tone stimuli.We found that the FSLs of neurons responding to characteristic frequency(CF)of sound stimulus were usually the shortest,regardless of sound intensity,and that spike rates of most neurons showed a variety of function according to sound frequency,especially at high intensities.These results strongly suggest that FSL of auditory IC neurons can represent sound frequency more precisely than spike rate.

  3. Latency represents sound frequency in mouse IC

    Institute of Scientific and Technical Information of China (English)

    QIU Qiang; TANG Jie; YU ZuLin; ZHANG Juan; ZHOU YingJie; XIAO ZhongJu; SHEN JunXian

    2007-01-01

    Frequency is one of the fundamental parameters of sound. The frequency of an acoustic stimulus can be represented by a neural response such as spike rate, and/or first spike latency (FSL) of a given neuron. The spike rates/frequency function of most neurons changes with different acoustic amplitudes, whereas FSL/frequency function is highly stable. This implies that FSL might represent the frequency of a sound stimulus more efficiently than spike rate. This study involved representations of acoustic frequency by spike rate and FSL of central inferior colliculus (IC) neurons responding to free-field pure-tone stimuli. We found that the FSLs of neurons responding to characteristic frequency (CF) of sound stimulus were usually the shortest, regardless of sound intensity, and that spike rates of most neurons showed a variety of function according to sound frequency, especially at high intensities.These results strongly suggest that FSL of auditory IC neurons can represent sound frequency more precisely than spike rate.

  4. Human hair genealogies and stem cell latency

    Directory of Open Access Journals (Sweden)

    Tavaré Simon

    2006-02-01

    Full Text Available Abstract Background Stem cells divide to reproduce themselves and produce differentiated progeny. A fundamental problem in human biology has been the inability to measure how often stem cells divide. Although it is impossible to observe every division directly, one method for counting divisions is to count replication errors; the greater the number of divisions, the greater the numbers of errors. Stem cells with more divisions should produce progeny with more replication errors. Methods To test this approach, epigenetic errors (methylation in CpG-rich molecular clocks were measured from human hairs. Hairs exhibit growth and replacement cycles and "new" hairs physically reappear even on "old" heads. Errors may accumulate in long-lived stem cells, or in their differentiated progeny that are eventually shed. Results Average hair errors increased until two years of age, and then were constant despite decades of replacement, consistent with new hairs arising from infrequently dividing bulge stem cells. Errors were significantly more frequent in longer hairs, consistent with long-lived but eventually shed mitotic follicle cells. Conclusion Constant average hair methylation regardless of age contrasts with the age-related methylation observed in human intestine, suggesting that error accumulation and therefore stem cell latency differs among tissues. Epigenetic molecular clocks imply similar mitotic ages for hairs on young and old human heads, consistent with a restart with each new hair, and with genealogies surreptitiously written within somatic cell genomes.

  5. Low latency memory access and synchronization

    Energy Technology Data Exchange (ETDEWEB)

    Blumrich, Matthias A. (Ridgefield, CT); Chen, Dong (Croton On Hudson, NY); Coteus, Paul W. (Yorktown Heights, NY); Gara, Alan G. (Mount Kisco, NY); Giampapa, Mark E. (Irvington, NY); Heidelberger, Philip (Cortlandt Manor, NY); Hoenicke, Dirk (Ossining, NY); Ohmacht, Martin (Brewster, NY); Steinmacher-Burow, Burkhard D. (Mount Kisco, NY); Takken, Todd E. (Mount Kisco, NY), Vranas; Pavlos M. (Bedford Hills, NY)

    2010-10-19

    A low latency memory system access is provided in association with a weakly-ordered multiprocessor system. Bach processor in the multiprocessor shares resources, and each shared resource has an associated lock within a locking device that provides support for synchronization between the multiple processors in the multiprocessor and the orderly sharing of the resources. A processor only has permission to access a resource when it owns the lock associated with that resource, and an attempt by a processor to own a lock requires only a single load operation, rather than a traditional atomic load followed by store, such that the processor only performs a read operation and the hardware locking device performs a subsequent write operation rather than the processor. A simple prefetching for non-contiguous data structures is also disclosed. A memory line is redefined so that in addition to the normal physical memory data, every line includes a pointer that is large enough to point to any other line in the memory, wherein the pointers to determine which memory line to prefetch rather than some other predictive algorithm. This enables hardware to effectively prefetch memory access patterns that are non-contiguous, but repetitive.

  6. Low latency memory access and synchronization

    Science.gov (United States)

    Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E.; Heidelberger, Philip; Hoenicke, Dirk; Ohmacht, Martin; Steinmacher-Burow, Burkhard D.; Takken, Todd E. , Vranas; Pavlos M.

    2010-10-19

    A low latency memory system access is provided in association with a weakly-ordered multiprocessor system. Bach processor in the multiprocessor shares resources, and each shared resource has an associated lock within a locking device that provides support for synchronization between the multiple processors in the multiprocessor and the orderly sharing of the resources. A processor only has permission to access a resource when it owns the lock associated with that resource, and an attempt by a processor to own a lock requires only a single load operation, rather than a traditional atomic load followed by store, such that the processor only performs a read operation and the hardware locking device performs a subsequent write operation rather than the processor. A simple prefetching for non-contiguous data structures is also disclosed. A memory line is redefined so that in addition to the normal physical memory data, every line includes a pointer that is large enough to point to any other line in the memory, wherein the pointers to determine which memory line to prefetch rather than some other predictive algorithm. This enables hardware to effectively prefetch memory access patterns that are non-contiguous, but repetitive.

  7. Genetic variants in RBFOX3 are associated with sleep latency

    NARCIS (Netherlands)

    N. Amin (Najaf); K.V. Allebrandt; A. van der Spek (Ashley); B. Müller-Myhsok (B.); K. Hek (Karin); M. Teder-Laving (Maris); C. Hayward (Caroline); T. Esko (Tõnu); J. van Mill; H. Mbarek; N.F. Watson (Nathaniel F); S.A. Melville (Scott); F.M. Del Greco (Fabiola); E.M. Byrne (Enda); E. Oole (Edwin); I. Kolcic (Ivana); T.H. Chen; D.S. Evans (Daniel); J. Coresh (Josef); N. Vogelzangs (Nicole); J. Karjalainen (Juha); G.A.H.M. Willemsen (Gonneke); S.A. Gharib (Sina); L. Zgaga (Lina); E. Mihailov (Evelin); K.L. Stone (Katie L); H. Campbell (Harry); R.W.W. Brouwer (Rutger); A. Demirkan (Ayşe); A.J. Isaacs (Aaron); Z. Dogas; K. Marciante (Kristin); S. Campbell (Susan); F. Borovecki (Fran); A.I. Luik (Annemarie I); M. Li (Man); J.J. Hottenga (Jouke Jan); J.E. Huffman (Jennifer); M.C.G.N. van den hout (Mirjam); S.R. Cummings (Steven R.); Y.S. Aulchenko (Yurii); P.R. Gehrman (Philip); A.G. Uitterlinden (André); H.E. Wichmann (Heinz Erich); M. Müller-Nurasyid (Martina); R.S.N. Fehrmann (Rudolf); G.W. Montgomery (Grant); A. Hofman (Albert); W.H.L. Kao (Wen Hong Linda); B.A. Oostra (Ben); A. Wright (Alan); J.M. Vink (Jacqueline); J.F. Wilson (James F); P.P. Pramstaller (Peter Paul); A.A. Hicks (Andrew); O. Polasek (Ozren); N.M. Punjabi (Naresh); S. Redline (Susan); B.M. Psaty (Bruce); A.C. Heath (Andrew C.); M. Merrow; G.J. Tranah (Gregory); D.J. Gottlieb (Daniel J); D.I. Boomsma (Dorret); N.G. Martin (Nicholas); I. Rudan (Igor); H.W. Tiemeier (Henning); W.F.J. van IJcken (Wilfred); B.W.J.H. Penninx; A. Metspalu (Andres); T. Meitinger (Thomas); L. Franke (Lude); T. Roenneberg; C.M. van Duijn (Cock)

    2016-01-01

    textabstractTime to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep

  8. Inhibition of superinfection and the evolution of viral latency

    NARCIS (Netherlands)

    Berngruber, Thomas W.; Weissing, Franz J.; Gandon, Sylvain

    2010-01-01

    Latent viruses generally defend their host cell against superinfection by nonlatent virulent mutants that could destroy the host cell. Superinfection inhibition thus seems to be a prerequisite for the maintenance of viral latency. Yet viral latency can break down when resistance to superinfection in

  9. Simulation Based Studies of Low Latency Teleoperations for NASA Exploration Missions

    Science.gov (United States)

    Gernhardt, Michael L.; Crues, Edwin Z.; Bielski, Paul; Dexter, Dan; Litaker, Harry L.; Chappell, Steven P.; Beaton, Kara H.; Bekdash, Omar S.

    2017-01-01

    Human exploration of Mars will involve both crewed and robotic systems. Many mission concepts involve the deployment and assembly of mission support assets prior to crew arrival on the surface. Some of these deployment and assembly activities will be performed autonomously while others will be performed using teleoperations. However, significant communications latencies between the Earth and Mars make teleoperations challenging. Alternatively, low latency teleoperations are possible from locations in Mars orbit like Mars' moons Phobos and Deimos. To explore these latency opportunities, NASA is conducting a series of studies to investigate the effects of latency on telerobotic deployment and assembly activities. These studies are being conducted in laboratory environments at NASA's Johnson Space Center (JSC), the Human Exploration Research Analog (HERA) at JSC and the NASA Extreme Environment Mission Operations (NEEMO) underwater habitat off the coast of Florida. The studies involve two human-in-the-loop interactive simulations developed by the NASA Exploration Systems Simulations (NExSyS) team at JSC. The first simulation investigates manipulation related activities while the second simulation investigates mobility related activities. The first simulation provides a simple real-time operator interface with displays and controls for a simulated 6 degree of freedom end effector. The initial version of the simulation uses a simple control mode to decouple the robotic kinematic constraints and a communications delay to model latency effects. This provides the basis for early testing with more detailed manipulation simulations planned for the future. Subjects are tested using five operating latencies that represent teleoperation conditions from local surface operations to orbital operations at Phobos, Deimos and ultimately high Martian orbit. Subject performance is measured and correlated with three distance-to-target zones of interest. Each zone represents a target

  10. Novel technology for reducing wavefront image processing latency

    Science.gov (United States)

    Barr, David; Schwartz, Noah; Vick, Andy; Coughlan, John; Halsall, Rob; Basden, Alastair; Dipper, Nigel

    2016-07-01

    Adaptive optics is essential for the successful operation of the future Extremely Large Telescopes (ELTs). At the heart of these AO system lies the real-time control which has become computationally challenging. A majority of the previous efforts has been aimed at reducing the wavefront reconstruction latency by using many-core hardware accelerators such as Xeon Phis and GPUs. These modern hardware solutions offer a large numbers of cores combined with high memory bandwidths but have restrictive input/output (I/O). The lack of efficient I/O capability makes the data handling very inefficient and adds both to the overall latency and jitter. For example a single wavefront sensor for an ELT scale adaptive optics system can produce hundreds of millions of pixels per second that need to be processed. Passing all this data through a CPU and into GPUs or Xeon Phis, even by reducing memory copies by using systems such as GPUDirect, is highly inefficient. The Mellanox TILE series is a novel technology offering a high number of cores and multiple 10 Gbps Ethernet ports. We present results of the TILE-Gx36 as a front-end wavefront sensor processing unit. In doing so we are able to greatly reduce the amount of data needed to be transferred to the wavefront reconstruction hardware. We show that the performance of the Mellanox TILE-GX36 is in-line with typical requirements, in terms of mean calculation time and acceptable jitter, for E-ELT first-light instruments and that the Mellanox TILE series is a serious contender for all E-ELT instruments.

  11. Serial analysis of gene expression predicts structural differences in hippocampus of long attack latency and short attack latency mice

    NARCIS (Netherlands)

    Feldker, DEM; Datson, NA; Veenema, AH; Meulmeester, E; de Kloet, ER; Vreugdenhil, E

    2003-01-01

    The genetically selected long attack latency (LAL) and short attack latency (SAL) mice differ in a wide variety of behavioural traits and display differences in the serotonergic system and the hypothalamus-pituitary-adrenocortical (HPA)-axis. Serial analysis of gene expression (SAGE) was used to gen

  12. Auditory generalization gradients for response latency in the monkey1

    Science.gov (United States)

    Moody, David B.; Stebbins, William C.; Iglauer, Carol

    1971-01-01

    Two monkeys were trained to press and hold a response key in the presence of a light and to release it at the onset of a pure tone. Initially, all responses with latencies shorter than 1 sec were reinforced without regard to the frequency of the pure tone, and the intensity of the pure tone that resulted in equal latencies at each frequency was determined. The second stage of the experiment consisted of discrimination training, during which releases to one pure-tone frequency (positive stimulus) were reinforced and releases to a second frequency (negative stimulus) were extinguished. Median latencies to the negative stimulus slowly increased as did the variability of the latency distribution for the negative stimulus. There was no evidence of a concurrent decrease in latencies to the positive stimulus indicative of behavioral contrast. The third part of the experiment consisted of determining maintained generalization gradients by increasing the number of nonreinforcement stimuli. The gradients that eventually resulted showed approximately equal latencies to all frequencies of the negative stimulus and shorter latencies to the positive stimulus frequency. PMID:5003971

  13. Facility Location with Client Latencies: Linear-Programming based Techniques for Minimum-Latency Problems

    CERN Document Server

    Chakrabarty, Deeparnab

    2010-01-01

    We introduce a problem that is a common generalization of the uncapacitated facility location and minimum latency (ML) problems, where facilities need to be opened to serve clients and also need to be sequentially activated before they can provide service. Formally, we are given a set \\F of n facilities with facility-opening costs {f_i}, a set of m clients, and connection costs {c_{ij}} specifying the cost of assigning a client j to a facility i, a root node r denoting the depot, and a time metric d on \\F\\cup{r}. Our goal is to open a subset F of facilities, find a path P starting at r and spanning F to activate the open facilities, and connect each client j to a facility \\phi(j)\\in F, so as to minimize \\sum_{i\\in F}f_i +\\sum_{clients j}(c_{\\phi(j),j}+t_j), where t_j is the time taken to reach \\phi(j) along path P. We call this the minimum latency uncapacitated facility location (MLUFL) problem. Our main result is an O(\\log n\\max{\\log n,\\log m})-approximation for MLUFL. We also show that any improvement in th...

  14. Interaural intensity and latency difference in the dolphin's auditory system.

    Science.gov (United States)

    Popov, V V; Supin AYa

    1991-12-09

    Binaural hearing mechanisms were measured in dolphins (Inia geoffrensis) by recording the auditory nerve evoked response from the body surface. The azimuthal position of a sound source at 10-15 degrees from the longitudinal axis elicited interaural intensity disparity up to 20 dB and interaural latency difference as large as 250 microseconds. The latter was many times greater than the acoustical interaural time delay. This latency difference seems to be caused by the intensity disparity. The latency difference seems to be an effective way of coding of intensity disparity.

  15. Mechanism of latency relaxation in frog skeletal muscle.

    Science.gov (United States)

    Yagi, N

    2011-05-01

    The latency relaxation is a small drop of tension before skeletal muscle begins to develop active tension. This phenomenon was found nearly one century ago but its origin has not been clarified. In this review, the hypotheses for its mechanism are discussed in terms of the recent experimental results using X-ray diffraction. The latency relaxation takes place almost simultaneously as the structural change of the regulatory protein troponin, an unspecified structural change of the thick filament, and increase in stiffness. It seems difficult to associate all of these with the latency relaxation by assuming a simple mechanism. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin.

    Directory of Open Access Journals (Sweden)

    Claire Pardieu

    2010-04-01

    Full Text Available Tetherin (CD317/BST2 is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18 in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition.

  17. A viral nuclear noncoding RNA binds re-localized poly(A binding protein and is required for late KSHV gene expression.

    Directory of Open Access Journals (Sweden)

    Sumit Borah

    2011-10-01

    Full Text Available During the lytic phase of infection, the gamma herpesvirus Kaposi's Sarcoma-Associated Herpesvirus (KSHV expresses a highly abundant, 1.1 kb nuclear noncoding RNA of unknown function. We observe that this polyadenylated nuclear (PAN RNA avidly binds host poly(A-binding protein C1 (PABPC1, which normally functions in the cytoplasm to bind the poly(A tails of mRNAs, regulating mRNA stability and translation efficiency. During the lytic phase of KSHV infection, PABPC1 is re-localized to the nucleus as a consequence of expression of the viral shutoff exonuclease (SOX protein; SOX also mediates the host shutoff effect in which host mRNAs are downregulated while viral mRNAs are selectively expressed. We show that whereas PAN RNA is not required for the host shutoff effect or for PABPC1 re-localization, SOX strongly upregulates the levels of PAN RNA in transient transfection experiments. This upregulation is destroyed by the same SOX mutation that ablates the host shutoff effect and PABPC1 nuclear re-localization or by removal of the poly(A tail of PAN. In cells induced into the KSHV lytic phase, depletion of PAN RNA using RNase H-targeting antisense oligonucleotides reveals that it is necessary for the production of late viral proteins from mRNAs that are themselves polyadenylated. Our results add to the repertoire of functions ascribed to long noncoding RNAs and suggest a mechanism of action for nuclear noncoding RNAs in gamma herpesvirus infection.

  18. The amblyopic eye in subjects with anisometropia show increased saccadic latency in the delayed saccade task

    Directory of Open Access Journals (Sweden)

    Maciej ePerdziak

    2014-10-01

    Full Text Available The term amblyopia is used to describe reduced visual function in one eye (or both eyes, though not so often which cannot be fully improved by refractive correction and explained by the organic cause observed during regular eye examination. This developmental disorder of spatial vision affects about 2-5% of the population and is associated with abnormal visual experience (e.g. anisometropia, strabismus during infancy or early childhood. Several studies have shown prolongation of saccadic latency time in amblyopic eye. In our opinion, study of saccadic latency in the context of central vision deficits assessment, should be based on central retina stimulation. For this reason, we proposed saccade delayed task. It requires inhibitory processing for maintaining fixation on the central target until it disappears – what constitutes the GO signal for saccade. The experiment consisted of 100 trials for each eye and was performed under two viewing conditions: monocular amblyopic / non-dominant eye and monocular dominant eye. We examined saccadic latency in 16 subjects (mean age 30±11 years with anisometropic amblyopia (two subjects had also microtropia and in 17 control subjects (mean age 28±8 years. Participants were instructed to look at central (fixation target and when it disappears, to make the saccade toward the periphery (10 deg as fast as possible, either left or the right target. The study results have proved the significant difference in saccadic latency between the amblyopic (mean 262±48 ms and dominant (mean 237±45 ms eye, in anisometropic group. In the control group, the saccadic latency for dominant (mean 226±32ms and non-dominant (mean 230±29 ms eye was not significantly different.By the use of LATER (Linear Approach to the Threshold with Ergodic Rate decision model we interpret our findings as a decrease in accumulation of visual information acquired by means of central (affected retina in subjects with anisometropic amblyopia.

  19. Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells.

    Science.gov (United States)

    Evans, Vanessa A; Kumar, Nitasha; Filali, Ali; Procopio, Francesco A; Yegorov, Oleg; Goulet, Jean-Philippe; Saleh, Suha; Haddad, Elias K; da Fonseca Pereira, Candida; Ellenberg, Paula C; Sekaly, Rafick-Pierre; Cameron, Paul U; Lewin, Sharon R

    2013-01-01

    Latently infected resting CD4(+) T cells are a major barrier to HIV cure. Understanding how latency is established, maintained and reversed is critical to identifying novel strategies to eliminate latently infected cells. We demonstrate here that co-culture of resting CD4(+) T cells and syngeneic myeloid dendritic cells (mDC) can dramatically increase the frequency of HIV DNA integration and latent HIV infection in non-proliferating memory, but not naïve, CD4(+) T cells. Latency was eliminated when cell-to-cell contact was prevented in the mDC-T cell co-cultures and reduced when clustering was minimised in the mDC-T cell co-cultures. Supernatants from infected mDC-T cell co-cultures did not facilitate the establishment of latency, consistent with cell-cell contact and not a soluble factor being critical for mediating latent infection of resting CD4(+) T cells. Gene expression in non-proliferating CD4(+) T cells, enriched for latent infection, showed significant changes in the expression of genes involved in cellular activation and interferon regulated pathways, including the down-regulation of genes controlling both NF-κB and cell cycle. We conclude that mDC play a key role in the establishment of HIV latency in resting memory CD4(+) T cells, which is predominantly mediated through signalling during DC-T cell contact.

  20. Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Vanessa A Evans

    Full Text Available Latently infected resting CD4(+ T cells are a major barrier to HIV cure. Understanding how latency is established, maintained and reversed is critical to identifying novel strategies to eliminate latently infected cells. We demonstrate here that co-culture of resting CD4(+ T cells and syngeneic myeloid dendritic cells (mDC can dramatically increase the frequency of HIV DNA integration and latent HIV infection in non-proliferating memory, but not naïve, CD4(+ T cells. Latency was eliminated when cell-to-cell contact was prevented in the mDC-T cell co-cultures and reduced when clustering was minimised in the mDC-T cell co-cultures. Supernatants from infected mDC-T cell co-cultures did not facilitate the establishment of latency, consistent with cell-cell contact and not a soluble factor being critical for mediating latent infection of resting CD4(+ T cells. Gene expression in non-proliferating CD4(+ T cells, enriched for latent infection, showed significant changes in the expression of genes involved in cellular activation and interferon regulated pathways, including the down-regulation of genes controlling both NF-κB and cell cycle. We conclude that mDC play a key role in the establishment of HIV latency in resting memory CD4(+ T cells, which is predominantly mediated through signalling during DC-T cell contact.

  1. Reversible silencing of cytomegalovirus genomes by type I interferon governs virus latency.

    Directory of Open Access Journals (Sweden)

    Franziska Dağ

    2014-02-01

    Full Text Available Herpesviruses establish a lifelong latent infection posing the risk for virus reactivation and disease. In cytomegalovirus infection, expression of the major immediate early (IE genes is a critical checkpoint, driving the lytic replication cycle upon primary infection or reactivation from latency. While it is known that type I interferon (IFN limits lytic CMV replication, its role in latency and reactivation has not been explored. In the model of mouse CMV infection, we show here that IFNβ blocks mouse CMV replication at the level of IE transcription in IFN-responding endothelial cells and fibroblasts. The IFN-mediated inhibition of IE genes was entirely reversible, arguing that the IFN-effect may be consistent with viral latency. Importantly, the response to IFNβ is stochastic, and MCMV IE transcription and replication were repressed only in IFN-responsive cells, while the IFN-unresponsive cells remained permissive for lytic MCMV infection. IFN blocked the viral lytic replication cycle by upregulating the nuclear domain 10 (ND10 components, PML, Sp100 and Daxx, and their knockdown by shRNA rescued viral replication in the presence of IFNβ. Finally, IFNβ prevented MCMV reactivation from endothelial cells derived from latently infected mice, validating our results in a biologically relevant setting. Therefore, our data do not only define for the first time the molecular mechanism of IFN-mediated control of CMV infection, but also indicate that the reversible inhibition of the virus lytic cycle by IFNβ is consistent with the establishment of CMV latency.

  2. A systems biology approach identified different regulatory networks targeted by KSHV miR-K12-11 in B cells and endothelial cells.

    Science.gov (United States)

    Yang, Yajie; Boss, Isaac W; McIntyre, Lauren M; Renne, Rolf

    2014-08-08

    Kaposi's sarcoma associated herpes virus (KSHV) is associated with tumors of endothelial and lymphoid origin. During latent infection, KSHV expresses miR-K12-11, an ortholog of the human tumor gene hsa-miR-155. Both gene products are microRNAs (miRNAs), which are important post-transcriptional regulators that contribute to tissue specific gene expression. Advances in target identification technologies and molecular interaction databases have allowed a systems biology approach to unravel the gene regulatory networks (GRNs) triggered by miR-K12-11 in endothelial and lymphoid cells. Understanding the tissue specific function of miR-K12-11 will help to elucidate underlying mechanisms of KSHV pathogenesis. Ectopic expression of miR-K12-11 differentially affected gene expression in BJAB cells of lymphoid origin and TIVE cells of endothelial origin. Direct miRNA targeting accounted for a small fraction of the observed transcriptome changes: only 29 genes were identified as putative direct targets of miR-K12-11 in both cell types. However, a number of commonly affected biological pathways, such as carbohydrate metabolism and interferon response related signaling, were revealed by gene ontology analysis. Integration of transcriptome profiling, bioinformatic algorithms, and databases of protein-protein interactome from the ENCODE project identified different nodes of GRNs utilized by miR-K12-11 in a tissue-specific fashion. These effector genes, including cancer associated transcription factors and signaling proteins, amplified the regulatory potential of a single miRNA, from a small set of putative direct targets to a larger set of genes. This is the first comparative analysis of miRNA-K12-11's effects in endothelial and B cells, from tissues infected with KSHV in vivo. MiR-K12-11 was able to broadly modulate gene expression in both cell types. Using a systems biology approach, we inferred that miR-K12-11 establishes its GRN by both repressing master TFs and influencing

  3. Automatic latency equalization in VHDL-implemented complex pipelined systems

    Science.gov (United States)

    Zabołotny, Wojciech M.

    2016-09-01

    In the pipelined data processing systems it is very important to ensure that parallel paths delay data by the same number of clock cycles. If that condition is not met, the processing blocks receive data not properly aligned in time and produce incorrect results. Manual equalization of latencies is a tedious and error-prone work. This paper presents an automatic method of latency equalization in systems described in VHDL. The proposed method uses simulation to measure latencies and verify introduced correction. The solution is portable between different simulation and synthesis tools. The method does not increase the complexity of the synthesized design comparing to the solution based on manual latency adjustment. The example implementation of the proposed methodology together with a simple design demonstrating its use is available as an open source project under BSD license.

  4. The Role of Spike Temporal Latencies in Artificial Olfaction

    Science.gov (United States)

    Polese, D.; Martinelli, E.; Dini, F.; Paolesse, R.; Filippini, D.; Lundström, I.; Di Natale, C.

    2011-09-01

    In this paper we investigate the recognition power of spike time latencies in an artificial olfactory system. For the scope we used a recently introduced platform for artificial olfaction implementing an artificial olfactory epithelium, formed by thousands sensors, and an abstract olfactory bulb1. Results show that correct volatile compounds classification can be achieved considering only the first two spikes of the neural network output evidencing that the latency of the first spikes contains actually enough information for odor identification.

  5. Azidothymidine Sensitizes Primary Effusion Lymphoma Cells to Kaposi Sarcoma-Associated Herpesvirus-Specific CD4+ T Cell Control and Inhibits vIRF3 Function

    Science.gov (United States)

    Stürzl, Michael; Sabbah, Shereen

    2016-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them. To make KSHV-infected cells more sensitive to T cell control we treated PEL cells with the thymidine analogue azidothymidine (AZT), which sensitizes PEL lines to Fas-ligand and TRAIL challenge; effector mechanisms which T cells use. PELs co-cultured with KSHV-specific CD4+ T cells in the absence of AZT showed no control of PEL outgrowth. However in the presence of AZT PEL outgrowth was controlled in an MHC-restricted manner. To investigate how AZT sensitizes PELs to immune control we first examined BJAB cells transduced with individual KSHV-latent genes for their ability to resist apoptosis mediated by stimuli delivered through Fas and TRAIL receptors. This showed that in addition to the previously described vFLIP protein, expression of vIRF3 also inhibited apoptosis delivered by these stimuli. Importantly vIRF3 mediated protection from these apoptotic stimuli was inhibited in the presence of AZT as was a second vIRF3 associated phenotype, the downregulation of surface MHC class II. Although both vFLIP and vIRF3 are expressed in PELs, we propose that inhibiting vIRF3 function with AZT may be sufficient to restore T cell control of these tumor cells. PMID:27893813

  6. A new, ultra-low latency data transmission protocol for Earthquake Early Warning Systems

    Science.gov (United States)

    Hill, P.; Hicks, S. P.; McGowan, M.

    2016-12-01

    One measure used to assess the performance of Earthquake Early Warning Systems (EEWS) is the delay time between earthquake origin and issued alert. EEWS latency is dependent on a number of sources (e.g. P-wave propagation, digitisation, transmission, receiver processing, triggering, event declaration). Many regional seismic networks use the SEEDlink protocol; however, packet size is fixed to 512-byte miniSEED records, resulting in transmission latencies of >0.5 s. Data packetisation is seen as one of the main sources of delays in EEWS (Brown et al., 2011). Optimising data-logger and telemetry configurations is a cost-effective strategy to improve EEWS alert times (Behr et al., 2015). Digitisers with smaller, selectable packets can result in faster alerts (Sokos et al., 2016). We propose a new seismic protocol for regional seismic networks benefiting low-latency applications such as EEWS. The protocol, based on Güralp's existing GDI-link format is an efficient and flexible method to exchange data between seismic stations and data centers for a range of network configurations. The main principle is to stream data sample-by-sample instead of fixed-length packets to minimise transmission latency. Self-adaptive packetisation with compression maximises available telemetry bandwidth. Highly flexible metadata fields within GDI-link are compatible with existing miniSEED definitions. Data is sent as integers or floats, supporting a wide range of data formats, including discrete parameters such as Pd & τC for on-site earthquake early warning. Other advantages include: streaming station state-of-health information, instrument control, support of backfilling and fail-over strategies during telemetry outages. Based on tests carried out on the Güralp Minimus data-logger, we show our new protocol can reduce transmission latency to as low as 1 ms. The low-latency protocol is currently being implemented with common processing packages. The results of these tests will help to

  7. LATENCY DETERMINATION AND COMPENSATION IN REAL-TIME GNSS/INS INTEGRATED NAVIGATION SYSTEMS

    Directory of Open Access Journals (Sweden)

    P. D. Solomon

    2012-09-01

    Full Text Available Unmanned Aerial Vehicle (UAV technology is now commonplace in many defence and civilian environments. However, the high cost of owning and operating a sophisticated UAV has slowed their adoption in many commercial markets. Universities and research groups are actively experimenting with UAVs to further develop the technology, particularly for automated flying operations. The two main UAV platforms used are fixed-wing and helicopter. Helicopter-based UAVs offer many attractive features over fixed-wing UAVs, including vertical take-off, the ability to loiter, and highly dynamic flight. However the control and navigation of helicopters are significantly more demanding than those of fixed-wing UAVs and as such require a high bandwidth real-time Position, Velocity, Attitude (PVA navigation system. In practical Real-Time Navigation Systems (RTNS there are delays in the processing of the GNSS data prior to the fusion of the GNSS data with the INS measurements. This latency must be compensated for otherwise it degrades the solution of the navigation filter. This paper investigates the effect of latency in the arrival time of the GNSS data in a RTNS. Several test drives and flights were conducted with a low-cost RTNS, and compared with a high quality GNSS/INS solution. A technique for the real-time, automated and accurate estimation of the GNSS latency in low-cost systems was developed and tested. The latency estimates were then verified through cross-correlation with the time-stamped measurements from the reference system. A delayed measurement Extended Kalman Filter was then used to allow for the real-time fusing of the delayed measurements, and then a final system developed for on-the-fly measurement and compensation of GNSS latency in a RTNS.

  8. Latency Determination and Compensation in Real-Time Gnss/ins Integrated Navigation Systems

    Science.gov (United States)

    Solomon, P. D.; Wang, J.; Rizos, C.

    2011-09-01

    Unmanned Aerial Vehicle (UAV) technology is now commonplace in many defence and civilian environments. However, the high cost of owning and operating a sophisticated UAV has slowed their adoption in many commercial markets. Universities and research groups are actively experimenting with UAVs to further develop the technology, particularly for automated flying operations. The two main UAV platforms used are fixed-wing and helicopter. Helicopter-based UAVs offer many attractive features over fixed-wing UAVs, including vertical take-off, the ability to loiter, and highly dynamic flight. However the control and navigation of helicopters are significantly more demanding than those of fixed-wing UAVs and as such require a high bandwidth real-time Position, Velocity, Attitude (PVA) navigation system. In practical Real-Time Navigation Systems (RTNS) there are delays in the processing of the GNSS data prior to the fusion of the GNSS data with the INS measurements. This latency must be compensated for otherwise it degrades the solution of the navigation filter. This paper investigates the effect of latency in the arrival time of the GNSS data in a RTNS. Several test drives and flights were conducted with a low-cost RTNS, and compared with a high quality GNSS/INS solution. A technique for the real-time, automated and accurate estimation of the GNSS latency in low-cost systems was developed and tested. The latency estimates were then verified through cross-correlation with the time-stamped measurements from the reference system. A delayed measurement Extended Kalman Filter was then used to allow for the real-time fusing of the delayed measurements, and then a final system developed for on-the-fly measurement and compensation of GNSS latency in a RTNS.

  9. Latencies in BOLD response during visual attention processes.

    Science.gov (United States)

    Kellermann, Thilo; Reske, Martina; Jansen, Andreas; Satrapi, Peyman; Shah, N Jon; Schneider, Frank; Habel, Ute

    2011-04-22

    One well-investigated division of attentional processes focuses on alerting, orienting and executive control, which can be assessed applying the attentional network test (ANT). The goal of the present study was to add further knowledge about the temporal dynamics of relevant neural correlates. As a right hemispheric dominance for alerting and orienting has previously been reported for intrinsic but not for phasic alertness, we additionally addressed a potential impact of this lateralization of attention by employing a lateralized version of the ANT, capturing phasic alertness processes. Sixteen healthy subjects underwent event-related functional magnetic resonance imaging (fMRI) while performing the ANT. Analyses of BOLD magnitude replicated the engagement of a fronto-parietal network in the attentional subsystems. The amplitudes of the attentional contrasts interacted with visual field presentation in the sense that the thalamus revealed a greater involvement for spatially cued items presented in the left visual field. Comparisons of BOLD latencies in visual cortices, first, verified faster BOLD responses following contra-lateral stimulus presentation. Second and more importantly, we identified attention-modulated activation in secondary visual and anterior cingulate cortices. Results are discussed in terms of bottom-up and lateralization processes. Although intrinsic and phasic alertness are distinct cognitive processes, we propose that neural substrates of intrinsic alertness may be accessed by phasic alertness provided that the attention-dominant (i.e., the right) hemisphere is activated directly by a warning stimulus.

  10. Intraindividual reaction time variability affects P300 amplitude rather than latency

    Directory of Open Access Journals (Sweden)

    Anusha eRamchurn

    2014-07-01

    Full Text Available The neural correlates of intraindividual response variability were investigated in a serial choice reaction time (CRT task. Reaction times (RTs from the faster and slower portions of the RT distribution for the task were separately aggregated and associated P300 event-related potentials computed. Independent behavioral measures of executive function and IQ were also recorded. Across frontal, fronto-central, central, centro-parietal and parietal scalp regions, P300 amplitudes were significantly greater for faster relative to slower behavioral responses. However, P300 peak amplitude latencies did not differ according to the speed of the behavioral RT. Importantly, controlling for select independent measures of executive function attenuated shared variance in P300 amplitude for faster and slower trials. The findings suggest that P300 amplitude rather than latency is associated with the speed of behavioral RTs, and the possibility that fluctuations in executive control underlie variability in speeded responding.

  11. Latency of multifocal visual evoked potentials in nonoptic neuritis eyes of multiple sclerosis patients associated with optic radiation lesions.

    Science.gov (United States)

    Alshowaeir, Daniah; Yiannikas, Con; Garrick, Raymond; Parratt, John; Barnett, Michael H; Graham, Stuart L; Klistorner, Alexander

    2014-05-15

    The aim of the study was to test the hypothesis that latency delay of multifocal visual evoked potentials (mfVEP) in nonoptic neuritis (NON) eyes of multiple sclerosis (MS) patients is related to retrochiasmal demyelinating lesions. A total of 57 MS patients with no history of optic neuritis at least in one eye, and 25 age- and sex-matched healthy controls was enrolled. Probabilistic tractography was used to reconstruct optic radiation (OR) fibers. The MS lesion volume within and outside of OR was calculated. Diffusion tensor imaging (DTI) indices were measured along OR fibers. The relationship of the mfVEP latency with OR lesions and DTI indices was examined. Average mfVEP latency in the MS cohort was significantly delayed compared to controls (P < 0.0001). Of the patients, 77% demonstrated OR lesions. Axial, radial, and mean diffusivity were significantly abnormal in MS patients (P < 0.001). Partial correlation demonstrated significant association between mfVEP latency delay and OR lesion load. There was also significant correlation between MfVEP latency and OR DTI. Subgroup analysis revealed significantly higher correlations in patients without a history of ON in either eye compared to the fellow eye of patients with previous ON. The findings of this study support our hypothesis that latency delay of the mfVEP in eyes of MS patients without previous ON is related to retrogenicular demyelinating lesions. Additionally, this study demonstrated that a previous episode of ON in the fellow eye may be a significant confounding factor, masking the relationship between the latency and OR lesions. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  12. Reproducibility of multifocal VEP latency using different stimulus presentations.

    Science.gov (United States)

    Sriram, Prema; Klistorner, Alexander; Arvind, Hemamalini; Graham, Stuart L

    2012-08-01

    The aims of the article were to study the reproducibility of latency of multifocal visual evoked potential (mfVEP) recorded using different stimulus presentations and to identify the peak with least variability. Ten normal subjects, aged between 22 and 52 years (mean age 32 ± 8.37 years), participated in the study. All subjects underwent mfVEP testing with pattern reversal and pattern pulse stimulus presentations. The stimulus subtends 26° from fixation and includes 24 segments. Only the vertical channel was recorded on all subjects. Testing was repeated after 1-2 weeks. Only the right eye of all subjects was analysed. Segments with low signal-to-noise ratios (SNR < 1.5) were excluded from analysis. The latencies were analysed to confirm values from the same peak for the two tests. The latency values were then analysed for the start of the response, the first peak and the second peak. The waveforms were reproducible throughout the field. Reproducibility of latency at the "start of the response" was significantly lesser than the first and the second peaks studied, while the reproducibility of latency at the first peak was not statistically different from the second peak for either pattern reversal or pattern pulse stimulation. The latency values were not different between the first and the second sessions for either pattern reversal or pattern pulse stimulation for any of the peaks. The pattern reversal stimulus presentation produced less variability in latency. The first peak is the most reproducible among the three measures in both the stimulus presentation.

  13. Long latency trigemino-cervical reflex in patients with cervical dystonia.

    Science.gov (United States)

    Gündüz, Ayşegül; Ergin, Hayal; Kızıltan, Meral E

    2015-01-01

    Trigemino-cervical reflex (TCR) is elicited by stimulation of face using various modalities. TCR reflects the interaction between trigeminal system and cervical motoneurons. Such a specific interaction is assumed to play role in development of cervical dystonia (CD) through superior colliculus. In this study, we aimed to investigate alterations of the functional relationship between those structures in CD and in a subgroup with dystonic tremor. A total of consecutive 23 patients with primary CD (7 men, 16 women) and 16 age and sex matched control subjects (7 men, 9 women) were included in this study. TCR was obtained after percutaneous electrical stimulation (with duration of 0.5 ms) of infraorbital branch of trigeminal nerve while recording over splenius capitis and sternocleidomastoid muscles. Presence and onset latencies of TCR did not differ significantly between patients with CD and controls, and same pattern of muscle activation occurred in both groups. Responses of patient group seemed to have higher amplitudes and to be more persistent. There were no significant side-to-side differences of TCR probability, latency, amplitude or duration with respect to the side of head deviation in CD. Increased amplitudes and durations of responses probably reflect increased excitability of the reflex circuit. We suggest that similar latencies and response pattern in comparison to healthy individuals decrease the possibility of structural disturbance. TCR is probably under bilateral basal ganglia and dopaminergic control. Alterations of trigemino-cervical pathway are more extensive and are not solely due to local changes of brainstem interneurons.

  14. An improved approximation ratio for the minimum latency problem

    Energy Technology Data Exchange (ETDEWEB)

    Goemans, M.; Kleinberg, J. [MIT, Cambridge, MA (United States)

    1996-12-31

    Given a tour visiting n points in a metric space, the latency of one of these points p is the distance traveled in the tour before reaching p. The minimum latency problem asks for a tour passing through n given points for which the total latency of the n points is minimum; in effect, we are seeking the tour with minimum average {open_quotes}arrival time.{close_quotes} This problem has been studied in the operations research literature, where it has also been termed the {open_quotes}delivery-man problem{close_quotes} and the {open_quotes}traveling repairman problem.{close_quotes} The approximability of the minimum latency problem was first considered by Sahni and Gonzalez in 1976; however, unlike the classical traveling salesman problem, it is not easy to give any constant-factor approximation algorithm for the minimum latency problem. Recently, Blum, Chalasani, Coppersmith, Pulleyblank, Raghavan, and Sudan gave the first such algorithm, obtaining an approximation ratio of 144. In this work, we present an algorithm which improves this ratio to 21.55. The development of our algorithm involves a number of techniques that seem to be of interest from the perspective of the traveling salesman problem and its variants more generally.

  15. An evolutionary role for HIV latency in enhancing viral transmission.

    Science.gov (United States)

    Rouzine, Igor M; Weinberger, Ariel D; Weinberger, Leor S

    2015-02-26

    HIV latency is the chief obstacle to eradicating HIV but is widely believed to be an evolutionary accident providing no lentiviral fitness advantage. However, findings of latency being "hardwired" into HIV's gene-regulatory circuitry appear inconsistent with latency being an evolutionary accident, given HIV's rapid mutation rate. Here, we propose that latency is an evolutionary "bet-hedging" strategy whose frequency has been optimized to maximize lentiviral transmission by reducing viral extinction during mucosal infections. The model quantitatively fits the available patient data, matches observations of high-frequency latency establishment in cell culture and primates, and generates two counterintuitive but testable predictions. The first prediction is that conventional CD8-depletion experiments in SIV-infected macaques increase latent cells more than viremia. The second prediction is that strains engineered to have higher replicative fitness—via reduced latency—will exhibit lower infectivity in animal-model mucosal inoculations. Therapeutically, the theory predicts treatment approaches that may substantially enhance "activate-and-kill" HIV-cure strategies. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans.

    Science.gov (United States)

    Di Lazzaro, V; Oliviero, A; Saturno, E; Dileone, M; Pilato, F; Nardone, R; Ranieri, F; Musumeci, G; Fiorilla, T; Tonali, P

    2005-04-15

    Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA(A) receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA(A) activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA(A) activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI (F(3,9) = 3.19, P = 0.039). In contrast to SICI, SAI was significantly reduced by lorazepam (F(3,9) = 9.39, P = 0.0002). Our findings demonstrate that GABA(A) activity enhancement determines a suppression of SAI and an increase of SICI.

  17. Speeding up parallel GROMACS on high-latency networks.

    Science.gov (United States)

    Kutzner, Carsten; van der Spoel, David; Fechner, Martin; Lindahl, Erik; Schmitt, Udo W; de Groot, Bert L; Grubmüller, Helmut

    2007-09-01

    We investigate the parallel scaling of the GROMACS molecular dynamics code on Ethernet Beowulf clusters and what prerequisites are necessary for decent scaling even on such clusters with only limited bandwidth and high latency. GROMACS 3.3 scales well on supercomputers like the IBM p690 (Regatta) and on Linux clusters with a special interconnect like Myrinet or Infiniband. Because of the high single-node performance of GROMACS, however, on the widely used Ethernet switched clusters, the scaling typically breaks down when more than two computer nodes are involved, limiting the absolute speedup that can be gained to about 3 relative to a single-CPU run. With the LAM MPI implementation, the main scaling bottleneck is here identified to be the all-to-all communication which is required every time step. During such an all-to-all communication step, a huge amount of messages floods the network, and as a result many TCP packets are lost. We show that Ethernet flow control prevents network congestion and leads to substantial scaling improvements. For 16 CPUs, e.g., a speedup of 11 has been achieved. However, for more nodes this mechanism also fails. Having optimized an all-to-all routine, which sends the data in an ordered fashion, we show that it is possible to completely prevent packet loss for any number of multi-CPU nodes. Thus, the GROMACS scaling dramatically improves, even for switches that lack flow control. In addition, for the common HP ProCurve 2848 switch we find that for optimum all-to-all performance it is essential how the nodes are connected to the switch's ports. This is also demonstrated for the example of the Car-Parinello MD code.

  18. Predicting naming latencies for action pictures: Dutch norms.

    Science.gov (United States)

    Shao, Zeshu; Roelofs, Ardi; Meyer, Antje S

    2014-03-01

    The present study provides Dutch norms for age of acquisition, familiarity, imageability, image agreement, visual complexity, word frequency, and word length (in syllables) for 124 line drawings of actions. Ratings were obtained from 117 Dutch participants. Word frequency was determined on the basis of the SUBTLEX-NL corpus (Keuleers, Brysbaert, & New, Behavior Research Methods, 42, 643-650, 2010). For 104 of the pictures, naming latencies and name agreement were determined in a separate naming experiment with 74 native speakers of Dutch. The Dutch norms closely corresponded to the norms for British English. Multiple regression analysis showed that age of acquisition, imageability, image agreement, visual complexity, and name agreement were significant predictors of naming latencies, whereas word frequency and word length were not. Combined with the results of a principal-component analysis, these findings suggest that variables influencing the processes of conceptual preparation and lexical selection affect latencies more strongly than do variables influencing word-form encoding.

  19. [Long-latency auditory evoked potentials in cochlear implants].

    Science.gov (United States)

    Mata, J J; Jiménez, J M; Pérez, J; Postigo, A; Roldán, B

    1999-01-01

    Cortical evoked potentials were evaluated in patients with cochlear implants. In a group of 8 adults of different ages, the lingual state before implantation and during rehabilitation were evaluated. Using cortical evoked potentials, the results of the P300 wave in response to two tones, one frequent (1,000 Hz) and the other infrequent (2,000 Hz), presented at 70 and 80 dB HL were studied. Results were analyzed and compared in relation to locutive state, rehabilitation stage, and intensity of stimulus. Absolute latencies did not differ significantly. However, latency values in relation to reaction time were significantly longer in prelingual than in postlingual patients (p test). The results confirmed the normality of central cognitive processes in patients with cochlear implants in objective assessment of P300 latency. The results suggest differences between prelingual and postlingual patients in relation to central signal processing.

  20. Effects of psychot herapy on REM latency and REM time.

    Science.gov (United States)

    Karle, W; Hopper, M; Switzer, A; Corriere, R; Woldenberg, L

    1980-08-01

    This study investigated the effect of a functional psychotherapy on the sleep EEG patterns of 6 patients. Contrary to original expectations no significant group differences in REM time and REM latency were found between two nights following therapy sessions and two normal nights. However, across the 4 nights the patients exhibited an average REM latency of 71 min. which was significantly shorter than that recorded in an independent study with the same design and a similar subject population. Clausen, Sersen, and Lidsky (1974) reported an average REM latency of 107.3 min. for 10 normal subjects also recorded across four nights. This result is compared with those in several other studies and discussed in relation to possible changes in dream patterns.

  1. Low-latency multi-threaded processing of neuronal signals for brain-computer interfaces

    Directory of Open Access Journals (Sweden)

    Jörg eFischer

    2014-01-01

    Full Text Available Brain-computer interfaces (BCIs require demanding numerical computations to transfer brain signals into control signals driving an external actuator. Increasing the computational performance of the BCI algorithms carrying out these calculations enables faster reaction to user inputs and allows using more demanding decoding algorithms. Here we introduce a modular and extensible software architecture with a multi-threaded signal processing pipeline suitable for BCI applications. The computational load and latency (the time that the system needs to react to user input are measured for different pipeline implementations in typical BCI applications with realistic parameter settings. We show that BCIs can benefit substantially from the proposed parallelization: firstly, by reducing the latency and secondly, by increasing the amount of recording channels and signal features that can be used for decoding beyond the amount which can be handled by a single thread. The proposed software architecture provides a simple, yet flexible solution for BCI applications.

  2. [Multiple latency test in a patient with episodes of sleep induced by pergolide].

    Science.gov (United States)

    Jiménez-Jiménez, F J; Velasco, I; de Toledo, M; Sayed, Y; Zurdo, J; Ortí-Pareja, M

    Recently, there have been report sleep attacks in parkinsonian patients as a side effect of pramipexole and ropinirole. We report a patient with similar episodes related with pergolide. A 64 year old man with rigid akinetic parkinsonism, treated with carbidopa/levodopa and pergolide, developed sudden, irresistible sleep episodes after increasing the dose of pergolide to 2.25 mg/day because of bad control of parkinsonian symptoms. These episodes started 30 minutes after each dose of pergolide and lasted 2 hours. Following reduction of the dose of pergolide to 1.5 mg/day the sleep episodes disappeared. Two double blind multiple sleep latency tests were performed, one after intaking pergolide and other after intaking placebo. The latencies to sleep onset were lower with pergolide than with placebo, but the differences did not reach statistical significance. There was no premature REM sleep onset. Sleep episodes are likely a not specific effect of dopamine agonists

  3. Pudendal nerve latency time in normal women via intravaginal stimulation

    Directory of Open Access Journals (Sweden)

    Geraldo A. Cavalcanti

    2006-12-01

    Full Text Available INTRODUCTION & OBJECTIVES: Studies of motor conduction for the efferent functional assessment of the pudendal nerve in women with pelvic dysfunctions have been conducted through researching distal motor latency times. The transrectal approach has been the classic approach for this electrophysiological examination. The objective of the present study is to verify the viability of the transvaginal approach in performing the exam, to establish normal values for this method and to analyze the influence of age, stature and parity in the latency value of normal women. MATERIALS AND METHODS: A total of 23 volunteers without genitourinary pathologies participated in this study. In each, pudendal motor latency was investigated through the transvaginal approach, which was chosen due to patient’s higher tolerance levels. RESULTS: The motor response represented by registering the M-wave was obtained in all volunteers on the right side (100% and in 13 volunteers on the left side (56.5%. The mean motor latency obtained in the right and left was respectively: 1.99 ± 0.41 and 1.92 ± 0.48 milliseconds (ms. There was no difference between the sides (p = 0.66. Latency did not correlate with age, stature or obstetric history. The results obtained in the present study were in agreement with those found by other researchers using the transrectal approach. CONCLUSION: The vaginal approach represents an alternative for pudendal nerve distal motor latency time, with similar results to those achieved through the transrectal approach. Normative values obtained herein might serve as a comparative basis for subsequent physiopathological studies.

  4. Scalla: Structured Cluster Architecture for Low Latency Access

    Energy Technology Data Exchange (ETDEWEB)

    Hanushevsky, Andrew; Wang, Daniel L.; /SLAC

    2012-03-20

    Scalla is a distributed low-latency file access system that incorporates novel techniques that minimize latency and maximize scalability over a large distributed system with a distributed namespace. Scalla's techniques have shown to be effective in nearly a decade of service for the high-energy physics community using commodity hardware and interconnects. We describe the two components used in Scalla that are instrumental in its ability to provide low-latency, fault-tolerant name resolution and load distribution, and enable its use as a high-throughput, low-latency communication layer in the Qserv system, the Large Synoptic Survey Telescope's (LSST's) prototype astronomical query system. Scalla arguably exceeded its three main design objectives: low latency, scaling, and recoverability. In retrospect, these objectives were met using a simple but effective design. Low latency was met by uniformly using linear or constant time algorithms in all high-use paths, avoiding locks whenever possible, and using compact data structures to maximize the memory caching efficiency. Scaling was achieved by architecting the system as a 64-ary tree. Nodes can be added easily and as the number of nodes increases, search performance increases at an exponential rate. Recoverability is inherent in that no permanent state information is maintained and whatever state information is needed it can be quickly constructed or reconstructed in real time. This allows dynamic changes in a cluster of servers with little impact on over-all performance or usability. Today, Scalla is being deployed in environments and for uses that were never conceived in 2001. This speaks well for the systems adaptability but the underlying reason is that the system can meet its three fundamental objectives at the same time.

  5. Goal-dependent modulation of the long-latency stretch response at the shoulder, elbow, and wrist.

    Science.gov (United States)

    Weiler, Jeffrey; Gribble, Paul L; Pruszynski, J Andrew

    2015-12-01

    Many studies have demonstrated that muscle activity 50-100 ms after a mechanical perturbation (i.e., the long-latency stretch response) can be modulated in a manner that reflects voluntary motor control. These previous studies typically assessed modulation of the long-latency stretch response from individual muscles rather than how this response is concurrently modulated across multiple muscles. Here we investigated such concurrent modulation by having participants execute goal-directed reaches to visual targets after mechanical perturbations of the shoulder, elbow, or wrist while measuring activity from six muscles that articulate these joints. We found that shoulder, elbow, and wrist muscles displayed goal-dependent modulation of the long-latency stretch response, that the relative magnitude of participants' goal-dependent activity was similar across muscles, that the temporal onset of goal-dependent muscle activity was not reliably different across the three joints, and that shoulder muscles displayed goal-dependent activity appropriate for counteracting intersegmental dynamics. We also observed that the long-latency stretch response of wrist muscles displayed goal-dependent modulation after elbow perturbations and that the long-latency stretch response of elbow muscles displayed goal-dependent modulation after wrist perturbations. This pattern likely arises because motion at either joint could bring the hand to the visual target and suggests that the nervous system rapidly exploits such simple kinematic redundancy when processing sensory feedback to support goal-directed actions.

  6. Low-latency Science Exploration of Planetary Bodies: a Demonstration Using ISS in Support of Mars Human Exploration

    Science.gov (United States)

    Thronson, Harley A.; Valinia, Azita; Bleacher, Jacob; Eigenbrode, Jennifer; Garvin, Jim; Petro, Noah

    2014-01-01

    We summarize a proposed experiment to use the International Space Station to formally examine the application and validation of low-latency telepresence for surface exploration from space as an alternative, precursor, or potentially as an adjunct to astronaut "boots on the ground." The approach is to develop and propose controlled experiments, which build upon previous field studies and which will assess the effects of different latencies (0 to 500 msec), task complexity, and alternate forms of feedback to the operator. These experiments serve as an example of a pathfinder for NASA's roadmap of missions to Mars with low-latency telerobotic exploration as a precursor to astronaut's landing on the surface to conduct geological tasks.

  7. Hippocampal serotonin responses in short and long attack latency mice

    NARCIS (Netherlands)

    van Riel, E; Meijer, OC; Veenema, AH; Joëls, M

    2002-01-01

    Short and long attack latency mice, which are selected based on their offensive behaviour in a resident-intruder model, differ in their neuroendocrine regulation as well as in aspects of their brain serotonin system. Previous studies showed that the binding capacity and expression of serotonin-1A re

  8. Development of an RNA Assay to Assess HIV I Latency

    Science.gov (United States)

    1993-01-10

    current study is limited to examining cellular RNAs rather than free genomic RNA in the plasma. Ottmann and colleagues demonstrated HIV-1 genomic RNA in 95...aberrant pattern of viral RNA expression: a molecular model for latency. Cell 1990; 61:1271-1276. 25 Ottmann M, Innocenti P, Tenadey M, Micoud M

  9. Monitoring data transfer latency in CMS computing operations

    CERN Document Server

    Bonacorsi, D; Magini, N; Sartirana, A; Taze, M; Wildish, T

    2015-01-01

    During the first LHC run, the CMS experiment collected tens of Petabytes of collision and simulated data, which need to be distributed among dozens of computing centres with low latency in order to make efficient use of the resources. While the desired level of throughput has been successfully achieved, it is still common to observe transfer workflows that cannot reach full completion in a timely manner due to a small fraction of stuck files which require operator intervention.For this reason, in 2012 the CMS transfer management system, PhEDEx, was instrumented with a monitoring system to measure file transfer latencies, and to predict the completion time for the transfer of a data set. The operators can detect abnormal patterns in transfer latencies while the transfer is still in progress, and monitor the long-term performance of the transfer infrastructure to plan the data placement strategy.Based on the data collected for one year with the latency monitoring system, we present a study on the different fact...

  10. Latency requirements for head-worn display S/EVS applications

    Science.gov (United States)

    Bailey, Randall E.; Arthur, Jarvis J., III; Williams, Steven P.

    2004-08-01

    NASA's Aviation Safety Program, Synthetic Vision Systems Project is conducting research in advanced flight deck concepts, such as Synthetic/Enhanced Vision Systems (S/EVS), for commercial and business aircraft. An emerging thrust in this activity is the development of spatially-integrated, large field-of-regard information display systems. Head-worn or helmet-mounted display systems are being proposed as one method in which to meet this objective. System delays or latencies inherent to spatially-integrated, head-worn displays critically influence the display utility, usability, and acceptability. Research results from three different, yet similar technical areas - flight control, flight simulation, and virtual reality - are collectively assembled in this paper to create a global perspective of delay or latency effects in head-worn or helmet-mounted display systems. Consistent definitions and measurement techniques are proposed herein for universal application and latency requirements for Head-Worn Display S/EVS applications are drafted. Future research areas are defined.

  11. Is the long-latency stretch reflex in human masseter transcortical?

    Science.gov (United States)

    Pearce, Sophie L; Miles, Timothy S; Thompson, Philip D; Nordstrom, Michael A

    2003-06-01

    A long-latency stretch reflex (LLSR) has been described in the human masseter muscle, but its pathway remains uncertain. To investigate this, the excitability of corticomotoneuronal (CM) cells projecting to masseter motoneurons during the LLSR was assessed with transcranial magnetic stimulation (TMS). A facilitated response to TMS would be evidence of a LLSR pathway that traverses the motor cortex. Surface electromyogram electrodes were placed over the left or right masseter, and subjects ( n=10) bit on bars with their incisor teeth at 10% of maximal electromyographic activity (EMG). Servo-controlled displacements were imposed on the lower jaw to evoke a short- and long-latency stretch reflex in masseter. TMS intensity was just suprathreshold for a response in contralateral masseter. Trials consisted of: (1) stretch alone, (2) TMS alone, and (3) TMS with a preceding conditioning stretch at varied conditioning-testing (C-T) intervals chosen to combine TMS with the short-latency stretch reflex (3 ms, 5 ms) and the LLSR (23-41 ms). Masseter EMG was rectified and averaged. With TMS alone, mean (+/- SE) MEP area above baseline was 56+/-9%. The area of masseter MEPs above baseline in the C-T trials was calculated from each EMG average following subtraction of the response to stretch alone. Conditioning muscle stretch had no significant effect on masseter MEPs evoked by TMS with any C-T interval (ANOVA; P=0.90). In addition, subjects were unable to modify the SLSR or LLSR by voluntary command. It is concluded that the long-latency stretch reflex in the masseter does not involve the motor cortex and is not influenced by "motor set".

  12. Low-latency video transmission over high-speed WPANs based on low-power video compression

    DEFF Research Database (Denmark)

    Belyaev, Eugeniy; Turlikov, Andrey; Ukhanova, Ann

    2010-01-01

    This paper presents latency-constrained video transmission over high-speed wireless personal area networks (WPANs). Low-power video compression is proposed as an alternative to uncompressed video transmission. A video source rate control based on MINMAX quality criteria is introduced. Practical...

  13. Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi's sarcoma.

    Directory of Open Access Journals (Sweden)

    Bruno C Jham

    Full Text Available BACKGROUND: Kaposi's sarcoma (KS is a vascular neoplasm characterized by the dysregulated expression of angiogenic and inflammatory cytokines. The driving force of the KS lesion, the KSHV-infected spindle cell, secretes elevated levels of vascular endothelial growth factor (VEGF, essential for KS development. However, the origin of VEGF in this tumor remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that the KSHV G protein-coupled receptor (vGPCR upregulates VEGF in KS through an intricate paracrine mechanism. The cytokines secreted by the few vGPCR-expressing tumor cells activate in neighboring cells multiple pathways (including AKT, ERK, p38 and IKKβ that, in turn, converge on TSC1/2, promoting mTOR activation, HIF upregulation, and VEGF secretion. Conditioned media from vGPCR-expressing cells lead to an mTOR-dependent increase in HIF-1α and HIF-2α protein levels and VEGF upregulation. In a mouse allograft model for KS, specific inhibition of the paracrine activation of mTOR in non-vGPCR-expressing cells was sufficient to inhibit HIF upregulation in these cells, and abolished the ability of the vGPCR-expressing cells to promote tumor formation in vivo. Similarly, pharmacologic inhibition of HIF in this model blocked VEGF secretion and also lead to tumor regression. CONCLUSIONS/SIGNIFICANCE: Our findings provide a compelling explanation for how the few tumor cells expressing vGPCR can contribute to the dramatic amplification of VEGF secretion in KS, and further provide a molecular mechanism for how cytokine dysregulation in KS fuels angiogenesis and tumor development. These data further suggest that activation of HIF by vGPCR may be a vulnerable target for the treatment of patients with KS.

  14. NEEMO 18-20: Analog Testing for Mitigation of Communication Latency During Human Space Exploration

    Science.gov (United States)

    Chappell, Steven P.; Beaton, Kara H.; Miller, Matthew J.; Graff, Trevor G.; Abercromby, Andrew F. J.; Gernhardt, Michael L.; Halcon, Christopher

    2016-01-01

    NASA Extreme Environment Mission Operations (NEEMO) is an underwater spaceflight analog that allows a true mission-like operational environment and uses buoyancy effects and added weight to simulate different gravity levels. Three missions were undertaken from 2014-2015, NEEMO's 18-20. All missions were performed at the Aquarius undersea research habitat. During each mission, the effects of communication latencies on operations concepts, timelines, and tasks were studied. METHODS: Twelve subjects (4 per mission) were weighed out to simulate near-zero or partial gravity extravehicular activity (EVA) and evaluated different operations concepts for integration and management of a simulated Earth-based science team (ST) to provide input and direction during exploration activities. Exploration traverses were preplanned based on precursor data. Subjects completed science-related tasks including pre-sampling surveys, geologic-based sampling, and marine-based sampling as a portion of their tasks on saturation dives up to 4 hours in duration that were designed to simulate extravehicular activity (EVA) on Mars or the moons of Mars. One-way communication latencies, 5 and 10 minutes between space and mission control, were simulated throughout the missions. Objective data included task completion times, total EVA times, crew idle time, translation time, ST assimilation time (defined as time available for ST to discuss data/imagery after data acquisition). Subjective data included acceptability, simulation quality, capability assessment ratings, and comments. RESULTS: Precursor data can be used effectively to plan and execute exploration traverse EVAs (plans included detailed location of science sites, high-fidelity imagery of the sites, and directions to landmarks of interest within a site). Operations concepts that allow for pre-sampling surveys enable efficient traverse execution and meaningful Mission Control Center (MCC) interaction across communication latencies and can be

  15. A Detailed Chunk-Level Performance Study of Web Page Retrieve Latency

    Institute of Scientific and Technical Information of China (English)

    XIE Hai-guang; LI Jian-hua; LI Xiang

    2005-01-01

    It is a widely discussed question that where the web latency comes from. In this paper, we propose a novel chunk-level latency dependence model to give a better illustration of the web latency. Based on the fact that web content is delivered in chunk sequence, and clients care more about whole page retrieval latency, this paper carries out a detailed study on how the chunk sequence and relations affect the web retrieval latency. A series of thorough experiments are also conducted and data analysis are also made. The result is useful for further study on how to reduce the web latency.

  16. Performance Evaluation of L3 Handover Latency in MIPv6

    Directory of Open Access Journals (Sweden)

    D.Kavitha,

    2011-06-01

    Full Text Available Recent years in the field of mobile communications have brought two significant requirements – seamless service delivery and Quality of Service provisioning. Seamless mobility goes hand in hand withMobile IPv6 protocol and various handover schemes of this protocol are trying to solve the QoS issue. In this paper we are presenting a method for evaluation of the Layer 3 handover schemes from the handover latency point of view. A L3 handover procedure can be divided into four phases: Movement Detection, CoA Configuration, Home agent Registration and Route Optimization. We simulated the proposed protocol certificate based on Demand Approach in Route Optimization phase and compared it with the return routability procedure in Route Optimization phase of MIPv6 handover. The latencies in different handover phases have been measured in an operated wireless LAN (WLAN in order to determine the performance bottleneck of handover.

  17. A review of the methods for neuronal response latency estimation

    DEFF Research Database (Denmark)

    Levakovaa, Marie; Tamborrino, Massimiliano; Ditlevsen, Susanne;

    2015-01-01

    Neuronal response latency is usually vaguely defined as the delay between the stimulus onset and the beginning of the response. It contains important information for the understanding of the temporal code. For this reason, the detection of the response latency has been extensively studied...... in the last twenty years, yielding different estimation methods. They can be divided into two classes, one of them including methods based on detecting an intensity change in the firing rate profile after the stimulus onset and the other containing methods based on detection of spikes evoked...... by the stimulation using interspike intervals and spike times. The aim of this paper is to present a review of the main techniques proposed in both classes, highlighting their advantages and shortcomings....

  18. Rewards modulate saccade latency but not exogenous spatial attention.

    Directory of Open Access Journals (Sweden)

    Stephen eDunne

    2015-07-01

    Full Text Available The eye movement system is sensitive to reward. However, whilst the eye movement system is extremely flexible, the extent to which changes to oculomotor behaviour induced by reward paradigms persist beyond the training period or transfer to other oculomotor tasks is unclear. To address these issues we examined the effects of presenting feedback that represented small monetary rewards to spatial locations on the latency of saccadic eye movements, the time-course of learning and extinction of the effects of rewarding saccades on exogenous spatial attention and oculomotor IOR. Reward feedback produced a relative facilitation of saccadic latency in a stimulus driven saccade task which persisted for 3 blocks of extinction trials. However this hemifield-specific effect failed to transfer to peripheral cueing tasks. We conclude that rewarding specific spatial locations is unlikely to induce long-term, systemic changes to the human oculomotor or attention systems.

  19. A novel reversible carry-selected adder with low latency

    Science.gov (United States)

    Li, Ming-Cui; Zhou, Ri-Gui

    2016-07-01

    Reversible logic is getting more and more attention in quantum computing, optical computing, nanotechnology and low-power complementary metal oxide semiconductor designs since reversible circuits do not loose information during computation and have only small energy dissipation. In this paper, a novel carry-selected reversible adder is proposed primarily optimised for low latency. A 4-bit reversible full adder with two kinds of outputs, minimum delay and optimal quantum cost is presented as the building block for ?-bit reversible adder. Three new reversible gates NPG (new Peres gate), TEPG (triple extension of Peres gate) and RMUX21 (reversible 2-to-1 multiplexer) are proposed and utilised to design efficient adder units. The secondary carry propagation chain is carefully designed to reduce the time consumption. The novelty of the proposed design is the consideration of low latency. The comparative study shows that the proposed adder achieves the improvement from 61.46% to 95.29% in delay over the existing designs.

  20. Fundamental Tradeoffs among Reliability, Latency and Throughput in Cellular Networks

    DEFF Research Database (Denmark)

    Soret, Beatriz; Mogensen, Preben; Pedersen, Klaus I.

    2014-01-01

    We address the fundamental tradeoffs among latency, reliability and throughput in a cellular network. The most important elements influencing the KPIs in a 4G network are identified, and the inter-relationships among them is discussed. We use the effective bandwidth and the effective capacity...... theory as analytical framework for calculating the maximum achievable rate for a given latency and reliability constraint. The analysis is conducted in a simplified LTE network, providing baseline - yet powerful - insight of the main tradeoffs. Guidelines to extend the theory to more complex systems...... are also presented, including a semi-analytical approach for cases with intractable channel and traffic models. We also discuss the use of system-level simulations to explore the limits of LTE networks. Based on our findings, we give some recommendations for the imminent 5G technology design phase...

  1. Low latency remote memory access on the Intel Paragon

    Energy Technology Data Exchange (ETDEWEB)

    Rosing, M. [Pacific Northwest Lab., Richland, WA (United States); Pierce, P. [Idaho National Engineering Lab., Idaho Falls, ID (United States)

    1994-06-20

    We describe a cooperative project between Pacific Northwest Laboratory and Intel on providing low latency communications on the Intel Paragon. Our interest is in developing modules that are tailored to specific types of communication and are optimized for these cases. The modules described are implemented as simple extensions to the Paragon operating system. The first extension supports remote reads, writes, and accumulates on subsections of matrices. This module is intended to be used where the communication pattern is not known until run time. The second extension is designed to support low latency communication for short messages in a pipelined fashion. Finally, an interface for doing highly structured communication where the patterns of communication are well understood ahead of time is described. This is intended to be used in global communications such as global reduction.

  2. Influence of P300 latency jitter on event related potential-based brain-computer interface performance

    Science.gov (United States)

    Aricò, P.; Aloise, F.; Schettini, F.; Salinari, S.; Mattia, D.; Cincotti, F.

    2014-06-01

    Objective. Several ERP-based brain-computer interfaces (BCIs) that can be controlled even without eye movements (covert attention) have been recently proposed. However, when compared to similar systems based on overt attention, they displayed significantly lower accuracy. In the current interpretation, this is ascribed to the absence of the contribution of short-latency visual evoked potentials (VEPs) in the tasks performed in the covert attention modality. This study aims to investigate if this decrement (i) is fully explained by the lack of VEP contribution to the classification accuracy; (ii) correlates with lower temporal stability of the single-trial P300 potentials elicited in the covert attention modality. Approach. We evaluated the latency jitter of P300 evoked potentials in three BCI interfaces exploiting either overt or covert attention modalities in 20 healthy subjects. The effect of attention modality on the P300 jitter, and the relative contribution of VEPs and P300 jitter to the classification accuracy have been analyzed. Main results. The P300 jitter is higher when the BCI is controlled in covert attention. Classification accuracy negatively correlates with jitter. Even disregarding short-latency VEPs, overt-attention BCI yields better accuracy than covert. When the latency jitter is compensated offline, the difference between accuracies is not significant. Significance. The lower temporal stability of the P300 evoked potential generated during the tasks performed in covert attention modality should be regarded as the main contributing explanation of lower accuracy of covert-attention ERP-based BCIs.

  3. Stochastic Game Analysis and Latency Awareness for Self-Adaptation

    Science.gov (United States)

    2014-01-01

    Tactic: is a primitive action that corresponds to a single step of adaptation, and has an associated: (i) cost/benefit impact on the different quality...dimensions, and (ii) latency, which corresponds to the time it takes since a tactic is started until its effect is observed.2 For instance, in... Gandhi et al. considers the setup time of servers, and is able to deal with unpredictable changes in load by be- ing conservative about removing servers

  4. Herpes Simplex Virus Latency: The DNA Repair-Centered Pathway

    Directory of Open Access Journals (Sweden)

    Jay C. Brown

    2017-01-01

    Full Text Available Like all herpesviruses, herpes simplex virus 1 (HSV1 is able to produce lytic or latent infections depending on the host cell type. Lytic infections occur in a broad range of cells while latency is highly specific for neurons. Although latency suggests itself as an attractive target for novel anti-HSV1 therapies, progress in their development has been slowed due in part to a lack of agreement about the basic biochemical mechanisms involved. Among the possibilities being considered is a pathway in which DNA repair mechanisms play a central role. Repair is suggested to be involved in both HSV1 entry into latency and reactivation from it. Here I describe the basic features of the DNA repair-centered pathway and discuss some of the experimental evidence supporting it. The pathway is particularly attractive because it is able to account for important features of the latent response, including the specificity for neurons, the specificity for neurons of the peripheral compared to the central nervous system, the high rate of genetic recombination in HSV1-infected cells, and the genetic identity of infecting and reactivated virus.

  5. Using Arduino microcontroller boards to measure response latencies.

    Science.gov (United States)

    Schubert, Thomas W; D'Ausilio, Alessandro; Canto, Rosario

    2013-12-01

    Latencies of buttonpresses are a staple of cognitive science paradigms. Often keyboards are employed to collect buttonpresses, but their imprecision and variability decreases test power and increases the risk of false positives. Response boxes and data acquisition cards are precise, but expensive and inflexible, alternatives. We propose using open-source Arduino microcontroller boards as an inexpensive and flexible alternative. These boards connect to standard experimental software using a USB connection and a virtual serial port, or by emulating a keyboard. In our solution, an Arduino measures response latencies after being signaled the start of a trial, and communicates the latency and response back to the PC over a USB connection. We demonstrated the reliability, robustness, and precision of this communication in six studies. Test measures confirmed that the error added to the measurement had an SD of less than 1 ms. Alternatively, emulation of a keyboard results in similarly precise measurement. The Arduino performs as well as a serial response box, and better than a keyboard. In addition, our setup allows for the flexible integration of other sensors, and even actuators, to extend the cognitive science toolbox.

  6. Latencies of extracted distortion-product otoacoustic source components

    Science.gov (United States)

    Zelle, Dennis; Thiericke, John P.; Gummer, Anthony W.; Dalhoff, Ernst

    2015-12-01

    Distortion product otoacoustic emissions (DPOAEs) evolve as a byproduct of the nonlinear amplification process of two stimulus tones f2 ≥ f1 in the cochlea. According to a prevailing model, DPOAEs comprise a nonlinear-generation and a coherent-reflection component. Recently, we introduced a new technique using short f2 pulses which enables the extraction of both source components in the time domain by nonlinear least-square curve fitting to decompose the DPOAE response into pulse basis functions (PBFs). The analysis of the extracted DPOAE source components in the time domain enables determination of their latencies which may be used to estimate cochlear frequency tuning. Short-pulse DPOAEs were acquired from 16 subjects for f2 = 1.5, 2, 3, and 4 kHz using six primary-tone levels with L2 = 25 - 65 dB SPL. For the extracted nonlinear-generation and coherent-reflection components, latencies decrease with increasing stimulus frequency and level. The obtained latency values are in accordance with the expected behavior of the cochlear amplifier and may provide an additional diagnostic parameter to assess frequency tuning.

  7. HTLV-1 Tax activates HIV-1 transcription in latency models.

    Science.gov (United States)

    Geddes, Victor Emmanuel Viana; José, Diego Pandeló; Leal, Fabio E; Nixon, Douglas F; Tanuri, Amilcar; Aguiar, Renato Santana

    2017-04-01

    HIV-1 latency is a major obstacle to HIV-1 eradication. Coinfection with HTLV-1 has been associated with faster progression to AIDS. HTLV-1 encodes the transactivator Tax which can activate both HTLV-1 and HIV-1 transcription. Here, we demonstrate that Tax activates HIV transcription in latent CD4(+) T cells. Tax promotes the activation of P-TEFb, releasing CDK9 and Cyclin T1 from inactive forms, promoting transcription elongation and reactivation of latent HIV-1. Tax mutants lacking interaction with the HIV-1-LTR promoter were not able to activate P-TEFb, with no subsequent activation of latent HIV. In HIV-infected primary resting CD4(+) T cells, Tax-1 reactivated HIV-1 transcription up to five fold, confirming these findings in an ex vivo latency model. Finally, our results confirms that HTLV-1/Tax hijacks cellular partners, promoting HIV-1 transcription, and this interaction should be further investigated in HIV-1 latency studies in patients with HIV/HTLV-1 co-infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency.

    Science.gov (United States)

    Boehm, Daniela; Jeng, Mark; Camus, Gregory; Gramatica, Andrea; Schwarzer, Roland; Johnson, Jeffrey R; Hull, Philip A; Montano, Mauricio; Sakane, Naoki; Pagans, Sara; Godin, Robert; Deeks, Steven G; Krogan, Nevan J; Greene, Warner C; Ott, Melanie

    2017-05-10

    Transcriptional latency of HIV is a last barrier to viral eradication. Chromatin-remodeling complexes and post-translational histone modifications likely play key roles in HIV-1 reactivation, but the underlying mechanisms are incompletely understood. We performed an RNAi-based screen of human lysine methyltransferases and identified the SET and MYND domain-containing protein 2 (SMYD2) as an enzyme that regulates HIV-1 latency. Knockdown of SMYD2 or its pharmacological inhibition reactivated latent HIV-1 in T cell lines and in primary CD4(+) T cells. SMYD2 associated with latent HIV-1 promoter chromatin, which was enriched in monomethylated lysine 20 at histone H4 (H4K20me1), a mark lost in cells lacking SMYD2. Further, we find that lethal 3 malignant brain tumor 1 (L3MBTL1), a reader protein with chromatin-compacting properties that recognizes H4K20me1, was recruited to the latent HIV-1 promoter in a SMYD2-dependent manner. We propose that a SMYD2-H4K20me1-L3MBTL1 axis contributes to HIV-1 latency and can be targeted with small-molecule SMYD2 inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Epigenetic regulation of HIV-1 latency by cytosine methylation.

    Directory of Open Access Journals (Sweden)

    Steven E Kauder

    2009-06-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 persists in a latent state within resting CD4+ T cells of infected persons treated with highly active antiretroviral therapy (HAART. This reservoir must be eliminated for the clearance of infection. Using a cDNA library screen, we have identified methyl-CpG binding domain protein 2 (MBD2 as a regulator of HIV-1 latency. Two CpG islands flank the HIV-1 transcription start site and are methylated in latently infected Jurkat cells and primary CD4+ T cells. MBD2 and histone deacetylase 2 (HDAC2 are found at one of these CpG islands during latency. Inhibition of cytosine methylation with 5-aza-2'deoxycytidine (aza-CdR abrogates recruitment of MBD2 and HDAC2. Furthermore, aza-CdR potently synergizes with the NF-kappaB activators prostratin or TNF-alpha to reactivate latent HIV-1. These observations confirm that cytosine methylation and MBD2 are epigenetic regulators of HIV-1 latency. Clearance of HIV-1 from infected persons may be enhanced by inclusion of DNA methylation inhibitors, such as aza-CdR, and NF-kappaB activators into current antiviral therapies.

  10. Collecting and Using Low Latency Data at Berkeley Seismological Laboratory

    Science.gov (United States)

    Houlié, N.; Allen, R.; Hellweg, P.; Dreger, D.; Neuhauser, D.; Romanowicz, B.

    2008-12-01

    Northern California and the San Francisco Bay Area are among the US regions that combine high earthquake hazard and high population density. To rapidly and reliably monitor tectonic movement and develop an understanding of fault dynamics, measurements must cover a range of scales in time (0.1 s to years), space (mms to 100s of km) and displacement (microns to 10s of m). With these goals in mind, Berkeley Seismological Laboratory (BSL) continuously collects a wide variety of data at low latencies from seismic through geodetic, strain and electromagnetic instrumentation with sampling rates spanning 0.001 sps to 500 sps. Data from broadband seismometers and accelerometers, generally with latencies of less than 10 s, contribute to real time earthquake monitoring in Northern California including rapid assessments of source (moment tensor and finite fault) and shaking (ShakeMap). The BSL is also currently operating a real time system in test mode, using these data for earthquake early warning (ElarmS). Data from these instruments are also used for research on earthquake sources and scaling, fault-related tremor and studies of local, regional and global velocity structure. Low latency GPS data can complement seismic data, contributing robust real time continuous information especially for large earthquakes, and can potentially contribute to early warning. GPS-derived static deformation gives an independent estimate of fault orientation and dimensions, scalar seismic moment and magnitude. It also can extend the upper limits of a strong motion network to include the displacements of tens of meters expected in large and great earthquakes, and in the near field is less likely to be clipped during large movements. In an active tectonic context such as Northern California, low latency is important for data transmission, but also for reliability. At the BSL we are committed to using telemetry that is as robust as possible and often have more than one telemetry path to ensure

  11. Acceptable differences in sensory and motor latencies between the median and ulnar nerves.

    Science.gov (United States)

    Grossart, Elizabeth A; Prahlow, Nathan D; Buschbacher, Ralph M

    2006-01-01

    The median and ulnar nerves are often studied during the same electrodiagnostic examination. The sensory and motor latencies of these nerves have been compared to detect a common electrodiagnostic entity: median neuropathy at the wrist. However, this comparison could also be used to diagnose less common ulnar pathology. For this reason, it is important to establish normal values for comparing median and ulnar sensory and motor latencies. Previous research deriving these differences in latency has had some limitations. The purpose of this study was to derive an improved normative database for the acceptable differences in latency between the median and ulnar sensory and motor nerves of the same limb. Median and ulnar sensory and motor latencies were obtained from 219 and 238 asymptomatic risk-factor-free subjects, respectively. An analysis of variance was performed to determine whether physical characteristics, specifically age, race, gender, height, or body mass index (as an indicator of obesity), correlated with differences in latency. Differences in sensory latencies were unaffected by physical characteristics. The upper limit of normal difference between median and ulnar (median longer than ulnar) onset latency was 0.5 ms (97th percentile), whereas the peak latency value was 0.4 ms (97th percentile). The upper limit of normal difference between ulnar-versus-median (ulnar longer than median) onset latency was 0.3 ms (97th percentile), whereas the peak-latency value was 0.5 ms (97th percentile). The mean difference in motor latencies correlated with age, with older subjects having a greater variability. In subjects aged 50 and over, the mean difference in median-versus-ulnar latency was 0.9 ms +/- 0.4 ms. The upper limit of normal difference (median longer than ulnar) was 1.7 ms (97th percentile). The upper limit of normal ulnar motor latency is attained if the ulnar latency comes within 0.3 ms of the median latency. In individuals less than 50 years of age, the

  12. Latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus promotes angiogenesis through targeting notch signaling effector Hey1.

    Science.gov (United States)

    Wang, Xing; He, Zhiheng; Xia, Tian; Li, Xiaofan; Liang, Deguang; Lin, Xianzhi; Wen, Hao; Lan, Ke

    2014-04-01

    Notch signaling has been implicated in the pathogenesis of Kaposi sarcoma. Kaposi sarcoma is an angioproliferative neoplasm that originates from Kaposi sarcoma-associated herpesvirus (KSHV) infection. Previously, we showed that the KSHV LANA protein can stabilize intracellular Notch in KSHV-infected tumor cells and promote cell proliferation. However, whether Notch signaling functions in pathologic angiogenesis of Kaposi sarcoma remains largely unknown. Hey1, an essential downstream effector of the Notch signaling pathway, has been demonstrated to play a fundamental role in vascular development. In the present study, we performed whole transcriptome, paired-end sequencing on three patient-matched clinical Kaposi sarcoma specimens and their corresponding adjacent stroma samples, with an average depth of 42 million reads per sample. Dll4, Hey1, and HeyL displayed significant upregulation in Kaposi sarcoma. Further verification based on immunohistochemistry analysis demonstrated that Hey1 was indeed highly expressed in Kaposi sarcoma lesions. Using the Matrigel plug assay, we showed that downregulation of Hey1 and γ-secretase inhibitor treatment caused dramatic reduction in the formation of new blood vessels in mice. Interestingly, LANA was responsible for the elevated level of Hey1 through inhibition of its degradation. Importantly, Hey1 stabilized by LANA promoted the neoplastic vasculature. Taken together, our data suggest that hijacking of the proangiogenic property of Hey1 by LANA is an important strategy utilized by KSHV to achieve pathologic angiogenesis and that Hey1 is a potential therapeutic target in Kaposi sarcoma.

  13. Test Operations Procedure (TOP) 02-2-546 Teleoperated Unmanned Ground Vehicle (UGV) Latency Measurements

    Science.gov (United States)

    2017-01-11

    A. Approved for public release; distribution is unlimited. 13. SUPPLEMENTARY NOTES Defense Technical Information Center (DTIC), AD No.: 14. ABSTRACT...discrete system components or measurements of latency in autonomous systems. 15. SUBJECT TERMS Unmanned Ground Vehicles, Basic Video Latency, End -to... End System Latency, Command-to-Action Latency 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT SAR 18. NUMBER OF PAGES 23 19a

  14. Latency of auditory evoked potential monitoring the effects of general anesthetics on nerve fibers and synapses

    OpenAIRE

    Bowan Huang; Feixue Liang; Lei Zhong; Minlin Lin; Juan Yang; Linqing Yan; Jinfan Xiao; Zhongju Xiao

    2015-01-01

    Auditory evoked potential (AEP) is an effective index for the effects of general anesthetics. However, it’s unknown if AEP can differentiate the effects of general anesthetics on nerve fibers and synapses. Presently, we investigated AEP latency and amplitude changes to different acoustic intensities during pentobarbital anesthesia. Latency more regularly changed than amplitude during anesthesia. AEP Latency monotonically decreased with acoustic intensity increase (i.e., latency-intensity curv...

  15. Prolonged latency of preterm premature rupture of membranes and risk of neonatal sepsis.

    Science.gov (United States)

    Drassinower, Daphnie; Friedman, Alexander M; Običan, Sarah G; Levin, Heather; Gyamfi-Bannerman, Cynthia

    2016-06-01

    Preterm premature rupture of membranes (PPROM) is associated with inflammation and infection, and it may involve the loss of a barrier to ascending infection from the vagina, and it is possible that prolonged PPROM could be an independent risk factor for neonatal sepsis. The objective of the study was to determine whether prolonged latency after PPROM is associated with an increased risk of neonatal sepsis. This secondary analysis of the randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy evaluated whether the time interval between diagnosis of PPROM and delivery was associated with an increased risk of neonatal sepsis. Latency time was categorized by weeks of latency (0 weeks to ≥ 4 weeks). The primary outcome was confirmed neonatal sepsis. Logistic regression was used to control for confounders. A total of 1596 patients with PPROM were analyzed, of whom 1390 had a neonatal sepsis occurred in 15.5% of patients in the cohort. In the univariate analysis, patients in the prolonged PPROM group were less likely to have neonatal sepsis (6.8% vs 17.2%, relative risk, 0.40 95% confidence interval, 0.24-0.66). This relationship was retained in the multivariable model; patients with prolonged PPROM ≥ 4 weeks had an adjusted odds ratio of 0.21 (95% confidence interval, 0.10-0.41) for neonatal sepsis. Neonatal sepsis was also significantly associated with earlier gestational age at rupture of membranes. Prolonged exposure to an intrauterine environment of PPROM does not increase the risk of neonatal sepsis; prolonged PPROM ≥ 4 weeks was associated with decreased risk of neonatal sepsis. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Intranasal infection with Chlamydia abortus induces dose-dependent latency and abortion in sheep.

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    David Longbottom

    Full Text Available BACKGROUND: Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus. METHODOLOGY/PRINCIPAL FINDINGS: Three groups of sheep (groups 1, 2 and 3 were experimentally infected with different doses of C. abortus (5×10(3, 5×10(5 and 5×10(7 inclusion forming units (IFU, respectively prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b or were inoculated subcutaneously on day 70 of gestation with 2×10(6 IFU C. abortus (group 5. Animals in groups 1, 2 and 5 experienced an abortion rate of 50-67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium. CONCLUSIONS/SIGNIFICANCE: The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and

  17. Epigenetic Modification of the Epstein-Barr Virus BZLF1 Promoter Regulates Viral Reactivation from Latency

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    Takayuki eMurata

    2013-04-01

    Full Text Available The Epstein-Barr virus (EBV is an oncogenic human gamma-herpesvirus that predominantly establishes latent infection in B lymphocytes. Viral genomes exist as extrachromosomal episomes with a nucleosomal structure. Maintenance of virus latency or execution of reactivation is controlled by the expression of BZLF1, a viral immediate-early gene product, tightly controlled at the transcriptional level. In this article, we review how BZLF1 transcription is controlled, in other words how virus reactivation is regulated, especially in terms of epigenetics. We recently found that histone H3 lysine 27 trimethylation (H3K27me3 and H4K20me3 markers are crucial for suppression of BZLF1 in latent Raji cells. In addition, H3K9me2/3, HP1 and H2A ubiquitination are associated with latency, whereas positive markers, such as higher histone acetylation and H3K4me3, are concomitant with reactivation. Since lytic replication eventually causes cell cycle arrest and cell death, development of oncolytic therapy for EBV-positive cancers is conceivable using epigenetic disruptors. In addition, we note the difficulties in analyzing roles of epigenetics in EBV, including issues like cell type dependence and virus copy numbers.

  18. HIV-1 Tat promotes Kaposi's sarcoma-associated herpesvirus (KSHV vIL-6-induced angiogenesis and tumorigenesis by regulating PI3K/PTEN/AKT/GSK-3β signaling pathway.

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    Feng Zhou

    Full Text Available Kaposi's sarcoma (KS-associated herpesvirus (KSHV is etiologically associated with KS, the most common AIDS-related malignancy. KS is characterized by vast angiogenesis and hyperproliferative spindle cells. We have previously reported that HIV-1 Tat can trigger KSHV reactivation and accelerate Kaposin A-induced tumorigenesis. Here, we explored Tat promotion of KSHV vIL-6-induced angiogenesis and tumorigenesis. Tat promotes vIL-6-induced cell proliferation, cellular transformation, vascular tube formation and VEGF production in culture. Tat enhances vIL-6-induced angiogenesis and tumorigenesis of fibroblasts and human endothelial cells in a chicken chorioallantoic membrane (CAM model. In an allograft model, Tat promotes vIL-6-induced tumorigenesis and expression of CD31, CD34, SMA, VEGF, b-FGF, and cyclin D1. Mechanistic studies indicated Tat activates PI3K and AKT, and inactivates PTEN and GSK-3β in vIL-6 expressing cells. LY294002, a specific inhibitor of PI3K, effectively impaired Tat's promotion of vIL-6-induced tumorigenesis. Together, these results provide the first evidence that Tat might contribute to KS pathogenesis by synergizing with vIL-6, and identify PI3K/AKT pathway as a potential therapeutic target in AIDS-related KS patients.

  19. The effect of latency on bone lengthening force and bone mineralization: an investigation using strain gauge mounted on internal distractor device

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    Wang Jue

    2006-03-01

    Full Text Available Abstract Background The purpose of this study was to investigate the effect of latency on the development of bone lengthening force and bone mineralization during mandible distraction osteogenesis. Methods Distraction tensions were investigated at different latency period in 36 rabbits using internal unilateral distractor. Strain gauges were prepared and attached to the distractor to directly assess the level of distraction tension during mandible lengthening. The tensile force environment of the mandible of rabbit during distraction was evaluated through in vivo experiments using two gauges. The animals were divided into 3 groups each containing 12 rabbits. Latency periods of 0, 4 and 7 days respectively were observed prior to beginning distraction. The distraction protocol consisted of a lengthening rate of 1 mm once daily for 8 days, followed by a consolidation phase of 2 weeks after which the animals were killed. Biopsies specimens were taken from the distracted area at the end of the distraction period. A non-distracted area of the mandible bone served as control. The specimens were analyzed by scanning electron microscopy to assess the ultrastructural pattern, and the bone mineralization. Results The resting tension acting on the distraction gap increases through distraction. The 7-day latency groups exhibit higher tension then those of 0-day and 4-days latency groups. Quantitative energy dispersive spectral analysis confirmed that immediate distractions were associated with lower calcium and phosphate atomic weight ratio. Conclusion the latency periods could affect the bone lengthening tension and the bone mineralization process.

  20. Statistical learning methods for aero-optic wavefront prediction and adaptive-optic latency compensation

    Science.gov (United States)

    Burns, W. Robert

    Since the early 1970's research in airborne laser systems has been the subject of continued interest. Airborne laser applications depend on being able to propagate a near diffraction-limited laser beam from an airborne platform. Turbulent air flowing over the aircraft produces density fluctuations through which the beam must propagate. Because the index of refraction of the air is directly related to the density, the turbulent flow imposes aberrations on the beam passing through it. This problem is referred to as Aero-Optics. Aero-Optics is recognized as a major technical issue that needs to be solved before airborne optical systems can become routinely fielded. This dissertation research specifically addresses an approach to mitigating the deleterious effects imposed on an airborne optical system by aero-optics. A promising technology is adaptive optics: a feedback control method that measures optical aberrations and imprints the conjugate aberrations onto an outgoing beam. The challenge is that it is a computationally-difficult problem, since aero-optic disturbances are on the order of kilohertz for practical applications. High control loop frequencies and high disturbance frequencies mean that adaptive-optic systems are sensitive to latency in sensors, mirrors, amplifiers, and computation. These latencies build up to result in a dramatic reduction in the system's effective bandwidth. This work presents two variations of an algorithm that uses model reduction and data-driven predictors to estimate the evolution of measured wavefronts over a short temporal horizon and thus compensate for feedback latency. The efficacy of the two methods are compared in this research, and evaluated against similar algorithms that have been previously developed. The best version achieved over 75% disturbance rejection in simulation in the most optically active flow region in the wake of a turret, considerably outperforming conventional approaches. The algorithm is shown to be

  1. Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis.

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    Hanni S M Kiiski

    Full Text Available Conduction along the optic nerve is often slowed in multiple sclerosis (MS. This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis.

  2. Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis

    Science.gov (United States)

    Kiiski, Hanni S. M.; Ní Riada, Sinéad; Lalor, Edmund C.; Gonçalves, Nuno R.; Nolan, Hugh; Whelan, Robert; Lonergan, Róisín; Kelly, Siobhán; O'Brien, Marie Claire; Kinsella, Katie; Bramham, Jessica; Burke, Teresa; Ó Donnchadha, Seán; Hutchinson, Michael; Tubridy, Niall; Reilly, Richard B.

    2016-01-01

    Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis. PMID:26726800

  3. Voluntary reaction time and long-latency reflex modulation.

    Science.gov (United States)

    Forgaard, Christopher J; Franks, Ian M; Maslovat, Dana; Chin, Laurence; Chua, Romeo

    2015-12-01

    Stretching a muscle of the upper limb elicits short (M1) and long-latency (M2) reflexes. When the participant is instructed to actively compensate for a perturbation, M1 is usually unaffected and M2 increases in size and is followed by the voluntary response. It remains unclear if the observed increase in M2 is due to instruction-dependent gain modulation of the contributing reflex mechanism(s) or results from voluntary response superposition. The difficulty in delineating between these alternatives is due to the overlap between the voluntary response and the end of M2. The present study manipulated response accuracy and complexity to delay onset of the voluntary response and observed the corresponding influence on electromyographic activity during the M2 period. In all active conditions, M2 was larger compared with a passive condition where participants did not respond to the perturbation; moreover, these changes in M2 began early in the appearance of the response (∼ 50 ms), too early to be accounted for by voluntary overlap. Voluntary response latency influenced the latter portion of M2, with the largest activity seen when accuracy of limb position was not specified. However, when participants aimed for targets of different sizes or performed movements of various complexities, reaction time differences did not influence M2 period activity, suggesting voluntary activity was sufficiently delayed. Collectively, our results show that while a perturbation applied to the upper limbs can trigger a voluntary response at short latency (reflex gain modulation remains an important contributor to EMG changes during the M2 period. Copyright © 2015 the American Physiological Society.

  4. The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

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    Ole S Søgaard

    2015-09-01

    Full Text Available Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7–7.7 relative to baseline within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4–5.0; p = 0.03. Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46–103 copies/mL following the second infusion, p = 0.04. Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1–2 were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir.clinicaltrials.gov NTC02092116.

  5. Short latency cutaneous reflex responses of gamma-efferents in the decerebrate cat.

    Science.gov (United States)

    Murphy, P R; Hammond, G R

    1992-01-01

    The effect of single shock stimulation, up to 20 x threshold (T), of the sural nerve on the discharges of triceps surae gamma-efferents was investigated in decerebrate cats. Units were classified as static (12) or dynamic (7) on the basis of their resting discharge rates (Murphy et al. 1984). All neurones were excited at short latency by sural nerve stimulation and response size was graded with stimulus intensity. Short latency mixed or inhibitory responses were not evident. Although reflex effects first occurred at low stimulus strengths (less than or equal to 1.5T) in both types of efferent, most responses appeared at higher intensities (greater than 1.5T). The estimated central delays of the responses of static (3.0 +/- 1.1 ms, mean +/- SD) and dynamic (3.4 +/- 1.0 ms) gamma-motoneurones were not significantly different and are consistent with spinal oligosynaptic pathways. The present results differ from those of the only previous study (Johansson and Sojka 1985) of the short latency responses of triceps surae static and dynamic gamma-motoneurones to sural nerve stimulation, in which mixed and inhibitory effects were common in anaesthetised cats. Although differences in recording techniques and gamma sampling may account for the apparent disparity between these studies, it is also feasible that a difference in the setting of interneuronal pathways in the two types of preparation is responsible. The results are discussed in relation to the control of gamma-motoneurones with particular reference to the "final common input" hypothesis (Johansson 1981; Appelberg et al. 1983).

  6. LEFT: A Latency and Energy Efficient Flexible TDMA Protocol for Wireless Sensor Networks

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    Sachin Gajjar

    2015-01-01

    Full Text Available This paper proposes latency and energy efficient flexible TDMA (LEFT, a medium access control (MAC combined with routing protocol for data gathering from number of source nodes to a master station (MS in a wireless sensor network (WSN. TDMA provides fairness, collision-free communication and reduces idle listening, which saves network energy. Data latency is reduced by allocating same transmission slots to nodes falling out of interference range of each other. Unlike a conventional TDMA, LEFT provides flexibility through slot seizing, wherein a non-holder of a slot can use slot when holder does not have data to send. This increases channel utilization and adaption to dynamic traffic patterns of WSN applications. Further, a node on a multi-hop path towards MS decides to participate in routing based on (i its location with respect to MS, to forward data in correct direction, (ii its current status of residual energy, to uniformly distribute energy across network, (iii its transit traffic load, to prevent local congestion, (iv its communication link quality, to guarantee reliable data delivery. This decision requires simple comparisons against thresholds, and thus is very simple to implement on energy, storage and computationally constrained nodes. LEFT also encompasses techniques to cater to link and node breakdowns. Experimental analysis of LEFT; Advertisement-based TDMA; Data gathering MAC; Energy Efficient Fast Forwarding and Cross layer MAC protocols using TI's EZ430-RF2500T nodes shows that LEFT is 65% more energy efficient compared to Cross layer MAC. Data latency of LEFT is 27 % less, delivery ratio is 17 % more and goodput is 11 % more compared to Cross layer MAC.

  7. Alphaherpesvirus Latency: A Dynamic State of Transcription and Reactivation.

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    Bloom, David C

    2016-01-01

    Alphaherpesviruses infect a variety of species from sea turtles to man and can cause significant disease in mammals including humans and livestock. These viruses are characterized by a lytic and latent state in nerve ganglia, with the ability to establish a lifelong latent infection that is interrupted by periodic reactivation. Previously, it was accepted that latency was a dominant state and that only during relatively infrequent reactivation episodes did latent genomes within ganglia become transcriptionally active. Here, we review recent data, focusing mainly on Herpes Simplex Virus type 1 which indicate that the latent state is more dynamic than recently appreciated.

  8. Latency delay of visual evoked potential is a real measurement of demyelination in a rat model of optic neuritis.

    Science.gov (United States)

    You, Yuyi; Klistorner, Alexander; Thie, Johnson; Graham, Stuart L

    2011-08-29

    To investigate the relationship between size of demyelinated lesion, extent of axonal loss, and degree of latency delay of visual evoked potentials (VEPs) in a rat model of experimental demyelination. Lysolecithin 1% (0.4 or 0.8 μL) was microinjected into an optic nerve of each of 14 rats 2 mm posterior to the globe. Standard flash VEPs were recorded with skull-implanted electrodes before and 2, 4, and 6 days after the microinjection. The optic nerves were stained with Luxol-fast blue and Bielschowsky's silver to assess demyelination and axonal pathology, respectively. Demyelinated areas were measured on serial sections, and lesion volumes were deduced by three-dimensional reconstruction. Focal lesions of demyelination and variable axonal loss were observed. The mean volume of the lesion was 3.2 ± 1.1 × 10⁻² mm³. The injected eye showed a significant latency delay and amplitude decrease. Regression analysis demonstrated a strong correlation between N1 latency delay and lesion volume (r = 0.863, P < 0.0001), which remained significant after adjustment for axonal loss (r = 0.829, P < 0.001). N1 latency delay also showed a correlation with axonal loss (r = 0.552, P = 0.041), but the correlation became nonsignificant when controlling for demyelination (r = 0.387, P = 0.191). A linear association between N1-P2 amplitude decrease and axonal loss (r = 0.681, P = 0.007) was also observed. The latency of the VEP accurately reflected the amount of demyelination in the visual pathway, whereas the amplitude correlated with axonal damage. This study supports the concept that the VEP provides a highly sensitive tool with which to measure demyelination in optic neuritis.

  9. [Concentration-dependent changes in the latency and amplitude of somatosensory-evoked potentials by desflurane, isoflurane and sevoflurane].

    Science.gov (United States)

    Rehberg, B; Rüschner, R; Fischer, M; Ebeling, B J; Hoeft, A

    1998-07-01

    Comparison of the influence of desflurane, isoflurane, and sevoflurane on the parameters of cortical somatosensory evoked potentials (SEP). A total of 41 patients were randomly allocated to either the isoflurane, desflurane or sevoflurane group. Following induction with propofol and intubation, concentration of the volatile anaesthetic was kept constant at 1.3, 1.0, and 0.7 MAC for 15 minutes each in randomised sequences. No opioids or N2O were used. Cortical somatosensory evoked potentials were recorded following median nerve stimulation at the wrist with 1.5 times motor threshold current. SEP were evaluated for latencies of peak N20 and P25 as well as peak-to-peak amplitude N20P25. Measurements at the end of the 15 minute equilibration intervals were compared by analysis of variance for repeated measurements. Latencies and the logarithm of the amplitudes were assumed to be normally distributed. SEP could be recorded in all patients and at all concentrations. Latency of cortical SEP increased with anaesthetic concentration in a linear manner. No differences in latency increase were found between the three anaesthetics (ANOVA). In contrast, the decrease in amplitude with increasing anaesthetic concentration was non-linear. It was large from control to 0.7 MAC, but small in the range between 0.7 and 1.3 MAC. Amplitude reduction was larger with isoflurane than with sevoflurane or desflurane. 1) Sevoflurane and desflurane are better suited for anaesthetic management during intraoperative electrophysiological monitoring than isoflurane, because SEP amplitudes are better preserved. 2) SEP amplitude is less altered by changing anaesthetic concentrations in the concentration range from 0.7 to 1.3 MAC than SEP latency.

  10. Bounds on Stability and Latency in Wireless Communication

    CERN Document Server

    Cholvi, Vicent

    2010-01-01

    In this paper, we study stability and latency of routing in wireless networks where it is assumed that no collision will occur. Our approach is inspired by the adversarial queuing theory, which is amended in order to model wireless communication. More precisely, there is an adversary that specifies transmission rates of wireless links and injects data in such a way that an average number of data injected in a single round and routed through a single wireless link is at most $r$, for a given $r\\in (0,1)$. We also assume that the additional "burst" of data injected during any time interval and scheduled via a single link is bounded by a given parameter $b$. Under this scenario, we show that the nodes following so called {\\em work-conserving} scheduling policies, not necessarily the same, are guaranteed stability (i.e., bounded queues) and reasonably small data latency (i.e., bounded time on data delivery), for injection rates $r<1/d$, where $d$ is the maximum length of a routing path. Furthermore, we also sh...

  11. Effect of auditory training on the middle latency response in children with (central auditory processing disorder

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    E. Schochat

    2010-08-01

    Full Text Available The purpose of this study was to determine the middle latency response (MLR characteristics (latency and amplitude in children with (central auditory processing disorder [(CAPD], categorized as such by their performance on the central auditory test battery, and the effects of these characteristics after auditory training. Thirty children with (CAPD, 8 to 14 years of age, were tested using the MLR-evoked potential. This group was then enrolled in an 8-week auditory training program and then retested at the completion of the program. A control group of 22 children without (CAPD, composed of relatives and acquaintances of those involved in the research, underwent the same testing at equal time intervals, but were not enrolled in the auditory training program. Before auditory training, MLR results for the (CAPD group exhibited lower C3-A1 and C3-A2 wave amplitudes in comparison to the control group [C3-A1, 0.84 µV (mean, 0.39 (SD - standard deviation for the (CAPD group and 1.18 µV (mean, 0.65 (SD for the control group; C3-A2, 0.69 µV (mean, 0.31 (SD for the (CAPD group and 1.00 µV (mean, 0.46 (SD for the control group]. After training, the MLR C3-A1 [1.59 µV (mean, 0.82 (SD] and C3-A2 [1.24 µV (mean, 0.73 (SD] wave amplitudes of the (CAPD group significantly increased, so that there was no longer a significant difference in MLR amplitude between (CAPD and control groups. These findings suggest progress in the use of electrophysiological measurements for the diagnosis and treatment of (CAPD.

  12. Effect of auditory training on the middle latency response in children with (central) auditory processing disorder.

    Science.gov (United States)

    Schochat, E; Musiek, F E; Alonso, R; Ogata, J

    2010-08-01

    The purpose of this study was to determine the middle latency response (MLR) characteristics (latency and amplitude) in children with (central) auditory processing disorder [(C)APD], categorized as such by their performance on the central auditory test battery, and the effects of these characteristics after auditory training. Thirty children with (C)APD, 8 to 14 years of age, were tested using the MLR-evoked potential. This group was then enrolled in an 8-week auditory training program and then retested at the completion of the program. A control group of 22 children without (C)APD, composed of relatives and acquaintances of those involved in the research, underwent the same testing at equal time intervals, but were not enrolled in the auditory training program. Before auditory training, MLR results for the (C)APD group exhibited lower C3-A1 and C3-A2 wave amplitudes in comparison to the control group [C3-A1, 0.84 microV (mean), 0.39 (SD--standard deviation) for the (C)APD group and 1.18 microV (mean), 0.65 (SD) for the control group; C3-A2, 0.69 microV (mean), 0.31 (SD) for the (C)APD group and 1.00 microV (mean), 0.46 (SD) for the control group]. After training, the MLR C3-A1 [1.59 microV (mean), 0.82 (SD)] and C3-A2 [1.24 microV (mean), 0.73 (SD)] wave amplitudes of the (C)APD group significantly increased, so that there was no longer a significant difference in MLR amplitude between (C)APD and control groups. These findings suggest progress in the use of electrophysiological measurements for the diagnosis and treatment of (C)APD.

  13. Modeling neuroendocrine stress reactivity in salivary cortisol: adjusting for peak latency variability.

    Science.gov (United States)

    Lopez-Duran, Nestor L; Mayer, Stefanie E; Abelson, James L

    2014-07-01

    In this report, we present growth curve modeling (GCM) with landmark registration as an alternative statistical approach for the analysis of time series cortisol data. This approach addresses an often-ignored but critical source of variability in salivary cortisol analyses: individual and group differences in the time latency of post-stress peak concentrations. It allows for the simultaneous examination of cortisol changes before and after the peak while controlling for timing differences, and thus provides additional information that can help elucidate group differences in the underlying biological processes (e.g., intensity of response, regulatory capacity). We tested whether GCM with landmark registration is more sensitive than traditional statistical approaches (e.g., repeated measures ANOVA--rANOVA) in identifying sex differences in salivary cortisol responses to a psychosocial stressor (Trier Social Stress Test--TSST) in healthy adults (mean age 23). We used plasma ACTH measures as our "standard" and show that the new approach confirms in salivary cortisol the ACTH finding that males had longer peak latencies, higher post-stress peaks but a more intense post-peak decline. This finding would have been missed if only saliva cortisol was available and only more traditional analytic methods were used. This new approach may provide neuroendocrine researchers with a highly sensitive complementary tool to examine the dynamics of the cortisol response in a way that reduces risk of false negative findings when blood samples are not feasible.

  14. A Low-Latency TDMA Scheduler for Multi-hop Cluster Based MANETs with Directional Antennas

    Science.gov (United States)

    Iannacone, Michael; Al-Mousa, Yamin; Martin, Nicholas; Shenoy, Nirmala; Fischer, John

    For Mobile Ad Hoc Network (MANET) applications which involve large propagation delays and/or directional antennas, a Time Division Multiple Access (TDMA) Medium Access Control (MAC) is a resource- and bandwidth-efficient solution. Meanwhile, clustering is a solution to the scalability and high mobility which is commonly required by MANETs. Here we develop a system which combines a TDMA MAC using directional antennas with the Multi-Meshed Tree (MMT) algorithm, which handles clustering and routing tasks. Some of the benefits of this combination include being able to synchronously schedule all intra-cluster routes as they are formed, being able to optimize the intra-cluster schedules for low latency, and being able to calculate these schedules with knowledge of only the intra-cluster topology, which is already maintained by MMT. We first analytically determine the end-to-end latency under various cases, and then confirm these results for several cases through OPNET simulation. Additionally, we note the high degree of slot re-use which is possible due to the use of directional antennas, which is demonstrated by the simulation results.

  15. Robo-line storage: Low latency, high capacity storage systems over geographically distributed networks

    Science.gov (United States)

    Katz, Randy H.; Anderson, Thomas E.; Ousterhout, John K.; Patterson, David A.

    1991-01-01

    Rapid advances in high performance computing are making possible more complete and accurate computer-based modeling of complex physical phenomena, such as weather front interactions, dynamics of chemical reactions, numerical aerodynamic analysis of airframes, and ocean-land-atmosphere interactions. Many of these 'grand challenge' applications are as demanding of the underlying storage system, in terms of their capacity and bandwidth requirements, as they are on the computational power of the processor. A global view of the Earth's ocean chlorophyll and land vegetation requires over 2 terabytes of raw satellite image data. In this paper, we describe our planned research program in high capacity, high bandwidth storage systems. The project has four overall goals. First, we will examine new methods for high capacity storage systems, made possible by low cost, small form factor magnetic and optical tape systems. Second, access to the storage system will be low latency and high bandwidth. To achieve this, we must interleave data transfer at all levels of the storage system, including devices, controllers, servers, and communications links. Latency will be reduced by extensive caching throughout the storage hierarchy. Third, we will provide effective management of a storage hierarchy, extending the techniques already developed for the Log Structured File System. Finally, we will construct a protototype high capacity file server, suitable for use on the National Research and Education Network (NREN). Such research must be a Cornerstone of any coherent program in high performance computing and communications.

  16. Primary B Lymphocytes Infected with Kaposi's Sarcoma-Associated Herpesvirus Can Be Expanded In Vitro and Are Recognized by LANA-Specific CD4+ T Cells

    Science.gov (United States)

    Nicol, Samantha M.; Sabbah, Shereen; Brulois, Kevin F.; Jung, Jae U.; Bell, Andrew I.

    2016-01-01

    ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) has tropism for B lymphocytes, in which it establishes latency, and can also cause lymphoproliferative disorders of these cells manifesting as primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). T cell immunity is vital for the control of KSHV infection and disease; however, few models of B lymphocyte infection exist to study immune recognition of such cells. Here, we developed a model of B lymphocyte infection with KSHV in which infected tonsillar B lymphocytes were expanded by providing mitogenic stimuli and then challenged with KSHV-specific CD4+ T cells. The infected cells expressed viral proteins found in PELs, namely, LANA and viral IRF3 (vIRF3), albeit at lower levels, with similar patterns of gene expression for the major latency, viral interleukin 6 (vIL-6), and vIRF3 transcripts. Despite low-level expression of open reading frame 50 (ORF50), transcripts for the immune evasion genes K3 and K5 were detected, with some downregulation of cell surface-expressed CD86 and ICAM. The vast majority of infected lymphocytes expressed IgM heavy chains with Igλ light chains, recapitulating the features seen in infected cells in MCD. We assessed the ability of the infected lymphocytes to be targeted by a panel of major histocompatibility complex (MHC) class II-matched CD4+ T cells and found that LANA-specific T cells restricted to different epitopes recognized these infected cells. Given that at least some KSHV latent antigens are thought to be poor targets for CD8+ T cells, we suggest that CD4+ T cells are potentially important effectors for the in vivo control of KSHV-infected B lymphocytes. IMPORTANCE KSHV establishes a latent reservoir within B lymphocytes, but few models exist to study KSHV-infected B cells other than the transformed PEL cell lines, which have likely accrued mutations during the transformation process. We developed a model of KSHV-infected primary B lymphocytes that

  17. Neural network connectivity and response latency modelled by stochastic processes

    DEFF Research Database (Denmark)

    Tamborrino, Massimiliano

    is connected to thousands of other neurons. The rst question is: how to model neural networks through stochastic processes? A multivariate Ornstein-Uhlenbeck process, obtained as a diffusion approximation of a jump process, is the proposed answer. Obviously, dependencies between neurons imply dependencies...... between their spike times. Therefore, the second question is: how to detect neural network connectivity from simultaneously recorded spike trains? Answering this question corresponds to investigate the joint distribution of sequences of rst passage times. A non-parametric method based on copulas...... generation of pikes. When a stimulus is applied to the network, the spontaneous rings may prevail and hamper detection of the effects of the stimulus. Therefore, the spontaneous rings cannot be ignored and the response latency has to be detected on top of a background signal. Everything becomes more dicult...

  18. Short latency vestibular evoked potentials in the chicken embryo

    Science.gov (United States)

    Jones, S. M.; Jones, T. A.

    1996-01-01

    Electrophysiological responses to pulsed linear acceleration stimuli were recorded in chicken embryos incubated for 19 or 20 days (E19/E20). Responses occurred within the first 16 ms following the stimulus onset. The evoked potentials disappeared following bilateral labyrinthectomy, but persisted following cochlear destruction alone, thus demonstrating that the responses were vestibular. Approximately 8 to 10 response peaks could be identified. The first 4 positive and corresponding negative components (early peaks with latencies embryos was -15.9dBre 1.0 g/ms, which was significantly higher (P embryos and 2-week-old animals, but amplitude/intensity functions for embryos were significantly shallower than those for 2-week-old birds (P embryo and, as such, the method shows promise as an investigative tool. The results of the present study form the definitive basis for using vestibular evoked potentials in the detailed study of avian vestibular ontogeny and factors that may influence it.

  19. Cortical modulation of short-latency TMS-evoked potentials

    Directory of Open Access Journals (Sweden)

    Domenica eVeniero

    2013-01-01

    Full Text Available Transcranial magnetic stimulation - electroencephalogram (TMS-EEG co-registration offers the opportunity to test reactivity of brain areas across distinct conditions through TMS-evoked potentials (TEPs. Several TEPs have been described, their functional meaning being largely unknown. In particular, short-latency potentials peaking at 5 (P5 and 8 (N8 ms after the TMS pulse have been recently described, but because of their huge amplitude, the problem of whether their origin is cortical or not has been opened. To gain information about these components, we employed a protocol that modulates primary motor cortex excitability (MI through an exclusively cortical phenomena: low frequency stimulation of premotor area (PMC. TMS was applied simultaneously with EEG recording from 70 electrodes. Amplitude of TEPs evoked by 200 single-pulses TMS delivered over MI at 110% of resting motor threshold was measured before and after applying 900 TMS conditioning stimuli to left premotor cortex with 1 Hz repetition rate. Single subject analyses showed reduction in TEPs amplitude after PMC conditioning in a sample of participants and increase in TEPs amplitude in two subjects. No effects were found on corticospinal excitability as recorded by motor evoked potentials (MEPs. Furthermore, correlation analysis showed an inverse relation between the effects of the conditioning protocol on P5-N8 complex amplitude and MEPs amplitude. Because the effects of the used protocol have been ascribed to a cortical interaction between premotor area and MI, we suggest that despite the sign of P5-N8 amplitude modulation is not consistent across participant, this modulation could indicate, at least in part, their cortical origin. We conclude that with an accurate experimental procedure early-latency components can be used to evaluate the reactivity of the stimulated cortex.

  20. Long Latency Auditory Evoked Potential in Term and Premature Infants

    Directory of Open Access Journals (Sweden)

    Didoné, Dayane Domeneghini

    2014-01-01

    Full Text Available Introduction The research in long latency auditory evokes potentials (LLAEP in newborns is recent because of the cortical structure maturation, but studies note that these potentials may be evidenced at this age and could be considered as indicators of cognitive development. Purpose To research the exogenous potentials in term and premature infants during their first month of life. Materials and Methods The sample consisted of 25 newborns, 15 term and 10 premature infants. The infants with gestational age under 37 weeks were considered premature. To evaluate the cortical potentials, the infants remained in natural sleep. The LLAEPs were researched binaurally, through insertion earphones, with frequent /ba/ and rare /ga/ speech stimuli in the intensity of 80 dB HL (decibel hearing level. The frequent stimuli presented a total of 80% of the presentations, and the rare, 20%. The data were statistically analyzed. Results The average gestational age of the term infants was 38.9 weeks (± 1.3 and for the premature group, 33.9 weeks (± 1.6. It was possible to observe only the potentials P1 and N1 in both groups, but there was no statistically significant difference for the latencies of the components P1 and N1 (p > 0.05 between the groups. Conclusion It was possible to observe the exogenous components P1 and N1 of the cortical potentials in both term and preterm newborns of no more than 1 month of age. However, there was no difference between the groups.

  1. Multifocal visual evoked potential latency analysis: predicting progression to multiple sclerosis.

    Science.gov (United States)

    Fraser, Clare; Klistorner, Alexander; Graham, Stuart; Garrick, Raymond; Billson, Francis; Grigg, John

    2006-06-01

    To monitor the difference in conversion rates to multiple sclerosis (MS) in 46 patients with optic neuritis between patients with multifocal visual evoked potential latency delay and those with normal latency. Prospective case series. Metropolitan neuro-ophthalmology clinic. Forty-six patients with optic neuritis who did not have a diagnosis of MS on enrollment in the study. Conversion to MS according to the McDonald criteria. Analysis revealed that only 22 subjects had multifocal visual evoked potential latency delay. Over 1 year, 36.4% of patients with optic neuritis with latency delays progressed clinically to MS compared with 0% of those with normal latencies (P = .03, chi2). This may indicate that multifocal visual evoked potential latency delay can assist in predicting progression to future MS.

  2. Integer-valued Lévy processes and low latency financial econometrics

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole; Pollard, David G.; Shephard, Neil

    Motivated by features of low latency data in financial econometrics we study in detail integervalued Lévy processes as the basis of price processes for high frequency econometrics. We propose using models built out of the difference of two subordinators. We apply these models in practice to low...... latency data for a variety of different types of futures contracts.futures markets, high frequency econometrics, low latency data, negative binomial, Skellam, tempered stable...

  3. Key factors in web latency savings in an experimental prefetching system

    OpenAIRE

    De La Ossa Perez, Bernardo Antonio; Sahuquillo Borrás, Julio; Pont Sanjuan, Ana; Gil Salinas, José Antonio

    2012-01-01

    Although Internet service providers and communications companies are continuously offering higher and higher bandwidths, users still complain about the high latency they perceive when downloading pages from the web. Therefore, latency can be considered as the main web performance metric from the user's point of view. Many studies have demonstrated that web prefetching can be an interesting technique to reduce such latency at the expense of slightly increasing the network traffic. In this cont...

  4. Low-threshold, short-latency cutaneous reflexes during fictive locomotion in the "semi-chronic" spinal cat.

    Science.gov (United States)

    LaBella, L A; Niechaj, A; Rossignol, S

    1992-01-01

    stereotypic control over interneurons in specific cutaneous reflex pathways to motoneurons. The results are primarily discussed in terms of the existing evidence for short-latency excitatory cutaneous reflexes in extensors in a variety of locomotive and non-locomotive preparations.

  5. Performance Comparison of Latency for RSC-RSC and RS-RSC Concatenated Codes

    Directory of Open Access Journals (Sweden)

    Manish Kumar

    2013-09-01

    Full Text Available In this paper, we compare the latency of serially concatenated convolutional codes. In particular, we compare RSC-RSC   concatenated codes using non-iterative concatenated Viterbi decoding to RS-RSC concatenated codes using concatenation of Viterbi & Berklelamp-Massey decoding. We have also used puncturing to obtain different code rates & analyzed the effect of code rate on latency. On the basis of simulations, it is shown that RSC-RSC code is better than RS-RSC codes for low latency applications. It is also shown that a trade-off is needed between BER & latency for concatenated codes.

  6. Bridging HIV-1 cellular latency and clinical long-term non-progressor: an interactomic view.

    Directory of Open Access Journals (Sweden)

    Jin Yang

    Full Text Available Development of an effective HIV management is enticed by the fact that long-term non-progressors (LTNP restrict viral replication spontaneously, but is hindered by HIV-1 latency. Given that the most overlapping characteristics found between HIV-1 LTNP and latency, detailed analysis of the difference would disclose the essentials of latency. In this study, microarray data from our previous study was combined with HIV-1 latency and LTNP data obtained from NCBI GEO database. Principal variance component analysis and hierarchical clustering verified the removal of batch effect across platform. The analysis revealed a total of 456 differential expressed genes with >2-fold change and B-statistic >0. Bayesian inference was used to reconstitute the transcriptional network of HIV-1 latency or LTNP, respectively. Gene regulation was reprogrammed under different disease condition. By network interference, KPNA2 and ATP5G3 were identified as the hubs in latency network which mediate nuclear export and RNA processing. These data offer comparative insights into HIV-1 latency, which will facilitate the understanding of the genetic basis of HIV-1 latency in vivo and serve as a clue for future treatment dealing with key targets in HIV-1 latency.

  7. Small Molecule Inhibitors of BAF; A Promising Family of Compounds in HIV-1 Latency Reversal

    Directory of Open Access Journals (Sweden)

    Mateusz Stoszko

    2016-01-01

    Full Text Available Persistence of latently infected cells in presence of Anti-Retroviral Therapy presents the main obstacle to HIV-1 eradication. Much effort is thus placed on identification of compounds capable of HIV-1 latency reversal in order to render infected cells susceptible to viral cytopathic effects and immune clearance. We identified the BAF chromatin remodeling complex as a key player required for maintenance of HIV-1 latency, highlighting its potential as a molecular target for inhibition in latency reversal. Here, we screened a recently identified panel of small molecule inhibitors of BAF (BAFi's for potential to activate latent HIV-1. Latency reversal was strongly induced by BAFi's Caffeic Acid Phenethyl Ester and Pyrimethamine, two molecules previously characterized for clinical application. BAFi's reversed HIV-1 latency in cell line based latency models, in two ex vivo infected primary cell models of latency, as well as in HIV-1 infected patient's CD4+ T cells, without inducing T cell proliferation or activation. BAFi-induced HIV-1 latency reversal was synergistically enhanced upon PKC pathway activation and HDAC-inhibition. Therefore BAFi's constitute a promising family of molecules for inclusion in therapeutic combinatorial HIV-1 latency reversal.

  8. Toward Massive, Ultrareliable, and Low-Latency Wireless Communication With Short Packets

    DEFF Research Database (Denmark)

    Durisi, Giuseppe; Koch, Tobias; Popovski, Petar

    2016-01-01

    Most of the recent advances in the design of high-speed wireless systems are based on information-theoretic principles that demonstrate how to efficiently transmit long data packets. However, the upcoming wireless systems, notably the fifth-generation (5G) system, will need to support novel traffic...... types that use short packets. For example, short packets represent the most common form of traffic generated by sensors and other devices involved in machine-to-machine (M2M) communications. Furthermore, there are emerging applications in which small packets are expected to carry critical information...... that should be received with low latency and ultrahigh reliability. Current wireless systems are not designed to support short-packet transmissions. For example, the design of current systems relies on the assumption that the metadata (control information) is of negligible size compared to the actual...

  9. Design of a stateless low-latency router architecture for green software-defined networking

    Science.gov (United States)

    Saldaña Cercós, Silvia; Ramos, Ramon M.; Ewald Eller, Ana C.; Martinello, Magnos; Ribeiro, Moisés. R. N.; Manolova Fagertun, Anna; Tafur Monroy, Idelfonso

    2015-01-01

    Expanding software defined networking (SDN) to transport networks requires new strategies to deal with the large number of flows that future core networks will have to face. New south-bound protocols within SDN have been proposed to benefit from having control plane detached from the data plane offering a cost- and energy-efficient forwarding engine. This paper presents an overview of a new approach named KeyFlow to simultaneously reduce latency, jitter, and power consumption in core network nodes. Results on an emulation platform indicate that round trip time (RTT) can be reduced above 50% compared to the reference protocol OpenFlow, specially when flow tables are densely populated. Jitter reduction has been demonstrated experimentally on a NetFPGA-based platform, and 57.3% power consumption reduction has been achieved.

  10. Risk Factors for Kaposi’s sarcoma among HIV-Positive Individuals in a Case Control Study in Cameroon

    Science.gov (United States)

    Stolka, Kristen; Ndom, Paul; Hemingway-Foday, Jennifer; Iriondo-Perez, Jeniffer; Miley, Wendell; Labo, Nazzarena; Jennifer, Stella;; Abassora, Mahamat; Woelk, Godfrey; Ryder, Robin; Whitby, Denise; Smith, Jennifer S

    2014-01-01

    Background Individuals co-infected with Kaposi’s sarcoma herpesvirus (KSHV) and Human Immunodeficiency Virus (HIV) are at greatly increased risk of developing Kaposi’s sarcoma (KS). The objective of the current analysis is to identify risk cofactors, for KS among HIV-positive individuals. Methods We conducted a case-control study of KS in Cameroon on 161 HIV-positive and 14 HIV-negative cases and 680 HIV-positive and 322 HIV-negative controls. Participants answered a physician-administered questionnaire and provided blood and saliva specimens. Antibodies against KSHV lytic, K8.1, and latent, ORF73, antigens were measured by ELISA to determine KSHV serostatus. Conditional logistic regression was performed to determine multivariate odds ratios (OR) and 95% confidence intervals (CI) for risk factors associated with KS among HIV-positive cases and controls. Results Overall, 98% (158) of HIV-positive cases, 100% (14) of HIV-negative cases, 81% (550) of HIV-positive controls, and 80% (257) of HIV-negative controls were KSHV seropositive. Risk factors for KS among HIV-positive individuals included KSHV seropositivity (OR=9.6; 95% CI 2.9, 31.5), non-use of a mosquito bed net (OR 1.9; 95% CI 1.2, 2.9), minority ethnicity (OR=3.1; 95% CI 1.1, 9.3), treatment from a traditional healer (OR=2.3; 95% CI 1.5, 3.7), history of transfusion (OR=2.4; 95% CI 1.5, 3.9), and family history of cancer (OR=1.9; 95% CI 1.1, 3.1). Conclusion KSHV seroprevalence of ≥80% indicates a high prevalence in the general population in Cameroon. Among HIV-positive individuals, the strong association of KS with non-use of mosquito nets and treatment from traditional healers are compelling findings, consistent with recently reported data from East Africa. PMID:24631417

  11. Changes in the latencies of visual-evoked potentials in people undergoing tennis training Dynamic comparison before and after 8 weeks training

    Institute of Scientific and Technical Information of China (English)

    Jingguo Zhao; Shujuan Pang

    2008-01-01

    BACKGROUND: Some previous studies have shown that exercise is an important factor that affects the latencies of visual-evoked potentials (VEPs).OBJECTIVE: To investigate the effects of spending a period of time undergoing tennis training on the latencies of VEPs by comparing the latencies of VEPs before tennis training with those after 8 weeks of tennis training.DESIGN, TIME AND SETTING: The non-randomly concurrent controlled experiment was performed in the Department of Human Movement Sciences, Physical Education College, Shandong Normal University from April to June 2007.PARTICIPANTS: In total, 45 healthy volunteers from Shandong Normal University were selected as subjects, including 31 students majoring in physical education (11 males and 5 females participated in the tennis training plan for 8 weeks), and 14 students from other subjects. Informed consent was obtained. According to whether they were majoring in physical education or not, and whether or not they took part in tennis training, the students were divided into 3 groups: a tennis group of physical education students (n =16), a non-tennis group of physical education students (n =15) and a non-tennis group of non-physical education students (n =14). METHODS: The subjects in the tennis group took part in a regular tennis training plan of 2 hours a day and 3 days per week, for 8 weeks, while the subjects in two non-tennis groups were not in the tennis training plan. The NDI-200 neural electricity tester (Shanghai Haishen Medical Electronic Instrument Co., Ltd.) was used to measure VEPs before and after the experiment in all three groups, and to compare the latencies of VEPs recorded before training with those recorded after training.MAIN OUTCOME MEASURES: Comparison of the changes in latencies of VEPs before and after 8 weeks of tennis training.RESULTS: All 45 subjects finished the test and datas from all were included in the statistical analysis. There were no significant differences among all the three

  12. Increased seizure latency and decreased severity of pentylenetetrazol-induced seizures in mice after essential oil administration.

    Science.gov (United States)

    Koutroumanidou, Eleni; Kimbaris, Athanasios; Kortsaris, Alexandros; Bezirtzoglou, Eugenia; Polissiou, Moschos; Charalabopoulos, Konstantinos; Pagonopoulou, Olga

    2013-01-01

    The effect of pretreatment with essential oils (EOs) from eight aromatic plants on the seizure latency and severity of pentylenetetrazol- (PTZ-) induced seizures in mice was evaluated. Weight-dependent doses of Rosmarinus officinalis, Ocimum basilicum, Mentha spicata, Mentha pulegium, Lavandula angustifolia, Mentha piperita, Origanum dictamnus, and Origanum vulgare, isolated from the respective aromatic plants from NE Greece, were administered 60 minutes prior to intraperitoneal (i.p.) injection of a lethal dose of PTZ to eight respective groups of Balb-c mice. Control group received only one i.p. PTZ injection. Motor and behavioral activity of the animals after EOs administration, development of tonic-clonic seizures, seizure latency and severity, and percentage of survival after PTZ administration were determined for each group. All groups of mice treated with the EOs showed reduced activity and stability after the administration of the oil, except for those treated with O. vulgare (100% mortality after the administration of the oil). After PTZ administration, mice from the different groups showed increased latency and reduced severity of seizures (ranging from simple twitches to complete seizures). Mice who had received M. piperita demonstrated no seizures and 100% survival. The different drastic component and its concentration could account for the diversity of anticonvulsant effects.

  13. Increased Seizure Latency and Decreased Severity of Pentylenetetrazol-Induced Seizures in Mice after Essential Oil Administration

    Science.gov (United States)

    Koutroumanidou, Eleni; Kimbaris, Athanasios; Kortsaris, Alexandros; Bezirtzoglou, Eugenia; Polissiou, Moschos; Charalabopoulos, Konstantinos

    2013-01-01

    The effect of pretreatment with essential oils (EOs) from eight aromatic plants on the seizure latency and severity of pentylenetetrazol- (PTZ-) induced seizures in mice was evaluated. Weight-dependent doses of Rosmarinus officinalis, Ocimum basilicum, Mentha spicata, Mentha pulegium, Lavandula angustifolia, Mentha piperita, Origanum dictamnus, and Origanum vulgare, isolated from the respective aromatic plants from NE Greece, were administered 60 minutes prior to intraperitoneal (i.p.) injection of a lethal dose of PTZ to eight respective groups of Balb-c mice. Control group received only one i.p. PTZ injection. Motor and behavioral activity of the animals after EOs administration, development of tonic-clonic seizures, seizure latency and severity, and percentage of survival after PTZ administration were determined for each group. All groups of mice treated with the EOs showed reduced activity and stability after the administration of the oil, except for those treated with O. vulgare (100% mortality after the administration of the oil). After PTZ administration, mice from the different groups showed increased latency and reduced severity of seizures (ranging from simple twitches to complete seizures). Mice who had received M. piperita demonstrated no seizures and 100% survival. The different drastic component and its concentration could account for the diversity of anticonvulsant effects. PMID:23819045

  14. Increased Seizure Latency and Decreased Severity of Pentylenetetrazol-Induced Seizures in Mice after Essential Oil Administration

    Directory of Open Access Journals (Sweden)

    Eleni Koutroumanidou

    2013-01-01

    Full Text Available The effect of pretreatment with essential oils (EOs from eight aromatic plants on the seizure latency and severity of pentylenetetrazol- (PTZ- induced seizures in mice was evaluated. Weight-dependent doses of Rosmarinus officinalis, Ocimum basilicum, Mentha spicata, Mentha pulegium, Lavandula angustifolia, Mentha piperita, Origanum dictamnus, and Origanum vulgare, isolated from the respective aromatic plants from NE Greece, were administered 60 minutes prior to intraperitoneal (i.p. injection of a lethal dose of PTZ to eight respective groups of Balb-c mice. Control group received only one i.p. PTZ injection. Motor and behavioral activity of the animals after EOs administration, development of tonic-clonic seizures, seizure latency and severity, and percentage of survival after PTZ administration were determined for each group. All groups of mice treated with the EOs showed reduced activity and stability after the administration of the oil, except for those treated with O. vulgare (100% mortality after the administration of the oil. After PTZ administration, mice from the different groups showed increased latency and reduced severity of seizures (ranging from simple twitches to complete seizures. Mice who had received M. piperita demonstrated no seizures and 100% survival. The different drastic component and its concentration could account for the diversity of anticonvulsant effects.

  15. The latency complex: the dead hand of anti-development.

    Science.gov (United States)

    Proner, Barry D

    2017-09-01

    It is common knowledge that the same phenomena can be viewed in a variety of ways. This paper considers the implications of a constellation observed in some adult patients who have increasingly reminded the author of some of the children of latency age with whom he has also worked. In the literature these patients may also have been thought about in terms of 'defences of the self' (Fordham), patients who are 'difficult to reach' (Joseph), 'psychic retreats' (Steiner), and those who make 'attacks on linking' (Bion). They may equally be considered in terms of schizoid, narcissistic or borderline personalities, or as showing features on the autistic spectrum, such as mindlessness and extreme obsessionality. Writers such as Helene Deutsch with her concept of an 'as-if personality', Winnicott with his 'false self', and Rosenfeld, discussing the split-off parts of the personality in narcissistic patients, have also offered much to think about in their consideration of some of these phenomena. This paper proposes yet another vertex - the author's own imaginative conjecture - that is by no means mutually exclusive of any of these others. © 2017, The Society of Analytical Psychology.

  16. Software for analysing multifocal visual evoked potential signal latency progression.

    Science.gov (United States)

    de Santiago, L; Klistorner, A; Ortiz, M; Fernández-Rodríguez, A J; Rodríguez Ascariz, J M; Barea, R; Miguel-Jiménez, J M; Boquete, L

    2015-04-01

    This paper describes a new non-commercial software application (mfVEP(2)) developed to process multifocal visual-evoked-potential (mfVEP) signals in latency (monocular and interocular) progression studies. The software performs analysis by cross-correlating signals from the same patients. The criteria applied by the software include best channels, signal window, cross-correlation limits and signal-to-noise ratio (SNR). Software features include signal display comparing different tests and groups of sectors (quadrants, rings and hemispheres). The software's performance and capabilities are demonstrated on the results obtained from a patient with acute optic neuritis who underwent 9 follow-up mfVEP tests. Numerical values and graphics are presented and discussed for this case. The authors present a software application used to study progression in mfVEP signals. It is also useful in research projects designed to improve mfVEP techniques. This software makes it easier for users to manage the signals and allows them to choose various ways of selecting signals and representing results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Role of Frenular Web Preservation on Ejaculation Latency Time

    Directory of Open Access Journals (Sweden)

    Alborz Salavati

    2012-10-01

    Full Text Available Premature ejaculation (PE is one of prevalent male sexual dysfunctions worldwide. Despite many psychiatric backgrounds, yet there are speculations about organic etiologies considering both anatomic and physiologic points of view. This survey assesses effect of frenular web preservation on premature ejaculation. One thousand and forty otherwise healthy men being visited for urolithiasis (asymptomatic patients were asked for PE according to the International Society of Sexual Medicine definition criteria as intravaginal ejaculation latency time (IELT less than a minute according to stop watch checked by patients' partner and were examined for presence of frenular web. Frenular web defined as a residual of frenulum after a circumcision. Overall prevalence of PE was 18.2% (n=102. We found the presence of frenulum at physical examination in 255 out of 560 (45.5%. Prevalence of PE was 20.7% (n=53 and 16% (n=49 in patients with frenular web preserved and without it, respectively. PE was higher among the men with frenulum preserved; but no statistically significant differences were seen (P=0.70. We did not find any relationship between frenular web and PE, and concerns about this, during circumcision, may not be justified. PE is a not only a problem of local anatomical condition but many psychological and neurological factors could interact with it.

  18. Analysis of Latency Performance of Bluetooth Low Energy (BLE) Networks

    Science.gov (United States)

    Cho, Keuchul; Park, Woojin; Hong, Moonki; Park, Gisu; Cho, Wooseong; Seo, Jihoon; Han, Kijun

    2015-01-01

    Bluetooth Low Energy (BLE) is a short-range wireless communication technology aiming at low-cost and low-power communication. The performance evaluation of classical Bluetooth device discovery have been intensively studied using analytical modeling and simulative methods, but these techniques are not applicable to BLE, since BLE has a fundamental change in the design of the discovery mechanism, including the usage of three advertising channels. Recently, there several works have analyzed the topic of BLE device discovery, but these studies are still far from thorough. It is thus necessary to develop a new, accurate model for the BLE discovery process. In particular, the wide range settings of the parameters introduce lots of potential for BLE devices to customize their discovery performance. This motivates our study of modeling the BLE discovery process and performing intensive simulation. This paper is focused on building an analytical model to investigate the discovery probability, as well as the expected discovery latency, which are then validated via extensive experiments. Our analysis considers both continuous and discontinuous scanning modes. We analyze the sensitivity of these performance metrics to parameter settings to quantitatively examine to what extent parameters influence the performance metric of the discovery processes. PMID:25545266

  19. Analysis of latency performance of bluetooth low energy (BLE) networks.

    Science.gov (United States)

    Cho, Keuchul; Park, Woojin; Hong, Moonki; Park, Gisu; Cho, Wooseong; Seo, Jihoon; Han, Kijun

    2014-12-23

    Bluetooth Low Energy (BLE) is a short-range wireless communication technology aiming at low-cost and low-power communication. The performance evaluation of classical Bluetooth device discovery have been intensively studied using analytical modeling and simulative methods, but these techniques are not applicable to BLE, since BLE has a fundamental change in the design of the discovery mechanism, including the usage of three advertising channels. Recently, there several works have analyzed the topic of BLE device discovery, but these studies are still far from thorough. It is thus necessary to develop a new, accurate model for the BLE discovery process. In particular, the wide range settings of the parameters introduce lots of potential for BLE devices to customize their discovery performance. This motivates our study of modeling the BLE discovery process and performing intensive simulation. This paper is focused on building an analytical model to investigate the discovery probability, as well as the expected discovery latency, which are then validated via extensive experiments. Our analysis considers both continuous and discontinuous scanning modes. We analyze the sensitivity of these performance metrics to parameter settings to quantitatively examine to what extent parameters influence the performance metric of the discovery processes.

  20. Subtle role of latency for information diffusion in online social networks

    Science.gov (United States)

    Xiong, Fei; Wang, Xi-Meng; Cheng, Jun-Jun

    2016-10-01

    Information diffusion in online social networks is induced by the event of forwarding information for users, and latency exists widely in user spreading behaviors. Little work has been done to reveal the effect of latency on the diffusion process. In this paper, we propose a propagation model in which nodes may suspend their spreading actions for a waiting period of stochastic length. These latent nodes may recover their activity again. Meanwhile, the mechanism of forwarding information is also introduced into the diffusion model. Mean-field analysis and numerical simulations indicate that our model has three nontrivial results. First, the spreading threshold does not correlate with latency in neither homogeneous nor heterogeneous networks, but depends on the spreading and refractory parameter. Furthermore, latency affects the diffusion process and changes the infection scale. A large or small latency parameter leads to a larger final diffusion extent, but the intrinsic dynamics is different. Large latency implies forwarding information rapidly, while small latency prevents nodes from dropping out of interactions. In addition, the betweenness is a better descriptor to identify influential nodes in the model with latency, compared with the coreness and degree. These results are helpful in understanding some collective phenomena of the diffusion process and taking measures to restrain a rumor in social networks. Project supported by the National Natural Science Foundation of China (Grant Nos. 61401015 and 61271308), the Fundamental Research Funds for the Central Universities, China (Grant No. 2014JBM018), and the Talent Fund of Beijing Jiaotong University, China (Grant No. 2015RC013).

  1. Achieving low latency and energy consumption by 5G TDD mode optimization

    DEFF Research Database (Denmark)

    Lähetkangas, Eeva; Pajukoski, Kari; Vihriälä, Jaakko

    2014-01-01

    The target for a new 5G radio access technology is to support multi-Gbps and ms latency connectivity simultaneously at noticeably lower energy consumption and cost compared to the existing 4G technologies, such as LTE-Advanced. Extremely short air interface latency is required to achieve these re...

  2. Long-latency auditory evoked potentials with verbal and nonverbal stimuli,

    Directory of Open Access Journals (Sweden)

    Sheila Jacques Oppitz

    2015-12-01

    Full Text Available ABSTRACT INTRODUCTION: Long-latency auditory evoked potentials represent the cortical activity related to attention, memory, and auditory discrimination skills. Acoustic signal processing occurs differently between verbal and nonverbal stimuli, influencing the latency and amplitude patterns. OBJECTIVE: To describe the latencies of the cortical potentials P1, N1, P2, N2, and P3, as well as P3 amplitude, with different speech stimuli and tone bursts, and to classify them in the presence and absence of these data. METHODS: A total of 30 subjects with normal hearing were assessed, aged 18-32 years old, matched by gender. Nonverbal stimuli were used (tone burst; 1000 Hz - frequent and 4000 Hz - rare; and verbal (/ba/ - frequent; /ga/, /da/, and /di/ - rare. RESULTS: Considering the component N2 for tone burst, the lowest latency found was 217.45 ms for the BA/DI stimulus; the highest latency found was 256.5 ms. For the P3 component, the shortest latency with tone burst stimuli was 298.7 with BA/GA stimuli, the highest, was 340 ms. For the P3 amplitude, there was no statistically significant difference among the different stimuli. For latencies of components P1, N1, P2, N2, P3, there were no statistical differences among them, regardless of the stimuli used. CONCLUSION: There was a difference in the latency of potentials N2 and P3 among the stimuli employed but no difference was observed for the P3 amplitude.

  3. Low Latency Audio Video: Potentials for Collaborative Music Making through Distance Learning

    Science.gov (United States)

    Riley, Holly; MacLeod, Rebecca B.; Libera, Matthew

    2016-01-01

    The primary purpose of this study was to examine the potential of LOw LAtency (LOLA), a low latency audio visual technology designed to allow simultaneous music performance, as a distance learning tool for musical styles in which synchronous playing is an integral aspect of the learning process (e.g., jazz, folk styles). The secondary purpose was…

  4. Using Differential Reinforcement to Decrease Academic Response Latencies of an Adolescent with Acquired Brain Injury

    Science.gov (United States)

    Heinicke, Megan R.; Carr, James E.; Mozzoni, Michael P.

    2009-01-01

    The present study investigated the effects of contingency-specifying rules and a token economy to decrease the latency to comply with academic instructions by a 16-year-old girl with acquired brain injury. Results showed that treatment was successful in reducing academic response latencies. These results replicate previous research in which…

  5. MAC Layer Enhancements for Ultra-Reliable Low-Latency Communications in Cellular Networks

    DEFF Research Database (Denmark)

    Gerardino, Guillermo Andrés Pocovi; Alvarez, Beatriz Soret; Pedersen, Klaus I.

    2017-01-01

    Ultra-reliable low-latency communications (URLLC) entail the transmission of sporadic and small packets, with low latency and very high reliability. Among many potential areas of optimization for URLLC, the problems of large delays during HARQ retransmissions, and inaccurate link adaptation as a ...

  6. Antiretroviral drugs do not interfere with bryostatin-mediated HIV-1 latency reversal.

    Science.gov (United States)

    Martínez-Bonet, Marta; Clemente, Maria Isabel; Álvarez, Susana; Díaz, Laura; García-Alonso, Dolores; Muñoz, Eduardo; Moreno, Santiago; Muñoz-Fernández, Maria Ángeles

    2015-11-01

    Although an effective combination of antiretroviral therapy (cART) controls HIV-1 viraemia in infected patients, viral latency established soon after infection hinders HIV-1 eradication. It has been shown that bryostatin-1 (BRY) inhibits HIV-infection in vitro and reactivates the latent virus through the protein kinase C-NF-κB pathway. We determined the in vitro potential effect of BRY in combination with currently used antiretroviral drugs. BRY alone or in combination with maraviroc (MVC)/Atripla (ATP) was tested for its capacity to reactivate latent virus and inhibit new infections. JLTRG-R5 cells and two latent HIV-1-infected cell lines, J89GFP and THP89GFP, were used as latency models. To quantify HIV infection, the reporter cell line TZM-bl was used. We found that BRY reactivates HIV-1 even in combination with MVC or ATP. Antiretroviral combinations with BRY do not interfere with BRY activity (i.e., the reactivation of latently infected cells) or with the antiviral activity of antiretroviral drugs. In addition, BRY-mediated down-modulation of surface CD4 and CXCR4 was not affected when it was used in combination with other antiretrovirals, and no hyperactivation or high-proliferation effects were observed in primary T cells. Moreover, the BRY treatment was able to reactivate HIV-1 in CD4+ T cells from HIV-1-infected patients under cART. Thus, we propose the use of BRY to purge the viral reservoir and recommend its combination with current antiretroviral treatments. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Establishment of HSV1 latency in immunodeficient mice facilitates efficient in vivo reactivation.

    Directory of Open Access Journals (Sweden)

    Chandran Ramakrishna

    2015-03-01

    Full Text Available The establishment of latent infections in sensory neurons is a remarkably effective immune evasion strategy that accounts for the widespread dissemination of life long Herpes Simplex Virus type 1 (HSV1 infections in humans. Periodic reactivation of latent virus results in asymptomatic shedding and transmission of HSV1 or recurrent disease that is usually mild but can be severe. An in-depth understanding of the mechanisms regulating the maintenance of latency and reactivation are essential for developing new approaches to block reactivation. However, the lack of a reliable mouse model that supports efficient in vivo reactivation (IVR resulting in production of infectious HSV1 and/or disease has hampered progress. Since HSV1 reactivation is enhanced in immunosuppressed hosts, we exploited the antiviral and immunomodulatory activities of IVIG (intravenous immunoglobulins to promote survival of latently infected immunodeficient Rag mice. Latently infected Rag mice derived by high dose (HD, but not low dose (LD, HSV1 inoculation exhibited spontaneous reactivation. Following hyperthermia stress (HS, the majority of HD inoculated mice developed HSV1 encephalitis (HSE rapidly and synchronously, whereas for LD inoculated mice reactivated HSV1 persisted only transiently in trigeminal ganglia (Tg. T cells, but not B cells, were required to suppress spontaneous reactivation in HD inoculated latently infected mice. Transfer of HSV1 memory but not OVA specific or naïve T cells prior to HS blocked IVR, revealing the utility of this powerful Rag latency model for studying immune mechanisms involved in control of reactivation. Crossing Rag mice to various knockout strains and infecting them with wild type or mutant HSV1 strains is expected to provide novel insights into the role of specific cellular and viral genes in reactivation, thereby facilitating identification of new targets with the potential to block reactivation.

  8. Longer brainstem auditory evoked response latencies of individuals with fragile X syndrome related to sedation.

    Science.gov (United States)

    Miezejeski, C M; Heaney, G; Belser, R; Brown, W T; Jenkins, E C; Sersen, E A

    1997-04-18

    Brainstem auditory evoked response latencies were studies in 75 males (13 with fragile X syndrome, 18 with mental retardation due to other causes, and 44 with no disability). Latency values were obtained for each ear for the positive deflections of waves I (P1), III (P3), and V (P5). Some individuals with mental retardation required sedation. Contrary to previous report, latencies obtained for individuals with fragile X did not differ from those obtained for persons without mental retardation. Persons receiving sedation, whether or not their retardation was due to fragile X, had longer latencies for wave P5 than persons who did not receive sedation. This effect of sedation may also explain the previously reported increased latencies for persons with fragile X.

  9. Construction and Evaluation of an Ultra Low Latency Frameless Renderer for VR.

    Science.gov (United States)

    Friston, Sebastian; Steed, Anthony; Tilbury, Simon; Gaydadjiev, Georgi

    2016-04-01

    Latency - the delay between a user's action and the response to this action - is known to be detrimental to virtual reality. Latency is typically considered to be a discrete value characterising a delay, constant in time and space - but this characterisation is incomplete. Latency changes across the display during scan-out, and how it does so is dependent on the rendering approach used. In this study, we present an ultra-low latency real-time ray-casting renderer for virtual reality, implemented on an FPGA. Our renderer has a latency of ~1 ms from 'tracker to pixel'. Its frameless nature means that the region of the display with the lowest latency immediately follows the scan-beam. This is in contrast to frame-based systems such as those using typical GPUs, for which the latency increases as scan-out proceeds. Using a series of high and low speed videos of our system in use, we confirm its latency of ~1 ms. We examine how the renderer performs when driving a traditional sequential scan-out display on a readily available HMO, the Oculus Rift OK2. We contrast this with an equivalent apparatus built using a GPU. Using captured human head motion and a set of image quality measures, we assess the ability of these systems to faithfully recreate the stimuli of an ideal virtual reality system - one with a zero latency tracker, renderer and display running at 1 kHz. Finally, we examine the results of these quality measures, and how each rendering approach is affected by velocity of movement and display persistence. We find that our system, with a lower average latency, can more faithfully draw what the ideal virtual reality system would. Further, we find that with low display persistence, the sensitivity to velocity of both systems is lowered, but that it is much lower for ours.

  10. Preliminary investigation of plasma levels of sex hormones and human growth factor(s, and P300 latency as correlates to cognitive decline as a function of gender

    Directory of Open Access Journals (Sweden)

    Kerner Mallory M

    2009-07-01

    Full Text Available Abstract Background Aging is marked by declines in levels of many sex hormones and growth factors, as well as in cognitive function. The P300 event-related potential has been established as a predictor of cognitive decline. We decided to determine if this measure, as well as 2 standard tests of memory and attention, may be correlated with serum levels of sex hormones and growth factors, and if there are any generalizations that could be made based on these parameters and the aging process. Findings In this large clinically based preliminary study several sex-stratified associations between hormone levels and cognition were observed, including (1 for males aged 30 to 49, both IGF-1 and IGFBP-3 significantly associated negatively with prolonged P300 latency; (2 for males aged 30 to 49, the spearman correlation between prolonged P300 latency and low free testosterone was significant; (3 for males aged 60 to 69, there was a significant negative correlation between P300 latency and DHEA levels; (4 for females aged 50 to 59 IGFBP-3 significantly associated negatively with prolonged P300 latency; (5 for females at all age periods, estrogen and progesterone were uncorrelated with P300 latency; and (6 for females aged 40 to 69, there was significant negative correlation between DHEA levels and P300 latency. Moreover there were no statistically significant correlations between any hormone and Wechsler Memory Scale-III (WMS-111. However, in females, there was a significant positive correlation between estrogen levels and the number of Attention Deficit Disorder (ADD complaints. Conclusion Given certain caveats including confounding factors involving psychiatric and other chronic diseases as well as medications, the results may still have important value. If these results could be confirmed in a more rigorously controlled investigation, it may have important value in the diagnosis, prevention and treatment of cognitive impairments and decline.

  11. Detailed analysis of latencies in image-based dynamic MLC tracking

    Energy Technology Data Exchange (ETDEWEB)

    Poulsen, Per Rugaard; Cho, Byungchul; Sawant, Amit; Ruan, Dan; Keall, Paul J. [Department of Radiation Oncology, Stanford University, Stanford, California 94305 and Department of Oncology and Department of Medical Physics, Aarhus University Hospital, 8000 Aarhus (Denmark); Department of Radiation Oncology, Stanford University, Stanford, California 94305 and Department of Radiation Oncology, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Department of Radiation Oncology, Stanford University, Stanford, California 94305 (United States)

    2010-09-15

    Purpose: Previous measurements of the accuracy of image-based real-time dynamic multileaf collimator (DMLC) tracking show that the major contributor to errors is latency, i.e., the delay between target motion and MLC response. Therefore the purpose of this work was to develop a method for detailed analysis of latency contributions during image-based DMLC tracking. Methods: A prototype DMLC tracking system integrated with a linear accelerator was used for tracking a phantom with an embedded fiducial marker during treatment delivery. The phantom performed a sinusoidal motion. Real-time target localization was based on x-ray images acquired either with a portal imager or a kV imager mounted orthogonal to the treatment beam. Each image was stored in a file on the imaging workstation. A marker segmentation program opened the image file, determined the marker position in the image, and transferred it to the DMLC tracking program. This program estimated the three-dimensional target position by a single-imager method and adjusted the MLC aperture to the target position. Imaging intervals {Delta}T{sub image} from 150 to 1000 ms were investigated for both kV and MV imaging. After the experiments, the recorded images were synchronized with MLC log files generated by the MLC controller and tracking log files generated by the tracking program. This synchronization allowed temporal analysis of the information flow for each individual image from acquisition to completed MLC adjustment. The synchronization also allowed investigation of the MLC adjustment dynamics on a considerably finer time scale than the 50 ms time resolution of the MLC log files. Results: For {Delta}T{sub image}=150 ms, the total time from image acquisition to completed MLC adjustment was 380{+-}9 ms for MV and 420{+-}12 ms for kV images. The main part of this time was from image acquisition to completed image file writing (272 ms for MV and 309 ms for kV). Image file opening (38 ms), marker segmentation (4 ms

  12. Extravehicular Activity Operations Concepts Under Communication Latency and Bandwidth Constraints

    Science.gov (United States)

    Beaton, Kara H.; Chappell, Steven P.; Abercromby, Andrew F. J.; Miller, Matthew J.; Nawotniak, Shannon Kobs; Hughes, Scott; Brady, Allyson; Lim, Darlene S. S.

    2017-01-01

    The Biologic Analog Science Associated with Lava Terrains (BASALT) project is a multi-year program dedicated to iteratively develop, implement, and evaluate concepts of operations (ConOps) and supporting capabilities intended to enable and enhance human scientific exploration of Mars. This pa-per describes the planning, execution, and initial results from the first field deployment, referred to as BASALT-1, which consisted of a series of 10 simulated extravehicular activities (EVAs) on volcanic flows in Idaho's Craters of the Moon (COTM) National Monument. The ConOps and capabilities deployed and tested during BASALT-1 were based on previous NASA trade studies and analog testing. Our primary research question was whether those ConOps and capabilities work acceptably when performing real (non-simulated) biological and geological scientific exploration under 4 different Mars-to-Earth communication conditions: 5 and 15 min one-way light time (OWLT) communication latencies and low (0.512 Mb/s uplink, 1.54 Mb/s downlink) and high (5.0 Mb/s uplink, 10.0 Mb/s downlink) bandwidth conditions representing the lower and higher limits of technical communication capabilities currently proposed for future human exploration missions. The synthesized results of BASALT-1 with respect to the ConOps and capabilities assessment were derived from a variety of sources, including EVA task timing data, network analytic data, and subjective ratings and comments regarding the scientific and operational acceptability of the ConOp and the extent to which specific capabilities were enabling and enhancing, and are presented here. BASALT-1 established preliminary findings that baseline ConOp, software systems, and communication protocols were scientifically and operationally acceptable with minor improvements desired by the "Mars" extravehicular (EV) and intravehicular (IV) crewmembers, but unacceptable with improvements required by the "Earth" Mission Support Center. These data will provide a

  13. Fatal snake bites – sociodemography, latency pattern of injuries

    Science.gov (United States)

    2013-01-01

    Background India is a thickly populated country; apart from having biodiversity among people, climate does change from place to place. Western Ghats of South India harbors variety of plantations and diverse creatures. Agriculture is the primary occupation of the people and some tribes living in these regions. Here majority are callous/ ignorant in employing neither advanced farming techniques nor safety precautions, hence are exposed to bites and stings by animals. Of these, snake bites cause significant mortality and morbidity. Proper care for some of these individuals is out of reach. Identification of offending snake, snake bite injury or findings of envenomation is a key not only for the administration of antisnake venom but also for the victim to realize that he needs an expert care. Unless he believes it to be a critical snake bite and not a thorn prick, scorpion sting or a spider bite he will not approach a health care provider. To know about these dangerous signs that may help the victim to realize it as a case of snake bite, current study is employed on fatal cases in this region. Methods 60 fatal snakebite cases were studied retrospectively for 5 years with an objective to know the socio-demography, latency and pattern of injuries in rural Southern India. Results Most of the victims were males, in the age group of 31-50 years and were at risk of snake bites while farming. Large sample of subjects approached traditional therapists and were deprived of essential care in the critical first few hours after snake bite. Fang marks (90%), local ecchymoses (50%) and internal hemorrhage (28.3%), were the frequent demonstrable signs appreciated at autopsy. Conclusion Snakebite is a neglected, endemic, occupational (farming) disease of the poor and there is need for National Snakebite Prevention Programme for curtailing this menace. PMID:23522302

  14. Latency Entry of Herpes Simplex Virus 1 Is Determined by the Interaction of Its Genome with the Nuclear Environment.

    Directory of Open Access Journals (Sweden)

    Mohamed Ali Maroui

    2016-09-01

    Full Text Available Herpes simplex virus 1 (HSV-1 establishes latency in trigeminal ganglia (TG sensory neurons of infected individuals. The commitment of infected neurons toward the viral lytic or latent transcriptional program is likely to depend on both viral and cellular factors, and to differ among individual neurons. In this study, we used a mouse model of HSV-1 infection to investigate the relationship between viral genomes and the nuclear environment in terms of the establishment of latency. During acute infection, viral genomes show two major patterns: replication compartments or multiple spots distributed in the nucleoplasm (namely "multiple-acute". Viral genomes in the "multiple-acute" pattern are systematically associated with the promyelocytic leukemia (PML protein in structures designated viral DNA-containing PML nuclear bodies (vDCP-NBs. To investigate the viral and cellular features that favor the acquisition of the latency-associated viral genome patterns, we infected mouse primary TG neurons from wild type (wt mice or knock-out mice for type 1 interferon (IFN receptor with wt or a mutant HSV-1, which is unable to replicate due to the synthesis of a non-functional ICP4, the major virus transactivator. We found that the inability of the virus to initiate the lytic program combined to its inability to synthesize a functional ICP0, are the two viral features leading to the formation of vDCP-NBs. The formation of the "multiple-latency" pattern is favored by the type 1 IFN signaling pathway in the context of neurons infected by a virus able to replicate through the expression of a functional ICP4 but unable to express functional VP16 and ICP0. Analyses of TGs harvested from HSV-1 latently infected humans showed that viral genomes and PML occupy similar nuclear areas in infected neurons, eventually forming vDCP-NB-like structures. Overall our study designates PML protein and PML-NBs to be major cellular components involved in the control of HSV-1 latency

  15. Implications of event entry latency on anesthesia information management decision support systems.

    Science.gov (United States)

    Epstein, Richard H; Dexter, Franklin; Ehrenfeld, Jesse M; Sandberg, Warren S

    2009-03-01

    Decision support systems (DSSs) are being developed to use events entered in anesthesia information management systems (AIMS) for quality of care, compliance, billing, documentation, and management purposes. DSS performance is impacted by latency from the actual time an event occurs to when it is written to the database, as well as how often the database is queried. Such latencies may result in poor DSS recommendations. We analyzed approximately 48,000 cases at Hospital A for latency of two DSS prototype events, Surgery Begin and Surgery End. Each latency was measured from 1) the time that the event was recorded in the AIMS database as having taken place to 2) the time when the first DSS query would have been executed after the documentation of that event by the provider. The effects on latency of 1, 5, and 10 min query intervals were determined. Latencies for Surgery Begin and Surgery End were compared with those of Hospital B, where a different AIMS was used. Network delays and the event processing time of the AIMS contributed <1 s and 30 s, respectively, to latency. Average latencies for the two studied events were approximately half of the query interval, the expected value if the events occurred randomly within each interval. However, the longest 5% of latencies exceeded the query interval. This was not due to providers editing the times of the Begin or End Surgery events, as each occurred in only 0.7% of cases. Although the median latencies for the two events were longer at Hospital B than Hospital A by a few minutes, the 90th and 95th percentiles of the latencies were much longer at Hospital B (8-30 min, depending on the query interval and the percentile). DSS performance is influenced by the timeliness of documentation, the incidence of missing documentation and the query interval. Facilities using a DSS, including electronic whiteboards showing patient status, should assess the latencies of the measured events and critique the influence of the latencies on

  16. Reducing adaptive optics latency using Xeon Phi many-core processors

    Science.gov (United States)

    Barr, David; Basden, Alastair; Dipper, Nigel; Schwartz, Noah

    2015-11-01

    The next generation of Extremely Large Telescopes (ELTs) for astronomy will rely heavily on the performance of their adaptive optics (AO) systems. Real-time control is at the heart of the critical technologies that will enable telescopes to deliver the best possible science and will require a very significant extrapolation from current AO hardware existing for 4-10 m telescopes. Investigating novel real-time computing architectures and testing their eligibility against anticipated challenges is one of the main priorities of technology development for the ELTs. This paper investigates the suitability of the Intel Xeon Phi, which is a commercial off-the-shelf hardware accelerator. We focus on wavefront reconstruction performance, implementing a straightforward matrix-vector multiplication (MVM) algorithm. We present benchmarking results of the Xeon Phi on a real-time Linux platform, both as a standalone processor and integrated into an existing real-time controller (RTC). Performance of single and multiple Xeon Phis are investigated. We show that this technology has the potential of greatly reducing the mean latency and variations in execution time (jitter) of large AO systems. We present both a detailed performance analysis of the Xeon Phi for a typical E-ELT first-light instrument along with a more general approach that enables us to extend to any AO system size. We show that systematic and detailed performance analysis is an essential part of testing novel real-time control hardware to guarantee optimal science results.

  17. Latency of saccadic eye movement during contraction of bilateral and unilateral shoulder girdle elevators.

    Science.gov (United States)

    Fujiwara, Katsuo; Kunita, Kenji; Toyama, Hiroshi

    2003-02-01

    We compared the timed latencies of saccadic eye movement during isometric contraction of the bilateral and unilateral shoulder girdle elevators in a sitting posture. Muscle contraction force was increased in 10% increments from 0% to 60% of the maximal voluntary contraction (MVC) of each side. Saccadic latency was measured as the latency to the beginning of eye movement toward the lateral target that was moved at random intervals in 20 degree amplitude jumps. Eye movement was measured using the electro-oculogram technique. During bilateral contraction, saccadic latency decreased until 30% MVC and then began to increase at 40% MVC. During unilateral contraction, saccadic latency decreased until 30% MVC in a similar pattern as in bilateral condition, was constant from 30% MVC to 50% MVC, followed by a slight increase at 60% MVC. The saccadic latencies at 10% and 40-60% MVC were significantly shorter during unilateral contraction than bilateral contraction. Thus, the relative force for producing a marked shortening of saccadic latency is observed within a wider range during unilateral contraction than bilateral contraction.

  18. Fault and Error Latency Under Real Workload: an Experimental Study. Ph.D. Thesis

    Science.gov (United States)

    Chillarege, Ram

    1986-01-01

    A practical methodology for the study of fault and error latency is demonstrated under a real workload. This is the first study that measures and quantifies the latency under real workload and fills a major gap in the current understanding of workload-failure relationships. The methodology is based on low level data gathered on a VAX 11/780 during the normal workload conditions of the installation. Fault occurrence is simulated on the data, and the error generation and discovery process is reconstructed to determine latency. The analysis proceeds to combine the low level activity data with high level machine performance data to yield a better understanding of the phenomena. A strong relationship exists between latency and workload and that relationship is quantified. The sampling and reconstruction techniques used are also validated. Error latency in the memory where the operating system resides was studied using data on the physical memory access. Fault latency in the paged section of memory was determined using data from physical memory scans. Error latency in the microcontrol store was studied using data on the microcode access and usage.

  19. Orientation-reversal VEP: comparison of phase and peak latencies in adults and infants.

    Science.gov (United States)

    Lee, Jin; Birtles, Deirdre; Wattam-Bell, John; Atkinson, Janette; Braddick, Oliver

    2012-06-15

    The peak latency of pattern-reversal (PR)-VEP has been found to develop rapidly, reaching the adult level around 15 weeks of age. However, the development of orientation-reversal (OR)-VEP, reflecting the specific spatial organization of cortical receptive fields, still remains unknown. OR-VEP was tested in 81 adults at 1-12 reversals/sec (r/s) and 94 infants (age 4-79 weeks) at 2-8r/s. OR data at 4r/s from an additional 123 infants (age 4.0-20.3 weeks) studied previously were also analyzed. In addition to peak transient latencies at 1-4r/s, latency values derived from the gradient of phase against temporal frequency in steady-state recording were also calculated. For both adults and infants, no significant latency differences in the initial positive peaks were found among the low reversal rates. The calculated latency was statistically longer than the transient latency in both groups. While the transient latency asymptoted to adult value of 102 ms at around 50 weeks of age, the calculated latency, unlike that for PR-VEP, showed little variation across the age span. The data suggest a dominant effect of transmission delay on the initial peak in infancy, which reduces with age. However, the overall timing of the cortical response to orientation change remains slower than for pattern reversal in the fully developed visual cortex. Upon reaching maturity, the latencies of the initial positive peak in both pattern and orientation VEPs may arise from the same level of cortical processing in V1, but the overall time course reflected in the steady-state phase continues to show a much more prolonged response to orientation change than the transmission delay seen in the transient VEPs.

  20. Global dynamics of a vector-borne disease model with latency and saturating incidence rate

    Directory of Open Access Journals (Sweden)

    Ashrafur Rahman

    2014-06-01

    Full Text Available This paper deals with a vector-borne disease model containing latency and nonlinear incidence rates. Global analysis is completely determined by suitable Lyapunov functionals. We explicitely determine the basic reproduction number and find that if this number is less than one then disease dies out, but if the number is larger than one, the disease causing strain become endemic. The study shows that the latency delay explicitely in°uence the disease persistence. Keywords: Latency, saturating incidence, basic reproduction number, global attractivity, Lyapunov functionals.

  1. Latency Analysis of Systems with Multiple Interfaces for Ultra-Reliable M2M Communication

    DEFF Research Database (Denmark)

    Nielsen, Jimmy Jessen; Popovski, Petar

    2016-01-01

    One of the ways to satisfy the requirements of ultra-reliable low latency communication for mission critical Machine-type Communications (MTC) applications is to integrate multiple communication interfaces. In order to estimate the performance in terms of latency and reliability...... of such an integrated communication system, we propose an analysis framework that combines traditional reliability models with technology-specific latency probability distributions. In our proposed model we demonstrate how failure correlation between technologies can be taken into account. We show for the considered...

  2. Bifurcated method and apparatus for floating point addition with decreased latency time

    Energy Technology Data Exchange (ETDEWEB)

    Farmwald, Paul M. (Livermore, CA)

    1987-01-01

    Apparatus for decreasing the latency time associated with floating point addition and subtraction in a computer, using a novel bifurcated, pre-normalization/post-normalization approach that distinguishes between differences of floating point exponents.

  3. Judgment and judgment latency for freedom and responsibility relatedness as a function of subtle linguistic variations.

    Science.gov (United States)

    Wilkerson, Keith; McGahan, Joseph R; Stevens, Rick; Williamson, David; Low, Jean

    2009-12-01

    The goal of this study was to determine whether differential response formats to covariation problems influence corresponding response latencies. The authors provided participants with 3 trials of 16 statements addressing positive and negative relations between freedom and responsibility. The authors framed half of the items around responsibility given freedom and the other half around freedom given responsibility. Response formats comprised true-false, agree-disagree, and yes-no answers as a between-participants factor. Results indicated that the manipulation of response format did not affect latencies. However, latencies differed according to the framing of the items. For items framed around freedom given responsibility, latencies were shorter. In addition, participants were more likely to report a positive relation between freedom and responsibility when items were framed around freedom given responsibility. The authors discuss implications relative to previous research in this area and give recommendations for future research.

  4. Improving IEEE 802.15.4 for Low-Latency Energy-Efficient Industrial Applications

    Science.gov (United States)

    Chen, Feng

    The IEEE 802.15.4 standard for LR-WPAXs is becoming a de-facto standard for Wireless Sensor Xetworks (WSXs) applications in industrial fields. In this paper, we evaluate the latency performance of the IEEE 802.15.4 protocol based on a typical industrial scenario: a star network with 20 devices that send short messages (1 Byte) to the PAX coordinator. We analyzed the behavior of the GTS mechanism in the standard analytically. The results reveal essential limitations of the standard for low-latency applications in automation environments. According to our findings, we propose an enhanced protocol version that fully supports industry demands on low-latency communication. Our protocol version uses the original physical layer and, thus, can be implemented conveniently using cheap IEEE 802.15.4 hardware. The analytical results prove that we are able to meet the guaranteed low latency of 10 ms as specified by typical automation environments.

  5. Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated?

    Science.gov (United States)

    Al-Dujaili, Lena J; Clerkin, Patrick P; Clement, Christian; McFerrin, Harris E; Bhattacharjee, Partha S; Varnell, Emily D; Kaufman, Herbert E; Hill, James M

    2012-01-01

    Most humans are infected with herpes simplex virus (HSV) type 1 in early childhood and remain latently infected throughout life. While most individuals have mild or no symptoms, some will develop destructive HSV keratitis. Ocular infection with HSV-1 and its associated sequelae account for the majority of corneal blindness in industrialized nations. Neuronal latency in the peripheral ganglia is established when transcription of the viral genome is repressed (silenced) except for the latency-associated transcripts and microRNAs. The functions of latency-associated transcripts have been investigated since 1987. Roles have been suggested relating to reactivation, establishment of latency, neuronal protection, antiapoptosis, apoptosis, virulence and asymptomatic shedding. Here, we review HSV-1 latent infections, reactivation, recurrent disease and antiviral therapies for the ocular HSV diseases. PMID:21861620

  6. Industrial WSN Based on IR-UWB and a Low-Latency MAC Protocol

    Science.gov (United States)

    Reinhold, Rafael; Underberg, Lisa; Wulf, Armin; Kays, Ruediger

    2016-07-01

    Wireless sensor networks for industrial communication require high reliability and low latency. As current wireless sensor networks do not entirely meet these requirements, novel system approaches need to be developed. Since ultra wideband communication systems seem to be a promising approach, this paper evaluates the performance of the IEEE 802.15.4 impulse-radio ultra-wideband physical layer and the IEEE 802.15.4 Low Latency Deterministic Network (LLDN) MAC for industrial applications. Novel approaches and system adaptions are proposed to meet the application requirements. In this regard, a synchronization approach based on circular average magnitude difference functions (CAMDF) and on a clean template (CT) is presented for the correlation receiver. An adapted MAC protocol titled aggregated low latency (ALL) MAC is proposed to significantly reduce the resulting latency. Based on the system proposals, a hardware prototype has been developed, which proves the feasibility of the system and visualizes the real-time performance of the MAC protocol.

  7. Kleine-levin syndrome: clinical course, polysomnography and multiple sleep latency test. Case report

    Directory of Open Access Journals (Sweden)

    REIMÃO RUBENS

    1998-01-01

    Full Text Available A case of Kleine-Levin syndrome, with chronic severe periodic hypersomnia is described in a 17-year-old female. The first episode started when she was 15 years old. The episodes were characterized by periodic hypersomnia accompanied by hyperphagia, lasting 5 days, and repeating at 28 to 60 day intervals. The severity of hypersomnia prevented her from attending school activities. Outside the hypersomnia periods, she was asymptomatic. EEG, brain computerized tomography and brain nuclear magnetic resonance were normal; all-night polysomnography, Multiple Sleep Latency Test (MSLT and Epworth Sleepiness Scale (ESS were within normal limits. During the period of hypersomnolence, polysomnography showed short sleep latency and short REM latency. MSLT mean sleep latency was 1.8 min; and REM period was present in one subtest; the ESS was markedly elevated.

  8. Rein: Taming Tail Latency in Key-Value Stores via Multiget Scheduling

    KAUST Repository

    Reda, Waleed

    2017-04-17

    We tackle the problem of reducing tail latencies in distributed key-value stores, such as the popular Cassandra database.We focus on workloads of multiget requests, which batch together access to several data elements and parallelize read operations across the data store machines. We first analyze a production trace of a real system and quantify the skew due to multiget sizes, key popularity, and other factors. We then proceed to identify opportunities for reduction of tail latencies by recognizing the composition of aggregate requests and by carefully scheduling bottleneck operations that can otherwise create excessive queues. We design and implement a system called Rein, which reduces latency via inter-multiget scheduling using low overhead techniques. We extensively evaluate Rein via experiments in Amazon Web Services (AWS) and simulations. Our scheduling algorithms reduce the median, 95, and 99 percentile latencies by factors of 1.5, 1.5, and 1.9, respectively.

  9. Research on low-latency MAC protocols for wireless sensor networks

    Science.gov (United States)

    He, Chenguang; Sha, Xuejun; Lee, Chankil

    2007-11-01

    Energy-efficient should not be the only design goal in MAC protocols for wireless sensor networks, which involve the use of battery-operated computing and sensing devices. Low-latency operation becomes the same important as energy-efficient in the case that the traffic load is very heavy or the real-time constrain is used in applications like tracking or locating. This paper introduces some causes of traditional time delays which are inherent in a multi-hops network using existing WSN MAC protocols, illuminates the importance of low-latency MAC design for wireless sensor networks, and presents three MACs as examples of low-latency protocols designed specially for sleep delay, wait delay and wakeup delay in wireless sensor networks, respectively. The paper also discusses design trade-offs with emphasis on low-latency and points out their advantages and disadvantages, together with some design considerations and suggestions for MAC protocols for future applications and researches.

  10. Measurement and reduction of system latency in see-through helmet mounted display (HMD) systems

    Science.gov (United States)

    Vincenzi, Dennis A.; Deaton, John E.; Blickenderfer, Elizabeth L.; Pray, Rick; Williams, Barry; Buker, Timothy J.

    2010-04-01

    Future military aviation platforms such as the proposed Joint Strike Fighter F-35 will integrate helmet mounted displays (HMDs) with the avionics and weapon systems to the degree that the HMDs will become the aircraft's primary display system. In turn, training of pilot flight skills using HMDs will be essential in future training systems. In order to train these skills using simulation based training, improvements must be made in the integration of HMDs with out-thewindow (OTW) simulations. Currently, problems such as latency contribute to the onset of simulator sickness and provide distractions during training with HMD simulator systems that degrade the training experience. Previous research has used Kalman predictive filters as a means of mitigating the system latency present in these systems. While this approach has yielded some success, more work is needed to develop innovative and improved strategies that reduce system latency as well as to include data collected from the user perspective as a measured variable during test and evaluation of latency reduction strategies. The purpose of this paper is twofold. First, the paper describes a new method to measure and assess system latency from the user perspective. Second, the paper describes use of the testbed to examine the efficacy of an innovative strategy that combines a customized Kalman filter with a neural network approach to mitigate system latency. Results indicate that the combined approach reduced system latency significantly when compared to baseline data and the traditional Kalman filter. Reduced latency errors should mitigate the onset of simulator sickness and ease simulator sickness symptomology. Implications for training systems will be discussed.

  11. Long-latency auditory evoked potentials with verbal and nonverbal stimuli.

    Science.gov (United States)

    Oppitz, Sheila Jacques; Didoné, Dayane Domeneghini; Silva, Débora Durigon da; Gois, Marjana; Folgearini, Jordana; Ferreira, Geise Corrêa; Garcia, Michele Vargas

    2015-01-01

    Long-latency auditory evoked potentials represent the cortical activity related to attention, memory, and auditory discrimination skills. Acoustic signal processing occurs differently between verbal and nonverbal stimuli, influencing the latency and amplitude patterns. To describe the latencies of the cortical potentials P1, N1, P2, N2, and P3, as well as P3 amplitude, with different speech stimuli and tone bursts, and to classify them in the presence and absence of these data. A total of 30 subjects with normal hearing were assessed, aged 18-32 years old, matched by gender. Nonverbal stimuli were used (tone burst; 1000Hz - frequent and 4000Hz - rare); and verbal (/ba/ - frequent; /ga/, /da/, and /di/ - rare). Considering the component N2 for tone burst, the lowest latency found was 217.45ms for the BA/DI stimulus; the highest latency found was 256.5ms. For the P3 component, the shortest latency with tone burst stimuli was 298.7 with BA/GA stimuli, the highest, was 340ms. For the P3 amplitude, there was no statistically significant difference among the different stimuli. For latencies of components P1, N1, P2, N2, P3, there were no statistical differences among them, regardless of the stimuli used. There was a difference in the latency of potentials N2 and P3 among the stimuli employed but no difference was observed for the P3 amplitude. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  12. Self-esteem modulates the latency of P2 component in implicit self-relevant processing.

    Science.gov (United States)

    Yang, Juan; Qi, Mingming; Guan, Lili

    2014-03-01

    Previous study has shown that the latency of P2 component was more prolonged in processing self-relevant words compared to processing non-self-relevant words. However, the prolonged P2 latency may index the self-relevance of the words, the valence of the words, or an interaction of the two. The present study aimed to (1) further clarify the specific psychological significance of the prolonged P2 latency in implicit self-processing and (2) investigate the potential association between self-esteem and the latency of P2 in processing implicit self-relevant information. Nineteen participants were examined using event-related potentials (ERPs) technology. They were exposed to positive and negative words and were asked to make a judgment about the color of each word. For the data analysis, words were grouped individually according to their degree of self-relevance (low vs. high) for each participant. Results showed that the latency of P2 was more prolonged in processing the negative-high self-relevant words compared to processing the positive-high self-relevant words. Also, self-esteem was negatively correlated with the P2 latency in processing negative-high self-relevant words. Overall, the results of the present study suggested that levels of self-esteem might modulate neural correlates of self-referential processing.

  13. Photosensor-Based Latency Measurement System for Head-Mounted Displays

    Directory of Open Access Journals (Sweden)

    Min-Woo Seo

    2017-05-01

    Full Text Available In this paper, a photosensor-based latency measurement system for head-mounted displays (HMDs is proposed. The motion-to-photon latency is the greatest reason for motion sickness and dizziness felt by users when wearing an HMD system. Therefore, a measurement system is required to accurately measure and analyze the latency to reduce these problems. The existing measurement system does not consider the actual physical movement in humans, and its accuracy is also very low. However, the proposed system considers the physical head movement and is highly accurate. Specifically, it consists of a head position model-based rotary platform, pixel luminance change detector, and signal analysis and calculation modules. Using these modules, the proposed system can exactly measure the latency, which is the time difference between the physical movement for a user and the luminance change of an output image. In the experiment using a commercial HMD, the latency was measured to be up to 47.05 ms. In addition, the measured latency increased up to 381.17 ms when increasing the rendering workload in the HMD.

  14. Generation of spike latency tuning by thalamocortical circuits in auditory cortex.

    Science.gov (United States)

    Zhou, Yi; Mesik, Lukas; Sun, Yujiao J; Liang, Feixue; Xiao, Zhongju; Tao, Huizhong W; Zhang, Li I

    2012-07-18

    In many sensory systems, the latency of spike responses of individual neurons is found to be tuned for stimulus features and proposed to be used as a coding strategy. Whether the spike latency tuning is simply relayed along sensory ascending pathways or generated by local circuits remains unclear. Here, in vivo whole-cell recordings from rat auditory cortical neurons in layer 4 revealed that the onset latency of their aggregate thalamic input exhibited nearly flat tuning for sound frequency, whereas their spike latency tuning was much sharper with a broadly expanded dynamic range. This suggests that the spike latency tuning is not simply inherited from the thalamus, but can be largely reconstructed by local circuits in the cortex. Dissecting of thalamocortical circuits and neural modeling further revealed that broadly tuned intracortical inhibition prolongs the integration time for spike generation preferentially at off-optimal frequencies, while sharply tuned intracortical excitation shortens it selectively at the optimal frequency. Such push and pull mechanisms mediated likely by feedforward excitatory and inhibitory inputs respectively greatly sharpen the spike latency tuning and expand its dynamic range. The modulation of integration time by thalamocortical-like circuits may represent an efficient strategy for converting information spatially coded in synaptic strength to temporal representation.

  15. Temporal processing and long-latency auditory evoked potential in stutterers.

    Science.gov (United States)

    Prestes, Raquel; de Andrade, Adriana Neves; Santos, Renata Beatriz Fernandes; Marangoni, Andrea Tortosa; Schiefer, Ana Maria; Gil, Daniela

    Stuttering is a speech fluency disorder, and may be associated with neuroaudiological factors linked to central auditory processing, including changes in auditory processing skills and temporal resolution. To characterize the temporal processing and long-latency auditory evoked potential in stutterers and to compare them with non-stutterers. The study included 41 right-handed subjects, aged 18-46 years, divided into two groups: stutterers (n=20) and non-stutters (n=21), compared according to age, education, and sex. All subjects were submitted to the duration pattern tests, random gap detection test, and long-latency auditory evoked potential. Individuals who stutter showed poorer performance on Duration Pattern and Random Gap Detection tests when compared with fluent individuals. In the long-latency auditory evoked potential, there was a difference in the latency of N2 and P3 components; stutterers had higher latency values. Stutterers have poor performance in temporal processing and higher latency values for N2 and P3 components. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  16. Differential regulation of the overlapping Kaposi's sarcoma-associated herpesvirus vGCR (orf74) and LANA (orf73) promoters.

    Science.gov (United States)

    Jeong, J; Papin, J; Dittmer, D

    2001-02-01

    Similar to that of other herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) lytic replication destroys the host cell, while the virus can persist in a latent state in synchrony with the host. During latency only a few genes are transcribed, and the question becomes one of what determines latent versus lytic gene expression. Here we undertake a detailed analysis of the latency-associated nuclear antigen (LANA [orf73]) promoter (LANAp). We characterized a minimal region that is necessary and sufficient to maintain high-level transcription in all tissues tested, including primary endothelial cells and B cells, which are the suspected natural host for KSHV. We show that in transient-transfection assays LANAp mimics the expression pattern observed for the authentic promoter in the context of the KSHV episome. Unlike other KSHV promoters tested thus far, LANAp is not affected by tetradecanoyl phorbol acetate or viral lytic cycle functions. It is, however, subject to control by LANA itself and cellular regulatory factors, such as p53. This is in contrast to the K14/vGCR (orf74) promoter, which overlaps LANAp and directs transcription on the opposite strand. We isolated a minimal cis-regulatory region sufficient for K14/vGCR promoter activity and show that it, too, mimics the regulation observed for the authentic viral promoter. In particular, we demonstrate that its activity is absolutely dependent on the immediate-early transactivator orf50, the KSHV homolog of the Epstein-Barr virus Rta transactivator.

  17. Earlier visual N1 latencies in expert video-game players: a temporal basis of enhanced visuospatial performance?

    Directory of Open Access Journals (Sweden)

    Andrew J Latham

    Full Text Available Increasing behavioural evidence suggests that expert video game players (VGPs show enhanced visual attention and visuospatial abilities, but what underlies these enhancements remains unclear. We administered the Poffenberger paradigm with concurrent electroencephalogram (EEG recording to assess occipital N1 latencies and interhemispheric transfer time (IHTT in expert VGPs. Participants comprised 15 right-handed male expert VGPs and 16 non-VGP controls matched for age, handedness, IQ and years of education. Expert VGPs began playing before age 10, had a minimum 8 years experience, and maintained playtime of at least 20 hours per week over the last 6 months. Non-VGPs had little-to-no game play experience (maximum 1.5 years. Participants responded to checkerboard stimuli presented to the left and right visual fields while 128-channel EEG was recorded. Expert VGPs responded significantly more quickly than non-VGPs. Expert VGPs also had significantly earlier occipital N1s in direct visual pathways (the hemisphere contralateral to the visual field in which the stimulus was presented. IHTT was calculated by comparing the latencies of occipital N1 components between hemispheres. No significant between-group differences in electrophysiological estimates of IHTT were found. Shorter N1 latencies may enable expert VGPs to discriminate attended visual stimuli significantly earlier than non-VGPs and contribute to faster responding in visual tasks. As successful video-game play requires precise, time pressured, bimanual motor movements in response to complex visual stimuli, which in this sample began during early childhood, these differences may reflect the experience and training involved during the development of video-game expertise, but training studies are needed to test this prediction.

  18. Earlier visual N1 latencies in expert video-game players: a temporal basis of enhanced visuospatial performance?

    Science.gov (United States)

    Latham, Andrew J; Patston, Lucy L M; Westermann, Christine; Kirk, Ian J; Tippett, Lynette J

    2013-01-01

    Increasing behavioural evidence suggests that expert video game players (VGPs) show enhanced visual attention and visuospatial abilities, but what underlies these enhancements remains unclear. We administered the Poffenberger paradigm with concurrent electroencephalogram (EEG) recording to assess occipital N1 latencies and interhemispheric transfer time (IHTT) in expert VGPs. Participants comprised 15 right-handed male expert VGPs and 16 non-VGP controls matched for age, handedness, IQ and years of education. Expert VGPs began playing before age 10, had a minimum 8 years experience, and maintained playtime of at least 20 hours per week over the last 6 months. Non-VGPs had little-to-no game play experience (maximum 1.5 years). Participants responded to checkerboard stimuli presented to the left and right visual fields while 128-channel EEG was recorded. Expert VGPs responded significantly more quickly than non-VGPs. Expert VGPs also had significantly earlier occipital N1s in direct visual pathways (the hemisphere contralateral to the visual field in which the stimulus was presented). IHTT was calculated by comparing the latencies of occipital N1 components between hemispheres. No significant between-group differences in electrophysiological estimates of IHTT were found. Shorter N1 latencies may enable expert VGPs to discriminate attended visual stimuli significantly earlier than non-VGPs and contribute to faster responding in visual tasks. As successful video-game play requires precise, time pressured, bimanual motor movements in response to complex visual stimuli, which in this sample began during early childhood, these differences may reflect the experience and training involved during the development of video-game expertise, but training studies are needed to test this prediction.

  19. High-throughput and low-latency 60GHz small-cell network architectures over radio-over-fiber technologies

    Science.gov (United States)

    Pleros, N.; Kalfas, G.; Mitsolidou, C.; Vagionas, C.; Tsiokos, D.; Miliou, A.

    2017-01-01

    Future broadband access networks in the 5G framework will need to be bilateral, exploiting both optical and wireless technologies. This paper deals with new approaches and synergies on radio-over-fiber (RoF) technologies and how those can be leveraged to seamlessly converge wireless technology for agility and mobility with passive optical networks (PON)-based backhauling. The proposed convergence paradigm is based upon a holistic network architecture mixing mm-wave wireless access with photonic integration, dynamic capacity allocation and network coding schemes to enable high bandwidth and low-latency fixed and 60GHz wireless personal area communications for gigabit rate per user, proposing and deploying on top a Medium-Transparent MAC (MT-MAC) protocol as a low-latency bandwidth allocation mechanism. We have evaluated alternative network topologies between the central office (CO) and the access point module (APM) for data rates up to 2.5 Gb/s and SC frequencies up to 60 GHz. Optical network coding is demonstrated for SCM-based signaling to enhance bandwidth utilization and facilitate optical-wireless convergence in 5G applications, reporting medium-transparent network coding directly at the physical layer between end-users communicating over a RoF infrastructure. Towards equipping the physical layer with the appropriate agility to support MT-MAC protocols, a monolithic InP-based Remote Antenna Unit optoelectronic PIC interface is shown that ensures control over the optical resource allocation assisting at the same time broadband wireless service. Finally, the MT-MAC protocol is analysed and simulation and analytical theoretical results are presented that are found to be in good agreement confirming latency values lower than 1msec for small- to mid-load conditions.

  20. The effect of magnesium sulfate administration for neuroprotection on latency in women with preterm premature rupture of membranes

    Science.gov (United States)

    Horton, Amanda L.; Lai, Yinglei; Rouse, Dwight J.; Spong, Catherine Y.; Leveno, Kenneth J.; Varner, Michael W.; Mercer, Brian M.; Iams, Jay D.; Wapner, Ronald J.; Sorokin, Yoram; Thorp, John M.; Ramin, Susan M.; Malone, Fergal D.; O'Sullivan, Mary J.; Hankins, Gary D. V.; Caritis, Steve N.

    2015-01-01

    Objective To evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes between 24 and 31 6/7 weeks' gestation. Study Design This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 31 6/7 weeks' gestation with preterm premature rupture of membranes (pPROM) without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysis were delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death. Results A total of 1259 women were included. The rate of delivery < 48 hours was not different in the magnesium sulfate and the placebo groups (22.2% and 20.7%, p=0.51). Delivery < 7 days was similar between groups (55.4% and 51.4%, p=0.16). Median latency was also similar between groups (median [interquartile range] 6.0 days [2.4–13.8] and 6.6 days [2.4–15.1], p =0.29). Composite neonatal outcomes did not differ between groups. Conclusion: Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with preterm premature rupture of membranes and without labor before 32 weeks does not impact latency. PMID:25241107

  1. A template-free approach for determining the latency of single events of auditory evoked M100

    Energy Technology Data Exchange (ETDEWEB)

    Burghoff, M [Physikalisch-Technische Bundesanstalt (PTB), Berlin (Germany); Link, A [Physikalisch-Technische Bundesanstalt (PTB), Berlin (Germany); Salajegheh, A [Cognitive Neuroscience of Language Laboratory, University of Maryland College Park, MD (United States); Elster, C [Physikalisch-Technische Bundesanstalt (PTB), Berlin (Germany); Poeppel, D [Cognitive Neuroscience of Language Laboratory, University of Maryland College Park, MD (United States); Trahms, L [Physikalisch-Technische Bundesanstalt (PTB), Berlin (Germany)

    2005-02-07

    The phase of the complex output of a narrow band Gaussian filter is taken to define the latency of the auditory evoked response M100 recorded by magnetoencephalography. It is demonstrated that this definition is consistent with the conventional peak latency. Moreover, it provides a tool for reducing the number of averages needed for a reliable estimation of the latency. Single-event latencies obtained by this procedure can be used to improve the signal quality of the conventional average by latency adjusted averaging. (note)

  2. Ex Vivo Bioactivity and HIV-1 Latency Reversal by Ingenol Dibenzoate and Panobinostat in Resting CD4+ T Cells from Aviremic Patients

    Science.gov (United States)

    Spivak, Adam M.; Bosque, Alberto; Balch, Alfred H.; Smyth, David; Martins, Laura

    2015-01-01

    The human immunodeficiency virus type 1 (HIV-1) latent reservoir in resting CD4+ T cells represents a major barrier to viral eradication. Small compounds capable of latency reversal have not demonstrated uniform responses across in vitro HIV-1 latency cell models. Characterizing compounds that demonstrate latency-reversing activity in resting CD4+ T cells from aviremic patients ex vivo will help inform pilot clinical trials aimed at HIV-1 eradication. We have optimized a rapid ex vivo assay using resting CD4+ T cells from aviremic HIV-1+ patients to evaluate both the bioactivity and latency-reversing potential of candidate latency-reversing agents (LRAs). Using this assay, we characterize the properties of two candidate compounds from promising LRA classes, ingenol 3,20-dibenzoate (a protein kinase C agonist) and panobinostat (a histone deacetylase inhibitor), in cells from HIV-1+ antiretroviral therapy (ART)-treated aviremic participants, including the effects on cellular activation and cytotoxicity. Ingenol induced viral release at levels similar to those of the positive control (CD3/28 receptor stimulation) in cells from a majority of participants and represents an exciting LRA candidate, as it combines a robust viral reactivation potential with a low toxicity profile. At concentrations that blocked histone deacetylation, panobinostat displayed a wide range of potency among participant samples and consistently induced significant levels of apoptosis. The protein kinase C agonist ingenol 3,20-dibenzoate demonstrated significant promise in a rapid ex vivo assay using resting CD4+ T cells from treated HIV-1-positive patients to measure latent HIV-1 reactivation. PMID:26169416

  3. Neuromagnetic oscillations predict evoked-response latency delays and core language deficits in autism spectrum disorders.

    Science.gov (United States)

    Edgar, J Christopher; Khan, Sarah Y; Blaskey, Lisa; Chow, Vivian Y; Rey, Michael; Gaetz, William; Cannon, Katelyn M; Monroe, Justin F; Cornew, Lauren; Qasmieh, Saba; Liu, Song; Welsh, John P; Levy, Susan E; Roberts, Timothy P L

    2015-02-01

    Previous studies have observed evoked response latency as well as gamma band superior temporal gyrus (STG) auditory abnormalities in individuals with autism spectrum disorders (ASD). A limitation of these studies is that associations between these two abnormalities, as well as the full extent of oscillatory phenomena in ASD in terms of frequency and time, have not been examined. Subjects were presented pure tones at 200, 300, 500, and 1,000 Hz while magnetoencephalography assessed activity in STG auditory areas in a sample of 105 children with ASD and 36 typically developing controls (TD). Findings revealed a profile such that auditory STG processes in ASD were characterized by pre-stimulus abnormalities across multiple frequencies, then early high-frequency abnormalities followed by low-frequency abnormalities. Increased pre-stimulus activity was a 'core' abnormality, with pre-stimulus activity predicting post-stimulus neural abnormalities, group membership, and clinical symptoms (CELF-4 Core Language Index). Deficits in synaptic integration in the auditory cortex are associated with oscillatory abnormalities in ASD as well as patient symptoms. Increased pre-stimulus activity in ASD likely demonstrates a fundamental signal-to-noise deficit in individuals with ASD, with elevations in oscillatory activity suggesting an inability to maintain an appropriate 'neural tone' and an inability to rapidly return to a resting state prior to the next stimulus.

  4. Systematic analysis of human oncogenic viruses in colon cancer revealed EBV latency in lymphoid infiltrates.

    Science.gov (United States)

    Fiorina, Loretta; Ricotti, Mattia; Vanoli, Alessandro; Luinetti, Ombretta; Dallera, Elena; Riboni, Roberta; Paolucci, Stefania; Brugnatelli, Silvia; Paulli, Marco; Pedrazzoli, Paolo; Baldanti, Fausto; Perfetti, Vittorio

    2014-01-01

    Environmental factors may play a role in colon cancer. In this view, several studies investigated tumor samples for the presence of various viral DNA with conflicting results. We undertook a systematic DNA analysis of 44 consecutive, prospectively collected primary tumor samples by real time and qualitative PCR for viruses of known or potential oncogenic role in humans, including polyomavirus (JCV, BKV, Merkel cell polyomavirus), HPV, HTLV, HHV-8 and EBV. Negative controls consisted of surgical resection margins. No evidence of genomic DNA fragments from tested virus were detected, except for EBV, which was found in a significant portion of tumors (23/44, 52%). Real-time PCR showed that EBV DNA was present at a highly variable content (median 258 copies in 10(5) cells, range 15-4837). Presence of EBV DNA had a trend to be associated with high lymphocyte infiltration (p = 0.06, χ2 test), and in situ hybridization with EBER1-2 probes revealed latency in a fraction of these lymphoid cells, with just a few scattered plasma cells positive for BZLF-1, an immediate early protein expressed during lytic replication. LMP-1 expression was undetectable by immunohistochemistry. These results argue against a significant involvement of the tested oncogenic viruses in established colon cancer.

  5. PrP(c) expression influences the establishment of herpes simplex virus type 1 latency.

    Science.gov (United States)

    Thackray, Alana M; Bujdoso, Raymond

    2002-03-01

    PrP(c) is a glycophosphatidylinositol-linked cell-surface protein expressed principally by neural tissue. The normal function of this protein is unestablished, although a role in either transmembrane signaling, cell-cell adhesion, or copper metabolism has been proposed. In this study we have investigated the effect of the neurotropic virus herpes simplex virus type 1 (HSV-1) in strains of mice which express different levels of PrP(c). Viral gene expression under the control of the HSV-1 early promoter IE110, detected either by in situ hybridization for RNA transcripts or by beta-galactosidase (beta-Gal) activity from an inserted lacZ gene, showed that the magnitude of HSV replication was retarded in PrP-/- mice. This was reflected in the lower level of acute viral titers in tissues from these virus-inoculated mice. However, HSV-inoculated PrP-/- mice contained higher levels of latent virus in both peripheral and central nervous tissue than those seen in mice which express PrP(c). Our observations show that lack of PrP(c) expression favors the establishment of HSV latency whereas HSV replication proceeds more efficiently in neuronal tissue that expresses this protein. The data further suggest that PrP(c) may be involved in a metabolic pathway that culminates in apoptosis of neurons that have been infected by neurotropic viruses.

  6. PLRP-3: Operational Perspectives of Conducting Science-Driven Extravehicular Activity with Communications Latency

    Science.gov (United States)

    Miller, Matthew J.; Lim, Darlene S. S.; Brady, Allyson; Cardman, Zena; Bell, Ernest; Garry, Brent; Reid, Donnie; Chappell, Steve; Abercromby, Andrew F. J.

    2016-01-01

    The Pavilion Lake Research Project (PLRP) is a unique platform where the combination of scientific research and human space exploration concepts can be tested in an underwater spaceflight analog environment. The 2015 PLRP field season was performed at Pavilion Lake, Canada, where science-driven exploration techniques focusing on microbialite characterization and acquisition were evaluated within the context of crew and robotic extravehicular activity (EVA) operations. The primary objectives of this analog study were to detail the capabilities, decision-making process, and operational concepts required to meet non-simulated scientific objectives during 5-minute one-way communication latency utilizing crew and robotic assets. Furthermore, this field study served as an opportunity build upon previous tests at PLRP, NASA Desert Research and Technology Studies (DRATS), and NASA Extreme Environment Mission Operations (NEEMO) to characterize the functional roles and responsibilities of the personnel involved in the distributed flight control team and identify operational constraints imposed by science-driven EVA operations. The relationship and interaction between ground and flight crew was found to be dependent on the specific scientific activities being addressed. Furthermore, the addition of a second intravehicular operator was found to be highly enabling when conducting science-driven EVAs. Future human spaceflight activities will need to cope with the added complexity of dynamic and rapid execution of scientific priorities both during and between EVA execution to ensure scientific objectives are achieved.

  7. Research progress on TLR4 expression in Kaposi's sarcoma with KSHV%TLR4在KSHV感染的卡波西肉瘤中表达的研究进展

    Institute of Scientific and Technical Information of China (English)

    李肖然(综述); 鲁晓擘(审校)

    2014-01-01

    Toll-like receptor 4 (TLR4) is one of the important members of Toll like receptors, which is a rec-ognition receptor of lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria. Activation of TLR4 induced a series of inflammatory mediators, including cytokines and chemokines, to produce a strong inflammatory re-action. TLR4 played an important role in anti-bacteria, inflammation, antiviral, and stress. TLR4 was also expressed in kaposi's sarcoma, which is infected by Kaposi's sarcoma associated herpesvirus (KSHV). This paper reviewed the most recent advancements of signal transduction mechanism of TLR4 in Kaposi's sarcoma.%TLR4(Toll-like receptor 4)是Toll样受体的一个重要的组成成员,是革兰氏阴性细胞壁成份脂多糖(LPS)的识别受体。活化TLR4将诱导产生一系列炎症介质,包括细胞因子、趋化因子等从而产生强有力的炎症反应,TLR4在抗细菌,抗病毒的炎症反应中,以及在应激状态下均发挥重要作用。TLR4在KSHV (Kaposi's sarcoma-associated herpesvirus,卡波西肉瘤相关疱疹病毒)感染的卡波西肉瘤中也有表达,本文就TLR4在KSHV感染的卡波西肉瘤中的信号转导机制及研究进展做一综述。

  8. The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4(+) T-cells.

    Science.gov (United States)

    Kumar, Nitasha A; Cheong, Karey; Powell, David R; da Fonseca Pereira, Candida; Anderson, Jenny; Evans, Vanessa A; Lewin, Sharon R; Cameron, Paul U

    2015-09-11

    Combination antiretroviral therapy (cART) is able to control HIV-1 viral replication, however long-lived latent infection in resting memory CD4(+) T-cells persist. The mechanisms for establishment and maintenance of latent infection in resting memory CD4(+) T-cells remain unclear. Previously we have shown that HIV-1 infection of resting CD4(+) T-cells co-cultured with CD11c(+) myeloid dendritic cells (mDC) produced a population of non-proliferating T-cells with latent infection. Here we asked whether different antigen presenting cells (APC), including subpopulations of DC and monocytes, were able to induce post-integration latent infection in resting CD4(+) T-cells, and examined potential cell interactions that may be involved using RNA-seq. mDC (CD1c(+)), SLAN(+) DC and CD14(+) monocytes were most efficient in stimulating proliferation of CD4(+) T-cells during syngeneic culture and in generating post-integration latent infection in non-proliferating CD4(+) T-cells following HIV-1 infection of APC-T cell co-cultures. In comparison, plasmacytoid DC (pDC) and B-cells did not induce latent infection in APC-T-cell co-cultures. We compared the RNA expression profiles of APC subpopulations that could and could not induce latency in non-proliferating CD4(+) T-cells. Gene expression analysis, comparing the CD1c(+) mDC, SLAN(+) DC and CD14(+) monocyte subpopulations to pDC identified 53 upregulated genes that encode proteins expressed on the plasma membrane that could signal to CD4(+) T-cells via cell-cell interactions (32 genes), immune checkpoints (IC) (5 genes), T-cell activation (9 genes), regulation of apoptosis (5 genes), antigen presentation (1 gene) and through unknown ligands (1 gene). APC subpopulations from the myeloid lineage, specifically mDC subpopulations and CD14(+) monocytes, were able to efficiently induce post-integration HIV-1 latency in non-proliferating CD4(+) T-cells in vitro. Inhibition of key pathways involved in mDC-T-cell interactions and HIV-1

  9. Latency Entry of Herpes Simplex Virus 1 Is Determined by the Interaction of Its Genome with the Nuclear Environment

    Science.gov (United States)

    Cohen, Camille; Streichenberger, Nathalie; Texier, Pascale; Takissian, Julie; Rousseau, Antoine; Poccardi, Nolwenn; Welsch, Jérémy; Corpet, Armelle; Schaeffer, Laurent; Labetoulle, Marc; Lomonte, Patrick

    2016-01-01

    Herpes simplex virus 1 (HSV-1) establishes latency in trigeminal ganglia (TG) sensory neurons of infected individuals. The commitment of infected neurons toward the viral lytic or latent transcriptional program is likely to depend on both viral and cellular factors, and to differ among individual neurons. In this study, we used a mouse model of HSV-1 infection to investigate the relationship between viral genomes and the nuclear environment in terms of the establishment of latency. During acute infection, viral genomes show two major patterns: replication compartments or multiple spots distributed in the nucleoplasm (namely “multiple-acute”). Viral genomes in the “multiple-acute” pattern are systematically associated with the promyelocytic leukemia (PML) protein in structures designated viral DNA-containing PML nuclear bodies (vDCP-NBs). To investigate the viral and cellular features that favor the acquisition of the latency-associated viral genome patterns, we infected mouse primary TG neurons from wild type (wt) mice or knock-out mice for type 1 interferon (IFN) receptor with wt or a mutant HSV-1, which is unable to replicate due to the synthesis of a non-functional ICP4, the major virus transactivator. We found that the inability of the virus to initiate the lytic program combined to its inability to synthesize a functional ICP0, are the two viral features leading to the formation of vDCP-NBs. The formation of the “multiple-latency” pattern is favored by the type 1 IFN signaling pathway in the context of neurons infected by a virus able to replicate through the expression of a functional ICP4 but unable to express functional VP16 and ICP0. Analyses of TGs harvested from HSV-1 latently infected humans showed that viral genomes and PML occupy similar nuclear areas in infected neurons, eventually forming vDCP-NB-like structures. Overall our study designates PML protein and PML-NBs to be major cellular components involved in the control of HSV-1 latency

  10. Intact lexicon running slowly--prolonged response latencies in patients with subthalamic DBS and verbal fluency deficits.

    Science.gov (United States)

    Ehlen, Felicitas; Krugel, Lea K; Vonberg, Isabelle; Schoenecker, Thomas; Kühn, Andrea A; Klostermann, Fabian

    2013-01-01

    Verbal Fluency is reduced in patients with Parkinson's disease, particularly if treated with deep brain stimulation. This deficit could arise from general factors, such as reduced working speed or from dysfunctions in specific lexical domains. To test whether DBS-associated Verbal Fluency deficits are accompanied by changed dynamics of word processing. 21 Parkinson's disease patients with and 26 without deep brain stimulation of the subthalamic nucleus as well as 19 healthy controls participated in the study. They engaged in Verbal Fluency and (primed) Lexical Decision Tasks, testing phonemic and semantic word production and processing time. Most patients performed the experiments twice, ON and OFF stimulation or, respectively, dopaminergic drugs. Patients generally produced abnormally few words in the Verbal Fluency Task. This deficit was more severe in patients with deep brain stimulation who additionally showed prolonged response latencies in the Lexical Decision Task. Slowing was independent of semantic and phonemic word priming. No significant changes of performance accuracy were obtained. The results were independent from the treatment ON or OFF conditions. Low word production in patients with deep brain stimulation was accompanied by prolonged latencies for lexical decisions. No indication was found that the latter slowing was due to specific lexical dysfunctions, so that it probably reflects a general reduction of cognitive working speed, also evident on the level of Verbal Fluency. The described abnormalities seem to reflect subtle sequelae of the surgical procedure for deep brain stimulation rather than of the proper neurostimulation.

  11. Are there any left-right asymmetries in saccade parameters? Examination of latency, gain, and peak velocity.

    Science.gov (United States)

    Vergilino-Perez, Dorine; Fayel, Alexandra; Lemoine, Christelle; Senot, Patrice; Vergne, Judith; Doré-Mazars, Karine

    2012-06-05

    Hemispheric specialization in saccadic control is still under debate. Here we examine the latency, gain, and peak velocity of reactive and voluntary leftward and rightward saccades to assess the respective roles of eye and hand dominance. Participants with contrasting hand and eye dominance were asked to make saccades toward a target displayed at 5°, 10°, or 15° left or right of the central fixation point. In separate sessions, reactive and voluntary saccades were elicited by Gap-200, Gap-0, Overlap-600, and Antisaccade procedures. Left-right asymmetries were not found in saccade latencies but appeared in saccade gain and peak velocity. Regardless of the dominant hand, saccades directed to the ipsilateral side relative to the dominant eye had larger amplitudes and faster peak velocities. Left-right asymmetries can be explained by naso-temporal differences for some subjects and by eye dominance for others. Further investigations are needed to examine saccadic parameters more systematically in relation to eye dominance. Indeed, any method that allows one to determine ocular dominance from objective measures based on saccade parameters should greatly benefit clinical applications, such as monovision surgery.

  12. Ejaculatory training lengthens the ejaculation latency and facilitates the functioning of the spinal generator for ejaculation of rats with rapid ejaculation.

    Science.gov (United States)

    Rodríguez-Peña, M de L; Rodríguez-Manzo, G; Carro-Juárez, M

    2017-01-01

    A spinal pattern generator controls the ejaculatory response. Central pattern generators (CPGs) may be entrained to improve the motor patterns under their control. In the present study we tested the hypothesis that training of the spinal generator for ejaculation (SGE) by daily copulation until ejaculation, could promote substantive changes in its functioning permitting a better SGE control of the genital motor pattern of ejaculation (GMPE) and, as a consequence, a normalization of the ejaculation latency of rats with rapid ejaculation. To that aim, we evaluated in sexually experienced male rats with rapid ejaculation (1) the effects of daily copulation to ejaculation, following different entrainment schedules, on their ejaculation latencies, (2) the impact of these different ejaculatory entrainment schedules upon the parameters of the GMPE and (3) the possible emergence of persistent changes in the functioning of the SGE associated to the daily ejaculation entrainment schedules. The data obtained show that intense ejaculatory training of rats with rapid ejaculation lengthens the ejaculation latency during copulation and augments the ejaculatory capacity of the SGE in this population when spinalized. Thus, present data reveal that like other CPGs, the SGE can be trained and put forward that training of the SGE by daily copulation to ejaculation might be a promising alternative that should be taken into consideration for the treatment of premature ejaculation.

  13. CD8α dendritic cells drive establishment of HSV-1 latency.

    Directory of Open Access Journals (Sweden)

    Kevin R Mott

    Full Text Available It is generally accepted that CD8 T cells play the key role to maintain HSV-1 latency in trigeminal ganglia of ocularly infected mice. Yet, comparably little is known about the role of innate immunity in establishment of viral latency. In the current study, we investigated whether CD8α DCs impact HSV-1 latency by examining latency in the trigeminal ganglia (TG of wild-type (WT C57BL/6 versus CD8α-/- (lack functional CD8 T cells and CD8α+ DCs, CD8β-/- (have functional CD8α+ T cells and CD8α+ DCs, and β2m-/- (lack functional CD8 T cells but have CD8α+ DCs mice as well as BXH2 (have functional CD8 T cells but lack CD8α+ DCs versus WT C3H (have functional CD8α T cells and CD8α+ DCs mice. We also determined whether the phenotype of CD8α-/- and BXH2 mice could be restored to that of WT mice by adoptive transfer of WT CD8+ T cells or bone marrow (BM derived CD8α+ DCs. Our results clearly demonstrate that CD8α DCs, rather than CD8 T cells, are responsible for enhanced viral latency and recurrences.

  14. The effect of water immersion on short-latency somatosensory evoked potentials in human

    Directory of Open Access Journals (Sweden)

    Sato Daisuke

    2012-01-01

    Full Text Available Abstract Background Water immersion therapy is used to treat a variety of cardiovascular, respiratory, and orthopedic conditions. It can also benefit some neurological patients, although little is known about the effects of water immersion on neural activity, including somatosensory processing. To this end, we examined the effect of water immersion on short-latency somatosensory evoked potentials (SEPs elicited by median nerve stimuli. Short-latency SEP recordings were obtained for ten healthy male volunteers at rest in or out of water at 30°C. Recordings were obtained from nine scalp electrodes according to the 10-20 system. The right median nerve at the wrist was electrically stimulated with the stimulus duration of 0.2 ms at 3 Hz. The intensity of the stimulus was fixed at approximately three times the sensory threshold. Results Water immersion significantly reduced the amplitudes of the short-latency SEP components P25 and P45 measured from electrodes over the parietal region and the P45 measured by central region. Conclusions Water immersion reduced short-latency SEP components known to originate in several cortical areas. Attenuation of short-latency SEPs suggests that water immersion influences the cortical processing of somatosensory inputs. Modulation of cortical processing may contribute to the beneficial effects of aquatic therapy. Trial Registration UMIN-CTR (UMIN000006492

  15. HIV-1 Tat and Viral Latency: What We Can Learn from Naturally Occurring Sequence Variations

    Science.gov (United States)

    Kamori, Doreen; Ueno, Takamasa

    2017-01-01

    Despite the effective use of antiretroviral therapy, the remainder of a latently HIV-1-infected reservoir mainly in the resting memory CD4+ T lymphocyte subset has provided a great setback toward viral eradication. While host transcriptional silencing machinery is thought to play a dominant role in HIV-1 latency, HIV-1 protein such as Tat, may affect both the establishment and the reversal of latency. Indeed, mutational studies have demonstrated that insufficient Tat transactivation activity can result in impaired transcription of viral genes and the establishment of latency in cell culture experiments. Because Tat protein is one of highly variable proteins within HIV-1 proteome, it is conceivable that naturally occurring Tat mutations may differentially modulate Tat functions, thereby influencing the establishment and/or the reversal of viral latency in vivo. In this mini review, we summarize the recent findings of Tat naturally occurring polymorphisms associating with host immune responses and we highlight the implication of Tat sequence variations in relation to HIV latency.

  16. Middle latency auditory evoked responses in normal term infants: a longitudinal study.

    Science.gov (United States)

    Rogers, S H; Edwards, D A; Henderson-Smart, D J; Pettigrew, A G

    1989-05-01

    Middle latency auditory evoked responses (MLAERs) were measured in 21 normal term infants, three to five days after birth and then at 6 weeks, 7 months and 1 year of age. A polyphasic waveform was elicited during natural sleep in all infants at each recording session by monaural click stimulation at a rate of 9 per second. A 70 dBHL stimulus was found to be optimal as the MLAER became less well defined when the stimulus intensity approached the threshold hearing level. The first 60 to 70 msec of the waveform was found to be most stable, with decreasing detectability of peaks at longer latencies. There was no change in wave latency or reproducibility of MLAERs recorded during different sleep states. Waves Po and Na showed a significant decrease in latency with increasing stimulus intensity at term and/or 6 weeks of age. This was not evident for the remainder of the waveform. Waves Po, Na, Pa, Nb, Pb and Nc exhibited significant decreases in latency with age, attaining values indistinguishable from adults by 7 months of age.

  17. Latency correction of event-related potentials between different experimental protocols

    Science.gov (United States)

    Iturrate, I.; Chavarriaga, R.; Montesano, L.; Minguez, J.; Millán, JdR

    2014-06-01

    Objective. A fundamental issue in EEG event-related potentials (ERPs) studies is the amount of data required to have an accurate ERP model. This also impacts the time required to train a classifier for a brain-computer interface (BCI). This issue is mainly due to the poor signal-to-noise ratio and the large fluctuations of the EEG caused by several sources of variability. One of these sources is directly related to the experimental protocol or application designed, and may affect the amplitude or latency of ERPs. This usually prevents BCI classifiers from generalizing among different experimental protocols. In this paper, we analyze the effect of the amplitude and the latency variations among different experimental protocols based on the same type of ERP. Approach. We present a method to analyze and compensate for the latency variations in BCI applications. The algorithm has been tested on two widely used ERPs (P300 and observation error potentials), in three experimental protocols in each case. We report the ERP analysis and single-trial classification. Main results. The results obtained show that the designed experimental protocols significantly affect the latency of the recorded potentials but not the amplitudes. Significance. These results show how the use of latency-corrected data can be used to generalize the BCIs, reducing the calibration time when facing a new experimental protocol.

  18. ScriptingRT: A Software Library for Collecting Response Latencies in Online Studies of Cognition.

    Directory of Open Access Journals (Sweden)

    Thomas W Schubert

    Full Text Available ScriptingRT is a new open source tool to collect response latencies in online studies of human cognition. ScriptingRT studies run as Flash applets in enabled browsers. ScriptingRT provides the building blocks of response latency studies, which are then combined with generic Apache Flex programming. Six studies evaluate the performance of ScriptingRT empirically. Studies 1-3 use specialized hardware to measure variance of response time measurement and stimulus presentation timing. Studies 4-6 implement a Stroop paradigm and run it both online and in the laboratory, comparing ScriptingRT to other response latency software. Altogether, the studies show that Flash programs developed in ScriptingRT show a small lag and an increased variance in response latencies. However, this did not significantly influence measured effects: The Stroop effect was reliably replicated in all studies, and the found effects did not depend on the software used. We conclude that ScriptingRT can be used to test response latency effects online.

  19. Classifier-based latency estimation: a novel way to estimate and predict BCI accuracy

    Science.gov (United States)

    Thompson, David E.; Warschausky, Seth; Huggins, Jane E.

    2013-02-01

    Objective. Brain-computer interfaces (BCIs) that detect event-related potentials (ERPs) rely on classification schemes that are vulnerable to latency jitter, a phenomenon known to occur with ERPs such as the P300 response. The objective of this work was to investigate the role that latency jitter plays in BCI classification. Approach. We developed a novel method, classifier-based latency estimation (CBLE), based on a generalization of Woody filtering. The technique works by presenting the time-shifted data to the classifier, and using the time shift that corresponds to the maximal classifier score. Main results. The variance of CBLE estimates correlates significantly (p < 10-42) with BCI accuracy in the Farwell-Donchin BCI paradigm. Additionally, CBLE predicts same-day accuracy, even from small datasets or datasets that have already been used for classifier training, better than the accuracy on the small dataset (p < 0.05). The technique should be relatively classifier-independent, and the results were confirmed on two linear classifiers. Significance. The results suggest that latency jitter may be an important cause of poor BCI performance, and methods that correct for latency jitter may improve that performance. CBLE can also be used to decrease the amount of data needed for accuracy estimation, allowing research on effects with shorter timescales.

  20. A Simulation Based Investigation of High Latency Space Systems Operations

    Science.gov (United States)

    Li, Zu Qun; Moore, Michael; Bielski, Paul; Crues, Edwin Z.

    2017-01-01

    This study was the first in a series of planned tests to use physics-based subsystem simulations to investigate the interactions between a spacecraft's crew and a ground-based mission control center for vehicle subsystem operations across long communication delays. The simulation models the life support system of a deep space habitat. It contains models of an environmental control and life support system, an electrical power system, an active thermal control systems, and crew metabolic functions. The simulation has three interfaces: 1) a real-time crew interface that can be use to monitor and control the subsystems; 2) a mission control center interface with data transport delays up to 15 minute each way; and 3) a real-time simulation test conductor interface used to insert subsystem malfunctions and observe the interactions between the crew, ground, and simulated vehicle. The study was conducted at the 21st NASA Extreme Environment Mission Operations (NEEMO) mission. The NEEMO crew and ground support team performed a number of relevant deep space mission scenarios that included both nominal activities and activities with system malfunctions. While this initial test sequence was focused on test infrastructure and procedures development, the data collected in the study already indicate that long communication delays have notable impacts on the operation of deep space systems. For future human missions beyond cis-lunar, NASA will need to design systems and support tools to meet these challenges. These will be used to train the crew to handle critical malfunctions on their own, to predict malfunctions and assist with vehicle operations. Subsequent more detailed and involved studies will be conducted to continue advancing NASA's understanding of space systems operations across long communications delays.

  1. Repeater F waves: a comparison of sensitivity with sensory antidromic wrist-to-palm latency and distal motor latency in the diagnosis of carpal tunnel syndrome.

    Science.gov (United States)

    Macleod, W N

    1987-05-01

    Thirty-five thousand six hundred supramaximal shocks were applied to 209 healthy and 147 entrapped median nerves (carpal tunnel syndrome--CTS) to characterize the backfiring behavior of the alpha motor neuron pool of abductor pollicis brevis in health and the modifying effect of a compressive neuropathy. A contraction of the normal subpopulation of active F-wave generators was found in CTS, while active neurons backfired at higher than normal frequencies (p less than 0.001). These modifications in spinal behavior are reflected in the % Repeater F-wave value, whose sensitivity in the detection of CTS approaches that of sensory wrist-to-palm latency estimation. This technique offers an alternative to latency measurement in the diagnosis of CTS. An economical strategy for the electrodiagnosis of CTS is proposed.

  2. Stochastic coordination of multiple actuators reduces latency and improves chemotactic response in bacteria.

    Science.gov (United States)

    Sneddon, Michael W; Pontius, William; Emonet, Thierry

    2012-01-17

    Individual neuronal, signal transduction, and regulatory pathways often control multiple stochastic downstream actuators, which raises the question of how coordinated response to a single input can be achieved when individual actuators fluctuate independently. In Escherichia coli, the bacterial chemotaxis pathway controls the activity of multiple flagellar motors to generate the run-and-tumble motion of the cell. High-resolution microscopy experiments have identified the key conformational changes adopted by individual flagella during this process. By incorporating these observations into a stochastic model of the flagellar bundle, we demonstrate that the presence of multiple motors imposes a trade-off on chemotactic performance. Multiple motors reduce the latency of the response below the time scale of the stochastic switching of a single motor, which improves performance on steep gradients of attractants. However, the uncoordinated switching of multiple motors interrupts and shortens cell runs, which thereby reduces signal detection and performance on shallow gradients. Remarkably, when slow fluctuations generated by the adaptation mechanism of the chemotaxis system are incorporated in the model at levels measured in experiments, the chemotactic sensitivity and performance in shallow gradients is partially restored with marginal effects for steep gradients. The noise is beneficial because it simultaneously generates long events in the statistics of individual motors and coordinates the motors to generate a long tail in the run length distribution of the cell. Occasional long runs are known to enhance exploration of random walkers. Here we show that they have the additional benefit of enhancing the sensitivity of the bacterium to very shallow gradients.

  3. Visual evoked potential latencies of three-year-old children prenatally exposed to buprenorphine or methadone compared with non-opioid exposed children: The results of a longitudinal study.

    Science.gov (United States)

    Whitham, Justine N; Spurrier, Nicola J; Baghurst, Peter A; Weston, Paul; Sawyer, Michael G

    2015-01-01

    This study compared the latency of pattern reversal visual evoked potentials (VEP) of 36-month old children exposed to opioid pharmacotherapy in utero to that of a group of non-exposed children. Pregnant women were enrolled as part of an open-label non-randomised flexible dosing longitudinal study. Participants were 21 children whose mothers were treated with buprenorphine- (n=11) or methadone-pharmacotherapy (n=10) during pregnancy, and 15 children not exposed to opioids in pregnancy. One-way between groups analyses of variance (ANOVA) were conducted to test the statistical significance of differences between the mean latencies of the peak response to two different sized checkerboard patterns (48' and 69' of retinal arc). Standard multiple regression analyses were conducted to determine whether there was a significant relationship between group status and VEP latencies after adjusting for the effect of covariates. VEP latencies ranged from 98 to 112 milliseconds (ms) for checks of 48' arc, and from 95 to 113ms for checks of 69' arc. Latencies were comparable across groups. After adjusting for covariates children prenatally exposed to methadone or buprenorphine did not differ significantly from non-opioid exposed children in their responses to either check size. Nor were there any significant differences in VEP latencies between children prenatally exposed to methadone and children prenatally exposed to buprenorphine. Head circumference (HC) was significantly associated with P100 latencies for both check sizes. Data from this controlled, non-randomised study suggest that neither buprenorphine nor methadone appear to have any long-term effects on visual maturity assessed at 36months of age.

  4. Nocturnal Rapid Eye Movement Sleep Latency for Identifying Patients With Narcolepsy/Hypocretin Deficiency

    Science.gov (United States)

    Andlauer, Olivier; Moore, Hyatt; Jouhier, Laura; Drake, Christopher; Peppard, Paul E.; Han, Fang; Hong, Seung-Chul; Poli, Francesca; Plazzi, Giuseppe; O’Hara, Ruth; Haffen, Emmanuel; Roth, Thomas; Young, Terry; Mignot, Emmanuel

    2014-01-01

    IMPORTANCE Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically. OBJECTIVE To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency. DESIGN, SETTING, AND PARTICIPANTS Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels. MAIN OUTCOME AND MEASURES Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal

  5. Low latency on chip communication based on hybrid NOC Architecture using X-Y router

    Directory of Open Access Journals (Sweden)

    Tejas wini Deotare

    2014-05-01

    Full Text Available On-chip co mmunication has two different type of architecture which can be classified as Bus and mesh based Networks- on-Chip (No C. Each of them has diffe rent features and applications. In this paper, we construct the hybrid architecture with using bus and mesh NOC architecture. In the hybrid architecture, heavy communication affinity IPcores are placed in the same subsystem. and this large mesh No C get partitioned into several subsystems and one on one individual IPs, so that there is the reduction in the transmission latency of NoC.Efficient partition and mapping algorith m is proposed for reduction of the latency on the hybrid NOC arch itecture.It shows that an average latency improvement of 17.6% and more can be obtained when compared with the conventional mesh No C arch itecture.

  6. Managing Communication Latency-Hiding at Runtime for Parallel Programming Languages and Libraries

    CERN Document Server

    Kristensen, Mads Ruben Burgdorff

    2012-01-01

    This work introduces a runtime model for managing communication with support for latency-hiding. The model enables non-computer science researchers to exploit communication latency-hiding techniques seamlessly. For compiled languages, it is often possible to create efficient schedules for communication, but this is not the case for interpreted languages. By maintaining data dependencies between scheduled operations, it is possible to aggressively initiate communication and lazily evaluate tasks to allow maximal time for the communication to finish before entering a wait state. We implement a heuristic of this model in DistNumPy, an auto-parallelizing version of numerical Python that allows sequential NumPy programs to run on distributed memory architectures. Furthermore, we present performance comparisons for eight benchmarks with and without automatic latency-hiding. The results shows that our model reduces the time spent on waiting for communication as much as 27 times, from a maximum of 54% to only 2% of t...

  7. Fast response electromagnetic follow-ups from low latency GW triggers

    CERN Document Server

    Howell, E J; Rowlinson, A; Gao, H; Zhang, B; Tingay, S J; Boer, M; Wen, L

    2016-01-01

    We investigate joint low-latency gravitational wave (GW) detection and prompt electromagnetic (EM) follow-up observations of coalescing binary neutron stars (BNSs). Assuming that BNS mergers are associated with short duration gamma ray bursts (SGRBs), we evaluate if rapid EM follow-ups can capture the prompt emission, early engine activity or reveal any potential by-products such as magnetars or fast radio bursts. To examine the expected performance of extreme low-latency search pipelines, we simulate a population of coalescing BNSs and use these to estimate the detectability and localisation efficiency at different times before merger. Using observational SGRB flux data corrected to the range of the advanced GW interferometric detectors, we determine what EM observations could be achieved from low-frequency radio up to high energy $\\gamma$-ray. We show that while challenging, breakthrough multi-messenger science is possible through low latency pipelines.

  8. Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption

    DEFF Research Database (Denmark)

    Lee, Wen Shi; Kristensen, Anne B; Rasmussen, Thomas A

    2017-01-01

    There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may...... not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRA) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We find that treatment with the LRA panobinostat or a short analytical treatment......) trial robustly boosted HIV-1 gp120-specific Fc receptor-binding antibodies and ADCC against HIV-1-infected cells in vitro These results show there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies towards eliminating latently infected cells...

  9. Effects of gut passage, feces, and seed handling on latency and rate of germination in seeds consumed by capuchins (Cebus capucinus).

    Science.gov (United States)

    Valenta, Kim; Fedigan, Linda M

    2009-04-01

    One of the key measures of the effectiveness of primary seed dispersal by animals is the quality of seed dispersal (Schupp: Plant Ecol 107/108 [1993] 15-29). We present data on quality of seed dispersal by two groups of white-faced capuchins (Cebus capucinus) in Costa Rica to test the hypothesis that capuchin seed handling results in effective primary dispersal for some fruit species they consume. We examined seed handling for 27 plant species, and germination rates of 18 species consumed by capuchins. For five of the most commonly swallowed seed species, we determined germination rates and average time to germination (latency) for seeds ingested and defecated by capuchins and compared these to seeds removed directly from fruit and planted. For the same five species, we compared germination rates and latency for passed seeds planted in capuchin feces to those cleaned of feces and planted in soil. For three of five species, differences in proportion of germinated seeds were significantly higher for gut passed seeds than for controls. For four of five species, germination latency was significantly faster for gut passed seeds than for controls. Feces had either no effect on seed germination rate or precluded germination. Data presented here support the hypothesis that white-faced capuchins are effective primary dispersers.

  10. Latency to CNS oxygen toxicity in rats as a function of PCO(2) and PO(2).

    Science.gov (United States)

    Arieli, R; Ertracht, O

    1999-01-01

    Central nervous system (CNS) oxygen toxicity can occur as convulsions and loss of consciousness, without any premonitory symptoms. We have made a quantitative study of the effect of inspired carbon dioxide on sensitivity to oxygen toxicity in the rat. Rats were exposed to four oxygen pressures (PO(2); 456, 507, 608 and 709 kPa) and an inspired partial pressure of carbon dioxide (PCO(2)) in the range 0-12 kPa until the appearance of the electroencephalograph first electrical discharge (FED) that precedes the clinical convulsions. Exposures were conducted at a thermoneutral temperature of 27 degrees C. Latency to the FED decreased linearly with the increase in PCO(2) at all four PO(2) values studied. This decrease, which is probably related to the cerebral vasodilatory effect of carbon dioxide, reached a minimal value that remained constant on further elevation of PCO(2). The slopes (absolute value) and intercepts of latency to the FED as a function of carbon dioxide decreased with the increase in PO(2). This log-linear relationship made possible the derivation of equations that describe latency to the FED as a function of both PO(2) and PCO(2) in the PCO(2) - dependent range: Latency (min) = e((5.19-0.0040)(P)(O(2)))-e((2.77-0.0034)(P)(O(2))) x PCO(2) (kPa), and in the PCO(2)-independent range: Latency(min) = e((2.44-0. 0009)(P)(O(2))). A PCO(2) as low as 1 kPa significantly reduced the latency to the FED. It is suggested that in closed-circuit oxygen diving, any accumulation of carbon dioxide should be avoided in order to minimize the risk of CNS oxygen toxicity.

  11. Ablation of STAT3 in the B Cell Compartment Restricts Gammaherpesvirus Latency In Vivo

    Science.gov (United States)

    Reddy, Sandeep Steven; Foreman, Hui-Chen Chang; Sioux, Thubten Ozula; Park, Gee Ho; Poli, Valeria; Reich, Nancy C.

    2016-01-01

    ABSTRACT A challenging property of gammaherpesviruses is their ability to establish lifelong persistence. The establishment of latency in B cells is thought to involve active virus engagement of host signaling pathways. Pathogenic effects of these viruses during latency or following reactivation can be devastating to the host. Many cancers, including those associated with members of the gammaherpesvirus family, Kaposi’s sarcoma-associated herpesvirus and Epstein-Barr virus, express elevated levels of active host signal transducer and activator of transcription-3 (STAT3). STAT3 is activated by tyrosine phosphorylation in response to many cytokines and can orchestrate effector responses that include proliferation, inflammation, metastasis, and developmental programming. However, the contribution of STAT3 to gammaherpesvirus pathogenesis remains to be completely understood. This is the first study to have identified STAT3 as a critical host determinant of the ability of gammaherpesvirus to establish long-term latency in an animal model of disease. Following an acute infection, murine gammaherpesvirus 68 (MHV68) established latency in resident B cells, but establishment of latency was dramatically reduced in animals with a B cell-specific STAT3 deletion. The lack of STAT3 in B cells did not impair germinal center responses for immunoglobulin (Ig) class switching in the spleen and did not reduce either total or virus-specific IgG titers. Although ablation of STAT3 in B cells did not have a global effect on these assays of B cell function, it had long-term consequences for the viral load of the host, since virus latency was reduced at 6 to 8 weeks postinfection. Our findings establish host STAT3 as a mediator of gammaherpesvirus persistence. PMID:27486189

  12. Role of latency jittering correction in motion-onset VEP amplitude decay during prolonged visual stimulation.

    Science.gov (United States)

    Kremláček, J; Hulan, M; Kuba, M; Kubová, Z; Langrová, J; Vít, F; Szanyi, J

    2012-06-01

    Visual evoked potentials to motion-onset stimulation (M-VEPs) gradually attenuate in amplitude during examination. The observed decline in averaged responses can be caused by decreases in single response magnitudes and/or increased variability in a response delays, that is, latency jittering. To illuminate the origins of the suppression of M-VEPs during stimuli repetition, we used correlation technique to estimate an upper bound of possible latency jittering of single sweeps and we evaluated the effect of its correction on the amplitudes of three M-VEP dominant peaks P1, N2 and P3. During prolonged visual motion stimulation, the variability of corrective latency shifts in the occipital region increased (r = 0.35: 0.44) and the number of single responses corresponding to the average curve declined in occipital and parietal derivations (r = -0.48: -0.62). While the P1 peak amplitude did not exhibit any time-specific behaviour, the N2 amplitude exhibited a significant decay of 29.4% that was partially reduced to 16.6% in the central occipital derivation by the latency jitter and non-correspondence corrections. The strongest attenuation (32.7%) was observed in the P3 amplitude and was less sensitive to the corrections, dropping only to 27.9%. The main part of the response suppression to repeated motion stimulation was caused by amplitude drop and represents non-stationary process that likely correspond to a fatigue model. The rise of variability in latency jitter correction and the reduction in single responses correlated with the M-VEP were significant factors associated with prolonged motion stimulation. The relation of these parameters to a hypothetical veridical response is ambiguous and can be caused by a time shift of the response or by a change of signal-to-noise ratio. Using selective averaging and latency jitter correction, the effect of response suppression was partially removed.

  13. VARICELLA ZOSTER VIRUS-ITS PATHOGENESIS, LATENCY & CELL-MEDIATED IMMUNITY

    Directory of Open Access Journals (Sweden)

    Anis Ahmed

    2013-07-01

    Full Text Available Varicella zoster virus causes primary infection as chickenpox, at which time latencyis established in the neurons of the dorsal root ganglia or ganglia of the cranial nerves.Reactivation produces herpes zoster infection (HZI, commonly called shingles. Anunderstanding of the mechanisms of latency is crucial in developing effective therapies forVZV infections of the nervous system. This article describes the pathogenesis of VZVwhich includes immune response to the virus, immune evasion by the virus, mechanism ofits latency and cell-mediated immunity.

  14. An Ultra-Low-Latency Geo-Routing Scheme for Team-Based Unmanned Vehicular Applications

    KAUST Repository

    Bader, Ahmed

    2016-02-26

    Results and lessons learned from the implementation of a novel ultra low-latency geo-routing scheme are presented in this paper. The geo-routing scheme is intended for team-based mobile systems whereby a cluster of unmanned autonomous vehicles are deployed to accomplish a critical mission under human supervision. The contention-free nature of the developed scheme lends itself to jointly achieve lower latency and higher throughput. Implementation challenges are presented and corresponding resolutions are discussed herewith. © 2015 IEEE.

  15. Optimized Interface Diversity for Ultra-Reliable Low Latency Communication (URLLC)

    DEFF Research Database (Denmark)

    Nielsen, Jimmy Jessen; Liu, Rongkuan; Popovski, Petar

    2017-01-01

    technology. Our approach is to use rateless codes to seamlessly distribute coded payload and redundancy data across multiple available communication interfaces. We formulate an optimization problem to find the payload allocation weights that maximize the reliability at specific target latency values......An important ingredient of the future 5G systems will be Ultra-Reliable Low-Latency Communication (URLLC). A way to offer URLLC without intervention in the baseband/PHY layer design is to use interface diversity and integrate multiple communication interfaces, each interface based on a different...

  16. [Anesthesia with flunitrazepam/fentanyl and isoflurane/fentanyl. Unconscious perception and mid-latency auditory evoked potentials].

    Science.gov (United States)

    Schwender, D; Kaiser, A; Klasing, S; Faber-Züllig, E; Golling, W; Pöppel, E; Peter, K

    1994-05-01

    There is a high incidence of intraoperative awareness during cardiac surgery. Mid-latency auditory evoked potentials (MLAEP) reflect the primary cortical processing of auditory stimuli. In the present study, we investigated MLAEP and explicit and implicit memory for information presented during cardiac anaesthesia. PATIENTS AND METHODS. Institutional approval and informed consent was obtained in 30 patients scheduled for elective cardiac surgery. Anaesthesia was induced in group I (n = 10) with flunitrazepam/fentanyl (0.01 mg/kg) and maintained with flunitrazepam/fentanyl (1.2 mg/h). The patients in group II (n = 10) received etomidate (0.25 mg/kg) and fentanyl (0.005 mg/kg) for induction and isoflurane (0.6-1.2 vol%)/fentanyl (1.2 mg/h) for maintenance of general anaesthesia. Group III (n = 10) served as a control and patients were anaesthetized as in I or II. After sternotomy an audiotape that included an implicit memory task was presented to the patients in groups I and II. The story of Robinson Crusoe was told, and it was suggested to the patients that they remember Robinson Crusoe when asked what they associated with the word Friday 3-5 days postoperatively. Auditory evoked potentials were recorded awake and during general anaesthesia before and after the audiotape presentation on vertex (positive) and mastoids on both sides (negative). Auditory clicks were presented binaurally at 70 dBnHL at a rate of 9.3 Hz. Using the electrodiagnostic system Pathfinder I (Nicolet), 1000 successive stimulus responses were averaged over a 100 ms poststimulus interval and analyzed off-line. Latencies of the peak V, Na, Pa were measured. V belongs to the brainstem-generated potentials, which demonstrates that auditory stimuli were correctly transduced. Na, Pa are generated in the primary auditory cortex of the temporal lobe and are the electrophysiological correlate of the primary cortical processing of the auditory stimuli. RESULTS. None of the patients had an explicit memory

  17. Progesterone and the Latency Period: Threatened Preterm Labor

    Directory of Open Access Journals (Sweden)

    S Borna

    2008-06-01

    Full Text Available Background: Preterm labor is a major contributor to neonatal morbidity and mortality and results in increased obstetric and pediatric care costs. The purpose of this study was to assess the effects of vaginal progesterone for maintenance therapy following treatment of threatened preterm labor for preventing preterm birth.Methods: The study included 70 singleton pregnant women with preterm labor with intact membranes. Patients were randomized to receive either maintenance vaginal progesterone therapy (n=37 administered (400 mg daily or no treatment (controls, n=33 after discontinuation of acute intravenous tocolysis.Results: The two groups were similar with at respect to maternal age, race, parity, gestational age at admission, bishop score, and preterm delivery risk factors .Compared to the control group, the mean ±SD time gained from initiation of maintenance therapy to delivery (36/1117/9 versus 24/5227/2 (meanSD days, p=0.037 and the gestational age at delivery (36.071.56 vs. 34.51.3 weeks, p=0.041 were higher in the vaginal progesterone maintenance therapy group. No significant differences were found with recurrent preterm labor 13 (35.1% versus 19 (57.6%, p=0.092. Respiratory distress syndrome 4 (10.8% versus 12 (36.4% p=0.021, Low birth weight10 (27% versus, 17 (51.5% p=0.04, birth weight (3101.54±587.9gr versus r 2609.39±662.9gr, p=0.002 were significantly different between the two groups.Conclusion: The gestational age and time gained from initiation of maintenance therapy to delivery were longer in women receiving vaginal maintenance tocolysis with progesterone and improve perinatal outcomes. However, maintenance therapy did not decrease the recurrence of preterm labor episodes.

  18. Spatial task context makes short-latency reaches prone to induced Roelofs illusion

    Directory of Open Access Journals (Sweden)

    Bahareh eTaghizadeh

    2014-08-01

    Full Text Available The perceptual localization of an object is often more prone to illusions than an immediate visuomotor action towards that object. The induced Roelofs effect (IRE probes the illusory influence of task-irrelevant visual contextual stimuli on the processing of task-relevant visuospatial instructions during movement preparation. In the IRE, the position of a task-irrelevant visual object induces a shift in the localization of a visual target when subjects indicate the position of the target by verbal response, key-presses or delayed pointing to the target (‘perception’ tasks, but not when immediately pointing or reaching towards it without instructed delay (‘action’ tasks. This discrepancy was taken as evidence for the dual-visual-stream or perception-action hypothesis, but was later explained by a phasic distortion of the egocentric spatial reference frame which is centered on subjective straight-ahead and used for reach planning. Both explanations critically depend on delayed movements to explain the IRE for action tasks. Here we ask: first, if the IRE can be observed for short-latency reaches; second, if the IRE in fact depends on a distorted egocentric frame of reference. Human subjects were tested in new versions of the IRE task in which the reach goal had to be localized with respect to another object, i.e., in an allocentric reference frame. First, we found an IRE even for immediate reaches in our allocentric task, but not for an otherwise similar egocentric control task. Second, the IRE depended on the position of the task-irrelevant frame relative to the reference object, not relative to subjective straight-ahead. We conclude that the IRE for reaching does not mandatorily depend on prolonged response delays, nor does it depend on motor planning in an egocentric reference frame. Instead, allocentric encoding of a movement goal is sufficient to make immediate reaches susceptible to IRE, underlining the context dependence of

  19. Design Example of Useful Memory Latency for Developing a Hazard Preventive Pipeline High-Performance Embedded-Microprocessor

    Directory of Open Access Journals (Sweden)

    Ching-Hwa Cheng

    2013-01-01

    Full Text Available The existence of structural, control, and data hazards presents a major challenge in designing an advanced pipeline/superscalar microprocessor. An efficient memory hierarchy cache-RAM-Disk design greatly enhances the microprocessor's performance. However, there are complex relationships among the memory hierarchy and the functional units in the microprocessor. Most past architectural design simulations focus on the instruction hazard detection/prevention scheme from the viewpoint of function units. This paper emphasizes that additional inboard memory can be well utilized to handle the hazardous conditions. When the instruction meets hazardous issues, the memory latency can be utilized to prevent performance degradation due to the hazard prevention mechanism. By using the proposed technique, a better architectural design can be rapidly validated by an FPGA at the start of the design stage. In this paper, the simulation results prove that our proposed methodology has a better performance and less power consumption compared to the conventional hazard prevention technique.

  20. Spike latency and response properties of an excitable micropillar laser

    Science.gov (United States)

    Selmi, F.; Braive, R.; Beaudoin, G.; Sagnes, I.; Kuszelewicz, R.; Erneux, T.; Barbay, S.

    2016-10-01

    We present experimental measurements concerning the response of an excitable micropillar laser with saturable absorber to incoherent as well as coherent perturbations. The excitable response is similar to the behavior of spiking neurons but with much faster time scales. It is accompanied by a subnanosecond nonlinear delay that is measured for different bias pump values. This mechanism provides a natural scheme for encoding the strength of an ultrafast stimulus in the response delay of excitable spikes (temporal coding). Moreover, we demonstrate coherent and incoherent perturbations techniques applied to the micropillar with perturbation thresholds in the range of a few femtojoules. Responses to coherent perturbations assess the cascadability of the system. We discuss the physical origin of the responses to single and double perturbations with the help of numerical simulations of the Yamada model and, in particular, unveil possibilities to control the relative refractory period that we recently evidenced in this system. Experimental measurements are compared to both numerical simulations of the Yamada model and analytic expressions obtained in the framework of singular perturbation techniques. This system is thus a good candidate to perform photonic spike processing tasks in the framework of novel neuroinspired computing systems.

  1. HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal

    DEFF Research Database (Denmark)

    Wu, Guoxin; Swanson, Michael; Talla, Aarthi

    2017-01-01

    Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, an...

  2. Histone modifications induced by MDV infection at early cytolytic and latency phases

    Science.gov (United States)

    Background: Marek’s disease (MD) is a highly contagious, lymphomatous disease of chickens induced by a herpesvirus, Marek’s disease virus (MDV) that is the cause of major annual losses to the poultry industry. MD pathogenesis involves multiple stages including an early cytolytic phase and latency, a...

  3. Low Latency Network-on-Chip Router Microarchitecture Using Request Masking Technique

    Directory of Open Access Journals (Sweden)

    Alireza Monemi

    2015-01-01

    Full Text Available Network-on-Chip (NoC is fast emerging as an on-chip communication alternative for many-core System-on-Chips (SoCs. However, designing a high performance low latency NoC with low area overhead has remained a challenge. In this paper, we present a two-clock-cycle latency NoC microarchitecture. An efficient request masking technique is proposed to combine virtual channel (VC allocation with switch allocation nonspeculatively. Our proposed NoC architecture is optimized in terms of area overhead, operating frequency, and quality-of-service (QoS. We evaluate our NoC against CONNECT, an open source low latency NoC design targeted for field-programmable gate array (FPGA. The experimental results on several FPGA devices show that our NoC router outperforms CONNECT with 50% reduction of logic cells (LCs utilization, while it works with 100% and 35%~20% higher operating frequency compared to the one- and two-clock-cycle latency CONNECT NoC routers, respectively. Moreover, the proposed NoC router achieves 2.3 times better performance compared to CONNECT.

  4. Urethral sensory threshold and urethro-anal reflex latency in continent women.

    Science.gov (United States)

    Cavalcanti, Geraldo de Aguiar; Bruschini, Homero; Manzano, Gilberto M; Giuliano, Lydia P; Nóbrega, João Antônio M; Srougi, Miguel

    2007-01-01

    The sensory evaluation of the lower urinary tract is summarized in the bladder proprioceptive sensitivity during cystometry. Experimental studies suggest that abnormalities of the urethral innervation and micturition reflex can be related to the presence of continence disturbances. This study aimed to measure the urethral sensory threshold and the urethro-anal reflex latency in healthy volunteers, establishing reading criteria, comparing the results and technique used with the literature and verifying the effect of physiological factors. Thirty healthy female volunteers were studied. They had an absence of genital or urinary complaints and had undergone no previous pelvic or vaginal procedures. The measurement of the urethral sensory threshold and urethro-anal reflex latency were performed as described. The determination of the urethral sensory threshold and urethro-anal reflex latency were obtained in 96.6% of the volunteers. The electrophysiological parameters did not correlate with age, parity or number of vaginal deliveries. There was a positive association of the urethral sensory threshold with height. Technical aspects were considered and compared with those in the literature as well as the advantages and limitations of the method. The measurement of the urethral sensory threshold and urethro-anal reflex latency presented consistent recordings. The urethral sensory threshold should be analyzed carefully in individuals with height above the population average. Subsequent observations are necessary to clarify their function in patients with continence disturbances and to measure the urethral function, but these values can be used as normal parameters for comparison.

  5. Working Memory Updating Latency Reflects the Cost of Switching between Maintenance and Updating Modes of Operation

    Science.gov (United States)

    Kessler, Yoav; Oberauer, Klaus

    2014-01-01

    Updating and maintenance of information are 2 conflicting demands on working memory (WM). We examined the time required to update WM (updating latency) as a function of the sequence of updated and not-updated items within a list. Participants held a list of items in WM and updated a variable subset of them in each trial. Four experiments that vary…

  6. Flash Memory Reliability: Read, Program, and Erase Latency Versus Endurance Cycling

    Science.gov (United States)

    Heidecker, Jason

    2010-01-01

    This report documents the efforts and results of the fiscal year (FY) 2010 NASA Electronic Parts and Packaging Program (NEPP) task for nonvolatile memory (NVM) reliability. This year's focus was to measure latency (read, program, and erase) of NAND Flash memories and determine how these parameters drift with erase/program/read endurance cycling.

  7. Fuzzy Logic based Handoff Latency Reduction Mechanism in Layer 2 of Heterogeneous Mobile IPv6 Networks

    Science.gov (United States)

    Anwar, Farhat; Masud, Mosharrof H.; Latif, Suhaimi A.

    2013-12-01

    Mobile IPv6 (MIPv6) is one of the pioneer standards that support mobility in IPv6 environment. It has been designed to support different types of technologies for providing seamless communications in next generation network. However, MIPv6 and subsequent standards have some limitations due to its handoff latency. In this paper, a fuzzy logic based mechanism is proposed to reduce the handoff latency of MIPv6 for Layer 2 (L2) by scanning the Access Points (APs) while the Mobile Node (MN) is moving among different APs. Handoff latency occurs when the MN switches from one AP to another in L2. Heterogeneous network is considered in this research in order to reduce the delays in L2. Received Signal Strength Indicator (RSSI) and velocity of the MN are considered as the input of fuzzy logic technique. This technique helps the MN to measure optimum signal quality from APs for the speedy mobile node based on fuzzy logic input rules and makes a list of interfaces. A suitable interface from the list of available interfaces can be selected like WiFi, WiMAX or GSM. Simulation results show 55% handoff latency reduction and 50% packet loss improvement in L2 compared to standard to MIPv6.

  8. Measuring the Latency of an Augmented Reality System for Robot-Assisted Minimally Invasive Surgery

    DEFF Research Database (Denmark)

    Jørgensen, Martin Kibsgaard; Kraus, Martin

    2017-01-01

    visual communication in training for robot-assisted minimally invasive surgery with da Vinci surgical systems. To make sure that our augmented reality system provides the best possible user experience, we investigated the video latency of the da Vinci surgical system and how the components of our system...

  9. Phase-dependent modulation of short latency cutaneous reflexes during walking in man.

    NARCIS (Netherlands)

    Baken, B.C.M.; Dietz, V.; Duysens, J.E.J.

    2005-01-01

    In reduced animal preparation (cat fictive locomotion) most of our knowledge on the phase-dependent modulation of cutaneous reflexes concerns early- (P1 responses) rather than medium-latency (P2) responses. In contrast, in humans, virtually only P2 responses have been studied because P1 responses ar

  10. Auditory Middle Latency Response and Phonological Awareness in Students with Learning Disabilities.

    Science.gov (United States)

    Romero, Ana Carla Leite; Funayama, Carolina Araújo Rodrigues; Capellini, Simone Aparecida; Frizzo, Ana Claudia Figueiredo

    2015-10-01

    Introduction Behavioral tests of auditory processing have been applied in schools and highlight the association between phonological awareness abilities and auditory processing, confirming that low performance on phonological awareness tests may be due to low performance on auditory processing tests. Objective To characterize the auditory middle latency response and the phonological awareness tests and to investigate correlations between responses in a group of children with learning disorders. Methods The study included 25 students with learning disabilities. Phonological awareness and auditory middle latency response were tested with electrodes placed on the left and right hemispheres. The correlation between the measurements was performed using the Spearman rank correlation coefficient. Results There is some correlation between the tests, especially between the Pa component and syllabic awareness, where moderate negative correlation is observed. Conclusion In this study, when phonological awareness subtests were performed, specifically phonemic awareness, the students showed a low score for the age group, although for the objective examination, prolonged Pa latency in the contralateral via was observed. Negative weak to moderate correlation for Pa wave latency was observed, as was positive weak correlation for Na-Pa amplitude.

  11. Neural latencies do not explain the auditory and audio-visual flash-lag effect.

    Science.gov (United States)

    Arrighi, Roberto; Alais, David; Burr, David

    2005-11-01

    A brief flash presented physically aligned with a moving stimulus is perceived to lag behind, a well studied phenomenon termed the Flash-Lag Effect (FLE). It has been recently shown that the FLE also occurs in audition, as well as cross-modally between vision and audition. The present study has two goals: to investigate the acoustic and cross-modal FLE using a random motion technique; and to investigate whether neural latencies may account for the FLE in general. The random motion technique revealed a strong cross-modal FLE for visual motion stimuli and auditory probes, but not for the other conditions. Visual and auditory latencies for stimulus appearance and for motion were measured with three techniques: integration, temporal alignment and reaction times. All three techniques showed that a brief static acoustic stimulus is perceived more rapidly than a brief static visual stimulus, while a sound source in motion is perceived more slowly than a comparable visual stimulus. While the results of these three techniques agreed closely with each other, they were exactly opposite that required to account for the FLE by neural latencies. We conclude that neural latencies do not, in general, explain the flash-lag effect. Rather, our data suggest that neural integration times are more important.

  12. Short-latency crossed responses in the human biceps femoris muscle

    DEFF Research Database (Denmark)

    Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend S.

    2015-01-01

    , indicating their existence in humans. The aim of the present study was to investigate whether short-latency crossed-spinal reflexes are present in the contralateral biceps femoris (cBF) muscle following ipsilateral knee (iKnee) joint rotations during a sitting task, where participants maintained a slight pre...

  13. An Optimized WSN Design for Latency-Critical Smart Grid Applications

    Directory of Open Access Journals (Sweden)

    Mounib Khanafer

    2017-01-01

    Full Text Available The growing popularity of the Internet of Things (IoT systems such as the smart grid, Body Area Networks (BANs, and the Intelligent Transportation System (ITS is driving Wireless Sensor Network (WSN systems to the limit in terms of abilities and performance. WSNs were initially designed for low power, low data rate, and latency-tolerant applications. However, this paradigm is changing because of the nature of the new applications. Therefore, instead of only focusing on power-efficient WSN design, researchers and industries are now developing Quality of Service (QoS protocols for WSNs. In addition to that, latency- and reliability-critical protocol designs are also becoming significantly important in WSNs. In this paper, we present an overview of some important smart grid latency-critical applications and highlight WSNs implementation challenges for these smart grid applications. Furthermore, we develop and evaluate two novel optimization models that solve for the optimum values of the end-to-end latency and power consumption in a clustered WSN given lower bounds on reliability and other network parameters.

  14. No file left behind - monitoring transfer latencies in PhEDEx

    CERN Document Server

    Ratnikova, Natalia

    2012-01-01

    The CMS experiment has to move Petabytes of data among dozens of computing centres with low latency in order to make efficient use of its resources. Transfer operations are well established to achieve the desired level of throughput, but operators lack a system to identify early on transfers that will need manual intervention to reach completion. File transfer latencies are sensitive to the underlying problems in the transfer infrastructure, and their measurement can be used as prompt trigger for preventive actions. For this reason, PhEDEx, the CMS transfer management system, has recently implemented a monitoring system to measure the transfer latencies at the level of individual files. For the first time now, the system can predict the completion time for the transfer of a data set. The operators can detect abnormal patterns in transfer latencies early, and correct the issues while the transfer is still in progress. Statistics are aggregated for blocks of files, recording a historical log to monitor the long...

  15. Without Latency: Cathode Immersions and the Neglected Practice of Xenocasting for Television and Radio

    NARCIS (Netherlands)

    Hulbert, Adam

    2015-01-01

    abstractThis paper discusses a three-year radio project Cathode Immersions, which was aired on 2SER in Sydney Australia. The audio that accompanied free-to-air television was remixed and rebroadcast in real time without latency. It explores the human and non-human aspects of the convergence of these

  16. Analysis of Latency and MAC-layer Performance for Class A LoRaWAN

    DEFF Research Database (Denmark)

    Sørensen, René Brandborg; Kim, Dong Min; Nielsen, Jimmy Jessen

    2017-01-01

    We propose analytical models that allow to investigate the performance of Long Range Wide Area Network (LoRaWAN) uplink in terms of latency, collision rate, and throughput under the constraints of the regulatory duty cycling, when assuming exponential inter-arrival times. Our models take into acc...

  17. Choice Latency as a Cue for Children's Subjective Confidence in the Correctness of Their Answers

    Science.gov (United States)

    Koriat, Asher; Ackerman, Rakefet

    2010-01-01

    Research with adults indicates that confidence in the correctness of an answer decreases as a function of the amount of time it takes to reach that answer, suggesting that people use response latency as a mnemonic cue for subjective confidence. Experiment 1 extended investigation to 2nd, 3rd and 5th graders. When children chose the answer to…

  18. Length of Latency with Preterm Premature Rupture of Membranes before 32 Weeks’ Gestation

    Science.gov (United States)

    PEACEMAN, Alan M.; LAI, Yinglei; ROUSE, Dwight J.; SPONG, Catherine Y.; MERCER, Brian M.; VARNER, Michael W.; THORP, John M.; RAMIN, Susan M.; MALONE, Fergal D.; O'SULLIVAN, Mary J.; HANKINS, Gary D.V.

    2014-01-01

    Objective To describe latency for patients with preterm premature membrane rupture (PPROM) between 24 0/7 and 31 6/7 weeks’ gestation. Study Design Secondary analysis of data collected prospectively in a multicenter clinical trial of magnesium sulfate for cerebral palsy prevention. Women with PPROM and fewer than 6 contractions per hour at enrollment who were candidates for expectant management (n=1377) were included in this analysis. Length of latency was calculated in days by subtracting the time of delivery from the time of membrane rupture. Results At each week of gestation, median latency between 24-28 weeks was similar at approximately 9 days, but was significantly shorter with PPROM at 29, 30, and 31 weeks (p<0.001). In addition, the percentage of patients remaining undelivered at 7 days and 14 days was similar for PPROM between 24-28 weeks, but decreased significantly after that. For each gestational age, the proportion of patients remaining pregnant declined in a fashion similar to exponential pattern. Conclusion Median latency after PPROM is similar from 24-28 weeks’ gestation, but shortens with PPROM at and after 29 weeks. PMID:24819145

  19. The Middle Latency Response (MLR) and Steady State Evoked Potential (SSEP) in Neonates.

    Science.gov (United States)

    1985-05-01

    antibiotics, intracranial hemorrhage, and congenital malformations . Unfortunately, the items in this list often occur in combination rather than in isolation...JOURNAL OF THE AMERICAN AUDITORY SOCIETY 5: 156-162, 1979. Yamada, 0., Kodera, K. and Yagi, T. Cochlear processes affecting wave V latency of the

  20. Latency and Accuracy Characteristics of Saccades and Corrective Saccades in Children and Adults.

    Science.gov (United States)

    Cohen, Mark E.; Ross, Leonard E.

    1978-01-01

    Examines the latency and the accuracy of adult's and children's saccades under optimal warning and no-warning conditions. Subjects were nine adults (mean age =23.7) and nine elementary school students (mean age =8.5). (Author/MP)

  1. A Scheduling Discipline for Latency and Bandwidth Guarantees in Asynchronous Network-on-Chip

    DEFF Research Database (Denmark)

    Bjerregaard, Tobias; Sparsø, Jens

    2005-01-01

    Guaranteed services (GS) are important in that they provide predictability in the complex dynamics of shared communication structures. This paper discusses the implementation of GS in asynchronous Network-on-Chip. We present a novel scheduling discipline called Asynchronous Latency Guarantee (ALG...

  2. Flash Memory Reliability: Read, Program, and Erase Latency Versus Endurance Cycling

    Science.gov (United States)

    Heidecker, Jason

    2010-01-01

    This report documents the efforts and results of the fiscal year (FY) 2010 NASA Electronic Parts and Packaging Program (NEPP) task for nonvolatile memory (NVM) reliability. This year's focus was to measure latency (read, program, and erase) of NAND Flash memories and determine how these parameters drift with erase/program/read endurance cycling.

  3. Increasing accuracy and decreasing latency during clean intermittent self-catheterization procedures with young children.

    OpenAIRE

    McComas, J J; Lalli, J S; Benavides, C.

    1999-01-01

    We examined the effects of simulation training on performance of clean intermittent self-catheterization procedures with 2 young girls. Simulation training was conducted, after which independent performance was assessed within a multiple baseline design. The training resulted in increased accuracy and decreased latency for both girls.

  4. Long-latency reflexes of elbow and shoulder muscles suggest reciprocal excitation of flexors, reciprocal excitation of extensors, and reciprocal inhibition between flexors and extensors.

    Science.gov (United States)

    Kurtzer, Isaac; Meriggi, Jenna; Parikh, Nidhi; Saad, Kenneth

    2016-04-01

    Postural corrections of the upper limb are required in tasks ranging from handling an umbrella in the changing wind to securing a wriggling baby. One complication in this process is the mechanical interaction between the different segments of the arm where torque applied at one joint induces motion at multiple joints. Previous studies have shown the long-latency reflexes of shoulder muscles (50-100 ms after a limb perturbation) account for these mechanical interactions by integrating information about motion of both the shoulder and elbow. It is less clear whether long-latency reflexes of elbow muscles exhibit a similar capability and what is the relation between the responses of shoulder and elbow muscles. The present study utilized joint-based loads tailored to the subjects' arm dynamics to induce well-controlled displacements of their shoulder and elbow. Our results demonstrate that the long-latency reflexes of shoulder and elbow muscles integrate motion from both joints: the shoulder and elbow flexors respond to extension at both joints, whereas the shoulder and elbow extensors respond to flexion at both joints. This general pattern accounts for the inherent flexion-extension coupling of the two joints arising from the arm's intersegmental dynamics and is consistent with spindle-based reciprocal excitation of shoulder and elbow flexors, reciprocal excitation of shoulder and elbow extensors, and across-joint inhibition between the flexors and extensors. Copyright © 2016 the American Physiological Society.

  5. Tap Arduino: An Arduino microcontroller for low-latency auditory feedback in sensorimotor synchronization experiments.

    Science.gov (United States)

    Schultz, Benjamin G; van Vugt, Floris T

    2016-12-01

    Timing abilities are often measured by having participants tap their finger along with a metronome and presenting tap-triggered auditory feedback. These experiments predominantly use electronic percussion pads combined with software (e.g., FTAP or Max/MSP) that records responses and delivers auditory feedback. However, these setups involve unknown latencies between tap onset and auditory feedback and can sometimes miss responses or record multiple, superfluous responses for a single tap. These issues may distort measurements of tapping performance or affect the performance of the individual. We present an alternative setup using an Arduino microcontroller that addresses these issues and delivers low-latency auditory feedback. We validated our setup by having participants (N = 6) tap on a force-sensitive resistor pad connected to the Arduino and on an electronic percussion pad with various levels of force and tempi. The Arduino delivered auditory feedback through a pulse-width modulation (PWM) pin connected to a headphone jack or a wave shield component. The Arduino's PWM (M = 0.6 ms, SD = 0.3) and wave shield (M = 2.6 ms, SD = 0.3) demonstrated significantly lower auditory feedback latencies than the percussion pad (M = 9.1 ms, SD = 2.0), FTAP (M = 14.6 ms, SD = 2.8), and Max/MSP (M = 15.8 ms, SD = 3.4). The PWM and wave shield latencies were also significantly less variable than those from FTAP and Max/MSP. The Arduino missed significantly fewer taps, and recorded fewer superfluous responses, than the percussion pad. The Arduino captured all responses, whereas at lower tapping forces, the percussion pad missed more taps. Regardless of tapping force, the Arduino outperformed the percussion pad. Overall, the Arduino is a high-precision, low-latency, portable, and affordable tool for auditory experiments.

  6. Channel noise effects on first spike latency of a stochastic Hodgkin-Huxley neuron

    Science.gov (United States)

    Maisel, Brenton; Lindenberg, Katja

    2017-02-01

    While it is widely accepted that information is encoded in neurons via action potentials or spikes, it is far less understood what specific features of spiking contain encoded information. Experimental evidence has suggested that the timing of the first spike may be an energy-efficient coding mechanism that contains more neural information than subsequent spikes. Therefore, the biophysical features of neurons that underlie response latency are of considerable interest. Here we examine the effects of channel noise on the first spike latency of a Hodgkin-Huxley neuron receiving random input from many other neurons. Because the principal feature of a Hodgkin-Huxley neuron is the stochastic opening and closing of channels, the fluctuations in the number of open channels lead to fluctuations in the membrane voltage and modify the timing of the first spike. Our results show that when a neuron has a larger number of channels, (i) the occurrence of the first spike is delayed and (ii) the variation in the first spike timing is greater. We also show that the mean, median, and interquartile range of first spike latency can be accurately predicted from a simple linear regression by knowing only the number of channels in the neuron and the rate at which presynaptic neurons fire, but the standard deviation (i.e., neuronal jitter) cannot be predicted using only this information. We then compare our results to another commonly used stochastic Hodgkin-Huxley model and show that the more commonly used model overstates the first spike latency but can predict the standard deviation of first spike latencies accurately. We end by suggesting a more suitable definition for the neuronal jitter based upon our simulations and comparison of the two models.

  7. Brain targeted transcranial administration of diazepam and shortening of sleep latency in healthy human volunteers

    Directory of Open Access Journals (Sweden)

    W Pathirana

    2011-01-01

    Full Text Available Application of medicated oils on scalp had been practiced for centuries in the Ayurvedic system of medicine in diseases associated with the central nervous system. It is possible that the effectiveness of the therapy may be a result of targeted delivery of active compounds to the brain transcranially. Evidence also comes from two previous studies with positive results on brain targeted transcranial delivery of methadone base and diazepam on rat models. Possibility of transcranial drug delivery was investigated in healthy human volunteers using electroencephalography techniques by assessing the ability of transcranially administered diazepam in bringing about β activity in the electroencephalographic wave patterns and shortening of the sleep latency period. Non polar drug molecules dissolved in a non-aqueous sesame oil based vehicle is a significant feature in the transcranial dosage design. The study was under taken in two phases. In the Phase-I study scalp application of a single dose of 2 mg/3 ml of the oil was employed and in the Phase-II study repeat application of three doses 24 h apart were employed. Sleep latency changes were monitored with Multiple Sleep Latency Tests with 5 naps employing the standard electroencephalography, electroocculography and electromyography electrodes. Sleep onset was identified with the first epoch of any sleep stage non rapid eye movement 1, 2, 3, 4 or rapid eye movement using electroencephalography, electroocculography and electromyography criteria. In both phases of the study there was significant reduction in the sleep latencies. It was much more pronounced in the Phase-II study. None of the subjects however displayed beta activity in the electroencephalography. Sleep latency reduction following scalp application in both the phases are suggestive of transcranial migration of diazepam molecules to the receptor sites of the nerve tissue of the brain eliciting its pharmacological effect of sedation

  8. HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days--Implications for HIV Remission.

    Directory of Open Access Journals (Sweden)

    Mykola Pinkevych

    2015-07-01

    Full Text Available HIV infection can be effectively controlled by anti-retroviral therapy (ART in most patients. However therapy must be continued for life, because interruption of ART leads to rapid recrudescence of infection from long-lived latently infected cells. A number of approaches are currently being developed to 'purge' the reservoir of latently infected cells in order to either eliminate infection completely, or significantly delay the time to viral recrudescence after therapy interruption. A fundamental question in HIV research is how frequently the virus reactivates from latency, and thus how much the reservoir might need to be reduced to produce a prolonged antiretroviral-free HIV remission. Here we provide the first direct estimates of the frequency of viral recrudescence after ART interruption, combining data from four independent cohorts of patients undergoing treatment interruption, comprising 100 patients in total. We estimate that viral replication is initiated on average once every ≈6 days (range 5.1- 7.6 days. This rate is around 24 times lower than previous thought, and is very similar across the cohorts. In addition, we analyse data on the ratios of different 'reactivation founder' viruses in a separate cohort of patients undergoing ART-interruption, and estimate the frequency of successful reactivation to be once every 3.6 days. This suggests that a reduction in the reservoir size of around 50-70-fold would be required to increase the average time-to-recrudescence to about one year, and thus achieve at least a short period of anti-retroviral free HIV remission. Our analyses suggests that time-to-recrudescence studies will need to be large in order to detect modest changes in the reservoir, and that macaque models of SIV latency may have much higher frequencies of viral recrudescence after ART interruption than seen in human HIV infection. Understanding the mean frequency of recrudescence from latency is an important first step in

  9. In vivo persistence and protective efficacy of the bacille Calmette Guerin vaccine overexpressing the HspX latency antigen.

    Science.gov (United States)

    Spratt, Joanne M; Britton, Warwick J; Triccas, James A

    2010-01-01

    New strategies to control infection with Mycobacterium tuberculosis, the causative agent of tuberculosis, are urgently required, particularly in areas where acquired immunodeficiencies are prevalent. In this report we have determined if modification of the current tuberculosis vaccine, Mycobacterium bovis BCG, to constitutively express the mycobacterial HspX latency antigen altered its protective effect against challenge with virulent M. tuberculosis. Overexpression of M. tuberculosis HspX in BCG caused reduced growth in aerated cultures compared to control BCG, but growth under limited oxygen availability was not markedly altered. Upon infection of mice, BCG:HspX displayed tissue-specific attenuation compared to control BCG, with reduced growth within the lung and liver but not the spleen. Both BCG:HspX and control BCG protected mice against aerosol M. tuberculosis challenge to a similar extent, however, immunodeficient mice infected with BCG:HspX survived significantly longer than mice infected with the control BCG strain. Therefore, altering the in vivo persistence of BCG by overexpression of HspX may be one important step towards developing a new tuberculosis vaccine with an improved safety profile and suitable protective efficacy against M. tuberculosis infection.

  10. Treating Excessively Slow Responding of a Young Man with Asperger Syndrome Using Differential Reinforcement of Short Response Latencies

    Science.gov (United States)

    Tiger, Jeffrey H.; Bouxsein, Kelly J.; Fisher, Wayne W.

    2007-01-01

    Fjellstedt and Sulzer-Azaroff (1973) used differential reinforcement of short latencies to decrease a child's latency to comply with instructions. We replicated this contingency with a young man diagnosed with Asperger syndrome across two tasks (question answering and math problem solving). We added a differential reinforcement contingency to…

  11. Turkish validation of the premature ejaculation diagnostic tool and its association with intravaginal ejaculatory latency time.

    Science.gov (United States)

    Serefoglu, E C; Cimen, H I; Ozdemir, A T; Symonds, T; Berktas, M; Balbay, M D

    2009-01-01

    There are uncertain issues on the diagnostic methods of premature ejaculation (PE). The premature ejaculation diagnostic tool (PEDT) was developed to systematically apply the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria in diagnosing PE and the aim of this study is to carry out the Turkish validation of the PEDT and to evaluate its association with intravaginal ejaculatory latency time (IELT). A total of 94 patients with a self-reported complaint of PE and 88 men without PE were enrolled into the study and requested to complete the nine-item PEDT, which was translated into Turkish. The patients were also requested to measure IELT. All participants were requested to come for a second visit to assess the PEDT's retest reliability; data from 78 men in the PE group and 69 men in the control group were collected. The IELT data of 35 patients were also recorded. The mean age of the PE group and the control group were 39.4+/-9.7 (24-65) and 30.1+/-5.7 (20-56), respectively, (P=0.068). Among the patients in the PE group, 24 (68.5%) reported life-long PE, whereas 11 (31.5%) reported acquired PE. The geometric mean IELT of the PE group was 59.7+/-46.2 (6.5-197.7) s. The number of men reporting IELTs of 2 min were 20 (57.1%), 11 (31.5) and 4 (11.4%), respectively. The factor analysis assessment showed that the five-item combination (questions 1, 2, 3, 4 and 8) explained 74.4% of the variance, there were no other combinations that explained the variance more effectively. Cronbach's alpha score of five-item combination was calculated as 0.77, showing adequate internal consistency. The overall Cronbach's alpha score did not increase if any item combination was deleted. The test-retest correlation coefficients of each item were higher than 0.80 and the correlation coefficient of the total score was 0.90. The PEDT and IELT showed an adequate correlation (rho=0.44). As a conclusion, the validated five-item Turkish version of PEDT is a

  12. Restricted TET2 Expression in Germinal Center Type B Cells Promotes Stringent Epstein-Barr Virus Latency.

    Science.gov (United States)

    Wille, Coral K; Li, Yangguang; Rui, Lixin; Johannsen, Eric C; Kenney, Shannon C

    2017-03-01

    Epstein-Barr virus (EBV) latently infects normal B cells and contributes to the development of certain human lymphomas. Newly infected B cells support a highly transforming form (type III) of viral latency; however, long-term EBV infection in immunocompetent hosts is limited to B cells with a more restricted form of latency (type I) in which most viral gene expression is silenced by promoter DNA methylation. How EBV converts latency type is unclear, although it is known that type I latency is associated with a germinal center (GC) B cell phenotype, and type III latency with an activated B cell (ABC) phenotype. In this study, we have examined whether expression of TET2, a cellular enzyme that initiates DNA demethylation by converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates EBV latency type in B cells. We found that TET2 expression is inhibited in normal GC cells and GC type lymphomas. In contrast, TET2 is expressed in normal naive B cells and ABC type lymphomas. We also demonstrate that GC type cell lines have increased 5mC levels and reduced 5hmC levels in comparison to those of ABC type lines. Finally, we show that TET2 promotes the ability of the EBV transcription factor EBNA2 to convert EBV-infected cells from type I to type III latency. These findings demonstrate that TET2 expression is repressed in GC cells independent of EBV infection and suggest that TET2 promotes type III EBV latency in B cells with an ABC or naive phenotype by enhancing EBNA2 activation of methylated EBV promoters.IMPORTANCE EBV establishes several different types of viral latency in B cells. However, cellular factors that determine whether EBV enters the highly transforming type III latency, versus the more restricted type I latency, have not been well characterized. Here we show that TET2, a cellular enzyme that initiates DNA demethylation by converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates EBV latency type in B cells by

  13. A booster vaccine expressing a latency-associated antigen augments BCG induced immunity and confers enhanced protection against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bappaditya Dey

    Full Text Available BACKGROUND: In spite of a consistent protection against tuberculosis (TB in children, Mycobacterium bovis Bacille Calmette-Guerin (BCG fails to provide adequate protection against the disease in adults as well as against reactivation of latent infections or exogenous reinfections. It has been speculated that failure to generate adequate memory T cell response, elicitation of inadequate immune response against latency-associated antigens and inability to impart long-term immunity against M. tuberculosis infections are some of the key factors responsible for the limited efficiency of BCG in controlling TB. METHODS/PRINCIPAL FINDINGS: In this study, we evaluated the ability of a DNA vaccine expressing α-crystallin--a key latency antigen of M. tuberculosis to boost the BCG induced immunity. 'BCG prime-DNA boost' regimen (B/D confers robust protection in guinea pigs along with a reduced pathology in comparison to BCG vaccination (1.37 log(10 and 1.96 log(10 fewer bacilli in lungs and spleen, respectively; p<0.01. In addition, B/D regimen also confers enhanced protection in mice. Further, we show that B/D immunization in mice results in a heightened frequency of PPD and antigen specific multi-functional CD4 T cells (3(+ simultaneously producing interferon (IFNγ, tumor necrosis factor (TNFα and interleukin (IL2. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of α-crystallin based B/D regimen over BCG. Our study, also demonstrates that protection against TB is predictable by an increased frequency of 3(+ Th1 cells with superior effector functions. We anticipate that this study would significantly contribute towards the development of superior booster vaccines for BCG vaccinated individuals. In addition, this regimen can also be expected to reduce the risk of developing active TB due to reactivation of latent infection.

  14. Differential adaptation of REM sleep latency, intermediate stage and theta power effects of escitalopram after chronic treatment.

    Science.gov (United States)

    Vas, Szilvia; Kátai, Zita; Kostyalik, Diána; Pap, Dorottya; Molnár, Eszter; Petschner, Péter; Kalmár, Lajos; Bagdy, György

    2013-01-01

    The effects of the widely used selective serotonin reuptake inhibitor (SSRI) antidepressants on sleep have been intensively investigated. However, only a few animal studies examined the effect of escitalopram, the more potent S-enantiomer of citalopram, and conclusions of these studies on sleep architecture are limited due to the experimental design. Here, we investigate the acute (2 and 10 mg/kg, i.p. injected at the beginning of the passive phase) or chronic (10 mg/kg/day for 21 days, by osmotic minipumps) effects of escitalopram on the sleep and quantitative electroencephalogram (EEG) of Wistar rats. The first 3 h of EEG recording was analyzed at the beginning of passive phase, immediately after injections. The acutely injected 2 and 10 mg/kg and the chronically administered 10 mg/kg/day escitalopram caused an approximately three, six and twofold increases in rapid eye movement sleep (REMS) latency, respectively. Acute 2-mg/kg escitalopram reduced REMS, but increased intermediate stage of sleep (IS) while the 10 mg/kg reduced both. We also observed some increase in light slow wave sleep and passive wake parallel with a decrease in deep slow wave sleep and theta power in both active wake and REMS after acute dosing. Following chronic treatment, only the increase in REMS latency remained significant compared to control animals. In conclusion, adaptive changes in the effects of escitalopram, which occur after 3 weeks of treatment, suggest desensitization in the function of 5-HT(1A) and 5-HT(1B) receptors.

  15. Group II muscle afferents probably contribute to the medium latency soleus stretch reflex during walking in humans

    DEFF Research Database (Denmark)

    Grey, Michael James; Ladouceur, Michel; Andersen, Jacob B.

    2001-01-01

    1. The objective of this study was to determine which afferents contribute to the medium latency response of the soleus stretch reflex resulting from an unexpected perturbation during human walking. 2. Fourteen healthy subjects walked on a treadmill at approximately 3.5 km h(-1) with the left ankle...... component (P = 0.004), whereas the medium latency component was unchanged (P = 0.437). 6. Two hours after the ingestion of tizanidine, an alpha(2)-adrenergic receptor agonist known to selectively depress the transmission in the group II afferent pathway, the medium latency reflex was strongly depressed (P...... = 0.007), whereas the short latency component was unchanged (P = 0.653). 7. An ankle block with lidocaine hydrochloride was performed to suppress the cutaneous afferents of the foot and ankle. Neither the short (P = 0.453) nor medium (P = 0.310) latency reflexes were changed. 8. Our results support...

  16. HIV Latency

    OpenAIRE

    Robert F. Siliciano; Greene, Warner C.

    2011-01-01

    HIV-1 can establish a state of latent infection at the level of individual T cells. Latently infected cells are rare in vivo and appear to arise when activated CD4+ T cells, the major targets cells for HIV-1, become infected and survive long enough to revert back to a resting memory state, which is nonpermissive for viral gene expression. Because latent virus resides in memory T cells, it persists indefinitely even in patients on potent antiretroviral therapy. This latent reservoir is recogni...

  17. A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

    Science.gov (United States)

    Kennedy, Peter G. E.; Rovnak, Joel; Badani, Hussain

    2015-01-01

    Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephalitis; however, a third of the cases of HSV-1 encephalitis are associated with HSV-1 primary infection. Primary VZV infection causes varicella (chickenpox) following which latent virus may reactivate decades later to produce herpes zoster (shingles), as well as an increasingly recognized number of subacute, acute and chronic neurological conditions. Following primary infection, both viruses establish a latent infection in neuronal cells in human peripheral ganglia. However, the detailed mechanisms of viral latency and reactivation have yet to be unravelled. In both cases latent viral DNA exists in an ‘end-less’ state where the ends of the virus genome are joined to form structures consistent with unit length episomes and concatemers, from which viral gene transcription is restricted. In latently infected ganglia, the most abundantly detected HSV-1 RNAs are the spliced products originating from the primary latency associated transcript (LAT). This primary LAT is an 8.3 kb unstable transcript from which two stable (1.5 and 2.0 kb) introns are spliced. Transcripts mapping to 12 VZV genes have been detected in human ganglia removed at autopsy; however, it is difficult to ascribe these as transcripts present during latent infection as early-stage virus reactivation may have transpired in the post-mortem time period in the ganglia. Nonetheless, low-level transcription of VZV ORF63 has been repeatedly detected in multiple ganglia removed as close to death as possible. There is

  18. HSV-1 genome subnuclear positioning and associations with host-cell PML-NBs and centromeres regulate LAT locus transcription during latency in neurons.

    Directory of Open Access Journals (Sweden)

    Frédéric Catez

    PML-NBs and centromeres are functionally involved in the control of HSV-1 latency, and represent a key level of host/virus interaction.

  19. Reduced complexity and latency for a massive MIMO system using a parallel detection algorithm

    Directory of Open Access Journals (Sweden)

    Shoichi Higuchi

    2017-09-01

    Full Text Available In recent years, massive MIMO systems have been widely researched to realize high-speed data transmission. Since massive MIMO systems use a large number of antennas, these systems require huge complexity to detect the signal. In this paper, we propose a novel detection method for massive MIMO using parallel detection with maximum likelihood detection with QR decomposition and M-algorithm (QRM-MLD to reduce the complexity and latency. The proposed scheme obtains an R matrix after permutation of an H matrix and QR decomposition. The R matrix is also eliminated using a Gauss–Jordan elimination method. By using a modified R matrix, the proposed method can detect the transmitted signal using parallel detection. From the simulation results, the proposed scheme can achieve a reduced complexity and latency with a little degradation of the bit error rate (BER performance compared with the conventional method.

  20. Short-latency crossed responses in the human biceps femoris muscle

    DEFF Research Database (Denmark)

    Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend Sparre;

    Ipsilateral knee (iKnee) joint rotations in seated humans elicit short-latency crossed spinal reflexes in the contralateral biceps femoris (cBF) muscle (Stevenson et al., 2012). The short-latency cBF reflexes were inhibitory following iKnee extension perturbations, and facilitatory following...... of MUs. 11 seated participants (mean age 25 ± 5 years) performed a voluntary isometric knee extension with the ipsilateral leg and contralateral knee flexion to 10% of MVC. Surface EMG was recorded bilaterally from the BF and rectus femoris, and iEMG from the cBF. A mechanical actuator (MTS......-Systems Corporation) imposed iKnee flexion or extension perturbations (8° and 150°/s) in blocks of 60 trials. iEMG data for flexion and extension perturbations were decomposed (EMGLAB, McGill et al., 2005) into constituent MU action potentials (APs). The total number of APs was quantified using a 10 ms window...

  1. Group Ia afferents contribute to short-latency interlimb reflexes in the human biceps femoris muscle

    DEFF Research Database (Denmark)

    Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend Sparre

    2017-01-01

    and velocity of the iKnee rotations. Methods 11 seated participants (mean age: 25 ± 5 years) performed a voluntary isometric knee extension with the ipsilateral leg and contralateral knee flexion to 10% of maximum voluntary contraction (MVC). A mechanical actuator (MTS-Systems Corporation) imposed i...... amplitudes (4 vs. 8°) at the same 150°/s velocity (p’s > 0.08). Conclusion Because fast conducting group Ia muscle spindle afferents are sensitive to changes in muscle stretch velocity, while group II spindle afferents are sensitive to changes in amplitude (Grey et al., JPhysiol., 2001; Matthews, Trends...... Neurosci., 1991), group Ia velocity sensitive muscle spindle afferents likely contribute to the short-latency crossed spinal reflexes in the cBF muscle following iKnee joint rotations. This supports the findings for the short-latency crossed responses in the human soleus muscle (Stubbs & Mrachacz...

  2. Treatment of high-latency microcapsules containing an aluminium complex with an epoxy-functionalised trialkoxysilane.

    Science.gov (United States)

    Kamiya, Kazunobu; Suzuki, Noboru

    2016-12-01

    Some aluminium complexes are excellent catalysts of cationic polymerisation and are used for low-temperature and fast-curing adhesive, used in electronic part mounting. Microencapsulation is a suitable technique for getting high latency of the catalysts and long shelf life of the adhesives. For the higher latency in a cycloaliphatic epoxy compound, the microcapsule surface which retained small amount of aluminium complex was coated with epoxy polymer and the effect was examined. From the X-ray photoelectron spectroscopic results, the surface was recognised to be sufficiently coated and the differential scanning calorimetric analyses showed that the coating did not significantly affect the low-temperature and fast-curing properties of adhesive. After storing the mixture of cycloaliphatic epoxy compound, coated microcapsules, triphenylsilanol and silane coupling agent for 48 h at room temperature, the increase in viscosity was only 0.01 Pa s, resulting in the excellent shelf life.

  3. Short latency vestibular potentials evoked by electrical round window stimulation in the guinea pig.

    Science.gov (United States)

    Bordure, P; Desmadryl, G; Uziel, A; Sans, A

    1989-11-01

    Short-latency potentials evoked by round window electrical stimulation were recorded in guinea pig by means of vertex-pinna skin electrodes using averaging techniques. Constant current shocks of 20 microseconds or 50 microseconds (25-300 microA) were used to evoke both auditory and vestibular brain-stem potentials. Pure auditory potentials, comparable to those evoked by acoustic clicks, were obtained by 20 microseconds electrical stimuli and disappeared during an auditory masking procedure made with a continuous white noise (110 dB SPL). Short latency potentials labeled V1, V2 and V3 were obtained by 50 microseconds electrical stimuli during an auditory masking procedure. This response disappeared after specific vestibular neurectomy, whereas the auditory response evoked by acoustic clicks or by electrical stimulation remained unchanged, suggesting that these latter potentials had a vestibular origin.

  4. Zinc supplementation prolongs the latency of hyperthermia-induced febrile seizures in rats.

    Science.gov (United States)

    Aydın, L; Erdem, S R; Yazıcı, C

    2016-03-01

    Some studies have shown a relationship between febrile seizures and zinc levels. The lowest dose zinc supplementation in pentylenetetrazole seizure model has a protective effect. But, zinc pretreatment has no effect in maximal electroshock model. However, it is unclear how zinc supplementation affects hyperthermia-induced febrile seizures. The aim of the present study was to investigate the effects of zinc supplementation on febrile seizures in male Sprague-Dawley rats. The rats were randomly assigned to four groups. Zinc supplementation was commenced 5 days prior to febrile seizure induction by placing the animals in a water bath at 45°C. We measured the rectal temperature and determined the febrile seizure latency, duration, and stage. In the zinc-supplemented group, both the seizure latency and the rectal temperature triggering seizure initiation were significantly higher than in the other groups. We suggest that zinc supplementation can positively modulate febrile seizure pathogenesis in rats.

  5. Summed Parallel Infinite Impulse Response (SPIIR) Filters For Low-Latency Gravitational Wave Detection

    CERN Document Server

    Hooper, Shaun; Luan, Jing; Blair, David; Chen, Yanbei; Wen, Linqing

    2011-01-01

    With the upgrade of current gravitational wave detectors, the first detection of gravitational wave signals is expected to occur in the next decade. Low-latency gravitational wave triggers will be necessary to make fast follow-up electromagnetic observations of events related to their source, e.g., prompt optical emission associated with short gamma-ray bursts. In this paper we present a new time-domain low-latency algorithm for identifying the presence of gravitational waves produced by compact binary coalescence events in noisy detector data. Our method calculates the signal to noise ratio from the summation of a bank of parallel infinite impulse response (IIR) filters. We show that our summed parallel infinite impulse response (SPIIR) method can retrieve the signal to noise ratio to greater than 99% of that produced from the optimal matched filter. We emphasise the benefits of the SPIIR method for advanced detectors, which will require larger template banks.

  6. Low-latency analysis pipeline for compact binary coalescences in the advanced gravitational wave detector era

    CERN Document Server

    Adams, T; Germain, V; Guidi, G M; Marion, F; Montani, M; Mours, B; Piergiovanni, F; Wang, G

    2015-01-01

    The Multi-Band Template Analysis (MBTA) pipeline is a low-latency coincident analysis pipeline for the detection of gravitational waves (GWs) from compact binary coalescences (CBCs). MBTA runs with a low computational cost, and can identify candidate GW events online with a sub-minute latency. The low computational running cost of MBTA also makes it useful for data quality studies. Events detected by MBTA online can be used to alert astronomical partners for electromagnetic (EM) follow-up. We outline the current status of MBTA and give details of recent pipeline upgrades and validation tests that were performed in preparation for the first advanced detector observing period. The MBTA pipeline is ready for the outset of the advanced detector era and the exciting prospects it will bring.

  7. A strong law for the rate of growth of long latency periods in cloud computing service

    CERN Document Server

    Ghosh, Souvik

    2010-01-01

    Cloud-computing shares a common pool of resources across customers at a scale that is orders of magnitude larger than traditional multi-user systems. Constituent physical compute servers are allocated multiple "virtual machines" (VM) to serve simultaneously. Each VM user should ideally be unaffected by others' demand. Naturally, this environment produces new challenges for the service providers in meeting customer expectations while extracting an efficient utilization from server resources. We study a new cloud service metric that measures prolonged latency or delay suffered by customers. We model the workload process of a cloud server and analyze the process as the customer population grows. The capacity required to ensure that average workload does not exceed a threshold over long segments is characterized. This can be used by cloud operators to provide service guarantees on avoiding long durations of latency. As part of the analysis, we provide a uniform large-deviation principle for collections of random ...

  8. Capturing the electromagnetic counterparts of binary neutron star mergers through low latency gravitational wave triggers

    CERN Document Server

    Chu, Q; Rowlinson, A; Gao, H; Zhang, B; Tingay, S J; Boer, M; Wen, L

    2015-01-01

    We investigate the prospects for joint low-latency gravitational wave (GW) detection and prompt electromagnetic (EM) follow-up observations of coalescing binary neutron stars (BNSs). Assuming BNS mergers are associated with short duration gamma ray bursts (SGRBs), we evaluate if rapid EM follow-ups can capture the prompt emission, early engine activity or reveal any potential by-products such as magnetars or fast radio bursts. To examine the expected performance of low-latency search pipelines we simulate a population of coalescing BNSs using realistic distributions of source parameters to estimate the detectability and localisation efficiency at different times before merger. To determine what EM observations can be achieved, we consider a selection of facilities with GW follow-up agreements in place, from low-frequency radio to high energy $\\gamma$-ray; we assess the performance of each using observational SGRB flux data corrected to the range of the advanced GW interferometric detectors LIGO and Virgo. We ...

  9. Design and performance of a high resolution, low latency stripline beam position monitor system

    Science.gov (United States)

    Apsimon, R. J.; Bett, D. R.; Blaskovic Kraljevic, N.; Burrows, P. N.; Christian, G. B.; Clarke, C. I.; Constance, B. D.; Dabiri Khah, H.; Davis, M. R.; Perry, C.; Resta López, J.; Swinson, C. J.

    2015-03-01

    A high-resolution, low-latency beam position monitor (BPM) system has been developed for use in particle accelerators and beam lines that operate with trains of particle bunches with bunch separations as low as several tens of nanoseconds, such as future linear electron-positron colliders and free-electron lasers. The system was tested with electron beams in the extraction line of the Accelerator Test Facility at the High Energy Accelerator Research Organization (KEK) in Japan. It consists of three stripline BPMs instrumented with analogue signal-processing electronics and a custom digitizer for logging the data. The design of the analogue processor units is presented in detail, along with measurements of the system performance. The processor latency is 15.6 ±0.1 ns . A single-pass beam position resolution of 291 ±10 nm has been achieved, using a beam with a bunch charge of approximately 1 nC.

  10. Low-latency analysis pipeline for compact binary coalescences in the advanced gravitational wave detector era

    Science.gov (United States)

    Adams, T.; Buskulic, D.; Germain, V.; Guidi, G. M.; Marion, F.; Montani, M.; Mours, B.; Piergiovanni, F.; Wang, G.

    2016-09-01

    The multi-band template analysis (MBTA) pipeline is a low-latency coincident analysis pipeline for the detection of gravitational waves (GWs) from compact binary coalescences. MBTA runs with a low computational cost, and can identify candidate GW events online with a sub-minute latency. The low computational running cost of MBTA also makes it useful for data quality studies. Events detected by MBTA online can be used to alert astronomical partners for electromagnetic follow-up. We outline the current status of MBTA and give details of recent pipeline upgrades and validation tests that were performed in preparation for the first advanced detector observing period. The MBTA pipeline is ready for the outset of the advanced detector era and the exciting prospects it will bring.

  11. A Type of Low-Latency Data Gathering Method with Multi-Sink for Sensor Networks

    Directory of Open Access Journals (Sweden)

    Chao Sha

    2016-06-01

    Full Text Available To balance energy consumption and reduce latency on data transmission in Wireless Sensor Networks (WSNs, a type of low-latency data gathering method with multi-Sink (LDGM for short is proposed in this paper. The network is divided into several virtual regions consisting of three or less data gathering units and the leader of each region is selected according to its residual energy as well as distance to all of the other nodes. Only the leaders in each region need to communicate with the mobile Sinks which have effectively reduced energy consumption and the end-to-end delay. Moreover, with the help of the sleep scheduling and the sensing radius adjustment strategies, redundancy in network coverage could also be effectively reduced. Simulation results show that LDGM is energy efficient in comparison with MST as well as MWST and its time efficiency on data collection is higher than one Sink based data gathering methods.

  12. A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

    OpenAIRE

    2015-01-01

    Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephaliti...

  13. Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis.

    Science.gov (United States)

    Coppola, Mariateresa; van den Eeden, Susan J F; Wilson, Louis; Franken, Kees L M C; Ottenhoff, Tom H M; Geluk, Annemieke

    2015-09-01

    Responsible for 9 million new cases of active disease and nearly 2 million deaths each year, tuberculosis (TB) remains a global health threat of overwhelming dimensions. Mycobacterium bovis BCG, the only licensed vaccine available, fails to confer lifelong protection and to prevent reactivation of latent infection. Although 15 new vaccine candidates are now in clinical trials, an effective vaccine against TB remains elusive, and new strategies for vaccination are vital. BCG vaccination fails to induce immunity against Mycobacterium tuberculosis latency antigens. Synthetic long peptides (SLPs) combined with adjuvants have been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved to induce efficient antitumor immunity. This study investigated an SLP derived from Rv1733c, a major M. tuberculosis latency antigen which is highly expressed by "dormant" M. tuberculosis and well recognized by T cells from latently M. tuberculosis-infected individuals. In order to assess its in vivo immunogenicity and protective capacity, Rv1733c SLP in CpG was administered to HLA-DR3 transgenic mice. Immunization with Rv1733c SLP elicited gamma interferon-positive/tumor necrosis factor-positive (IFN-γ(+)/TNF(+)) and IFN-γ(+) CD4(+) T cells and Rv1733c-specific antibodies and led to a significant reduction in the bacterial load in the lungs of M. tuberculosis-challenged mice. This was observed both in a pre- and in a post-M. tuberculosis challenge setting. Moreover, Rv1733c SLP immunization significantly boosted the protective efficacy of BCG, demonstrating the potential of M. tuberculosis latency antigens to improve BCG efficacy. These data suggest a promising role for M. tuberculosis latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a prophylactic and in a postinfection setting.

  14. Relation between derived-band auditory brainstem response latencies and behavioral frequency selectivity

    DEFF Research Database (Denmark)

    Strelcyk, Olaf; Christoforidis, Dimitrios; Dau, Torsten

    2009-01-01

    Derived-band click-evoked auditory brainstem responses ABRs were obtained for normal-hearing NH and sensorineurally hearing-impaired HI listeners. The latencies extracted from these responses, as a function of derived-band center frequency and click level, served as objective estimates of cochlear...... selectivity in human listeners and offer a window to better understand how hearing impairment affects the spatiotemporal cochlear response pattern....

  15. Note on changes in response latency following discrimination training in the monkey1

    Science.gov (United States)

    Stebbins, William C.; Reynolds, Robert W.

    1964-01-01

    Two monkeys were trained to press and hold down a telegraph key in the presence of a red light. Subsequent release of the key in response to a white cross superimposed on the red background was followed by reinforcement. Key release in response to a white circle on the red background was never reinforced. Latencies for the key release response to the reinforced stimulus (cross) were considerably shorter and less variable than those to the unreinforced stimulus (circle). PMID:14143909

  16. Bryostatin-1 synergizes with histone deacetylase inhibitors to reactivate HIV-1 from latency.

    Science.gov (United States)

    Pérez, Moisés; de Vinuesa, Amaya García; Sanchez-Duffhues, Gonzalo; Marquez, Nieves; Bellido, M Luz; Muñoz-Fernandez, M Angeles; Moreno, Santiago; Castor, Trevor P; Calzado, Marco A; Muñoz, Eduardo

    2010-09-01

    The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication on patients treated with HAART. It has been suggested that successful depletion of such latent reservoirs will require a combination of therapeutic agents that can specifically and efficiently act on cells harboring latent HIV-1 provirus. Using Jurkat-LAT-GFP cells, a tractable model of HIV-1 latency, we have found that bryostatin -1 reactivates HIV-1 through a classical PKC-dependent pathway. Bryostatin-1 also activates MAPKs and NF-κB pathways and synergizes with HDAC inhibitors to reactivate HIV-1 from latency. Bryostatin-1 downregulates the expression of the HIV-1 co-receptors CD4 and CXCR4 and prevented de novo HIV-1 infection in susceptible cells. We applied proteomic methods to investigate major changes in protein expression in Jurkat-LAT-GFP under latency and reactivation conditions. We identified up-regulation of proteins that may be involved in the innate anti-HIV-1 response (NKEF-A and MHD2) and in different cell functions (i.e. cofilin-1 and transgelin-2) of the host cells. PKC agonists may represent a valuable pharmacological approach to purge latent HIV from cellular reservoirs and at the moment, the only clinically available PKC agonist is bryostatin-1. This drug has been tested in numerous clinical trials and its pharmacokinetics and toxicity in humans is well known. Moreover, bryostatin-1 potently synergizes with other HDAC inhibitors commonly used in the medical practice such as valproic acid. Therefore, bryostatin-1, alone or in combination with HDAC inhibitors, could be used in HAART treated patients to validate the hypothesis that reactivating HIV-1 from latency could purge HIV-1 reservoirs.

  17. Area/latency optimized early output asynchronous full adders and relative-timed ripple carry adders.

    Science.gov (United States)

    Balasubramanian, P; Yamashita, S

    2016-01-01

    This article presents two area/latency optimized gate level asynchronous full adder designs which correspond to early output logic. The proposed full adders are constructed using the delay-insensitive dual-rail code and adhere to the four-phase return-to-zero handshaking. For an asynchronous ripple carry adder (RCA) constructed using the proposed early output full adders, the relative-timing assumption becomes necessary and the inherent advantages of the relative-timed RCA are: (1) computation with valid inputs, i.e., forward latency is data-dependent, and (2) computation with spacer inputs involves a bare minimum constant reverse latency of just one full adder delay, thus resulting in the optimal cycle time. With respect to different 32-bit RCA implementations, and in comparison with the optimized strong-indication, weak-indication, and early output full adder designs, one of the proposed early output full adders achieves respective reductions in latency by 67.8, 12.3 and 6.1 %, while the other proposed early output full adder achieves corresponding reductions in area by 32.6, 24.6 and 6.9 %, with practically no power penalty. Further, the proposed early output full adders based asynchronous RCAs enable minimum reductions in cycle time by 83.4, 15, and 8.8 % when considering carry-propagation over the entire RCA width of 32-bits, and maximum reductions in cycle time by 97.5, 27.4, and 22.4 % for the consideration of a typical carry chain length of 4 full adder stages, when compared to the least of the cycle time estimates of various strong-indication, weak-indication, and early output asynchronous RCAs of similar size. All the asynchronous full adders and RCAs were realized using standard cells in a semi-custom design fashion based on a 32/28 nm CMOS process technology.

  18. Does behavioral response to novelty influence paw withdrawal latencies in repeated Hargreaves test?

    OpenAIRE

    Tvrdeić, Ante; Kočevski, Dragana

    2008-01-01

    Background and Purpose: Only recently, we have reported that single retesting session significantly decreases rat paw withdrawal latencies (PWL) in Hargreaves tests.We wondered, whether decrease in PWL values obtained during reexposure toHargreaves testmight be associated with reaction to the new environment. Therefore, we investigated PWL together with the open field behavior in an enclosure of the Hargreaves test device during the period of 3 subsequent days. Materials and Methods: Ten...

  19. Pemodelan dan Verifikasi Formal Pengaruh Mobility pattern Terhadap Handoff Latency pada Jaringan WiMAX

    Directory of Open Access Journals (Sweden)

    I Nym Saputra Wahyu Wijaya

    2016-01-01

    Full Text Available In order to decrease handoff latency and increase the successful of HHO conventional scheme, a development of handover scheme is done in standard protocol WiMAX IEEE 802.16e by adding mobility pattern. The superiority of handover scheme with mobility pattern can reduce handoff latency up to 50%, mean while the weakness of this scheme is a wrong act in determining target base station are often happen. Simulation can not showing the cause of that error. So, we do formal verification in to hard handover model with mobility pattern.             In this research, behaviour system is modeled with continuous-time Markov chain (CTMC. The model is foccused to aproximating the influence of mobility pattern in to handoff latency from WiMAX hard handover mechanism. In order to set up a series markov chain models handover system can follow steps, such as: represents the state space, give a number in all transitions, generate the rate transition matrix (infinitesimal generator.             Probabilistic model checking in the research are using quantitative properties and qualitative properties. Formal verification concerning properties has relation with handover in WiMAX network showing that 70% from mobile station which doing scanning with mobility pattern are success doing handover. 24% of them doing scanning conventional as a result of wrongness in act determining target base station, so handoff latency which is pictured will bigger than a system that is only use conventional scanning method.

  20. Latency-Efficient Communication in Wireless Mesh Networks under Consideration of Large Interference Range

    Science.gov (United States)

    Xin, Qin; Yao, Xiaolan; Engelstad, Paal E.

    2010-09-01

    Wireless Mesh Networking is an emerging communication paradigm to enable resilient, cost-efficient and reliable services for the future-generation wireless networks. We study here the minimum-latency communication primitive of gossiping (all-to-all communication) in multi-hop ad-hoc Wireless Mesh Networks (WMNs). Each mesh node in the WMN is initially given a message and the objective is to design a minimum-latency schedule such that each mesh node distributes its message to all other mesh nodes. Minimum-latency gossiping problem is well known to be NP-hard even for the scenario in which the topology of the WMN is known to all mesh nodes in advance. In this paper, we propose a new latency-efficient approximation scheme that can accomplish gossiping task in polynomial time units in any ad-hoc WMN under consideration of Large Interference Range (LIR), e.g., the interference range is much larger than the transmission range. To the best of our knowledge, it is first time to investigate such a scenario in ad-hoc WMNs under LIR, our algorithm allows the labels (e.g., identifiers) of the mesh nodes to be polynomially large in terms of the size of the WMN, which is the first time that the scenario of large labels has been considered in ad-hoc WMNs under LIR. Furthermore, our gossiping scheme can be considered as a framework which can be easily implied to the scenario under consideration of mobility-related issues since we assume that the mesh nodes have no knowledge on the network topology even for its neighboring mesh nodes.

  1. Design and performance of a high resolution, low latency stripline beam position monitor system

    OpenAIRE

    R. J. Apsimon; D. R. Bett; N. Blaskovic Kraljevic; P. N. Burrows; G. B. Christian; C. I. Clarke; B. D. Constance; Dabiri Khah, H.; M. R. Davis; Perry, C; J. Resta López; C. J. Swinson

    2015-01-01

    A high-resolution, low-latency beam position monitor (BPM) system has been developed for use in particle accelerators and beam lines that operate with trains of particle bunches with bunch separations as low as several tens of nanoseconds, such as future linear electron-positron colliders and free-electron lasers. The system was tested with electron beams in the extraction line of the Accelerator Test Facility at the High Energy Accelerator Research Organization (KEK) in Japan. It consists of...

  2. Analysis of variance of communication latencies in anesthesia: comparing means of multiple log-normal distributions.

    Science.gov (United States)

    Ledolter, Johannes; Dexter, Franklin; Epstein, Richard H

    2011-10-01

    Anesthesiologists rely on communication over periods of minutes. The analysis of latencies between when messages are sent and responses obtained is an essential component of practical and regulatory assessment of clinical and managerial decision-support systems. Latency data including times for anesthesia providers to respond to messages have moderate (> n = 20) sample sizes, large coefficients of variation (e.g., 0.60 to 2.50), and heterogeneous coefficients of variation among groups. Highly inaccurate results are obtained both by performing analysis of variance (ANOVA) in the time scale or by performing it in the log scale and then taking the exponential of the result. To overcome these difficulties, one can perform calculation of P values and confidence intervals for mean latencies based on log-normal distributions using generalized pivotal methods. In addition, fixed-effects 2-way ANOVAs can be extended to the comparison of means of log-normal distributions. Pivotal inference does not assume that the coefficients of variation of the studied log-normal distributions are the same, and can be used to assess the proportional effects of 2 factors and their interaction. Latency data can also include a human behavioral component (e.g., complete other activity first), resulting in a bimodal distribution in the log-domain (i.e., a mixture of distributions). An ANOVA can be performed on a homogeneous segment of the data, followed by a single group analysis applied to all or portions of the data using a robust method, insensitive to the probability distribution.

  3. Auditory Brainstem and Middle Latency Responses Measured Pre- and Posttreatment for Hyperacusic Hearing-Impaired Persons Successfully Treated to Improve Sound Tolerance and to Expand the Dynamic Range for Loudness: Case Evidence.

    Science.gov (United States)

    Formby, Craig; Korczak, Peggy; Sherlock, LaGuinn P; Hawley, Monica L; Gold, Susan

    2017-02-01

    In this report of three cases, we consider electrophysiologic measures from three hyperacusic hearing-impaired individuals who, prior to treatment to expand their dynamic ranges for loudness, were problematic hearing aid candidates because of their diminished sound tolerance and reduced dynamic ranges. Two of these individuals were treated with structured counseling combined with low-level broadband sound therapy from bilateral sound generators and the third case received structured counseling in combination with a short-acting placebo sound therapy. Each individual was highly responsive to his or her assigned treatment as revealed by expansion of the dynamic range by at least 20 dB at one or more frequencies posttreatment. Of specific interest in this report are their latency and amplitude measures taken from tone burst-evoked auditory brainstem response (ABR) and cortically derived middle latency response (MLR) recordings, measured as a function of increasing loudness at 500 and 2,000 Hz pre- and posttreatment. The resulting ABR and MLR latency and amplitude measures for each case are considered here in terms of pre- and posttreatment predictions. The respective pre- and posttreatment predictions anticipated larger pretreatment response amplitudes and shorter pretreatment response latencies relative to typical normal control values and smaller normative-like posttreatment response amplitudes and longer posttreatment response latencies relative to the corresponding pretreatment values for each individual. From these results and predictions, we conjecture about the neural origins of the hyperacusis conditions (i.e., brainstem versus cortical) and the neuronal sites responsive to treatment. The only consistent finding in support of the pre- and posttreatment predictions and, thus, the strongest index of hyperacusis and positive treatment-related effects was measured for MLR latency responses for wave Pa at 2,000 Hz. Other response indices, including ABR wave V

  4. Mismatch field latency, but not power, may mark a shared autistic and schizotypal trait phenotype.

    Science.gov (United States)

    Ford, Talitha C; Woods, Will; Crewther, David P

    2017-02-21

    The auditory mismatch negativity (MMN), a preattentive processing potential, and its magnetic counterpart (MMF) are consistently reported as reduced in schizophrenia and autism spectrum disorders. This study investigates whether MMF characteristics differ between subclinically high and low scorers on the recently discovered shared autism and schizophrenia phenotype, Social Disorganisation. A total of 18 low (10 females) and 19 high (9 females) Social Disorganisation scorers underwent magnetoencephalography (MEG) during a MMF paradigm of 50ms standard (1000Hz, 85%) and 100ms duration deviant tones. MMF was measured from the strongest active magnetometer over the right and left hemispheres (consistent across groups) after 100ms. No differences in MMF power were found, however there was a significant delay in the MMF peak (p=0.007). The P3am (following the MMF) was significantly reduced across both hemispheres for the high Social Disorganisation group (p=0.025), there were no specific hemispheric differences in P3am power or latency. Right MMF peak latency increased with higher scores on the schizotypal subscales Odd Speech, Odd Behaviour and Constricted Affect. Findings suggest that MMF peak latency delay marks a convergence of the autism and schizophrenia spectra at a subclinical. These findings have significant implications for future research methodology, as well as clinical practice.

  5. The Relationship between Parameters of Long-Latency Evoked Potentials in a Multisensory Design.

    Science.gov (United States)

    Hernández, Oscar H; García-Martínez, Rolando; Monteón, Victor

    2016-10-01

    In previous papers, we have shown that parameters of the omitted stimulus potential (OSP), which occurs at the end of a train of sensory stimuli, strongly depend on the modality. A train of stimuli also produces long-latency evoked potentials (LLEP) at the beginning of the train. This study is an extension of the OSP research, and it tested the relationship between parameters (ie, rate of rise, amplitude, and peak latency) of the P2 waves when trains of auditory, visual, or somatosensory stimuli were applied. The dynamics of the first 3 potentials in the train, related to habituation, were also studied. Twenty healthy young college volunteers participated in the study. As in the OSP, the P2 was faster and higher for auditory than for visual or somatosensory stimuli. The first P2 was swifter and higher than the second and the third potentials. The strength of habituation depends on the sensory modality and the parameter used. All these findings support the view that many long-latency brain potentials could share neural mechanisms related to wave generation.

  6. Human Space Exploration and Human Space Flight: Latency and the Cognitive Scale of the Universe

    Science.gov (United States)

    Lester, Dan; Thronson, Harley

    2011-01-01

    The role of telerobotics in space exploration as placing human cognition on other worlds is limited almost entirely by the speed of light, and the consequent communications latency that results from large distances. This latency is the time delay between the human brain at one end, and the telerobotic effector and sensor at the other end. While telerobotics and virtual presence is a technology that is rapidly becoming more sophisticated, with strong commercial interest on the Earth, this time delay, along with the neurological timescale of a human being, quantitatively defines the cognitive horizon for any locale in space. That is, how distant can an operator be from a robot and not be significantly impacted by latency? We explore that cognitive timescale of the universe, and consider the implications for telerobotics, human space flight, and participation by larger numbers of people in space exploration. We conclude that, with advanced telepresence, sophisticated robots could be operated with high cognition throughout a lunar hemisphere by astronauts within a station at an Earth-Moon Ll or L2 venue. Likewise, complex telerobotic servicing of satellites in geosynchronous orbit can be carried out from suitable terrestrial stations.

  7. Latencies in action potential stimulation in a two-dimensional bidomain: A numerical simulation

    Science.gov (United States)

    Barach, John Paul

    1991-05-01

    A numerical simulation is performed in which a uniform planar slab of idealized cardiac tissue is stimulated at the center. The cardiac slab is modeled as an anisotropic bidomain; within each domain current flow is determined by a forced diffusion equation in which the transmembrane current connecting the domains provides the forcing term. An action potential (AP) propagates outward after a time latency dependent upon the stimulus size and the physiological variables. Its isochrones are elliptical with an asymmetry that is a small fraction of the imposed asymmetry in resistivity. External voltages resemble the first derivative of those in the internal domain and tests with continuing stimuli exhibit a relaxation time of about 3 ms and space constants that agree with other work. The AP latency increases very strongly near threshold stimulus and decreases as the log (stimulus) for large stimuli in the ``virtual cathode'' range. Latencies in the longitudinal, transverse, and diagonal directions are found to be the same over a wide range of stimulus size and type.

  8. Short-latency tachycardia evoked by stimulation of muscle and cutaneous afferents.

    Science.gov (United States)

    Gelsema, A J; Bouman, L N; Karemaker, J M

    1985-04-01

    The short-latency effect on heart rate of peripheral nerve stimulation was studied in decerebrate cats. Selective activation (17-40 microA, 100 Hz, 1 s long) of low-threshold fibers in the nerves to the triceps surae muscle yielded isometric contractions of maximal force that were accompanied by a cardiac cycle length shortening within 0.4 s from the start of stimulation. This effect was abolished by pharmacologically induced neuromuscular blockade. The cardiac cycle length shortening during paralysis reappeared after a 6- to 10-fold increase of the stimulation strength. Cutaneous (sural) nerve stimulation (15-25 microA, 100 Hz, 1 s long) elicited reflex contractions in the stimulated limb, which were also accompanied by a cardiac acceleration with similar latency. Paralysis prevented the reflex contractions and reduced the cardiac response in some cats and abolished it in others. The response reappeared in either case after a 5- to 10-fold increase of the stimulus strength. It is concluded that muscle nerve and cutaneous nerve activity both cause a similar cardiac acceleration with a latency of less than 0.4 s. The response to muscle nerve stimulation is elicited by activity in group III afferents. It is excluded that the cardiac response to nerve stimulation is secondary to a change in the respiratory pattern.

  9. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

    Directory of Open Access Journals (Sweden)

    Julia K Bialek

    Full Text Available CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs, act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR, for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

  10. Experiences from Implementing a Mobile Multiplayer Real-Time Game for Wireless Networks with High Latency

    Directory of Open Access Journals (Sweden)

    Alf Inge Wang

    2009-01-01

    Full Text Available This paper describes results and experiences from designing, implementing, and testing a multiplayer real-time game over mobile networks with high latency. The paper reports on network latency and bandwidth measurements from playing the game live over GPRS, EDGE, UMTS, and WLAN using the TCP and the UDP protocols. These measurements describe the practical constraints of various wireless networks and protocols when used for mobile multiplayer game purposes. Further, the paper reports on experiences from implementing various approaches to minimize issues related to high latency. Specifically, the paper focuses on a discussion about how much of the game should run locally on the client versus on the server to minimize the load on the mobile device and obtain sufficient consistency in the game. The game was designed to reveal all kinds of implementation issues of mobile network multiplayer games. The goal of the game is for a player to push other players around and into traps where they loose their lives. The game relies heavily on collision detection between the players and game objects. The paper presents experiences from experimenting with various approaches that can be used to handle such collisions, and highlights the advantages and disadvantages of the various approaches.

  11. Redundant Logic Insertion and Latency Reduction in Self-Timed Adders

    Directory of Open Access Journals (Sweden)

    P. Balasubramanian

    2012-01-01

    Full Text Available A novel concept of logic redundancy insertion is presented that facilitates significant latency reduction in self-timed adder circuits. The proposed concept is universal in the sense that it can be extended to a variety of self-timed design methods. Redundant logic can be incorporated to generate efficient self-timed realizations of iterative logic specifications. Based on the case study of a 32-bit self-timed carry-ripple adder, it has been found that redundant implementations minimize the data path latency by 21.1% at the expense of increases in area and power by 2.3% and 0.8% on average compared to their nonredundant counterparts. However, when considering further peephole logic optimizations, it has been observed in a specific scenario that the delay reduction could be as high as 31% while accompanied by only meager area and power penalties of 0.6% and 1.2%, respectively. Moreover, redundant logic adders pave the way for spacer propagation in constant time and garner actual case latency for addition of valid data.

  12. Energy-Latency Tradeoff for In-Network Function Computation in Random Networks

    CERN Document Server

    Balister, Paul; Anandkumar, Animashree; Willsky, Alan

    2011-01-01

    The problem of designing policies for in-network function computation with minimum energy consumption subject to a latency constraint is considered. The scaling behavior of the energy consumption under the latency constraint is analyzed for random networks, where the nodes are uniformly placed in growing regions and the number of nodes goes to infinity. The special case of sum function computation and its delivery to a designated root node is considered first. A policy which achieves order-optimal average energy consumption in random networks subject to the given latency constraint is proposed. The scaling behavior of the optimal energy consumption depends on the path-loss exponent of wireless transmissions and the dimension of the Euclidean region where the nodes are placed. The policy is then extended to computation of a general class of functions which decompose according to maximal cliques of a proximity graph such as the $k$-nearest neighbor graph or the geometric random graph. The modified policy achiev...

  13. Thermal and Cure Kinetics of Epoxy Molding Compounds Cured with Thermal Latency Accelerators

    Directory of Open Access Journals (Sweden)

    Chean-Cheng Su

    2013-01-01

    Full Text Available The cure kinetics and mechanisms of a biphenyl type epoxy molding compounds (EMCs with thermal latency organophosphine accelerators were studied using differential scanning calorimetry (DSC. Although the use of triphenylphosphine-1,4-benzoquinone (TPP-BQ and triphenylphosphine (TPP catalysts in biphenyl type EMCs exhibited autocatalytic mechanisms, thermal latency was higher in the TPP-BQ catalyst in EMCs than in the TPP catalyst in EMCs. Analyses of thermal characteristics indicated that TPP-BQ is inactive at low temperatures. At high temperatures, however, TPP-BQ increases the curing rate of EMC in dynamic and isothermal curing experiments. The reaction of EMCs with the TPP-BQ latent catalyst also had a higher temperature sensitivity compared to the reaction of EMCs with TPP catalyst. In resin transfer molding, EMCs containing the TPP-BQ thermal latency accelerator are least active at a low temperature. Consequently, EMCs have a low melt viscosity before gelation, and the resins and filler are evenly mixed in the kneading process. Additionally, flowability is increased before the EMCs form a network structure in the molding process. The proposed kinetic model adequately describes curing behavior in EMCs cured with two different organophosphine catalysts up to the rubber state in the progress of curing.

  14. Zebra Alphaherpesviruses (EHV-1 and EHV-9: Genetic Diversity, Latency and Co-Infections

    Directory of Open Access Journals (Sweden)

    Azza Abdelgawad

    2016-09-01

    Full Text Available Alphaherpesviruses are highly prevalent in equine populations and co-infections with more than one of these viruses’ strains frequently diagnosed. Lytic replication and latency with subsequent reactivation, along with new episodes of disease, can be influenced by genetic diversity generated by spontaneous mutation and recombination. Latency enhances virus survival by providing an epidemiological strategy for long-term maintenance of divergent strains in animal populations. The alphaherpesviruses equine herpesvirus 1 (EHV-1 and 9 (EHV-9 have recently been shown to cross species barriers, including a recombinant EHV-1 observed in fatal infections of a polar bear and Asian rhinoceros. Little is known about the latency and genetic diversity of EHV-1 and EHV-9, especially among zoo and wild equids. Here, we report evidence of limited genetic diversity in EHV-9 in zebras, whereas there is substantial genetic variability in EHV-1. We demonstrate that zebras can be lytically and latently infected with both viruses concurrently. Such a co-occurrence of infection in zebras suggests that even relatively slow-evolving viruses such as equine herpesviruses have the potential to diversify rapidly by recombination. This has potential consequences for the diagnosis of these viruses and their management in wild and captive equid populations.

  15. Global mRNA degradation during lytic gammaherpesvirus infection contributes to establishment of viral latency.

    Directory of Open Access Journals (Sweden)

    Justin M Richner

    2011-07-01

    Full Text Available During a lytic gammaherpesvirus infection, host gene expression is severely restricted by the global degradation and altered 3' end processing of mRNA. This host shutoff phenotype is orchestrated by the viral SOX protein, yet its functional significance to the viral lifecycle has not been elucidated, in part due to the multifunctional nature of SOX. Using an unbiased mutagenesis screen of the murine gammaherpesvirus 68 (MHV68 SOX homolog, we isolated a single amino acid point mutant that is selectively defective in host shutoff activity. Incorporation of this mutation into MHV68 yielded a virus with significantly reduced capacity for mRNA turnover. Unexpectedly, the MHV68 mutant showed little defect during the acute replication phase in the mouse lung. Instead, the virus exhibited attenuation at later stages of in vivo infections suggestive of defects in both trafficking and latency establishment. Specifically, mice intranasally infected with the host shutoff mutant accumulated to lower levels at 10 days post infection in the lymph nodes, failed to develop splenomegaly, and exhibited reduced viral DNA levels and a lower frequency of latently infected splenocytes. Decreased latency establishment was also observed upon infection via the intraperitoneal route. These results highlight for the first time the importance of global mRNA degradation during a gammaherpesvirus infection and link an exclusively lytic phenomenon with downstream latency establishment.

  16. HIVed, a knowledgebase for differentially expressed human genes and proteins during HIV infection, replication and latency

    Science.gov (United States)

    Li, Chen; Ramarathinam, Sri H.; Revote, Jerico; Khoury, Georges; Song, Jiangning; Purcell, Anthony W.

    2017-01-01

    Measuring the altered gene expression level and identifying differentially expressed genes/proteins during HIV infection, replication and latency is fundamental for broadening our understanding of the mechanisms of HIV infection and T-cell dysfunction. Such studies are crucial for developing effective strategies for virus eradication from the body. Inspired by the availability and enrichment of gene expression data during HIV infection, replication and latency, in this study, we proposed a novel compendium termed HIVed (HIV expression database; http://hivlatency.erc.monash.edu/) that harbours comprehensive functional annotations of proteins, whose genes have been shown to be dysregulated during HIV infection, replication and latency using different experimental designs and measurements. We manually curated a variety of third-party databases for structural and functional annotations of the protein entries in HIVed. With the goal of benefiting HIV related research, we collected a number of biological annotations for all the entries in HIVed besides their expression profile, including basic protein information, Gene Ontology terms, secondary structure, HIV-1 interaction and pathway information. We hope this comprehensive protein-centric knowledgebase can bridge the gap between the understanding of differentially expressed genes and the functions of their protein products, facilitating the generation of novel hypotheses and treatment strategies to fight against the HIV pandemic. PMID:28358052

  17. Measurement-based analysis of error latency. [in computer operating system

    Science.gov (United States)

    Chillarege, Ram; Iyer, Ravishankar K.

    1987-01-01

    This paper demonstrates a practical methodology for the study of error latency under a real workload. The method is illustrated with sampled data on the physical memory activity, gathered by hardware instrumentation on a VAX 11/780 during the normal workload cycle of the installation. These data are used to simulate fault occurrence and to reconstruct the error discovery process in the system. The technique provides a means to study the system under different workloads and for multiple days. An approach to determine the percentage of undiscovered errors is also developed and a verification of the entire methodology is performed. This study finds that the mean error latency, in the memory containing the operating system, varies by a factor of 10 to 1 (in hours) between the low and high workloads. It is found that of all errors occurring within a day, 70 percent are detected in the same day, 82 percent within the following day, and 91 percent within the third day. The increase in failure rate due to latency is not so much a function of remaining errors but is dependent on whether or not there is a latent error.

  18. The Role of Sports in the Development of the Superego of the Male Latency Child.

    Science.gov (United States)

    Shopper, Moisy

    2014-01-01

    Psychoanalytic literature has often overlooked the child's participation in organized sports, which often can facilitate or impede not only expression of aggression and narcissism, but enhance or skew the growth of the child's superego and ego ideal. Specific outcomes are largely determined by the experience and knowledge of the parents, the coaches, and sports organizations for latency-aged youth. Sports participation facilitates a major step forward in psychic development, that is, an agreed-upon adherence to a set of rules and regulations, monitored by an official embodying the final word regarding rules and their infractions. This paper is an attempt to delineate the role of sports in the life of the latency child, the parents who become involved, the coaches who teach and supervise, and the social and individual milieu within which sports take place. All these contribute to common goals: the engendering of good sportsmanship and the encouragement of psychic growth, particularly regarding how aggression and narcissism contribute to the development of superego and ego ideals. The fate of aggression and narcissism in superego and ego ideal development is influenced to a large degree by the nature, orientation, and motivations of all involved in sports for the latency-aged.

  19. Mapping and correction of vascular hemodynamic latency in the BOLD signal.

    Science.gov (United States)

    Chang, Catie; Thomason, Moriah E; Glover, Gary H

    2008-10-15

    Correlation and causality metrics can be applied to blood-oxygen level-dependent (BOLD) signal time series in order to infer neural synchrony and directions of information flow from fMRI data. However, the BOLD signal reflects both the underlying neural activity and the vascular response, the latter of which is governed by local vasomotor physiology. The presence of potential vascular latency differences thus poses a confound in the detection of neural synchrony as well as inferences about the causality of neural processes. In the present study, we investigate the use of a breath holding (BH) task for characterizing and correcting for voxel-wise neurovascular latency differences across the whole brain. We demonstrate that BH yields reliable measurements of relative timing differences between voxels, and further show that a BH-derived latency correction can impact both functional connectivity maps of the resting-state default-mode network and activation maps of an event-related working memory (WM) task.

  20. Use of a latency-based demand assessment to identify potential demands for functional analyses.

    Science.gov (United States)

    Call, Nathan A; Miller, Sarah J; Mintz, Joslyn Cynkus; Mevers, Joanna Lomas; Scheithauer, Mindy C; Eshelman, Julie E; Beavers, Gracie A

    2016-12-01

    Unlike potential tangible positive reinforcers, which are typically identified for inclusion in functional analyses empirically using preference assessments, demands are most often selected arbitrarily or based on caregiver report. The present study evaluated the use of a demand assessment with 12 participants who exhibited escape-maintained problem behavior. Participants were exposed to 10 demands, with aversiveness measured by average latency to the first instance of problem behavior. In subsequent functional analyses, results of a demand condition that included the demand with the shortest latency to problem behavior resulted in identification of an escape function for 11 of the participants. In contrast, a demand condition that included the demand with the longest latency resulted in identification of an escape function for only 5 participants. The implication of these findings is that for the remaining 7 participants, selection of the demand for the functional analysis without using the results of the demand assessment could have produced a false-negative finding. © 2016 Society for the Experimental Analysis of Behavior.

  1. Low-Latency Teleoperations for Human Exploration and Evolvable Mars Campaign

    Science.gov (United States)

    Lupisella, Mark; Wright, Michael; Arney, Dale; Gershman, Bob; Stillwagen, Fred; Bobskill, Marianne; Johnson, James; Shyface, Hilary; Larman, Kevin; Lewis, Ruthan; Bleacher, Jake; Gernhardt, Mike; Mueller, Rob; Sanders, Gerald; Watts, Kevin; Eigenbrode, Jen; Garry, Brent; Freeh, Joshua; Manzella, David; Hack, Kurt; Aranyos, Tom

    2015-01-01

    NASA has been analyzing a number of mission concepts and activities that involve low-latency telerobotic (LLT) operations. One mission concept that will be covered in this presentation is Crew-Assisted Sample Return which involves the crew acquiring samples (1) that have already been delivered to space, and or acquiring samples via LLT from orbit to a planetary surface and then launching the samples to space to be captured in space and then returned to the earth with the crew. Both versions of have key roles for low-latency teleoperations. More broadly, the NASA Evolvable Mars Campaign is exploring a number of other activities that involve LLT, such as: (a) human asteroid missions, (b) PhobosDeimos missions, (c) Mars human landing site reconnaissance and site preparation, and (d) Mars sample handling and analysis. Many of these activities could be conducted from Mars orbit and also with the crew on the Mars surface remotely operating assets elsewhere on the surface, e.g. for exploring Mars special regions and or teleoperating a sample analysis laboratory both of which may help address planetary protection concerns. The operational and technology implications of low-latency teleoperations will be explored, including discussion of relevant items in the NASA Technology Roadmap and also how previously deployed robotic assets from any source could subsequently be used by astronauts via LLT.

  2. First low-latency LIGO+Virgo search for binary inspirals and their electromagnetic counterparts

    Science.gov (United States)

    Abadie, J.; Abbott, B. P.; Abbott, R.; Abbott, T. D.; Abernathy, M.; Accadia, T.; Acernese, F.; Adams, C.; Adhikari, R.; Affeldt, C.; Agathos, M.; Agatsuma, K.; Ajith, P.; Allen, B.; Amador Ceron, E.; Amariutei, D.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Arain, M. A.; Araya, M. C.; Aston, S. M.; Astone, P.; Atkinson, D.; Aufmuth, P.; Aulbert, C.; Aylott, B. E.; Babak, S.; Baker, P.; Ballardin, G.; Ballmer, S.; Barayoga, J. C. B.; Barker, D.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barton, M. A.; Bartos, I.; Bassiri, R.; Bastarrika, M.; Basti, A.; Batch, J.; Bauchrowitz, J.; Bauer, Th. S.; Bebronne, M.; Beck, D.; Behnke, B.; Bejger, M.; Beker, M. G.; Bell, A. S.; Belletoile, A.; Belopolski, I.; Benacquista, M.; Berliner, J. M.; Bertolini, A.; Betzwieser, J.; Beveridge, N.; Beyersdorf, P. T.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Biswas, R.; Bitossi, M.; Bizouard, M. A.; Black, E.; Blackburn, J. K.; Blackburn, L.; Blair, D.; Bland, B.; Blom, M.; Bock, O.; Bodiya, T. P.; Bogan, C.; Bondarescu, R.; Bondu, F.; Bonelli, L.; Bonnand, R.; Bork, R.; Born, M.; Boschi, V.; Bose, S.; Bosi, L.; Bouhou, B.; Braccini, S.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brau, J. E.; Breyer, J.; Briant, T.; Bridges, D. O.; Brillet, A.; Brinkmann, M.; Brisson, V.; Britzger, M.; Brooks, A. F.; Brown, D. A.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Burguet-Castell, J.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Calloni, E.; Camp, J. B.; Campsie, P.; Cannizzo, J.; Cannon, K.; Canuel, B.; Cao, J.; Capano, C. D.; Carbognani, F.; Carbone, L.; Caride, S.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C.; Cesarini, E.; Chaibi, O.; Chalermsongsak, T.; Charlton, P.; Chassande-Mottin, E.; Chelkowski, S.; Chen, W.; Chen, X.; Chen, Y.; Chincarini, A.; Chiummo, A.; Cho, H. S.; Chow, J.; Christensen, N.; Chua, S. S. Y.; Chung, C. T. Y.; Chung, S.; Ciani, G.; Clara, F.; Clark, D. E.; Clark, J.; Clayton, J. H.; Cleva, F.; Coccia, E.; Cohadon, P.-F.; Colacino, C. N.; Colas, J.; Colla, A.; Colombini, M.; Conte, A.; Conte, R.; Cook, D.; Corbitt, T. R.; Cordier, M.; Cornish, N.; Corsi, A.; Costa, C. A.; Coughlin, M.; Coulon, J.-P.; Couvares, P.; Coward, D. M.; Cowart, M.; Coyne, D. C.; Creighton, J. D. E.; Creighton, T. D.; Cruise, A. M.; Cumming, A.; Cunningham, L.; Cuoco, E.; Cutler, R. M.; Dahl, K.; Danilishin, S. L.; Dannenberg, R.; D'Antonio, S.; Danzmann, K.; Dattilo, V.; Daudert, B.; Daveloza, H.; Davier, M.; Daw, E. J.; Day, R.; Dayanga, T.; De Rosa, R.; DeBra, D.; Debreczeni, G.; Del Pozzo, W.; del Prete, M.; Dent, T.; Dergachev, V.; DeRosa, R.; DeSalvo, R.; Dhurandhar, S.; Di Fiore, L.; Di Lieto, A.; Di Palma, I.; Emilio, M. Di Paolo; Di Virgilio, A.; Díaz, M.; Dietz, A.; Donovan, F.; Dooley, K. L.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Dumas, J.-C.; Dwyer, S.; Eberle, T.; Edgar, M.; Edwards, M.; Effler, A.; Ehrens, P.; Endrőczi, G.; Engel, R.; Etzel, T.; Evans, K.; Evans, M.; Evans, T.; Factourovich, M.; Fafone, V.; Fairhurst, S.; Fan, Y.; Farr, B. F.; Fazi, D.; Fehrmann, H.; Feldbaum, D.; Feroz, F.; Ferrante, I.; Fidecaro, F.; Finn, L. S.; Fiori, I.; Fisher, R. P.; Flaminio, R.; Flanigan, M.; Foley, S.; Forsi, E.; Forte, L. A.; Fotopoulos, N.; Fournier, J.-D.; Franc, J.; Frasca, S.; Frasconi, F.; Frede, M.; Frei, M.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Friedrich, D.; Fritschel, P.; Frolov, V. V.; Fujimoto, M.-K.; Fulda, P. J.; Fyffe, M.; Gair, J.; Galimberti, M.; Gammaitoni, L.; Garcia, J.; Garufi, F.; Gáspár, M. E.; Gemme, G.; Geng, R.; Genin, E.; Gennai, A.; Gergely, L. Á.; Ghosh, S.; Giaime, J. A.; Giampanis, S.; Giardina, K. D.; Giazotto, A.; Gil-Casanova, S.; Gill, C.; Gleason, J.; Goetz, E.; Goggin, L. M.; González, G.; Gorodetsky, M. L.; Goßler, S.; Gouaty, R.; Graef, C.; Graff, P. B.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Gray, N.; Greenhalgh, R. J. S.; Gretarsson, A. M.; Greverie, C.; Grosso, R.; Grote, H.; Grunewald, S.; Guidi, G. M.; Guido, C.; Gupta, R.; Gustafson, E. K.; Gustafson, R.; Ha, T.; Hallam, J. M.; Hammer, D.; Hammond, G.; Hanks, J.; Hanna, C.; Hanson, J.; Harms, J.; Harry, G. M.; Harry, I. W.; Harstad, E. D.; Hartman, M. T.; Haughian, K.; Hayama, K.; Hayau, J.-F.; Heefner, J.; Heidmann, A.; Heintze, M. C.; Heitmann, H.; Hello, P.; Hendry, M. A.; Heng, I. S.; Heptonstall, A. W.; Herrera, V.; Hewitson, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Holt, K.; Holtrop, M.; Hong, T.; Hooper, S.; Hosken, D. J.; Hough, J.; Howell, E. J.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh-Dinh, T.; Ingram, D. R.; Inta, R.; Isogai, T.; Ivanov, A.; Izumi, K.; Jacobson, M.; James, E.; Jang, Y. J.; Jaranowski, P.; Jesse, E.; Johnson, W. W.; Jones, D. I.; Jones, G.; Jones, R.; Ju, L.; Kalmus, P.; Kalogera, V.; Kandhasamy, S.

    2012-05-01

    Aims: The detection and measurement of gravitational-waves from coalescing neutron-star binary systems is an important science goal for ground-based gravitational-wave detectors. In addition to emitting gravitational-waves at frequencies that span the most sensitive bands of the LIGO and Virgo detectors, these sources are also amongst the most likely to produce an electromagnetic counterpart to the gravitational-wave emission. A joint detection of the gravitational-wave and electromagnetic signals would provide a powerful new probe for astronomy. Methods: During the period between September 19 and October 20, 2010, the first low-latency search for gravitational-waves from binary inspirals in LIGO and Virgo data was conducted. The resulting triggers were sent to electromagnetic observatories for followup. We describe the generation and processing of the low-latency gravitational-wave triggers. The results of the electromagnetic image analysis will be described elsewhere. Results: Over the course of the science run, three gravitational-wave triggers passed all of the low-latency selection cuts. Of these, one was followed up by several of our observational partners. Analysis of the gravitational-wave data leads to an estimated false alarm rate of once every 6.4 days, falling far short of the requirement for a detection based solely on gravitational-wave data.

  3. Measurement-based analysis of error latency. [in computer operating system

    Science.gov (United States)

    Chillarege, Ram; Iyer, Ravishankar K.

    1987-01-01

    This paper demonstrates a practical methodology for the study of error latency under a real workload. The method is illustrated with sampled data on the physical memory activity, gathered by hardware instrumentation on a VAX 11/780 during the normal workload cycle of the installation. These data are used to simulate fault occurrence and to reconstruct the error discovery process in the system. The technique provides a means to study the system under different workloads and for multiple days. An approach to determine the percentage of undiscovered errors is also developed and a verification of the entire methodology is performed. This study finds that the mean error latency, in the memory containing the operating system, varies by a factor of 10 to 1 (in hours) between the low and high workloads. It is found that of all errors occurring within a day, 70 percent are detected in the same day, 82 percent within the following day, and 91 percent within the third day. The increase in failure rate due to latency is not so much a function of remaining errors but is dependent on whether or not there is a latent error.

  4. Understanding Factors That Modulate the Establishment of HIV Latency in Resting CD4+ T-Cells In Vitro.

    Directory of Open Access Journals (Sweden)

    Jenny L Anderson

    Full Text Available Developing robust in vitro models of HIV latency is needed to better understand how latency is established, maintained and reversed. In this study, we examined the effects of donor variability, HIV titre and co-receptor usage on establishing HIV latency in vitro using two models of HIV latency. Using the CCL19 model of HIV latency, we found that in up to 50% of donors, CCL19 enhanced latent infection of resting CD4+ T-cells by CXCR4-tropic HIV in the presence of low dose IL-2. Increasing the infectious titre of CXCR4-tropic HIV increased both productive and latent infection of resting CD4+ T-cells. In a different model where myeloid dendritic cells (mDC were co-cultured with resting CD4+ T-cells, we observed a higher frequency of latently infected cells in vitro than CCL19-treated or unstimulated CD4+ T-cells in the presence of low dose IL-2. In the DC-T-cell model, latency was established with both CCR5- and CXCR4-tropic virus but higher titres of CCR5-tropic virus was required in most donors. The establishment of latency in vitro through direct infection of resting CD4+ T-cells is significantly enhanced by CCL19 and mDC, but the efficiency is dependent on virus titre, co-receptor usage and there is significant donor variability.

  5. Evaluation of the relation between triceps surae H-reflex, M-response latencies and thigh length in normal population

    Directory of Open Access Journals (Sweden)

    Saeid Khosrawi

    2013-01-01

    Full Text Available Background: The H-reflex is a useful electrophysiological procedure for evaluating the status of the peripheral nervous system, especially at the proximal segment of the peripheral nerve. The purpose of this study is to investigate the relation between triceps surae H-reflex and M- response latencies and thigh length in normal population, in order to determine if there is any regression equation between them. Materials and Methods: After screening 75 volunteers by considering inclusion and exclusion criteria, 72 of them were selected to enroll into our study (34 men and 38 women with the mean age of 36.04 ± 7.7 years. In all of the subjects H-reflex and M-response latencies were recorded by standard electrophysiological techniques and thigh length was measured. Finally, our data was analyzed for its relations with respect to ages in both sexes by appropriate statistical and mathematical methods. Results: Mean ± SD for H-reflex latency was 27.94 ± 1.6 ms. We found a significant correlation between H-reflex latency and M-latency (r = 0.28, no significant correlation was found between H-reflex latency and thigh length (r = -0.051. Finally based on our findings we introduce a new formula in this paper.Conclusion: We found a significant correlation among of M-response latency and other variables (H-reflex latency and thigh length. Despite this it was eliminated from our formula. The relationship between H-reflex latency and age was significant. Further studies are required to delineate the clinical usage and interpretation of the formula, which we found in this study.

  6. [Decrease in N170 evoked potential component latency during repeated presentation of face images].

    Science.gov (United States)

    Verkhliutov, V M; Ushakov, V L; Strelets, V B

    2009-01-01

    The 15 healthy volunteers EEG from 28 channels was recorded during the presentation of visual stimuli in the form of face and building images. The stimuli were presented in two series. The first series consisted of 60 face and 60 building images presented in random order. The second series consisted of 30 face and 30 building images. The second series began 1.5-2 min after the end of the first ore. No instruction was given to the participants. P1, N170 and VPP EP components were identified for both stimuli categories. These components were located in the medial parietal area (Brodmann area 40). P1 and N170 components were recorded in the superior temporal fissure (Brodmann area 21, STS region), the first component had the latency 120 ms, the second one--155 ms. VPP was recorded with the latency 190 ms (Brodmann area 19). Dynamic mapping of EP components with the latency from 97 to 242 ms revealed the removal of positive maximums from occipital to frontal areas through temporal ones and their subsequent returning to occipital areas through the central ones. During the comparison of EP components to face and building images the amplitude differences were revealed in the following areas: P1--in frontal, central and anterior temporal areas, N170--in frontal, central, temporal and parietal areas, VPP--in all areas. It was also revealed that N170 latency was 12 ms shorter for face than for building images. It was proposed that the above mentioned N170 latency decrease for face in comparison with building images is connected with the different space location of the fusiform area responsible for face and building images recognition. Priming--the effect that is revealed during the repetitive face images presentation is interpreted as the manifestation of functional heterogeneity of the fusiform area responsible for the face images recognition. The hypothesis is put forward that the parts of extrastriate cortex which are located closer to the central retinotopical

  7. A hundred years of latency: from Freudian psychosexual theory to dynamic systems nonlinear development in middle childhood.

    Science.gov (United States)

    Knight, Rona

    2014-04-01

    A focus on the latency phase is used to illustrate how theory and developmental research have influenced our psychoanalytic views of development over the past hundred years. Beginning with Freud's psychosexual theory and his conception of latency, an historical overview of the major psychoanalytic contributions bearing on this developmental period over the past century is presented. Recent longitudinal research in latency supports a nonlinear dynamic systems approach to development. This approach obliges us to reconsider our linear theories and how we think about and work with our patients.

  8. An In-Depth Comparison of Latency-Reversing Agent Combinations in Various In Vitro and Ex Vivo HIV-1 Latency Models Identified Bryostatin-1+JQ1 and Ingenol-B+JQ1 to Potently Reactivate Viral Gene Expression.

    Science.gov (United States)

    Darcis, Gilles; Kula, Anna; Bouchat, Sophie; Fujinaga, Koh; Corazza, Francis; Ait-Ammar, Amina; Delacourt, Nadège; Melard, Adeline; Kabeya, Kabamba; Vanhulle, Caroline; Van Driessche, Benoit; Gatot, Jean-Stéphane; Cherrier, Thomas; Pianowski, Luiz F; Gama, Lucio; Schwartz, Christian; Vila, Jorge; Burny, Arsène; Clumeck, Nathan; Moutschen, Michel; De Wit, Stéphane; Peterlin, B Matija; Rouzioux, Christine; Rohr, Olivier; Van Lint, Carine

    2015-07-01

    The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART) is a major hurdle to HIV-1 eradication. Strategies to purge these reservoirs are needed and activation of viral gene expression in latently infected cells is one promising strategy. Bromodomain and Extraterminal (BET) bromodomain inhibitors (BETi) are compounds able to reactivate latent proviruses in a positive transcription elongation factor b (P-TEFb)-dependent manner. In this study, we tested the reactivation potential of protein kinase C (PKC) agonists (prostratin, bryostatin-1 and ingenol-B), which are known to activate NF-κB signaling pathway as well as P-TEFb, used alone or in combination with P-TEFb-releasing agents (HMBA and BETi (JQ1, I-BET, I-BET151)). Using in vitro HIV-1 post-integration latency model cell lines of T-lymphoid and myeloid lineages, we demonstrated that PKC agonists and P-TEFb-releasing agents alone acted as potent latency-reversing agents (LRAs) and that their combinations led to synergistic activation of HIV-1 expression at the viral mRNA and protein levels. Mechanistically, combined treatments led to higher activations of P-TEFb and NF-κB than the corresponding individual drug treatments. Importantly, we observed in ex vivo cultures of CD8+-depleted PBMCs from 35 cART-treated HIV-1+ aviremic patients that the percentage of reactivated cultures following combinatory bryostatin-1+JQ1 treatment was identical to the percentage observed with anti-CD3+anti-CD28 antibodies positive control stimulation. Remarkably, in ex vivo cultures of resting CD4+ T cells isolated from 15 HIV-1+ cART-treated aviremic patients, the combinations bryostatin-1+JQ1 and ingenol-B+JQ1 released infectious viruses to levels similar to that obtained with the positive control stimulation. The potent effects of these two combination treatments were already detected 24 hours post-stimulation. These results constitute the first demonstration of LRA combinations

  9. An In-Depth Comparison of Latency-Reversing Agent Combinations in Various In Vitro and Ex Vivo HIV-1 Latency Models Identified Bryostatin-1+JQ1 and Ingenol-B+JQ1 to Potently Reactivate Viral Gene Expression.

    Directory of Open Access Journals (Sweden)

    Gilles Darcis

    2015-07-01

    Full Text Available The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART is a major hurdle to HIV-1 eradication. Strategies to purge these reservoirs are needed and activation of viral gene expression in latently infected cells is one promising strategy. Bromodomain and Extraterminal (BET bromodomain inhibitors (BETi are compounds able to reactivate latent proviruses in a positive transcription elongation factor b (P-TEFb-dependent manner. In this study, we tested the reactivation potential of protein kinase C (PKC agonists (prostratin, bryostatin-1 and ingenol-B, which are known to activate NF-κB signaling pathway as well as P-TEFb, used alone or in combination with P-TEFb-releasing agents (HMBA and BETi (JQ1, I-BET, I-BET151. Using in vitro HIV-1 post-integration latency model cell lines of T-lymphoid and myeloid lineages, we demonstrated that PKC agonists and P-TEFb-releasing agents alone acted as potent latency-reversing agents (LRAs and that their combinations led to synergistic activation of HIV-1 expression at the viral mRNA and protein levels. Mechanistically, combined treatments led to higher activations of P-TEFb and NF-κB than the corresponding individual drug treatments. Importantly, we observed in ex vivo cultures of CD8+-depleted PBMCs from 35 cART-treated HIV-1+ aviremic patients that the percentage of reactivated cultures following combinatory bryostatin-1+JQ1 treatment was identical to the percentage observed with anti-CD3+anti-CD28 antibodies positive control stimulation. Remarkably, in ex vivo cultures of resting CD4+ T cells isolated from 15 HIV-1+ cART-treated aviremic patients, the combinations bryostatin-1+JQ1 and ingenol-B+JQ1 released infectious viruses to levels similar to that obtained with the positive control stimulation. The potent effects of these two combination treatments were already detected 24 hours post-stimulation. These results constitute the first demonstration of LRA

  10. Injury of mitochondria and the expressions of fas and bax mRNA in the hip-pus of epileptic rats of different latency

    Institute of Scientific and Technical Information of China (English)

    Shuhai Tang; Jianying Sun; Xiaojun Pan; Li Zhang

    2006-01-01

    BACKGROUND: It has been confirmed that Fas and Bax respectively mediate the exogenous and endogenous pathways of neuronal apoptosis, and then mediate the neuronal injury after status epilepticus.OBJECTIVE: To comparatively observe the injury of mitochondrial ultrastructure and the expressions of fas and bax in hippocampal tissue of rats with status epilepticus of different latency.DESIGN: A randomized control study.SETTING: Department of Anesthesiology and Department of Neurology, Qilu Hospital of Shandong University.MATERIALS: Totally 110 male adult SD rats of 260-300 g were used. Kainic acid was purchased from American Sigma Company.METHODS: The experiment was carried out in the Pathological Laboratory of Shandong Academy of Medical Sciences between March and July 2005.① Totally 100 SD rats were divided into two groups according to the random number table method:intraperitoneal injection group and caudal venous injection group.The rats were given kainic acid injected intraperitoneally(12 mg/kg)and through caudal vein (10 mg/kg) respectively. Each group was observed at 3, 6, 24, 48 and 72 hours after status epilepticus respectively.Ten rats were selected for each time point, including 2 for examination of electron microscope and 8 for the diction of the fas and bax mRNA expressions. The time and manifestations of seizure were observed, and the seizure was lasted for 2 hours, and then it was terminated by intraperitoneal injection of diazepam (10 mg/kg). Another 10 rats were used as the normal control group, and the materials were taken at 24 hours after status epilepticus, 2 of rats for the examination of electron microscope and 8 of them for the reverse transcription-polymerase chain reaction (RT-PCR). ② The ultrastructure of hippocampal neurons and its mitochondria were observed with transmission electron microscope. ③ The fas and bax mRNA expressions were detected with reverse transcription-polymerase chain reaction (RT-PCR).MAIN OUTCOME MEASURES: The

  11. A Comparison Between House Mouse Lines Selected for Attack Latency or Nest-Building : Evidence for a Genetic Basis of Alternative Behavioral Strategies

    NARCIS (Netherlands)

    Sluyter, Frans; Bult, Abel; Lynch, Carol B.; Oortmerssen, Geert A. van; Koolhaas, Jaap M.

    1995-01-01

    House mouse lines bidirectionally selected for either nest-building behavior or attack latency were tested for both attack latency and nest-building behavior under identical conditions. Male mice selected for high nest-building behavior had shorter attack latencies, i.e., were more aggressive, than

  12. Fast, multi-channel real-time processing of signals with microsecond latency using graphics processing units.

    Science.gov (United States)

    Rath, N; Kato, S; Levesque, J P; Mauel, M E; Navratil, G A; Peng, Q

    2014-04-01

    Fast, digital signal processing (DSP) has many applications. Typical hardware options for performing DSP are field-programmable gate arrays (FPGAs), application-specific integrated DSP chips, or general purpose personal computer systems. This paper presents a novel DSP platform that has been developed for feedback control on the HBT-EP tokamak device. The system runs all signal processing exclusively on a Graphics Processing Unit (GPU) to achieve real-time performance with latencies below 8 μs. Signals are transferred into and out of the GPU using PCI Express peer-to-peer direct-memory-access transfers without involvement of the central processing unit or host memory. Tests were performed on the feedback control system of the HBT-EP tokamak using forty 16-bit floating point inputs and outputs each and a sampling rate of up to 250 kHz. Signals were digitized by a D-TACQ ACQ196 module, processing done on an NVIDIA GTX 580 GPU programmed in CUDA, and analog output was generated by D-TACQ AO32CPCI modules.

  13. Fast, multi-channel real-time processing of signals with microsecond latency using graphics processing units

    Science.gov (United States)

    Rath, N.; Kato, S.; Levesque, J. P.; Mauel, M. E.; Navratil, G. A.; Peng, Q.

    2014-04-01

    Fast, digital signal processing (DSP) has many applications. Typical hardware options for performing DSP are field-programmable gate arrays (FPGAs), application-specific integrated DSP chips, or general purpose personal computer systems. This paper presents a novel DSP platform that has been developed for feedback control on the HBT-EP tokamak device. The system runs all signal processing exclusively on a Graphics Processing Unit (GPU) to achieve real-time performance with latencies below 8 μs. Signals are transferred into and out of the GPU using PCI Express peer-to-peer direct-memory-access transfers without involvement of the central processing unit or host memory. Tests were performed on the feedback control system of the HBT-EP tokamak using forty 16-bit floating point inputs and outputs each and a sampling rate of up to 250 kHz. Signals were digitized by a D-TACQ ACQ196 module, processing done on an NVIDIA GTX 580 GPU programmed in CUDA, and analog output was generated by D-TACQ AO32CPCI modules.

  14. Decreased reactivation of a herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) mutant using the in vivo mouse UV-B model of induced reactivation.

    Science.gov (United States)

    BenMohamed, Lbachir; Osorio, Nelson; Srivastava, Ruchi; Khan, Arif A; Simpson, Jennifer L; Wechsler, Steven L

    2015-10-01

    Blinding ocular herpetic disease in humans is due to herpes simplex virus type 1 (HSV-1) reactivations from latency, rather than to primary acute infection. The cellular and molecular immune mechanisms that control the HSV-1 latency-reactivation cycle remain to be fully elucidated. The aim of this study was to determine if reactivation of the HSV-1 latency-associated transcript (LAT) deletion mutant (dLAT2903) was impaired in this model, as it is in the rabbit model of induced and spontaneous reactivation and in the trigeminal ganglia (TG) explant-induced reactivation model in mice. The eyes of mice latently infected with wild-type HSV-1 strain McKrae (LAT((+)) virus) or dLAT2903 (LAT((-)) virus) were irradiated with UV-B, and reactivation was determined. We found that compared to LAT((-)) virus, LAT((+)) virus reactivated at a higher rate as determined by shedding of virus in tears on days 3 to 7 after UV-B treatment. Thus, the UV-B-induced reactivation mouse model of HSV-1 appears to be a useful small animal model for studying the mechanisms involved in how LAT enhances the HSV-1 reactivation phenotype. The utility of the model for investigating the immune evasion mechanisms regulating the HSV-1 latency/reactivation cycle and for testing the protective efficacy of candidate therapeutic vaccines and drugs is discussed.

  15. Residue iteration decomposition (RIDE): A new method to separate ERP components on the basis of latency variability in single trials.

    Science.gov (United States)

    Ouyang, Guang; Herzmann, Grit; Zhou, Changsong; Sommer, Werner

    2011-12-01

    Event-related brain potentials (ERPs) are important research tools because they provide insights into mental processing at high temporal resolution. Their usefulness, however, is limited by the need to average over a large number of trials, sacrificing information about the trial-by-trial variability of latencies or amplitudes of specific ERP components. Here we propose a novel method based on an iteration strategy of the residues of averaged ERPs (RIDE) to separate latency-variable component clusters. The separated component clusters can then serve as templates to estimate latencies in single trials with high precision. By applying RIDE to data from a face-priming experiment, we separate priming effects and show that they are robust against latency shifts and within-condition variability. RIDE is useful for a variety of data sets that show different degrees of variability and temporal overlap between ERP components.

  16. Effect of magnesium sulfate administration for neuroprotection on latency in women with preterm premature rupture of membranes.

    LENUS (Irish Health Repository)

    Horton, Amanda L

    2015-03-01

    This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 31(6\\/7) weeks\\' gestation.

  17. Outcomes of a NASA Workshop to Develop a Portfolio of Low Latency Datasets for Time-Sensitive Applications

    Science.gov (United States)

    Davies, Diane K.; Brown, Molly E.; Green, David S.; Michael, Karen A.; Murray, John J