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Sample records for latency requires pim-1

  1. Kinase Control of Latent HIV-1 Infection: PIM-1 Kinase as a Major Contributor to HIV-1 Reactivation

    PubMed Central

    Duverger, Alexandra; Wolschendorf, Frank; Anderson, Joshua C.; Wagner, Frederic; Bosque, Alberto; Shishido, Takao; Jones, Jennifer; Planelles, Vicente; Willey, Christopher; Cron, Randall Q.

    2014-01-01

    Despite the clinical relevance of latent HIV-1 infection as a block to HIV-1 eradication, the molecular biology of HIV-1 latency remains incompletely understood. We recently demonstrated the presence of a gatekeeper kinase function that controls latent HIV-1 infection. Using kinase array analysis, we here expand on this finding and demonstrate that the kinase activity profile of latently HIV-1-infected T cells is altered relative to that of uninfected T cells. A ranking of altered kinases generated from these kinome profile data predicted PIM-1 kinase as a key switch involved in HIV-1 latency control. Using genetic and pharmacologic perturbation strategies, we demonstrate that PIM-1 activity is indeed required for HIV-1 reactivation in T cell lines and primary CD4 T cells. The presented results thus confirm that kinases are key contributors to HIV-1 latency control. In addition, through mutational studies we link the inhibitory effect of PIM-1 inhibitor IV (PIMi IV) on HIV-1 reactivation to an AP-1 motif in the CD28-responsive element of the HIV-1 long terminal repeat (LTR). The results expand our conceptual understanding of the dynamic interactions of the host cell and the latent HIV-1 integration event and position kinome profiling as a research tool to reveal novel molecular mechanisms that can eventually be targeted to therapeutically trigger HIV-1 reactivation. PMID:24155393

  2. Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation.

    PubMed

    Duverger, Alexandra; Wolschendorf, Frank; Anderson, Joshua C; Wagner, Frederic; Bosque, Alberto; Shishido, Takao; Jones, Jennifer; Planelles, Vicente; Willey, Christopher; Cron, Randall Q; Kutsch, Olaf

    2014-01-01

    Despite the clinical relevance of latent HIV-1 infection as a block to HIV-1 eradication, the molecular biology of HIV-1 latency remains incompletely understood. We recently demonstrated the presence of a gatekeeper kinase function that controls latent HIV-1 infection. Using kinase array analysis, we here expand on this finding and demonstrate that the kinase activity profile of latently HIV-1-infected T cells is altered relative to that of uninfected T cells. A ranking of altered kinases generated from these kinome profile data predicted PIM-1 kinase as a key switch involved in HIV-1 latency control. Using genetic and pharmacologic perturbation strategies, we demonstrate that PIM-1 activity is indeed required for HIV-1 reactivation in T cell lines and primary CD4 T cells. The presented results thus confirm that kinases are key contributors to HIV-1 latency control. In addition, through mutational studies we link the inhibitory effect of PIM-1 inhibitor IV (PIMi IV) on HIV-1 reactivation to an AP-1 motif in the CD28-responsive element of the HIV-1 long terminal repeat (LTR). The results expand our conceptual understanding of the dynamic interactions of the host cell and the latent HIV-1 integration event and position kinome profiling as a research tool to reveal novel molecular mechanisms that can eventually be targeted to therapeutically trigger HIV-1 reactivation. PMID:24155393

  3. Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload

    PubMed Central

    Muraski, John A.; Fischer, Kimberlee M.; Wu, Weitao; Cottage, Christopher T.; Quijada, Pearl; Mason, Matt; Din, Shabana; Gude, Natalie; Alvarez, Roberto; Rota, Marcello; Kajstura, Jan; Wang, Zeping; Schaefer, Erik; Chen, Xiongen; MacDonnel, Scott; Magnuson, Nancy; Houser, Stephen R.; Anversa, Piero; Sussman, Mark A.

    2008-01-01

    Pim-1 kinase exerts potent cardioprotective effects in the myocardium downstream of AKT, but the participation of Pim-1 in cardiac hypertrophy requires investigation. Cardiac-specific expression of Pim-1 (Pim-WT) or the dominant-negative mutant of Pim-1 (Pim-DN) in transgenic mice together with adenoviral-mediated overexpression of these Pim-1 constructs was used to delineate the role of Pim-1 in hypertrophy. Transgenic overexpression of Pim-1 protects mice from pressure-overload-induced hypertrophy relative to wild-type controls as evidenced by improved hemodynamic function, decreased apoptosis, increases in antihypertrophic proteins, smaller myocyte size, and inhibition of hypertrophic signaling after challenge. Similarly, Pim-1 overexpression in neonatal rat cardiomyocyte cultures inhibits hypertrophy induced by endothelin-1. On the cellular level, hearts of Pim-WT mice show enhanced incorporation of BrdU into myocytes and a hypercellular phenotype compared to wild-type controls after hypertrophic challenge. In comparison, transgenic overexpression of Pim-DN leads to dilated cardiomyopathy characterized by increased apoptosis, fibrosis, and severely depressed cardiac function. Furthermore, overexpression of Pim-DN leads to reduced contractility as evidenced by reduced Ca2+ transient amplitude and decreased percentage of cell shortening in isolated myocytes. These data support a pivotal role for Pim-1 in modulation of hypertrophy by impacting responses on molecular, cellular, and organ levels. PMID:18784362

  4. Pim-1 kinase as cancer drug target: An update

    PubMed Central

    TURSYNBAY, YERNAR; ZHANG, JINFU; LI, ZHI; TOKAY, TURSONJAN; ZHUMADILOV, ZHAXYBAY; WU, DENGLONG; XIE, YINGQIU

    2016-01-01

    Proviral integration site for Moloney murine leukemia virus-1 (Pim-1) is a serine/threonine kinase that regulates multiple cellular functions such as cell cycle, cell survival, drug resistance. Aberrant elevation of Pim-1 kinase is associated with numerous types of cancer. Two distinct isoforms of Pim-1 (Pim-1S and Pim-1L) show distinct cellular functions. Pim-1S predominately localizes to the nucleus and Pim-1L localizes to plasma membrane for drug resistance. Recent studies show that mitochondrial Pim-1 maintains mitochondrial integrity. Pim-1 is emerging as a cancer drug target, particularly in prostate cancer. Recently the potent new functions of Pim-1 in immunotherapy, senescence bypass, metastasis and epigenetic dynamics have been found. The aim of the present updated review is to provide brief information regarding networks of Pim-1 kinase and focus on its recent advances as a novel drug target. PMID:26893828

  5. Functional Effect of Pim1 Depends upon Intracellular Localization in Human Cardiac Progenitor Cells.

    PubMed

    Samse, Kaitlen; Emathinger, Jacqueline; Hariharan, Nirmala; Quijada, Pearl; Ilves, Kelli; Völkers, Mirko; Ormachea, Lucia; De La Torre, Andrea; Orogo, Amabel M; Alvarez, Roberto; Din, Shabana; Mohsin, Sadia; Monsanto, Megan; Fischer, Kimberlee M; Dembitsky, Walter P; Gustafsson, Åsa B; Sussman, Mark A

    2015-05-29

    Human cardiac progenitor cells (hCPC) improve heart function after autologous transfer in heart failure patients. Regenerative potential of hCPCs is severely limited with age, requiring genetic modification to enhance therapeutic potential. A legacy of work from our laboratory with Pim1 kinase reveals effects on proliferation, survival, metabolism, and rejuvenation of hCPCs in vitro and in vivo. We demonstrate that subcellular targeting of Pim1 bolsters the distinct cardioprotective effects of this kinase in hCPCs to increase proliferation and survival, and antagonize cellular senescence. Adult hCPCs isolated from patients undergoing left ventricular assist device implantation were engineered to overexpress Pim1 throughout the cell (PimWT) or targeted to either mitochondrial (Mito-Pim1) or nuclear (Nuc-Pim1) compartments. Nuc-Pim1 enhances stem cell youthfulness associated with decreased senescence-associated β-galactosidase activity, preserved telomere length, reduced expression of p16 and p53, and up-regulation of nucleostemin relative to PimWT hCPCs. Alternately, Mito-Pim1 enhances survival by increasing expression of Bcl-2 and Bcl-XL and decreasing cell death after H2O2 treatment, thereby preserving mitochondrial integrity superior to PimWT. Mito-Pim1 increases the proliferation rate by up-regulation of cell cycle modulators Cyclin D, CDK4, and phospho-Rb. Optimal stem cell traits such as proliferation, survival, and increased youthful properties of aged hCPCs are enhanced after targeted Pim1 localization to mitochondrial or nuclear compartments. Targeted Pim1 overexpression in hCPCs allows for selection of the desired phenotypic properties to overcome patient variability and improve specific stem cell characteristics. PMID:25882843

  6. Functional Effect of Pim1 Depends upon Intracellular Localization in Human Cardiac Progenitor Cells

    PubMed Central

    Samse, Kaitlen; Emathinger, Jacqueline; Hariharan, Nirmala; Quijada, Pearl; Ilves, Kelli; Völkers, Mirko; Ormachea, Lucia; De La Torre, Andrea; Orogo, Amabel M.; Alvarez, Roberto; Din, Shabana; Mohsin, Sadia; Monsanto, Megan; Fischer, Kimberlee M.; Dembitsky, Walter P.; Gustafsson, Åsa B.; Sussman, Mark A.

    2015-01-01

    Human cardiac progenitor cells (hCPC) improve heart function after autologous transfer in heart failure patients. Regenerative potential of hCPCs is severely limited with age, requiring genetic modification to enhance therapeutic potential. A legacy of work from our laboratory with Pim1 kinase reveals effects on proliferation, survival, metabolism, and rejuvenation of hCPCs in vitro and in vivo. We demonstrate that subcellular targeting of Pim1 bolsters the distinct cardioprotective effects of this kinase in hCPCs to increase proliferation and survival, and antagonize cellular senescence. Adult hCPCs isolated from patients undergoing left ventricular assist device implantation were engineered to overexpress Pim1 throughout the cell (PimWT) or targeted to either mitochondrial (Mito-Pim1) or nuclear (Nuc-Pim1) compartments. Nuc-Pim1 enhances stem cell youthfulness associated with decreased senescence-associated β-galactosidase activity, preserved telomere length, reduced expression of p16 and p53, and up-regulation of nucleostemin relative to PimWT hCPCs. Alternately, Mito-Pim1 enhances survival by increasing expression of Bcl-2 and Bcl-XL and decreasing cell death after H2O2 treatment, thereby preserving mitochondrial integrity superior to PimWT. Mito-Pim1 increases the proliferation rate by up-regulation of cell cycle modulators Cyclin D, CDK4, and phospho-Rb. Optimal stem cell traits such as proliferation, survival, and increased youthful properties of aged hCPCs are enhanced after targeted Pim1 localization to mitochondrial or nuclear compartments. Targeted Pim1 overexpression in hCPCs allows for selection of the desired phenotypic properties to overcome patient variability and improve specific stem cell characteristics. PMID:25882843

  7. KSHV encoded LANA upregulates Pim-1 and is a substrate for its kinase activity

    SciTech Connect

    Bajaj, Bharat G.; Verma, Subhash C.; Lan, Ke; Cotter, Murray A.; Woodman, Zenda L.; Robertson, Erle S. . E-mail: erle@mail.med.upenn.edu

    2006-07-20

    Pim kinases are proto-oncogenes that are upregulated in a number of B cell cancers, including Epstein-Barr Virus (EBV) associated Burkitt's lymphoma. They have also been shown to be upregulated in Kaposi sarcoma-associated herpes virus (KSHV) infected primary B cells. Most cells in KSHV-associated tumors are latently infected and express only a small subset of viral genes, with KSHV latency associated nuclear antigen (LANA) being constitutively expressed. LANA regulates the transcription of a large number of cellular and viral genes. Here, we show that LANA upregulates transcription from the Pim-1 promoter (pPim-1) and map this activation to a region in the promoter located within the sequence (-681 to +37). We show that LANA expressing cells can proliferate faster and are better protected from drug induced apoptosis. Since transition through cell cycle check points and anti-apoptosis are functions associated with Pim-1, it is likely that higher Pim-1 expression in cells expressing LANA is responsible, at least in part, for this effect. A Pim-1 phosphorylation site was also identified within the amino-terminal domain of LANA. Using in vitro kinase assays, we confirmed that LANA was indeed a Pim-1 substrate, and the failure of Pim-1 to phosphorylate LANA mutated at SS205/6RR identified this site as the specific serine residues phosphorylated by Pim-1. This report provides valuable insight into yet another cellular signaling pathway subverted by KSHV LANA and suggests a contribution to KSHV related oncogenesis.

  8. Pim-1 kinase expression during murine mammary development

    SciTech Connect

    Gapter, Leslie A.; Magnuson, Nancy S.; Ng, Ka-yun; Hosick, Howard L. . E-mail: hosick@wsu.edu

    2006-07-07

    Pim-1 kinase phosphorylates substrates whose activities are linked to proliferation, survival, differentiation, and apoptosis. Although pim-1 is induced by hormones and cytokines, the hormonal control and contribution of Pim-1 to mammary gland development have not been evaluated. We examined Pim-1 expression in mammary cell lines, investigated whether Pim-1 levels could be altered in breast epithelia by mammogenic hormones, and evaluated Pim-1 expression during mammary development. We found that Pim-1 was elevated in most mammary carcinoma cell lines and progesterone increased Pim-1 protein to some extent in non-tumorigenic mammary epithelia. Pim-1 expression in situ was consistent with the documented profile of progesterone activity in mouse mammary glands. Pim-1 nuclear localization correlated with cytoplasmic distribution for its substrate, p21{sup CIP/Waf1}, and we found that Pim-1 and p21 associate in vitro. Our results suggest that Pim-1 expression may be regulated by progesterone during mammary development and Pim-1 associates with p21 in mammary epithelial cells.

  9. PIM1 polymorphism and PIM1 expression as predisposing factors of esophageal squamous cell carcinoma in the Asian population

    PubMed Central

    Wu, Yuan-Bo; Lu, Di; He, Zhi-Feng; Jin, Chan-Guan

    2016-01-01

    Our study aimed to identify the association between a PIM1 polymorphism and PIM1 expression levels with clinicopathological features of esophageal squamous cell carcinoma (ESCC). A total of 168 patients with ESCC were recruited as the case group, and 180 healthy individuals were included as the control group. Polymerase chain reaction-direct sequencing was employed to analyze all genotypes containing the PIM1 −1 882 A>T mutation. Immunohistochemistry was used to detect PIM1 expression. The distributions of genotype AA and allele A of PIM1 −1 882 A>T were higher in the case group than in the control group (both P<0.05). AT + TT carriers had a lower risk of ESCC than AA carriers (P<0.05). PIM1 polymorphism was related to the invasion depth, degree of differentiation, and lymphatic metastasis of ESCC (P<0.05). PIM1 expression was associated with lymphatic metastasis of ESCC and PIM1 polymorphism (both P<0.05). PIM1 −1 882 A>T and the overexpression of PIM1 were associated with the clinicopathological features of ESCC, and PIM1 −1 882 A>T may help to reduce the risk of ESCC in the Asian population. PMID:27274285

  10. Pim-1 Kinase Protects Mitochondrial Integrity in Cardiomyocytes

    PubMed Central

    Borillo, Gwynngelle A.; Mason, Matt; Quijada, Pearl; Völkers, Mirko; Cottage, Christopher; McGregor, Michael; Din, Shabana; Fischer, Kimberlee; Gude, Natalie; Avitable, Daniele; Barlow, Steven; Gustafsson, Asa B.; Glembotski, Christopher; Gottlieb, Roberta A.; Brown, Joan Heller; Sussman, Mark A.

    2010-01-01

    Rationale Cardioprotective signaling mediates anti-apoptotic actions through multiple mechanisms including maintenance of mitochondrial integrity. Pim-1 kinase is an essential downstream effector of AKT-mediated cardioprotection but the mechanistic basis for maintenance of mitochondrial integrity by Pim-1 remains unexplored. This study details anti-apoptotic actions responsible for enhanced cell survival in cardiomyocytes with elevated Pim-1 activity. Objective The purpose of this study is to demonstrate that the cardioprotective kinase Pim-1 acts to inhibit cell death by preserving mitochondrial integrity in cardiomyocytes. Methods and Results A combination of biochemical, molecular, and microscopic analyses demonstrate beneficial effects of Pim-1 upon mitochondrial integrity. Pim-1 protein level increases in the mitochondrial fraction with a corresponding decrease in the cytosolic fraction of myocardial lysates from hearts subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Cardiac-specific overexpression of Pim-1 results in higher levels of anti-apoptotic Bcl-XL and Bcl-2 compared to samples from normal hearts. In response to oxidative stress challenge Pim-1 preserves the inner mitochondrial membrane potential (ΔΨm). Ultrastructure of the mitochondria is maintained by Pim-1 activity, which prevents swelling induced by calcium overload. Finally, mitochondria isolated from hearts created with cardiac-specific overexpression of Pim-1 show inhibition of cytochrome c release triggered by a truncated form of pro-apoptotic Bid. Conclusion Cardioprotective action of Pim-1 kinase includes preservation of mitochondrial integrity during cardiomyopathic challenge conditions, thereby raising the potential for Pim-1 kinase activation as a therapeutic interventional approach to inhibit cell death by antagonizing pro-apoptotic Bcl-2 family members that regulate the intrinsic apoptotic pathway. PMID:20203306

  11. Human CD180 Transmits Signals via the PIM-1L Kinase

    PubMed Central

    Egli, Nicole; Zajonz, Alexandra; Burger, Matthew T.; Schweighoffer, Tamas

    2015-01-01

    Toll-like receptors (TLRs) are important sensors of the innate immune system that recognize conserved structural motifs and activate cells via a downstream signaling cascade. The CD180/MD1 molecular complex is an unusual member of the TLR family, since it lacks the components that are normally required for signal transduction by other TLRs. Therefore the CD180/MD 1 complex has been considered of being incapable of independently initiating cellular signals. Using chemogenetic approaches we identified specifically the membrane bound long form of PIM-1 kinase, PIM-1L as the mediator of CD180-dependent signaling. A dominant negative isoform of PIM-1L, but not of other PIM kinases, inhibited signaling elicited by cross-linking of CD180, and this effect was phenocopied by PIM inhibitors. PIM-1L was directed to the cell membrane by its N-terminal extension, where it colocalized and physically associated with CD180. Triggering CD180 also induced increased phosphorylation of the anti-apoptotic protein BAD in a PIM kinase-dependent fashion. Also in primary human B cells, which are the main cells expressing CD180 in man, cross-linking of CD180 by monoclonal antibodies stimulated cell survival and proliferation that was abrogated by specific inhibitors. By associating with PIM-1L, CD180 can thus obtain autonomous signaling capabilities, and this complex is then channeling inflammatory signals into B cell survival programs. Pharmacological inhibition of PIM-1 should therefore provide novel therapeutic options in diseases that respond to innate immune stimulation with subsequently increased B cell activity, such as lupus erythematosus or myasthenia gravis. PMID:26555723

  12. Human CD180 Transmits Signals via the PIM-1L Kinase.

    PubMed

    Egli, Nicole; Zajonz, Alexandra; Burger, Matthew T; Schweighoffer, Tamas

    2015-01-01

    Toll-like receptors (TLRs) are important sensors of the innate immune system that recognize conserved structural motifs and activate cells via a downstream signaling cascade. The CD180/MD1 molecular complex is an unusual member of the TLR family, since it lacks the components that are normally required for signal transduction by other TLRs. Therefore the CD180/MD 1 complex has been considered of being incapable of independently initiating cellular signals. Using chemogenetic approaches we identified specifically the membrane bound long form of PIM-1 kinase, PIM-1L as the mediator of CD180-dependent signaling. A dominant negative isoform of PIM-1L, but not of other PIM kinases, inhibited signaling elicited by cross-linking of CD180, and this effect was phenocopied by PIM inhibitors. PIM-1L was directed to the cell membrane by its N-terminal extension, where it colocalized and physically associated with CD180. Triggering CD180 also induced increased phosphorylation of the anti-apoptotic protein BAD in a PIM kinase-dependent fashion. Also in primary human B cells, which are the main cells expressing CD180 in man, cross-linking of CD180 by monoclonal antibodies stimulated cell survival and proliferation that was abrogated by specific inhibitors. By associating with PIM-1L, CD180 can thus obtain autonomous signaling capabilities, and this complex is then channeling inflammatory signals into B cell survival programs. Pharmacological inhibition of PIM-1 should therefore provide novel therapeutic options in diseases that respond to innate immune stimulation with subsequently increased B cell activity, such as lupus erythematosus or myasthenia gravis. PMID:26555723

  13. Latency in Visionic Systems: Test Methods and Requirements

    NASA Technical Reports Server (NTRS)

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

    2005-01-01

    A visionics device creates a pictorial representation of the external scene for the pilot. The ultimate objective of these systems may be to electronically generate a form of Visual Meteorological Conditions (VMC) to eliminate weather or time-of-day as an operational constraint and provide enhancement over actual visual conditions where eye-limiting resolution may be a limiting factor. Empirical evidence has shown that the total system delays or latencies including the imaging sensors and display systems, can critically degrade their utility, usability, and acceptability. Definitions and measurement techniques are offered herein as common test and evaluation methods for latency testing in visionics device applications. Based upon available data, very different latency requirements are indicated based upon the piloting task, the role in which the visionics device is used in this task, and the characteristics of the visionics cockpit display device including its resolution, field-of-regard, and field-of-view. The least stringent latency requirements will involve Head-Up Display (HUD) applications, where the visionics imagery provides situational information as a supplement to symbology guidance and command information. Conversely, the visionics system latency requirement for a large field-of-view Head-Worn Display application, providing a Virtual-VMC capability from which the pilot will derive visual guidance, will be the most stringent, having a value as low as 20 msec.

  14. Inhibition of the Pim1 Oncogene Results in Diminished Visual Function

    PubMed Central

    Yin, Jun; Shine, Lisa; Raycroft, Francis; Deeti, Sudhakar; Reynolds, Alison; Ackerman, Kristin M.; Glaviano, Antonino; O'Farrell, Sean; O'Leary, Olivia; Kilty, Claire; Kennedy, Ciaran; McLoughlin, Sarah; Rice, Megan; Russell, Eileen; Higgins, Desmond G.; Hyde, David R.; Kennedy, Breandan N.

    2012-01-01

    Our objective was to profile genetic pathways whose differential expression correlates with maturation of visual function in zebrafish. Bioinformatic analysis of transcriptomic data revealed Jak-Stat signalling as the pathway most enriched in the eye, as visual function develops. Real-time PCR, western blotting, immunohistochemistry and in situ hybridization data confirm that multiple Jak-Stat pathway genes are up-regulated in the zebrafish eye between 3–5 days post-fertilisation, times associated with significant maturation of vision. One of the most up-regulated Jak-Stat genes is the proto-oncogene Pim1 kinase, previously associated with haematological malignancies and cancer. Loss of function experiments using Pim1 morpholinos or Pim1 inhibitors result in significant diminishment of visual behaviour and function. In summary, we have identified that enhanced expression of Jak-Stat pathway genes correlates with maturation of visual function and that the Pim1 oncogene is required for normal visual function. PMID:23300608

  15. Cardiac Progenitor Cell Cycling Stimulated by Pim-1 Kinase

    PubMed Central

    Cottage, Christopher T.; Bailey, Brandi; Fischer, Kimberlee M.; Avitable, Daniele; Collins, Brett; Tuck, Savilla; Quijada, Pearl; Gude, Natalie; Alvarez, Roberto; Muraski, John; Sussman, Mark A.

    2011-01-01

    Rationale Cardioprotective effects of Pim-1 kinase have been previously reported but the underlying mechanistic basis may involve a combination of cellular and molecular mechanisms that remain unresolved. The elucidation of the mechanistic basis for Pim-1 mediated cardioprotection provides important insights for designing therapeutic interventional strategies to treat heart disease. Objective Effects of cardiac-specific Pim-1 kinase expression on the cardiac progenitor cell (CPC) population were examined to determine whether Pim-1 mediates beneficial effects through augmenting CPC activity. Methods and Results Transgenic mice created with cardiac-specific Pim-1 overexpression (Pim-wt) exhibit enhanced Pim-1 expression in both cardiomyocytes and CPCs, both of which show increased proliferative activity assessed using 5-bromodeoxyuridine (BrdU), Ki-67, and c-Myc relative to nontransgenic controls. However, the total number of CPCs was not increased in the Pim-wt hearts during normal postnatal growth or after infarction challenge. These results suggest that Pim-1 overexpression leads to asymmetric division resulting in maintenance of the CPC population. Localization and quantitation of cell fate determinants Numb and α-adaptin by confocal microscopy were used to assess frequency of asymmetric division in the CPC population. Polarization of Numb in mitotic phospho-histone positive cells demonstrates asymmetric division in 65% of the CPC population in hearts of Pim-wt mice versus 26% in nontransgenic hearts after infarction challenge. Similarly, Pim-wt hearts had fewer cells with uniform α-adaptin staining indicative of symmetrically dividing CPCs, with 36% of the CPCs versus 73% in nontransgenic sections. Conclusions These findings define a mechanistic basis for enhanced myocardial regeneration in transgenic mice overexpressing Pim-1 kinase. PMID:20075333

  16. Identification of quinones as novel PIM1 kinase inhibitors.

    PubMed

    Schroeder, Richard L; Goyal, Navneet; Bratton, Melyssa; Townley, Ian; Pham, Nancy A; Tram, Phan; Stone, Treasure; Geathers, Jasmine; Nguyen, Kathy; Sridhar, Jayalakshmi

    2016-07-01

    PIM1 is a proto-oncogene encoding the serine/threonine PIM1 kinase. PIM1 kinase plays important roles in regulating aspects of cell cycle progression, apoptosis resistance, and has been implicated in the development of such malignancies as prostate cancer and acute myeloid leukemia among others. Knockout of PIM1 kinase in mice has been shown to be non-lethal without any obvious phenotypic changes, making it an attractive therapeutic target. Our investigation of anthraquinones as kinase inhibitors revealed a series of quinone analogs showing high selectivity for inhibition of the PIM kinases. Molecular modeling studies were used to identify key interactions and binding poses of these compounds within the PIM1 binding pocket. Compounds 1, 4, 7 and 9 inhibited the growth of DU-145 prostate cancer cell lines with a potency of 8.21μM, 4.06μM, 3.21μM and 2.02μM. PMID:27173800

  17. The Pim-1 Protein Kinase Is an Important Regulator of MET Receptor Tyrosine Kinase Levels and Signaling

    PubMed Central

    Xiong, Ying; Song, Jin H.; Mahajan, Sandeep; DuPont, Rachel; McEachern, Kristen; DeAngelo, Daniel J.; Cortes, Jorge E.; Minden, Mark D.; Ebens, Allen; Mims, Alice; LaRue, Amanda C.

    2014-01-01

    MET, the receptor for hepatocyte growth factor (HGF), plays an important role in signaling normal and tumor cell migration and invasion. Here, we describe a previously unrecognized mechanism that promotes MET expression in multiple tumor cell types. The levels of the Pim-1 protein kinase show a positive correlation with the levels of MET protein in human tumor cell lines and patient-derived tumor materials. Using small interfering RNA (siRNA), Pim knockout mice, small-molecule inhibitors, and overexpression of Pim-1, we confirmed this correlation and found that Pim-1 kinase activity regulates HGF-induced tumor cell migration, invasion, and cell scattering. The novel biochemical mechanism for these effects involves the ability of Pim-1 to control the translation of MET by regulating the phosphorylation of eukaryotic initiation factor 4B (eIF4B) on S406. This targeted phosphorylation is required for the binding of eIF4B to the eIF3 translation initiation complex. Importantly, Pim-1 action was validated by the evaluation of patient blood and bone marrow from a phase I clinical trial of a Pim kinase inhibitor, AZD1208. These results suggest that Pim inhibitors may have an important role in the treatment of patients where MET is driving tumor biology. PMID:24777602

  18. PIM1 kinase as a promise of targeted therapy in prostate cancer stem cells

    PubMed Central

    XIE, YINGQIU; BAYAKHMETOV, SAMAT

    2016-01-01

    Since the last decade, the PIM family serine/threonine kinases have become a focus in cancer research. Numerous clinical data supports that overexpression of PIM1 is associated with tumor formation in various tissues. However, little is known regarding the function of PIM1 in cancer stem cells. In cancer cells, PIM1 has essential roles in the regulation of the cell cycle, cell proliferation, cell survival and multiple drug resistance. In stem cells, PIM1 kinase exhibits a significant function in stem cell proliferation, self-renewal and expansion. Thus, PIM1 shows a great promise in cancer therapy by targeting stem cells. Furthermore, it is imperative to investigate Pim-1 targeting in cancer stem cells by applicable inhibitors for improving future outcomes. The present review investigated the potential of PIM1 as a therapy target in prostate cancer stem cells. PMID:26835011

  19. Functional Role and Therapeutic Potential of the Pim-1 Kinase in Colon Carcinoma12

    PubMed Central

    Weirauch, Ulrike; Beckmann, Nadine; Thomas, Maren; Grünweller, Arnold; Huber, Kilian; Bracher, Franz; Hartmann, Roland K; Aigner, Achim

    2013-01-01

    Purpose The provirus integration site for Moloney murine leukemia virus 1 (Pim-1) kinase is overexpressed in various tumors and has been linked to poor prognosis. Its role as proto-oncogene is based on several Pim-1 target proteins involved in pivotal cellular processes. Here, we explore the functional relevance of Pim-1 in colon carcinoma. Experimental Design RNAi-based knockdown approaches, as well as a specific small molecule inhibitor, were used to inhibit Pim-1 in colon carcinoma cells. The effects were analyzed regarding proliferation, apoptosis, sensitization toward cytostatic treatment, and overall antitumor effect in vitro and in mouse tumor models in vivo. Results We demonstrate antiproliferative, proapoptotic, and overall antitumor effects of Pim-1 inhibition. The sensitization to 5-fluorouracil (5-FU) treatment upon Pim-1 knockdown offers new possibilities for combinatorial treatment approaches. Importantly, this also antagonizes a 5-FU-triggered Pim-1 up-regulation, which is mediated by decreased levels of miR-15b, a microRNA we newly identify to regulate Pim-1. The analysis of the molecular effects of Pim-1 inhibition reveals a complex regulatory network, with therapeutic Pim-1 repression leading to major changes in oncogenic signal transduction with regard to p21Cip1/WAF1, STAT3, c-jun-N-terminal kinase (JNK), c-Myc, and survivin and in the levels of apoptosis-related proteins Puma, Bax, and Bcl-xL. Conclusions We demonstrate that Pim-1 plays a pivotal role in several tumor-relevant signaling pathways and establish the functional relevance of Pim-1 in colon carcinoma. Our results also substantiate the RNAi-mediated Pim-1 knockdown based on polymeric polyethylenimine/small interfering RNA nanoparticles as a promising therapeutic approach. PMID:23814490

  20. PIM1 regulates glycolysis and promotes tumor progression in hepatocellular carcinoma.

    PubMed

    Leung, Carmen Oi-ning; Wong, Carmen Chak-lui; Fan, Dorothy Ngo-yin; Kai, Alan Ka-lun; Tung, Edmund Kwok-kwan; Xu, Iris Ming-jing; Ng, Irene Oi-lin; Lo, Regina Cheuk-lam

    2015-05-10

    Hepatocellular carcinoma (HCC) is characteristically one of the most rapidly proliferating tumors which outgrows functional blood supply and results in regional oxygen deprivation. Overexpression of PIM1, a serine/threonine kinase, has been identified recently in human cancers. Knowledge on PIM1 in HCC is however, scarce. By immunohistochemical analysis on 56 human primary HCC samples, we observed overexpression of PIM1 in 39% of the cases. In two independent cohorts of paired primary and extra-hepatic metastatic HCC tissues, PIM1 expression was higher (p=0.002) in the extra-hepatic metastatic HCC tissues as compared with the corresponding primary HCCs. PIM1 was markedly up-regulated in multiple HCC cell lines in hypoxic condition (1% O2) versus normoxia (20% O2). Silencing of PIM1 suppressed HCC cell invasion in vitro as compared to non-target control, and decreased HCC cell proliferation in vitro and tumor growth and metastatic potential in vivo. Knockdown of PIM1 significantly reduced glucose uptake by HCC cells and was associated with decreased levels of p-AKT and key molecules in the glycolytic pathway. Taken together, PIM1 is up-regulated by hypoxia in HCC and promotes tumor growth and metastasis through facilitating cancer cell glycolysis. Targeting PIM1 may have potential role in the management of HCC. PMID:25834102

  1. Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation

    SciTech Connect

    Walpen, Thomas; Kalus, Ina; Schwaller, Juerg; Peier, Martin A.; Battegay, Edouard J.; Humar, Rok

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer Pim1{sup -/-} endothelial cell proliferation displays increased sensitivity to rapamycin. Black-Right-Pointing-Pointer mTOR inhibition by rapamycin enhances PIM1 cytosolic and nuclear protein levels. Black-Right-Pointing-Pointer Truncation of Pim1 beyond serine 276 results in nuclear localization of the kinase. Black-Right-Pointing-Pointer Nuclear PIM1 increases endothelial proliferation independent of rapamycin. -- Abstract: The PIM serine/threonine kinases and the mTOR/AKT pathway integrate growth factor signaling and promote cell proliferation and survival. They both share phosphorylation targets and have overlapping functions, which can partially substitute for each other. In cancer cells PIM kinases have been reported to produce resistance to mTOR inhibition by rapamycin. Tumor growth depends highly on blood vessel infiltration into the malignant tissue and therefore on endothelial cell proliferation. We therefore investigated how the PIM1 kinase modulates growth inhibitory effects of rapamycin in mouse aortic endothelial cells (MAEC). We found that proliferation of MAEC lacking Pim1 was significantly more sensitive to rapamycin inhibition, compared to wildtype cells. Inhibition of mTOR and AKT in normal MAEC resulted in significantly elevated PIM1 protein levels in the cytosol and in the nucleus. We observed that truncation of the C-terminal part of Pim1 beyond Ser 276 resulted in almost exclusive nuclear localization of the protein. Re-expression of this Pim1 deletion mutant significantly increased the proliferation of Pim1{sup -/-} cells when compared to expression of the wildtype Pim1 cDNA. Finally, overexpression of the nuclear localization mutant and the wildtype Pim1 resulted in complete resistance to growth inhibition by rapamycin. Thus, mTOR inhibition-induced nuclear accumulation of PIM1 or expression of a nuclear C-terminal PIM1 truncation mutant is sufficient to increase endothelial cell proliferation

  2. The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation

    SciTech Connect

    Vu, Hoang Anh; Xinh, Phan Thi; Kano, Yasuhiko; Tokunaga, Katsushi; Sato, Yuko

    2009-06-05

    We recently reported that the ETV6/FLT3 fusion protein conferred interleukin-3-independent growth on Ba/F3 cells. The present study has been conducted to assess role of the juxtamembrane domain of FLT3 for signal transduction and cell transformation. The wild-type ETV6/FLT3 fusion protein in transfected cells was a constitutively activated tyrosine kinase that led to up-regulation of PIM-1 and activations of STAT5, AKT, and MAPK. Deletion of the juxtamembrane domain abrogated interleukin-3-independent growth of the transfected cells and PIM-1 up-regulation, whereas it retained compatible levels of phosphorylations of STAT5, AKT, and MAPK. Further deletion of N-terminal region of the tyrosine kinase I domain of FLT3 completely abolished these phosphorylations. Our data indicate that the juxtamembrane domain of FLT3 in ETV6/FLT3 fusion protein is critical for cell proliferation and PIM-1 up-regulation that might be independent of a requirement for signaling through STAT5, MAPK, and AKT pathways.

  3. Pim1 kinase activity preserves airway epithelial integrity upon house dust mite exposure.

    PubMed

    de Vries, M; Hesse, L; Jonker, M R; van den Berge, M; van Oosterhout, A J M; Heijink, I H; Nawijn, M C

    2015-12-01

    Most patients with allergic asthma are sensitized to house dust mite (HDM). The allergenicity of HDM largely depends on disruption of the integrity and proinflammatory activation of the airway epithelium. In this study, we hypothesized that Pim1 kinase activity attenuates HDM-induced asthma by preserving airway epithelial integrity. The effects of Pim1 kinase activity on barrier function and release of the proinflammatory mediators IL-1α and CCL20 were studied in vitro in 16HBE and primary bronchial epithelial cells (PBECs). Pim1-proficient and -deficient mice were exposed to a HDM-driven model of allergic asthma, and airway hyperresponsiveness (AHR) was measured upon methacholine challenge. Airway inflammation and proinflammatory mediators in lung tissue and BAL fluid were determined. We observed that inhibition of Pim1 kinase prolongs the HDM-induced loss of barrier function in 16HBE cells and sensitizes PBECs to HDM-induced barrier dysfunction. Additionally, inhibition of Pim1 kinase increased the HDM-induced proinflammatory activity of 16HBE cells as measured by IL-1α secretion. In line herewith, HDM exposure induced an enhanced production of the proinflammatory chemokines CCL17 and CCL20 in Pim1-deficient mice compared with wild-type controls. While we observed a marked increase in eosinophilic and neutrophilic granulocytes as well as mucus cell metaplasia and AHR to methacholine in mice exposed to HDM, these parameters were independent of Pim1 kinase activity. In contrast, levels of the Th2-cytokines IL-5 and IL-10 were significantly augmented in HDM-treated Pim1-deficient mice. Taken together, our study shows that Pim1 kinase activity maintains airway epithelial integrity and protects against HDM-induced proinflammatory activation of the airway epithelium. PMID:26453516

  4. Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase

    PubMed Central

    Fischer, Kimberlee M.; Cottage, Chistopher T.; Wu, Weitao; Din, Shabana; Gude, Natalie A.; Avitable, Daniele; Quijada, Pearl; Collins, Brett L.; Fransioli, Jenna; Sussman, Mark A.

    2009-01-01

    Background Despite numerous studies demonstrating efficacy of cellular adoptive transfer for therapeutic myocardial regeneration, problems remain for donated cells with regard to survival, persistence, engraftment, and long-term benefits. This study redresses these concerns by enhancing the regenerative potential of adoptively transferred cardiac progenitor cells (CPCs) via genetic engineering to overexpress Pim-1, a cardioprotective kinase that enhances cell survival and proliferation. Methods and Results Intramyocardial injections of CPCs overexpressing Pim-1 were given to infarcted female mice. Animals were monitored over 4, 12, and 32-weeks to assess cardiac function and engraftment of Pim-1 CPCs using echocardiography, in vivo hemodynamics, and confocal imagery. CPCs overexpressing Pim-1 show increased proliferation and expression of markers consistent with cardiogenic lineage commitment following dexamethasone exposure in vitro. Animals that received CPCs overexpressing Pim-1 also produce greater levels of cellular engraftment, persistence, and functional improvement relative to control CPCs up to 32-weeks post-delivery. Salutary effects include reduction of infarct size, greater number of c-kit+ cells, and increased vasculature in the damaged region. Conclusions Myocardial repair is significantly enhanced by genetic engineering of CPCs using Pim-1 kinase. Ex vivo gene delivery to enhance cellular survival, proliferation, and regeneration may overcome current limitations of stem cell-based therapeutic approaches. PMID:19901187

  5. Expression, purification, crystallization and preliminary crystallographic analysis of human Pim-1 kinase

    SciTech Connect

    Qian, Kevin C.; Studts, Joey; Wang, Lian; Barringer, Kevin; Kronkaitis, Anthony; Peng, Charline; Baptiste, Alistair; LaFrance, Roger; Mische, Sheenah; Farmer, Bennett

    2005-01-01

    Pim kinases, belong to a distinctive serine/threonine protein-kinase family and are involved in cytokine-induced signal transduction and the development of lymphoid malignancies. Human Pim-1 kinase has been cloned, expressed and crystallized Pim kinases, including Pim-1, Pim-2 and Pim-3, belong to a distinctive serine/threonine protein-kinase family. They are involved in cytokine-induced signal transduction and the development of lymphoid malignancies. Their kinase domains are highly homologous to one another, but share low sequence identity to other kinases. Specifically, there are two proline residues in the conserved hinge-region sequence ERPXPX separated by a residue that is non-conserved among Pim kinases. Full-length human Pim-1 kinase (1–313) was cloned and expressed in Escherichia coli as a GST-fusion protein and truncated to Pim-1 (14–313) by thrombin digestion during purification. The Pim-1 (14–313) protein was purified to high homogeneity and monodispersity. This protein preparation yielded small crystals in the initial screening and large crystals after optimization. The large crystals of apo Pim-1 enzyme diffracted to 2.1 Å resolution and belong to space group P6{sub 5}, with unit-cell parameters a = b = 95.9, c = 80.0 Å, β = 120° and one molecule per asymmetric unit.

  6. MicroRNA-124-3p regulates cell proliferation, invasion, apoptosis, and bioenergetics by targeting PIM1 in astrocytoma.

    PubMed

    Deng, Danni; Wang, Lei; Chen, Yao; Li, Bowen; Xue, Lian; Shao, Naiyuan; Wang, Qiang; Xia, Xiwei; Yang, Yilin; Zhi, Feng

    2016-07-01

    The PIM1 protein is an important regulator of cell proliferation, the cell cycle, apoptosis, and metabolism in various human cancers. MicroRNAs (miRNAs) are powerful post-transcriptional gene regulators that function through translational repression or transcript destabilization. Therefore, we aimed to identify whether a close relationship exists between PIM1 and miRNAs. PIM1 protein levels and mRNA levels were significantly upregulated in astrocytoma tissues, indicating the oncogenic role of PIM1 in astrocytoma. Further bioinformatics analysis indicated that miR-124-3p targeted the 3'-UTR of PIM1. We also observed an inverse correlation between the miR-124-3p levels and PIM1 protein or mRNA levels in astrocytoma samples. Next, we experimentally confirmed that miR-124-3p directly recognizes the 3'-UTR of the PIM1 transcript and regulates PIM1 expression at both the protein and mRNA levels. Furthermore, we examined the biological consequences of miR-124-3p targeting PIM1 in vitro. We showed that the repression of PIM1 in astrocytoma cancer cells by miR-124-3p suppressed proliferation, invasion, and aerobic glycolysis and promoted apoptosis. We observed that the restoration or inhibition of PIM1 activity resulted in effects that were similar to those induced by miR-124-3p inhibitors or mimics in cancer cells. Finally, overexpression of PIM1 rescued the inhibitory effects of miR-124-3p. In summary, these findings aid in understanding the tumor-suppressive role of miR-124-3p in astrocytoma pathogenesis through the inhibition of PIM1 translation. PMID:27088547

  7. PIM1 destabilization activates a p53-dependent response to ribosomal stress in cancer cells.

    PubMed

    Sagar, Vinay; Caldarola, Sara; Aria, Valentina; Monteleone, Valentina; Fuoco, Claudia; Gargioli, Cesare; Cannata, Stefano; Loreni, Fabrizio

    2016-04-26

    Defects in ribosome biogenesis triggers a stress response (ribosomal stress) that can lead to growth arrest and apoptosis. Signaling pathways activated by ribosomal stress are specifically involved in the pathological mechanism of a group of disorders defined as ribosomopathies. However, more generally, the quality control of ribosome synthesis is part of the regulatory circuits that control cell metabolism. A number of studies identified tumor suppressor p53 as a central player in ribosomal stress. We have previously reported that the kinase PIM1 plays a role as a sensor for ribosome deficiency. In this report we address the relationship between PIM1 and p53 in cancer cell lines after depletion of a ribosomal protein. We identified a novel signaling pathway that includes the kinase AKT and the ubiquitin ligase MDM2. In fact, our results indicate that the lower level of PIM1, induced by ribosomal stress, causes inactivation of AKT, inhibition of MDM2 and a consequent p53 stabilization. Therefore, we propose that activation of p53 in response to ribosomal stress, is dependent on the pathway PIM1-AKT-MDM2. In addition, we report evidence that PIM1 level may be relevant to assess the sensitivity of cancer cells to chemotherapeutic drugs that induce ribosomal stress. PMID:26993775

  8. Constitutive activation of Pim1 kinase is a therapeutic target for adult T-cell leukemia.

    PubMed

    Bellon, Marcia; Lu, Ling; Nicot, Christophe

    2016-05-19

    Human T-cell leukemia virus type 1 (HTLV-1)-associated adult T-cell leukemia and T-cell lymphoma (ATL) are aggressive diseases with poor prognoses, limited therapeutic options, and no curative treatment. In this study, we used a mouse model of ATL and restored expression of the microRNA, miR-124a, to identify in vivo downstream effectors responsible for its tumor-suppressive functions in ATL cells. Our results revealed that STAT3, a direct target of miR-124a, is constitutively activated in HTLV-I-transformed cells and ATL cells, and activating STAT3 mutations were detected in 25.5% of primary ATL patients. Interestingly, we found that the STAT3 downstream kinase effector, Pim1, is constitutively activated in ATL cells. The dependence of ATL cells to Pim1 activity was demonstrated using 2 Pim1 small inhibitors, SMI-4a and AZD1208. These studies indicated that HTLV-I-transformed and ATL cells, but not normal peripheral blood mononuclear cells, are highly sensitive to AZD1208, and the inhibition of Pim1 signaling triggers an apoptotic signal in leukemic cells. Finally, preclinical testing of AZD1208 in a mouse model of ATL resulted in significant prevention of tumor growth in vivo. In conclusion, our studies suggest that constitutive activation of the STAT3-Pim1 pathway represents a novel therapeutic target for the treatment of ATL. PMID:26813676

  9. Inhibition of Pim1 kinase, new therapeutic approach in virus-induced asthma exacerbations.

    PubMed

    Vries, Maaike de; Bedke, Nicole; Smithers, Natalie P; Loxham, Matthew; Howarth, Peter H; Nawijn, Martijn C; Davies, Donna E

    2016-03-01

    Therapeutic options to treat virus-induced asthma exacerbations are limited and urgently needed. Therefore, we tested Pim1 kinase as potential therapeutic target in human rhinovirus (HRV) infections. We hypothesised that inhibition of Pim1 kinase reduces HRV replication by augmenting the interferon-induced anti-viral response due to increased activity of the janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway.Air-liquid interface (ALI) cultures of primary bronchial epithelial cells (PBECs) from healthy individuals and moderate-to-severe asthmatic volunteers were infected with HRV-16 with or without a specific Pim1 inhibitor; viral replication and induction of anti-viral responses were measured using RT-qPCR. Viral titres were measured by 50% tissue culture infective dose and release of interferon-γ-induced protein 10 (IP-10) and RANTES protein assessed by ELISA. Phosphorylation of STAT-1 was determined using western blotting.Viral replication was reduced in ALI cultures of healthy and asthmatic PBECs treated with the Pim1 inhibitor. Using cultures from healthy donors, enhanced STAT-1 phosphorylation upon inhibition of Pim1 kinase activity resulted in increased mRNA expression of interferon-β, interleukin-29, IP-10 and RANTES 12 h after infection and increased protein levels of IP-10 and RANTES 24 h after infection.We have identified Pim1 kinase as novel target to reduce viral replication in ALI cultures of PBECs. This may open new avenues for therapeutic interventions in virus-induced asthma exacerbations. PMID:26869670

  10. Pim-1 preserves mitochondrial morphology by inhibiting dynamin-related protein 1 translocation

    PubMed Central

    Din, Shabana; Mason, Matthew; Völkers, Mirko; Johnson, Bevan; Cottage, Christopher T.; Wang, Zeping; Joyo, Anya Y.; Quijada, Pearl; Erhardt, Peter; Magnuson, Nancy S.; Konstandin, Mathias H.; Sussman, Mark A.

    2013-01-01

    Mitochondrial morphological dynamics affect the outcome of ischemic heart damage and pathogenesis. Recently, mitochondrial fission protein dynamin-related protein 1 (Drp1) has been identified as a mediator of mitochondrial morphological changes and cell death during cardiac ischemic injury. In this study, we report a unique relationship between Pim-1 activity and Drp1 regulation of mitochondrial morphology in cardiomyocytes challenged by ischemic stress. Transgenic hearts overexpressing cardiac Pim-1 display reduction of total Drp1 protein levels, increased phosphorylation of Drp1-S637, and inhibition of Drp1 localization to the mitochondria. Consistent with these findings, adenoviral-induced Pim-1 neonatal rat cardiomyocytes (NRCMs) retain a reticular mitochondrial phenotype after simulated ischemia (sI) and decreased Drp1 mitochondrial sequestration. Interestingly, adenovirus Pim-dominant negative NRCMs show increased expression of Bcl-2 homology 3 (BH3)-only protein p53 up-regulated modulator of apoptosis (PUMA), which has been previously shown to induce Drp1 accumulation at mitochondria and increase sensitivity to apoptotic stimuli. Overexpression of the p53 up-regulated modulator of apoptosis–dominant negative adenovirus attenuates localization of Drp1 to mitochondria in adenovirus Pim-dominant negative NRCMs promotes reticular mitochondrial morphology and inhibits cell death during sI. Therefore, Pim-1 activity prevents Drp1 compartmentalization to the mitochondria and preserves reticular mitochondrial morphology in response to sI. PMID:23530233

  11. Molecular chaperones cooperate with PIM1 protease in the degradation of misfolded proteins in mitochondria.

    PubMed Central

    Wagner, I; Arlt, H; van Dyck, L; Langer, T; Neupert, W

    1994-01-01

    ATP dependent proteolytic degradation of misfolded proteins in the mitochondrial matrix is mediated by the PIM1 protease and depends on the molecular chaperone proteins mt-hsp70 and Mdj1p. Chaperone function is essential to maintain misfolded proteins in a soluble state, a prerequisite for their degradation by PIM1 protease. In the absence of functional mt-hsp70 or Mdj1p misfolded proteins either remain associated with mt-hsp70 or form aggregates and thereby are no longer substrates for PIM1 protease. Mdj1p is shown to regulate the ATP dependent association of an unfolded polypeptide chain with mt-hsp70 affecting binding to as well as release from mt-hsp70. These findings establish a central role of molecular chaperone proteins in the degradation of misfolded proteins by PIM1 protease and thereby demonstrate a functional interrelation between components of the folding machinery and the proteolytic system within mitochondria. Images PMID:7957078

  12. Latency Requirements for Head-Worn Display S/EVS Applications

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

    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.

  13. Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in E(mu)-pim-1 transgenic mice.

    PubMed

    Sørensen, I K; Mortensen, A; Kristiansen, E; van Kreijl, C; Adamson, R H; Thorgeirsson, S S

    1996-10-01

    The usefulness of transgenic E(mu)-pim-1 mice over-expressing the pim-1 oncogene in lymphoid tissues, as sensitive test organisms was studied in a short-term carcinogenicity study. The mice were fed standard diet Altromin 1314 supplemented either with 0.03% 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) for 7 months or with 0.03% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for 6 months. PhIP and IQ are heterocyclic amines formed during cooking of meat and fish and are mutagenic to bacteria and cultured mammalian cells. PhIP is a potent mouse lymphomagen, while IQ is a liver carcinogen and also causes lung tumors and tumors of the forestomach in mice. We found that transgenic E(mu)-pim-1 mice are highly susceptible to PhIP induced lymphomagenesis but do not respond to the IQ treatment. PhIP feeding of E(mu)-pim-1 mice not only increased the total number of T-cell lymphomas but also decreased the latency time compared to either transgenic or wild-type controls. The effect was most pronounced in the treated female E(mu)-pim-1 mice, which showed a higher incidence of PhIP induced T-cell lymphomas than transgenic males and a strongly reduced latency period after PhIP treatment compared to non-transgenic mice. Our results suggest that the transgenic E(mu)-pim-1 mouse may be a useful model for short-term carcinogenicity screening of potential genotoxic carcinogens having the lymphoid system as target tissue. The carcinogen IQ which does not have the lymphoid system as a target was not recognized in this model. PMID:8895492

  14. The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG.

    PubMed Central

    Saris, C J; Domen, J; Berns, A

    1991-01-01

    The pim-1 gene is frequently found activated by proviral insertion in murine T cell lymphomas. Overexpression of pim-1 in lymphoid cells by transgenesis formally proved its oncogenic potential. The pim-1 cDNA sequence predicts that both murine and human pim-1 encode a 34 kd protein with homology to protein kinases. In this study, we show that the murine pim-1 gene encodes a 44 kd protein in addition to the predicted 34 kd protein. The 44 kd protein is an amino-terminal extension of the 34 kd protein and is synthesized by alternative translation initiation at an upstream CUG codon. Contrary to previous findings by others, we provide evidence that both murine and human pim-1 gene products are protein-serine/threonine kinases. Murine 44 kd and 34 kd pim-1 proteins exhibit comparable in vitro kinase activity and are both mainly cytoplasmic, but they differ in in vivo association state and half-life. Images PMID:1825810

  15. Transcriptional induction of pim-1 protein kinase gene expression by interferon gamma and posttranscriptional effects on costimulation with steel factor.

    PubMed

    Yip-Schneider, M T; Horie, M; Broxmeyer, H E

    1995-06-15

    Steel factor (SLF) synergizes with interferon gamma (IFN gamma) to stimulate proliferation of the human factor-dependent cell line MO7e. We examined the effects of IFN gamma and SLF treatment, alone or in combination, on the expression of a 33-kD cytoplasmic protein serine/threonine kinase designated pim-1 whose expression has been closely associated with proliferation induced by related myeloid cytokines. IFN gamma alone, but not SLF, stimulated expression of pim-1 RNA and protein in MO7e cells; compared with IFN gamma alone, costimulation with IFN gamma and SLF resulted in a twofold to threefold increase in pim-1 message and protein expression, correlating with synergistic effects on cell proliferation. Both IFN gamma and IFN gamma/SLF induced pim-1 mRNA in the absence of de novo protein synthesis. Nuclear run-on assays showed that, although IFN gamma alone increased the rate of pim-1 gene transcription, costimulation with IFN gamma and SLF did not further potentiate this effect; however, the stability of pim-1 message was significantly enhanced in the presence of both cytokines. An IFN gamma-responsive element within the 5' flanking region of the pim-1 gene that could confer IFN gamma responsiveness on a heterologous promoter was identified. This sequence, designated PMGAS, formed a specific complex with Stat (signal transducers and activators of transcription) 1 alpha (the p91 subunit of the transcription factor ISGF3 [interferon-stimulated gene factor 3]) in IFN gamma-treated cell extracts, suggesting that the transcriptional effects of IFN gamma on pim-1 expression may be mediated by Stat 1 alpha. PMID:7540064

  16. In utero exposure to benzene increases embryonic c-Myb and Pim-1 protein levels in CD-1 mice

    SciTech Connect

    Wan, Joanne; Winn, Louise M.

    2008-05-01

    Benzene is a known human leukemogen, but its role as an in utero leukemogen remains controversial. Epidemiological studies have correlated parental exposure to benzene with an increased incidence of childhood leukemias. We hypothesize that in utero exposure to benzene may cause leukemogenesis by affecting the embryonic c-Myb/Pim-1 signaling pathway and that this is mediated by oxidative stress. To investigate this hypothesis, pregnant CD-1 mice were treated with either 800 mg/kg of benzene or corn oil (i.p.) on days 10 and 11 of gestation and in some cases pretreated with 25 kU/kg of PEG-catalase. Phosphorylated and total embryonic c-Myb and Pim-1 protein levels were assessed using Western blotting and maternal and embryonic oxidative stress were assessed by measuring reduced to oxidized glutathione ratios. Our results show increased oxidative stress at 4 and 24 h after exposure, increased phosphorylated Pim-1 protein levels 4 h after benzene exposure, and increased Pim-1 levels at 24 and 48 h after benzene exposure. Embryonic c-Myb levels were elevated at 24 h after exposure. PEG-catalase pretreatment prevented benzene-mediated increases in embryonic c-Myb and Pim-1 protein levels, and benzene-induced oxidative stress. These results support a role for ROS in c-Myb and Pim-1 alterations after in utero benzene exposure.

  17. Preservation of Myocardial Structure is Enhanced by Pim-1 Engineering of Bone Marrow Cells

    PubMed Central

    Quijada, Pearl; Toko, Haruhiro; Fischer, Kimberlee M; Bailey, Brandi; Reilly, Patrick; Hunt, Kristin D; Gude, Natalie A; Avitabile, Daniele; Sussman, Mark A

    2012-01-01

    Rationale Bone marrow derived cells to treat myocardial injury improve cardiac function and support beneficial cardiac remodeling. However, survival of stem cells is limited due to low proliferation of transferred cells. Objective Demonstrate long-term potential of c-kit+ bone marrow stem cells (BMCs) enhanced with Pim-1 kinase to promote positive cardiac remodeling. Methods and Results Lentiviral modification of c-kit+ BMCs to express Pim-1 (BMCeP) increases proliferation and expression of pro-survival proteins relative to BMCs expressing GFP (BMCe). Intramyocardial delivery of BMCeP at time of infarction supports improvements in anterior wall dimensions and prevents left ventricle dilation compared to hearts treated with vehicle alone. Reduction of the akinetic left ventricular wall was observed in BMCeP treated hearts at 4 and 12 weeks after infarction. Early recovery of cardiac function in BMCeP-injected hearts facilitated modest improvements in hemodynamic function up to 12 weeks post infarction between cell treated groups. Persistence of BMCeP is improved relative to BMCe within the infarct together with increased recruitment of endogenous c-kit+ cells. Delivery of BMC populations promotes cellular hypertrophy in the border and infarcted regions coupled with an up regulation of hypertrophic genes. Thus, BMCeP treatment yields improved structural remodeling of infarcted myocardium compared to control BMCs. Conclusions Genetic modification of BMCs with Pim-1 may serve as a therapeutic approach to promote recovery of myocardial structure. Future approaches may take advantage of salutary BMC actions in conjunction with other stem cell types to increase efficacy of cellular therapy and improve myocardial performance in the injured myocardium. PMID:22619278

  18. HUMAN CARDIAC PROGENITOR CELLS ENGINEERED WITH PIM-1 KINASE ENHANCE MYOCARDIAL REPAIR

    PubMed Central

    Mohsin, Sadia; Khan, Mohsin; Toko, Haruhiro; Bailey, Brandi; Cottage, Christopher T.; Wallach, Kathleen; Nag, Divya; Lee, Andrew; Siddiqi, Sailay; Lan, Feng; Fischer, Kimberlee M.; Gude, Natalie; Quijada, Pearl; Avitabile, Daniele; Truffa, Silvia; Collins, Brett; Dembitsky, Walter; Wu, Joseph C; Sussman, Mark A

    2012-01-01

    Objective Enhancement of human cardiac progenitor cell (hCPC) reparative and regenerative potential by genetic modification for treatment of myocardial infarction. Background Regenerative potential of stem cells to repair acute infarction is limited. Improved hCPC survival, proliferation and differentiation into functional myocardium will increase efficacy and advance translational implementation of cardiac regeneration. Methods hCPCs isolated from myocardium of heart failure patients undergoing left ventricular assist device (LVAD) implantation are engineered to express green fluorescent protein (GFP; hCPCe) or Pim-1-GFP (hCPCeP). Functional tests of hCPC regenerative potential are performed with immunocompromised mice by intramyocardial adoptive transfer injection after infarction. Myocardial structure and function is monitored by echocardiographic and hemodynamic assessment for 20 weeks following delivery. hCPCe and hCPCeP expressing luciferase are followed by bioluminesence imaging (BLI) to non-invasively track persistence. Results hCPCeP exhibit augmentation of reparative potential relative to hCPCe control cells as demonstrated by significantly increased proliferation coupled with amelioration of infarction injury and increased hemodynamic performance at 20 weeks post-transplantation. Concurrent with enhanced cardiac structure and function, hCPCeP demonstrate increased cellular engraftment and differentiation with improved vasculature and reduced infarct size. Enhanced persistence of hCPCeP versus hCPCe is revealed by BLI at up to 8 weeks post delivery. Conclusion Genetic engineering of hCPCs with Pim-1 enhances repair of damaged myocardium. Ex vivo gene delivery to modify stem cells has emerged as a viable option addressing current limitations in the field. This study demonstrates that efficacy of human CPCs from the failing myocardium can be safely and significantly enhanced through expression of Pim-1 kinase, setting the stage for use of engineered cells

  19. The latency-associated promoter of herpes simplex virus type 1 requires a region downstream of the transcription start site for long-term expression during latency.

    PubMed Central

    Lokensgard, J R; Berthomme, H; Feldman, L T

    1997-01-01

    The latency-associated transcript (LAT) promoter of herpes simplex virus type 1 (HSV-1) is unique among the many promoters on the viral genome in that it remains active during the latent state. We have previously shown that a DNA fragment comprising the LAT promoter element through the cap site, when moved from the LAT locus to the glycoprotein C gene, is capable of only short-term expression. These and other data suggested that an HSV DNA element from the repeat region, not included in the LAT promoter itself, might be needed to preserve long-term expression. Based on a number of recombinant viruses, we narrowed our search for this putative element to a region 3' of the LAT transcription start site. In the present study, we have shown that a 1.1-kb DNA fragment containing the putative long-term expression element (LTE) is able to restore latent-phase gene expression to the LAT promoter. The element appeared to function best when it was placed in its natural location, which is 3' of the LAT promoter; however, partial function was obtained when the LTE was inserted upstream of the LAT promoter in the reverse direction. These data indicate that the LAT promoter region is more complex than originally anticipated and that in addition to requiring both core promoter and neuronal transcription factor binding sites, the promoter requires a specific region of DNA to prevent its shutoff during a latent infection. PMID:9261395

  20. Discovery and Optimization of Macrocyclic Quinoxaline-pyrrolo-dihydropiperidinones as Potent Pim-1/2 Kinase Inhibitors.

    PubMed

    Cee, Victor J; Chavez, Frank; Herberich, Bradley; Lanman, Brian A; Pettus, Liping H; Reed, Anthony B; Wu, Bin; Wurz, Ryan P; Andrews, Kristin L; Chen, Jie; Hickman, Dean; Laszlo, Jimmy; Lee, Matthew R; Guerrero, Nadia; Mattson, Bethany K; Nguyen, Yen; Mohr, Christopher; Rex, Karen; Sastri, Christine E; Wang, Paul; Wu, Qiong; Wu, Tian; Xu, Yang; Zhou, Yihong; Winston, Jeffrey T; Lipford, J Russell; Tasker, Andrew S; Wang, Hui-Ling

    2016-04-14

    The identification of Pim-1/2 kinase overexpression in B-cell malignancies suggests that Pim kinase inhibitors will have utility in the treatment of lymphoma, leukemia, and multiple myeloma. Starting from a moderately potent quinoxaline-dihydropyrrolopiperidinone lead, we recognized the potential for macrocyclization and developed a series of 13-membered macrocycles. The structure-activity relationships of the macrocyclic linker were systematically explored, leading to the identification of 9c as a potent, subnanomolar inhibitor of Pim-1 and -2. This molecule also potently inhibited Pim kinase activity in KMS-12-BM, a multiple myeloma cell line with relatively high endogenous levels of Pim-1/2, both in vitro (pBAD IC50 = 25 nM) and in vivo (pBAD EC50 = 30 nM, unbound), and a 100 mg/kg daily dose was found to completely arrest the growth of KMS-12-BM xenografts in mice. PMID:27096050

  1. Cell-permeable Carboxyl-terminal p27Kip1 Peptide Exhibits Anti-tumor Activity by Inhibiting Pim-1 Kinase*

    PubMed Central

    Morishita, Daisuke; Takami, Miho; Yoshikawa, Seiko; Katayama, Ryohei; Sato, Shigeo; Kukimoto-Niino, Mutsuko; Umehara, Takashi; Shirouzu, Mikako; Sekimizu, Kazuhisa; Yokoyama, Shigeyuki; Fujita, Naoya

    2011-01-01

    The incidence and death rate of prostate cancer is increasing rapidly. In addition, the low sensitivity of prostate cancer to chemotherapy makes it difficult to treat this condition. The serine/threonine kinase Pim-1 plays an important role in cell cycle progression and apoptosis inhibition, resulting in prostate tumorigenesis. Therefore, Pim-1 inhibition has been expected to be an attractive target for developing new anti-cancer drugs. However, no small compounds targeting Pim-1 have progressed to clinical use because of their lack of specificity. Here, we have reported a new cell-permeable Pim-1 inhibitory p27Kip1 peptide that could interfere with the binding of Pim-1 to its substrates and act as an anti-cancer drug. The peptide could bind to Pim-1 and inhibit phosphorylation of endogenous p27Kip1 and Bad by Pim-1. Treatment of prostate cancer with the peptide induces G1 arrest and subsequently apoptosis in vitro. However, the peptide showed almost no growth inhibitory or apoptosis-inducing effects in normal cells. The peptide could inhibit tumor growth in in vivo prostate cancer xenograft models. Moreover, the peptide treatment could overcome resistance to taxol, one of the first line chemotherapeutic agents for prostate cancer, and a combination of the peptide with taxol synergistically inhibited prostate cancer growth in vivo. These results indicate that a Pim-1 inhibitory p27Kip1 peptide could be developed as an anti-cancer drug against prostate cancer. PMID:21062737

  2. The influence of few-layer graphene on the gas permeability of the high-free-volume polymer PIM-1

    PubMed Central

    Althumayri, Khalid; Harrison, Wayne J.; Shin, Yuyoung; Gardiner, John M.; Casiraghi, Cinzia; Bernardo, Paola; Clarizia, Gabriele

    2016-01-01

    Gas permeability data are presented for mixed matrix membranes (MMMs) of few-layer graphene in the polymer of intrinsic microporosity PIM-1, and the results compared with previously reported data for two other nanofillers in PIM-1: multiwalled carbon nanotubes functionalized with poly(ethylene glycol) (f-MWCNTs) and fused silica. For few-layer graphene, a significant enhancement in permeability is observed at very low graphene content (0.05 vol.%), which may be attributed to the effect of the nanofiller on the packing of the polymer chains. At higher graphene content permeability decreases, as expected for the addition of an impermeable filler. Other nanofillers, reported in the literature, also give rise to enhancements in permeability, but at substantially higher loadings, the highest measured permeabilities being at 1 vol.% for f-MWCNTs and 24 vol.% for fused silica. These results are consistent with the hypothesis that packing of the polymer chains is influenced by the curvature of the nanofiller surface at the nanoscale, with an increasingly pronounced effect on moving from a more-or-less spherical nanoparticle morphology (fused silica) to a cylindrical morphology (f-MWCNT) to a planar morphology (graphene). While the permeability of a high-free-volume polymer such as PIM-1 decreases over time through physical ageing, for the PIM-1/graphene MMMs a significant permeability enhancement was retained after eight months storage. PMID:26712643

  3. The influence of few-layer graphene on the gas permeability of the high-free-volume polymer PIM-1.

    PubMed

    Althumayri, Khalid; Harrison, Wayne J; Shin, Yuyoung; Gardiner, John M; Casiraghi, Cinzia; Budd, Peter M; Bernardo, Paola; Clarizia, Gabriele; Jansen, Johannes C

    2016-02-13

    Gas permeability data are presented for mixed matrix membranes (MMMs) of few-layer graphene in the polymer of intrinsic microporosity PIM-1, and the results compared with previously reported data for two other nanofillers in PIM-1: multiwalled carbon nanotubes functionalized with poly(ethylene glycol) (f-MWCNTs) and fused silica. For few-layer graphene, a significant enhancement in permeability is observed at very low graphene content (0.05 vol.%), which may be attributed to the effect of the nanofiller on the packing of the polymer chains. At higher graphene content permeability decreases, as expected for the addition of an impermeable filler. Other nanofillers, reported in the literature, also give rise to enhancements in permeability, but at substantially higher loadings, the highest measured permeabilities being at 1 vol.% for f-MWCNTs and 24 vol.% for fused silica. These results are consistent with the hypothesis that packing of the polymer chains is influenced by the curvature of the nanofiller surface at the nanoscale, with an increasingly pronounced effect on moving from a more-or-less spherical nanoparticle morphology (fused silica) to a cylindrical morphology (f-MWCNT) to a planar morphology (graphene). While the permeability of a high-free-volume polymer such as PIM-1 decreases over time through physical ageing, for the PIM-1/graphene MMMs a significant permeability enhancement was retained after eight months storage. PMID:26712643

  4. Crystal Structure of Pim1 Kinase in Complex with a Pyrido[4,3-D]Pyrimidine Derivative Suggests a Unique Binding Mode

    PubMed Central

    Cho, Jea-Won; Choi, Jang-Sik; Lee, Jaekyoo; Song, Ho-Juhn; Koh, Jong Sung; Lee, Byung Il

    2013-01-01

    Human Pim1 kinase is a serine/threonine protein kinase that plays important biological roles in cell survival, apoptosis, proliferation, and differentiation. Moreover, Pim1 is up-regulated in various hematopoietic malignancies and solid tumors. Thus, Pim1 is an attractive target for cancer therapeutics, and there has been growing interest in developing small molecule inhibitors for Pim1. Here, we describe the crystal structure of Pim1 in complex with a newly developed pyrido[4,3-d]pyrimidine-derivative inhibitor (SKI-O-068). Our inhibitor exhibits a half maximum inhibitory concentration (IC50) of 123 (±14) nM and has an unusual binding mode in complex with Pim1 kinase. The interactions between SKI-O-068 and the Pim1 active site pocket residue are different from those of other scaffold inhibitor-bound structures. The binding mode analysis suggests that the SKI-O-068 inhibitor can be improved by introducing functional groups that facilitate direct interaction with Lys67, which aid in the design of an optimized inhibitor. PMID:23936194

  5. Synthesis and biological evaluation of quinoline derivatives as potential anti-prostate cancer agents and Pim-1 kinase inhibitors.

    PubMed

    Li, Kun; Li, Ying; Zhou, Di; Fan, Yinbo; Guo, Hongye; Ma, Tianyi; Wen, Jiachen; Liu, Dan; Zhao, Linxiang

    2016-04-15

    In this work, a series of quinoline derivatives were designed and synthesized as antitumor agents. Most quinolines showed potent anti-proliferative activity against human prostatic cancer PC-3 cell line. Among which, 9d, 9f and 9g were the most effective compounds with GI50 values of 2.60, 2.81 and 1.29μM, respectively. Structure-activity relationship analysis indicated that the secondary amine linked quinoline and pyridine ring played an important role in the anti-proliferative effects. Mechanistic studies revealed that 9g was a potential Pim-1 kinase inhibitor with abilities of cell cycle arrest and apoptosis induction. Considering of the increased activity of Pim-1 in prostate cancer, such compounds have potential to be developed as anti-prostate cancer agents. PMID:26979485

  6. Identification of the human pim-1 gene product as a 33-kilodalton cytoplasmic protein with tyrosine kinase activity

    SciTech Connect

    Telerman, A.; Amson, R.; Zakut-Houri, R.; Givol, D.

    1988-04-01

    The human pim-1 gene was recently identified as a new putative oncogene located on chromosome 6p21, a region showing karyotypic abnormalities in particular leukemias. In the present work the authors characterized the pim protein product. In vitro translation of positively selected poly(A)/sup +/ mRNA indicates that this gene encodes a 33-kilodalton protein. Anti-pim antibodies were raised against a fused TrpE-pim protein induced in a bacterial expression vector. This antibody immunoprecipitated a 33-kilodalton protein from in vivo (/sup 35/S)methionine-labeled K562 and KCl myelogenous origin cell lines. This protein was localized to the cytoplasm, and in vivo labeling as well as in vitro kinase assay suggests that it is a phosphoprotein with tyrosine kinase activity. This was further confirmed by performing autophosphorylation directly on a p33/sup pim/-containing gel band cut out after sodium dodecyl sulfate-polyacrylamide gel electrphoresis. The results imply that the tyrosine kinase activity of pim can be recovered after boiling the pim-1 protein in sample buffer: a feature not described yet for this class of protein. These results suggest that pim-1 is a new member of the subgroup of oncogenes encoding tyrosine kinases.

  7. Association of Nuclear PIM1 Expression with Lymph Node Metastasis and Poor Prognosis in Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma

    PubMed Central

    Jiang, Richeng; Wang, Xinyue; Jin, Ziliang; Li, Kai

    2016-01-01

    Increasing evidence indicates that aberrant expression of PIM1, p-STAT3 and c-MYC is involved in the pathogenesis of various solid tumors, but its prognostic value is still unclear in non-small cell lung cancer (NSCLC). Here, we sought to evaluate the expression and prognostic role of these markers in patients with lung adenocarcinoma (AD) and squamous cell carcinoma (SCC). Real time RT-PCR and Western blotting was used to analyze the mRNA and protein expression of PIM1 in NSCLC cell lines, respectively. The expression of PIM1, p-STAT3, and c-MYC was immunohistochemically tested in archival tumor samples from 194 lung AD and SCC patients. High nuclear PIM1 expression was detected in 43.3% of ADs and SCCs, and was significantly correlated with lymph node (LN) metastasis (P = 0.028) and histology (P = 0.003). High nuclear PIM1 expression (P = 0.034), locally advanced stage (P < 0.001), AD (P = 0.007) and poor pathologic differentiation (P = 0.002) were correlated with worse disease-free survival (DFS). High nuclear PIM1 expression (P = 0.009), advanced clinical stage (P < 0.001) and poor pathologic differentiation (P = 0.004) were independent unfavorable prognostic factors for overall survival (OS). High p-STAT3 expression was not associated with OS but significantly correlated with LN metastasis, while c-MYC was not significantly correlated with any clinicopathological parameter or survival. Therefore, in AD and SCC patients, nuclear PIM1 expression level is an independent factor for DFS and OS and it might serve as a predictive biomarker for outcome. PMID:26918046

  8. The mRNA-binding protein HuR promotes hypoxia-induced chemoresistance through posttranscriptional regulation of the proto-oncogene PIM1 in pancreatic cancer cells.

    PubMed

    Blanco, F F; Jimbo, M; Wulfkuhle, J; Gallagher, I; Deng, J; Enyenihi, L; Meisner-Kober, N; Londin, E; Rigoutsos, I; Sawicki, J A; Risbud, M V; Witkiewicz, A K; McCue, P A; Jiang, W; Rui, H; Yeo, C J; Petricoin, E; Winter, J M; Brody, J R

    2016-05-01

    Previously, it has been shown that pancreatic ductal adenocarcinoma (PDA) tumors exhibit high levels of hypoxia, characterized by low oxygen pressure (pO2) and decreased O2 intracellular perfusion. Chronic hypoxia is strongly associated with resistance to cytotoxic chemotherapy and chemoradiation in an understudied phenomenon known as hypoxia-induced chemoresistance. The hypoxia-inducible, pro-oncogenic, serine-threonine kinase PIM1 (Proviral Integration site for Moloney murine leukemia virus 1) has emerged as a key regulator of hypoxia-induced chemoresistance in PDA and other cancers. Although its role in therapeutic resistance has been described previously, the molecular mechanism behind PIM1 overexpression in PDA is unknown. Here, we demonstrate that cis-acting AU-rich elements (ARE) present within a 38-base pair region of the PIM1 mRNA 3'-untranslated region mediate a regulatory interaction with the mRNA stability factor HuR (Hu antigen R) in the context of tumor hypoxia. Predominantly expressed in the nucleus in PDA cells, HuR translocates to the cytoplasm in response to hypoxic stress and stabilizes the PIM1 mRNA transcript, resulting in PIM1 protein overexpression. A reverse-phase protein array revealed that HuR-mediated regulation of PIM1 protects cells from hypoxic stress through phosphorylation and inactivation of the apoptotic effector BAD and activation of MEK1/2. Importantly, pharmacological inhibition of HuR by MS-444 inhibits HuR homodimerization and its cytoplasmic translocation, abrogates hypoxia-induced PIM1 overexpression and markedly enhances PDA cell sensitivity to oxaliplatin and 5-fluorouracil under physiologic low oxygen conditions. Taken together, these results support the notion that HuR has prosurvival properties in PDA cells by enabling them with growth advantages in stressful tumor microenvironment niches. Accordingly, these studies provide evidence that therapeutic disruption of HuR's regulation of PIM1 may be a key strategy in

  9. Time of flight and the MUSE experiment in the PIM1 Channel at the Paul Sherrer Institute

    NASA Astrophysics Data System (ADS)

    Lin, Wan; MUSE Collaboration

    2015-10-01

    The MUSE experiment in the PIM1 Channel at the Paul Sherrer Institute in Villigen, Switzerland, measures scattering of electrons and muons from a liquid hydrogen target. The intent of the experiment is to deduce from the scattering probabilities whether the radius of the proton is the same when determined from the scattering of the two different particle types. An important technique for the experiment is precise timing measurements, using high precision scintillators and a beam Cerenkov counter. We will describe the motivations for the precise timing measurement. We will present results for the timing measurements from prototype experimental detectors. We will also present results from a simulation program, Geant4, that was used to calculate energy loss corrections to the time of flight determined between the beam Cherenkov counter and the scintillator. This work is supported in part by the U.S. National Science Foundation Grant PHY 1306126 and the Douglass Project for Women in Math, Science, and Engineering.

  10. Discovery of novel Pim-1 kinase inhibitors by a hierarchical multistage virtual screening approach based on SVM model, pharmacophore, and molecular docking.

    PubMed

    Ren, Ji-Xia; Li, Lin-Li; Zheng, Ren-Lin; Xie, Huan-Zhang; Cao, Zhi-Xing; Feng, Shan; Pan, You-Li; Chen, Xin; Wei, Yu-Quan; Yang, Sheng-Yong

    2011-06-27

    In this investigation, we describe the discovery of novel potent Pim-1 inhibitors by employing a proposed hierarchical multistage virtual screening (VS) approach, which is based on support vector machine-based (SVM-based VS or SB-VS), pharmacophore-based VS (PB-VS), and docking-based VS (DB-VS) methods. In this approach, the three VS methods are applied in an increasing order of complexity so that the first filter (SB-VS) is fast and simple, while successive ones (PB-VS and DB-VS) are more time-consuming but are applied only to a small subset of the entire database. Evaluation of this approach indicates that it can be used to screen a large chemical library rapidly with a high hit rate and a high enrichment factor. This approach was then applied to screen several large chemical libraries, including PubChem, Specs, and Enamine as well as an in-house database. From the final hits, 47 compounds were selected for further in vitro Pim-1 inhibitory assay, and 15 compounds show nanomolar level or low micromolar inhibition potency against Pim-1. In particular, four of them were found to have new scaffolds which have potential for the chemical development of Pim-1 inhibitors. PMID:21618971

  11. Identification of the First Inhibitor of the GBP1:PIM1 Interaction. Implications for the Development of a New Class of Anticancer Agents against Paclitaxel Resistant Cancer Cells

    PubMed Central

    2015-01-01

    Class III β-tubulin plays a prominent role in the development of drug resistance to paclitaxel by allowing the incorporation of the GBP1 GTPase into microtubules. Once in the cytoskeleton, GBP1 binds to prosurvival kinases such as PIM1 and initiates a signaling pathway that induces resistance to paclitaxel. Therefore, the inhibition of the GBP1:PIM1 interaction could potentially revert resistance to paclitaxel. A panel of 44 4-azapodophyllotoxin derivatives was screened in the NCI-60 cell panel. The result is that 31 are active and the comparative analysis demonstrated specific activity in paclitaxel-resistant cells. Using surface plasmon resonance, we were able to prove that NSC756093 is a potent in vitro inhibitor of the GBP1:PIM1 interaction and that this property is maintained in vivo in ovarian cancer cells resistant to paclitaxel. Through bioinformatics, molecular modeling, and mutagenesis studies, we identified the putative NSC756093 binding site at the interface between the helical and the LG domain of GBP1. According to our results by binding to this site, the NSC756093 compound is able to stabilize a conformation of GBP1 not suitable for binding to PIM1. PMID:25211704

  12. In Silico Determination of Gas Permeabilities by Non-Equilibrium Molecular Dynamics: CO2 and He through PIM-1

    PubMed Central

    Frentrup, Hendrik; Hart, Kyle E.; Colina, Coray M.; Müller, Erich A.

    2015-01-01

    We study the permeation dynamics of helium and carbon dioxide through an atomistically detailed model of a polymer of intrinsic microporosity, PIM-1, via non-equilibrium molecular dynamics (NEMD) simulations. This work presents the first explicit molecular modeling of gas permeation through a high free-volume polymer sample, and it demonstrates how permeability and solubility can be obtained coherently from a single simulation. Solubilities in particular can be obtained to a very high degree of confidence and within experimental inaccuracies. Furthermore, the simulations make it possible to obtain very specific information on the diffusion dynamics of penetrant molecules and yield detailed maps of gas occupancy, which are akin to a digital tomographic scan of the polymer network. In addition to determining permeability and solubility directly from NEMD simulations, the results shed light on the permeation mechanism of the penetrant gases, suggesting that the relative openness of the microporous topology promotes the anomalous diffusion of penetrant gases, which entails a deviation from the pore hopping mechanism usually observed in gas diffusion in polymers. PMID:25764366

  13. Varicella zoster virus latency

    PubMed Central

    Eshleman, Emily; Shahzad, Aamir; Cohrs, Randall J

    2011-01-01

    Primary infection by varicella zoster virus (VZV) typically results in childhood chickenpox, at which time latency is established in the neurons of the cranial nerve, dorsal root and autonomic ganglia along the entire neuraxis. During latency, the histone-associated virus genome assumes a circular episomal configuration from which transcription is epigenetically regulated. The lack of an animal model in which VZV latency and reactivation can be studied, along with the difficulty in obtaining high-titer cell-free virus, has limited much of our understanding of VZV latency to descriptive studies of ganglia removed at autopsy and analogy to HSV-1, the prototype alphaherpesvirus. However, the lack of miRNA, detectable latency-associated transcript and T-cell surveillance during VZV latency highlight basic differences between the two neurotropic herpesviruses. This article focuses on VZV latency: establishment, maintenance and reactivation. Comparisons are made with HSV-1, with specific attention to differences that make these viruses unique human pathogens. PMID:21695042

  14. Low latency long wave infrared visible fusion

    NASA Astrophysics Data System (ADS)

    Robison, Derek

    2014-06-01

    Human factors issues related to head mounted imaging systems have driven the requirements for system latency to nearly the bounds of sensor physics. Image processing must therefore be performed in an envelope that is ever decreasing in size. This paper presents a complete method for intelligent fusion of a long wave infrared and visible sensor, including contrast enhancement in both spectrums, with end to end processing latency of less than 1 millisecond. The use of image statistics and opponent color theory allows fusion with minimal computational resources and latency. This algorithm has demonstrated performance without inducing any noticeable human factors issues during user trials.

  15. Marek's disease virus latency.

    PubMed

    Morgan, R W; Xie, Q; Cantello, J L; Miles, A M; Bernberg, E L; Kent, J; Anderson, A

    2001-01-01

    MDV latency is defined as the persistence of the viral genome in the absence of production of infectious virus except during reactivation. A number of systems for studying MDV latency exist, and most involve the use of lymphoblastoid cells or tumors. It has been difficult to divorce latency and transformation. Understanding the relationship between these two states remains a major challenge for the MDV system. Based on their patterns of expression, the MDV LATs are apt to be important in the balance between latent and lytic infections. The LATs are a complex group of transcripts. The profile of gene expression that characterizes latency differs among all herpesviruses, and MDV is no exception. MDV LATs bear little resemblance to LATs of other alphaherpesviruses or to the LATs of other lymphotropic herpesviruses. LAT splicing patterns are complex and the relationships among various spliced species or between these species and the large 10-kb transcript are unknown. In addition, the existence of any protein gene products of significance is unknown at this time. More work is needed to further investigate the significance and function of these RNAs. Better technology to construct mutants in the MDV system is badly needed, since the analysis of mutants in the chicken is a powerful and unique advantage of the MDV system. PMID:11217424

  16. Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6.

    PubMed

    Uras, Iris Z; Walter, Gina J; Scheicher, Ruth; Bellutti, Florian; Prchal-Murphy, Michaela; Tigan, Anca S; Valent, Peter; Heidel, Florian H; Kubicek, Stefan; Scholl, Claudia; Fröhling, Stefan; Sexl, Veronika

    2016-06-01

    Up to 30% of patients with acute myeloid leukemia have constitutively activating internal tandem duplications (ITDs) of the FLT3 receptor tyrosine kinase. Such mutations are associated with a poor prognosis and a high propensity to relapse after remission. FLT3 inhibitors are being developed as targeted therapy for FLT3-ITD(+) acute myeloid leukemia; however, their use is complicated by rapid development of resistance, which illustrates the need for additional therapeutic targets. We show that the US Food and Drug Administration-approved CDK4/6 kinase inhibitor palbociclib induces apoptosis of FLT3-ITD leukemic cells. The effect is specific for FLT3-mutant cells and is ascribed to the transcriptional activity of CDK6: CDK6 but not its functional homolog CDK4 is found at the promoters of the FLT3 and PIM1 genes, another important leukemogenic driver. There CDK6 regulates transcription in a kinase-dependent manner. Of potential clinical relevance, combined treatment with palbociclib and FLT3 inhibitors results in synergistic cytotoxicity. Simultaneously targeting two critical signaling nodes in leukemogenesis could represent a therapeutic breakthrough, leading to complete remission and overcoming resistance to FLT3 inhibitors. PMID:27099147

  17. Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6

    PubMed Central

    Uras, Iris Z.; Walter, Gina J.; Scheicher, Ruth; Bellutti, Florian; Prchal-Murphy, Michaela; Tigan, Anca S.; Valent, Peter; Heidel, Florian H.; Kubicek, Stefan; Scholl, Claudia; Fröhling, Stefan

    2016-01-01

    Up to 30% of patients with acute myeloid leukemia have constitutively activating internal tandem duplications (ITDs) of the FLT3 receptor tyrosine kinase. Such mutations are associated with a poor prognosis and a high propensity to relapse after remission. FLT3 inhibitors are being developed as targeted therapy for FLT3-ITD+ acute myeloid leukemia; however, their use is complicated by rapid development of resistance, which illustrates the need for additional therapeutic targets. We show that the US Food and Drug Administration–approved CDK4/6 kinase inhibitor palbociclib induces apoptosis of FLT3-ITD leukemic cells. The effect is specific for FLT3-mutant cells and is ascribed to the transcriptional activity of CDK6: CDK6 but not its functional homolog CDK4 is found at the promoters of the FLT3 and PIM1 genes, another important leukemogenic driver. There CDK6 regulates transcription in a kinase-dependent manner. Of potential clinical relevance, combined treatment with palbociclib and FLT3 inhibitors results in synergistic cytotoxicity. Simultaneously targeting two critical signaling nodes in leukemogenesis could represent a therapeutic breakthrough, leading to complete remission and overcoming resistance to FLT3 inhibitors. PMID:27099147

  18. Handling qualities effects of display latency

    NASA Technical Reports Server (NTRS)

    King, David W.

    1993-01-01

    Display latency is the time delay between aircraft response and the corresponding response of the cockpit displays. Currently, there is no explicit specification for allowable display lags to ensure acceptable aircraft handling qualities in instrument flight conditions. This paper examines the handling qualities effects of display latency between 70 and 400 milliseconds for precision instrument flight tasks of the V-22 Tiltrotor aircraft. Display delay effects on the pilot control loop are analytically predicted through a second order pilot crossover model of the V-22 lateral axis, and handling qualities trends are evaluated through a series of fixed-base piloted simulation tests. The results show that the effects of display latency for flight path tracking tasks are driven by the stability characteristics of the attitude control loop. The data indicate that the loss of control damping due to latency can be simply predicted from knowledge of the aircraft's stability margins, control system lags, and required control bandwidths. Based on the relationship between attitude control damping and handling qualities ratings, latency design guidelines are presented. In addition, this paper presents a design philosophy, supported by simulation data, for using flight director display augmentation to suppress the effects of display latency for delays up to 300 milliseconds.

  19. Synchronization by elastic neuronal latencies

    NASA Astrophysics Data System (ADS)

    Vardi, Roni; Timor, Reut; Marom, Shimon; Abeles, Moshe; Kanter, Ido

    2013-01-01

    Psychological and physiological considerations entail that formation and functionality of neuronal cell assemblies depend upon synchronized repeated activation such as zero-lag synchronization. Several mechanisms for the emergence of this phenomenon have been suggested, including the global network quantity, the greatest common divisor of neuronal circuit delay loops. However, they require strict biological prerequisites such as precisely matched delays and connectivity, and synchronization is represented as a stationary mode of activity instead of a transient phenomenon. Here we show that the unavoidable increase in neuronal response latency to ongoing stimulation serves as a nonuniform gradual stretching of neuronal circuit delay loops. This apparent nuisance is revealed to be an essential mechanism in various types of neuronal time controllers, where synchronization emerges as a transient phenomenon and without predefined precisely matched synaptic delays. These findings are described in an experimental procedure where conditioned stimulations were enforced on a circuit of neurons embedded within a large-scale network of cortical cells in vitro, and are corroborated and extended by simulations of circuits composed of Hodgkin-Huxley neurons with time-dependent latencies. These findings announce a cortical time scale for time controllers based on tens of microseconds stretching of neuronal circuit delay loops per spike. They call for a reexamination of the role of the temporal periodic mode in brain functionality using advanced in vitro and in vivo experiments.

  20. Epigenetics and Genetics of Viral Latency.

    PubMed

    Lieberman, Paul M

    2016-05-11

    Viral latency can be considered a metastable, nonproductive infection state that is capable of subsequent reactivation to repeat the infection cycle. Viral latent infections have numerous associated pathologies, including cancer, birth defects, neuropathy, cardiovascular disease, chronic inflammation, and immunological dysfunctions. The mechanisms controlling the establishment, maintenance, and reactivation from latency are complex and diversified among virus families, species, and strains. Yet, as examined in this review, common properties of latent viral infections can be defined. Eradicating latent virus has become an important but elusive challenge and will require a more complete understanding of the mechanisms controlling these processes. PMID:27173930

  1. Apparatus for fixing latency

    DOEpatents

    Hall, David R.; Bartholomew, David B.; Moon, Justin; Koehler, Roger O.

    2009-09-08

    An apparatus for fixing computational latency within a deterministic region on a network comprises a network interface modem, a high priority module and at least one deterministic peripheral device. The network interface modem is in communication with the network. The high priority module is in communication with the network interface modem. The at least one deterministic peripheral device is connected to the high priority module. The high priority module comprises a packet assembler/disassembler, and hardware for performing at least one operation. Also disclosed is an apparatus for executing at least one instruction on a downhole device within a deterministic region, the apparatus comprising a control device, a downhole network, and a downhole device. The control device is near the surface of a downhole tool string. The downhole network is integrated into the tool string. The downhole device is in communication with the downhole network.

  2. Minimizing Input-to-Output Latency in Virtual Environment

    NASA Technical Reports Server (NTRS)

    Adelstein, Bernard D.; Ellis, Stephen R.; Hill, Michael I.

    2009-01-01

    A method and apparatus were developed to minimize latency (time delay ) in virtual environment (VE) and other discrete- time computer-base d systems that require real-time display in response to sensor input s. Latency in such systems is due to the sum of the finite time requi red for information processing and communication within and between sensors, software, and displays.

  3. Short-latency primate vestibuloocular responses during translation

    NASA Technical Reports Server (NTRS)

    Angelaki, D. E.; McHenry, M. Q.

    1999-01-01

    Short-lasting, transient head displacements and near target fixation were used to measure the latency and early response gain of vestibularly evoked eye movements during lateral and fore-aft translations in rhesus monkeys. The latency of the horizontal eye movements elicited during lateral motion was 11.9 +/- 5.4 ms. Viewing distance-dependent behavior was seen as early as the beginning of the response profile. For fore-aft motion, latencies were different for forward and backward displacements. Latency averaged 7.1 +/- 9.3 ms during forward motion (same for both eyes) and 12.5 +/- 6.3 ms for the adducting eye (e.g., left eye during right fixation) during backward motion. Latencies during backward motion were significantly longer for the abducting eye (18.9 +/- 9.8 ms). Initial acceleration gains of the two eyes were generally larger than unity but asymmetric. Specifically, gains were consistently larger for abducting than adducting eye movements. The large initial acceleration gains tended to compensate for the response latencies such that the early eye movement response approached, albeit consistently incompletely, that required for maintaining visual acuity during the movement. These short-latency vestibuloocular responses could complement the visually generated optic flow responses that have been shown to exhibit much longer latencies.

  4. Pim kinase expression is induced by LTP stimulation and required for the consolidation of enduring LTP.

    PubMed Central

    Konietzko, U; Kauselmann, G; Scafidi, J; Staubli, U; Mikkers, H; Berns, A; Schweizer, M; Waltereit, R; Kuhl, D

    1999-01-01

    In animals and several cellular models of synaptic plasticity, long-lasting changes in synaptic strength are dependent on gene transcription and translation. Here we demonstrate that Pim-1, a serine/threonine kinase closely related to Pim-2 and Pim-3, is induced in hippocampus in response to stimuli that evoke long-term potentiation (LTP). Mice deficient for Pim-1 show normal synaptic transmission and short-term plasticity. However, they fail to consolidate enduring LTP even though Pim-2 and Pim-3 are constitutively expressed in the hippocampus and Pim-3 expression is similarly induced by synaptic activity. Thus, expression of Pim-1 is required for LTP. Its level of expression and, consequently, its capacity to phosphorylate target proteins in dendritic and nuclear compartments of stimulated neurons might be a determining factor for the establishment of long-lasting changes in synaptic strength. PMID:10369676

  5. A hardwired HIV latency program

    PubMed Central

    Razooky, Brandon S.; Pai, Anand; Aull, Katherine; Rouzine, Igor M.; Weinberger, Leor S.

    2015-01-01

    SUMMARY Biological circuits can be controlled by two general schemes: environmental sensing or autonomous programs. For viruses such as HIV, the prevailing hypothesis is that latent infection is controlled by cellular state (i.e. environment) with latency simply an epiphenomenon of infected cells transitioning from an activated to resting state. However, we find HIV expression persists despite the activated-to-resting cellular transition. Mathematical modeling indicates that HIV’s Tat positive-feedback circuitry enables this persistence and strongly controls latency. To overcome the inherent crosstalk between viral circuitry and cellular activation, and directly test this hypothesis, we synthetically decouple viral dependence on cellular environment from viral transcription. These circuits enable control of viral transcription without cellular activation and show that Tat feedback is sufficient to regulate latency independent of cellular activation. Overall, synthetic reconstruction demonstrates that a largely autonomous, viral-encoded program underlies HIV latency—potentially explaining why cell-targeted latency-reversing agents exhibit incomplete penetrance. PMID:25723172

  6. Data latency and the user community

    NASA Astrophysics Data System (ADS)

    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

  7. Monitoring data transfer latency in CMS computing operations

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

    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 factors that contribute to transfer completion time. As case studies, we analyze several typical CMS transfer workflows, such as distribution of collision event data from CERN or upload of simulated event data from the Tier-2 centres to the archival Tier-1 centres. For each workflow, we present the typical patterns of transfer latencies that have been identified with the latency monitor. We identify the areas in PhEDEx where a development effort can reduce the latency, and we show how we are able to detect stuck transfers which need operator intervention. We propose a set of metrics to alert about stuck subscriptions and prompt for manual intervention, with the aim of improving transfer completion times.

  8. The Biology of Papillomavirus Latency

    PubMed Central

    Maglennon, Gareth Adam; Doorbar, John

    2012-01-01

    The presence of viral DNA in the absence of disease has suggested that papillomaviruses, like many other viruses, can exist as latent infections in the skin or other epithelial sites. In animal models, where detailed investigation has been carried out, papillomavirus DNA can be found at sites of previous infection following immune regression, with the site of latent infection being the epithelial basal layer. Such studies suggest that immune surveillance can restrict viral gene expression in the basal and parabasal layers without efficiently suppressing viral genome replication, most probably through the action of memory T-cells in the skin or dermis. Although gradual papillomavirus genome loss appears to occur over time at latent sites, immunosuppression can arrest this, and can lead to an elevation in viral genome copy number in experimental systems. In addition to immune-mediated latency, it appears that a similar situation can be achieved following infection at low virus titres and/or infection at epithelial sites where the virus life cycle is not properly supported. Such silent of asymptomatic infections do not necessarily involve the host immune system and may be controlled by different mechanisms. It appears that virus reactivation can be triggered by mechanical irritation, wounding or by UV irradiation which changes the local environment. Although the duration of papillomavirus latency in humans is not yet known, it is likely that some of the basic principles will resemble those elucidated in these model systems, and that persistence in the absence of disease may be the default outcome for at least some period of time following regression. PMID:23341854

  9. Negative elongation factor is required for the maintenance of proviral latency but does not induce promoter-proximal pausing of RNA polymerase II on the HIV long terminal repeat.

    PubMed

    Jadlowsky, Julie K; Wong, Julian Y; Graham, Amy C; Dobrowolski, Curtis; Devor, Renee L; Adams, Mark D; Fujinaga, Koh; Karn, Jonathan

    2014-06-01

    The role of the negative elongation factor (NELF) in maintaining HIV latency was investigated following small hairpin RNA (shRNA) knockdown of the NELF-E subunit, a condition that induced high levels of proviral transcription in latently infected Jurkat T cells. Chromatin immunoprecipitation (ChIP) assays showed that latent proviruses accumulate RNA polymerase II (RNAP II) on the 5' long terminal repeat (LTR) but not on the 3' LTR. NELF colocalizes with RNAP II, and its level increases following proviral induction. RNAP II pause sites on the HIV provirus were mapped to high resolution by ChIP with high-throughput sequencing (ChIP-Seq). Like cellular promoters, RNAP II accumulates at around position +30, but HIV also shows additional pausing at +90, which is immediately downstream of a transactivation response (TAR) element and other distal sites on the HIV LTR. Following NELF-E knockdown or tumor necrosis factor alpha (TNF-α) stimulation, promoter-proximal RNAP II levels increase up to 3-fold, and there is a dramatic increase in RNAP II levels within the HIV genome. These data support a kinetic model for proviral transcription based on continuous replacement of paused RNAP II during both latency and productive transcription. In contrast to most cellular genes, HIV is highly activated by the combined effects of NELF-E depletion and activation of initiation by TNF-α, suggesting that opportunities exist to selectively activate latent HIV proviruses. PMID:24636995

  10. Negative Elongation Factor Is Required for the Maintenance of Proviral Latency but Does Not Induce Promoter-Proximal Pausing of RNA Polymerase II on the HIV Long Terminal Repeat

    PubMed Central

    Jadlowsky, Julie K.; Wong, Julian Y.; Graham, Amy C.; Dobrowolski, Curtis; Devor, Renee L.; Adams, Mark D.; Fujinaga, Koh

    2014-01-01

    The role of the negative elongation factor (NELF) in maintaining HIV latency was investigated following small hairpin RNA (shRNA) knockdown of the NELF-E subunit, a condition that induced high levels of proviral transcription in latently infected Jurkat T cells. Chromatin immunoprecipitation (ChIP) assays showed that latent proviruses accumulate RNA polymerase II (RNAP II) on the 5′ long terminal repeat (LTR) but not on the 3′ LTR. NELF colocalizes with RNAP II, and its level increases following proviral induction. RNAP II pause sites on the HIV provirus were mapped to high resolution by ChIP with high-throughput sequencing (ChIP-Seq). Like cellular promoters, RNAP II accumulates at around position +30, but HIV also shows additional pausing at +90, which is immediately downstream of a transactivation response (TAR) element and other distal sites on the HIV LTR. Following NELF-E knockdown or tumor necrosis factor alpha (TNF-α) stimulation, promoter-proximal RNAP II levels increase up to 3-fold, and there is a dramatic increase in RNAP II levels within the HIV genome. These data support a kinetic model for proviral transcription based on continuous replacement of paused RNAP II during both latency and productive transcription. In contrast to most cellular genes, HIV is highly activated by the combined effects of NELF-E depletion and activation of initiation by TNF-α, suggesting that opportunities exist to selectively activate latent HIV proviruses. PMID:24636995

  11. CHRONIC DISSEMINATED HISTOPLASMOSIS WITH PROLONGED LATENCY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  12. Host-cell-determined methylation of specific Epstein-Barr virus promoters regulates the choice between distinct viral latency programs.

    PubMed Central

    Schaefer, B C; Strominger, J L; Speck, S H

    1997-01-01

    Epstein-Barr virus (EBV) is capable of adopting three distinct forms of latency: the type III latency program, in which six EBV-encoded nuclear antigens (EBNAs) are expressed, and the type I and type II latency programs, in which only a single viral nuclear protein, EBNA1, is produced. Several groups have reported heavy CpG methylation of the EBV genome in Burkitt's lymphoma cell lines which maintain type I latency, and loss of viral genome methylation in tumor cell lines has been correlated with a switch to type III latency. Here, evidence that the type III latency program must be inactivated by methylation to allow EBV to enter the type I or type II restricted latency program is provided. The data demonstrates that the EBNA1 gene promoter, Qp, active in types I and II latency, is encompassed by a CpG island which is protected from methylation. CpG methylation inactivates the type III latency program and consequently allows the type I or II latency program to operate by alleviating EBNA1-mediated repression of Qp. Methylation of the type III latency EBNA gene promoter, Cp, appears to be essential to prevent type III latency, since EBNA1 is expressed in all latently infected cells and, as shown here, is the only viral antigen required for activation of Cp. EBV is thus a pathogen which subverts host-cell-determined methylation to regulate distinct genetic programs. PMID:8972217

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

    PubMed

    Stoszko, Mateusz; De Crignis, Elisa; Rokx, Casper; Khalid, Mir Mubashir; Lungu, Cynthia; Palstra, Robert-Jan; Kan, Tsung Wai; Boucher, Charles; Verbon, Annelies; Dykhuizen, Emily C; Mahmoudi, Tokameh

    2016-01-01

    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. PMID:26870822

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

    PubMed Central

    Stoszko, Mateusz; De Crignis, Elisa; Rokx, Casper; Khalid, Mir Mubashir; Lungu, Cynthia; Palstra, Robert-Jan; Kan, Tsung Wai; Boucher, Charles; Verbon, Annelies; Dykhuizen, Emily C.; Mahmoudi, Tokameh

    2015-01-01

    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. PMID:26870822

  15. EBV latency types adopt alternative chromatin conformations.

    PubMed

    Tempera, Italo; Klichinsky, Michael; Lieberman, Paul M

    2011-07-01

    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. PMID:21829357

  16. Advanced LIGO low-latency searches

    NASA Astrophysics Data System (ADS)

    Kanner, Jonah; LIGO Scientific Collaboration, The 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.

  17. Primary display latency criteria based on flying qualities and performance data

    NASA Technical Reports Server (NTRS)

    Funk, John D., Jr.; Beck, Corin P.; Johns, John B.

    1993-01-01

    With a pilots' increasing use of visual cue augmentation, much requiring extensive pre-processing, there is a need to establish criteria for new avionics/display design. The timeliness and synchronization of the augmented cues is vital to ensure the performance quality required for precision mission task elements (MTEs) where augmented cues are the primary source of information to the pilot. Processing delays incurred while transforming sensor-supplied flight information into visual cues are unavoidable. Relationships between maximum control system delays and associated flying qualities levels are documented in MIL-F-83300 and MIL-F-8785. While cues representing aircraft status may be just as vital to the pilot as prompt control response for operations in instrument meteorological conditions, presently, there are no specification requirements on avionics system latency. To produce data relating avionics system latency to degradations in flying qualities, the Navy conducted two simulation investigations. During the investigations, flying qualities and performance data were recorded as simulated avionics system latency was varied. Correlated results of the investigation indicates that there is a detrimental impact of latency on flying qualities. Analysis of these results and consideration of key factors influencing their application indicate that: (1) Task performance degrades and pilot workload increases as latency is increased. Inconsistency in task performance increases as latency increases. (2) Latency reduces the probability of achieving Level 1 handling qualities with avionics system latency as low as 70 ms. (3) The data suggest that the achievement of desired performance will be ensured only at display latency values below 120 ms. (4) These data also suggest that avoidance of inadequate performance will be ensured only at display latency values below 150 ms.

  18. Experimental investigation of herpes simplex virus latency.

    PubMed Central

    Wagner, E K; Bloom, D C

    1997-01-01

    The clinical manifestations of herpes simplex virus infection generally involve a mild and localized primary infection followed by asymptomatic (latent) infection interrupted sporadically by periods of recrudescence (reactivation) where virus replication and associated cytopathologic findings are manifest at the site of initial infection. During the latent phase of infection, viral genomes, but not infectious virus itself, can be detected in sensory and autonomic neurons. The process of latent infection and reactivation has been subject to continuing investigation in animal models and, more recently, in cultured cells. The initiation and maintenance of latent infection in neurons are apparently passive phenomena in that no virus gene products need be expressed or are required. Despite this, a single latency-associated transcript (LAT) encoded by DNA encompassing about 6% of the viral genome is expressed during latent infection in a minority of neurons containing viral DNA. This transcript is spliced, and the intron derived from this splicing is stably maintained in the nucleus of neurons expressing it. Reactivation, which can be induced by stress and assayed in several animal models, is facilitated by the expression of LAT. Although the mechanism of action of LAT-mediated facilitation of reactivation is not clear, all available evidence argues against its involving the expression of a protein. Rather, the most consistent models of action involve LAT expression playing a cis-acting role in a very early stage of the reactivation process. PMID:9227860

  19. Low latency memory access and synchronization

    DOEpatents

    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.

    2007-02-06

    A low latency memory system access is provided in association with a weakly-ordered multiprocessor system. Each 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.

  20. Low latency memory access and synchronization

    DOEpatents

    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.

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

    PubMed

    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. PMID:26529463

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

    NASA Astrophysics Data System (ADS)

    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.

  3. HSV Latency In Vitro : In Situ Hybridization Methods.

    PubMed

    Wilcox, C L; Smith, R L

    1998-01-01

    We have developed an in vitro model of herpes simplex virus (HSV) latency in primary neurons that mimics many aspects of HSV latency in animal models and the human disease (1-3). Using this model, we demonstrated that HSV-1 and HSV-2 establish latent infections in vitro in the same neuronal cell types that are shown to harbor latent HSV in humans (3). Latent HSV infections can be produced in neuronal cultures from ganglia of rodents and primates with similar results (3). In all cases examined, the neurotrophin, nerve growth factor (NGF), is required to maintain the latent infections. Depletion of NGF results in the reactivation of latent virus (1-3). Depending upon the conditions and the use of a high multiplicity of infection, latent HSV-1 infections are established in the majority of primary sensory or sympathetic neurons in tissue culture (2,4). To achieve high efficiency of establishment of latency with little or no evidence of lytic infection, an antiviral agent (e.g., acyclovir) is added to the neuronal cultures during the first week after inoculation with virus. However, latency can be established in the absence of antiviral treatment provided that the multiplicity of infection (MOI) is very low (1,2). At least one of the actions of the antiviral treatment is to prevent amplification of the input virus in the nonneuronal cells that are present in the culture at the outset of the infection. These nonneuronal cells are destroyed in the presence of acyclovir and virus (4). Latency is maintained in neurons in culture for as long as 10 wk in the presence of NGF. Viral transcripts and antigens associated with the productive infection are not detected during the latent infection (2,3,5). Viral transcription is restricted to the latency-associated transcripts (LAT) during the latent infection and is present in the nuclei of 80-90% of the neurons by 3 wk postinfection (4,5) Upon removal of NGF from the culture medium, for as brief as 1 h, reactivation of latent virus

  4. Low Latency Messages on Distributed Memory Multiprocessors

    DOE PAGESBeta

    Rosing, Matt; Saltz, Joel

    1995-01-01

    This article describes many of the issues in developing an efficient interface for communication on distributed memory machines. Although the hardware component of message latency is less than 1 ws on many distributed memory machines, the software latency associated with sending and receiving typed messages is on the order of 50 μs. The reason for this imbalance is that the software interface does not match the hardware. By changing the interface to match the hardware more closely, applications with fine grained communication can be put on these machines. This article describes several tests performed and many of the issues involvedmore » in supporting low latency messages on distributed memory machines.« less

  5. MicroRNA-155 Reinforces HIV Latency.

    PubMed

    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. PMID:25873391

  6. MicroRNA-155 Reinforces HIV Latency*

    PubMed Central

    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

  7. Long Latency Auditory Evoked Potentials during Meditation.

    PubMed

    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 (P<.001; analysis of variance and post hoc analysis with Bonferroni adjustment). The P1, P2, and N2 components showed a significant decrease in peak amplitudes during random thinking (P<.01; P<.001; P<.01, respectively) and nonmeditative focused thinking (P<.01; P<.01; P<.05, respectively). The results suggest that meditation 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. PMID:25380593

  8. Using Response Latency within a Preference Assessment

    ERIC Educational Resources Information Center

    Meador, Stephanie K.; Derby, K. Mark; McLaughlin, T. F.; Barretto, Anjali; Weber, Kim

    2007-01-01

    This study evaluated the effects of using differential reinforcement of other behavior (DRO) with a differential reinforcement of alternative behavior (DRA) resetting time schedule to reduce stereotypy in a child with Rett Syndrome. The primary purpose of the investigation was to compare latency and choice as dependent measures to identify…

  9. Arbitration in crossbar interconnect for low latency

    DOEpatents

    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.

  10. Detecting Intermediary Hosts by TCP Latency Measurements

    NASA Astrophysics Data System (ADS)

    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.

  11. Investigation of Koi Herpesvirus Latency in Koi▿

    PubMed Central

    Eide, Kathleen E.; Miller-Morgan, Tim; Heidel, Jerry R.; Kent, Michael L.; Bildfell, Rob J.; LaPatra, Scott; Watson, Gregory; Jin, Ling

    2011-01-01

    Koi herpesvirus (KHV) has recently been classified as a member of the family of Alloherpesviridae within the order of Herpesvirales. One of the unique features of Herpesviridae is latent infection following a primary infection. However, KHV latency has not been recognized. To determine if latency occurs in clinically normal fish from facilities with a history of KHV infection or exposure, the presence of the KHV genome was investigated in healthy koi by PCR and Southern blotting. KHV DNA, but not infectious virus or mRNAs from lytic infection, was detected in white blood cells from investigated koi. Virus shedding was examined via tissue culture and reverse transcription-PCR (RT-PCR) testing of gill mucus and feces from six koi every other day for 1 month. No infectious virus or KHV DNA was detected in fecal secretion or gill swabs, suggesting that neither acute nor persistent infection was present. To determine if KHV latent infections can be reactivated, six koi were subjected to a temperature stress regime. KHV DNA and infectious virus were detected in both gill and fecal swabs by day 8 following temperature stress. KHV DNA was also detectable in brain, spleen, gills, heart, eye, intestine, kidney, liver, and pancreas in euthanized koi 1 month post-temperature stress. Our study suggests that KHV may become latent in leukocytes and other tissues, that it can be reactivated from latency by temperature stress, and that it may be more widespread in the koi population than previously suspected. PMID:21389134

  12. Low latency messages on distributed memory multiprocessors

    NASA Technical Reports Server (NTRS)

    Rosing, Matthew; Saltz, Joel

    1993-01-01

    Many of the issues in developing an efficient interface for communication on distributed memory machines are described and a portable interface is proposed. Although the hardware component of message latency is less than one microsecond on many distributed memory machines, the software latency associated with sending and receiving typed messages is on the order of 50 microseconds. The reason for this imbalance is that the software interface does not match the hardware. By changing the interface to match the hardware more closely, applications with fine grained communication can be put on these machines. Based on several tests that were run on the iPSC/860, an interface that will better match current distributed memory machines is proposed. The model used in the proposed interface consists of a computation processor and a communication processor on each node. Communication between these processors and other nodes in the system is done through a buffered network. Information that is transmitted is either data or procedures to be executed on the remote processor. The dual processor system is better suited for efficiently handling asynchronous communications compared to a single processor system. The ability to send data or procedure is very flexible for minimizing message latency, based on the type of communication being performed. The test performed and the proposed interface are described.

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

    NASA Technical Reports Server (NTRS)

    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.

  14. Estimating the distribution of fault latency in a digital processor

    NASA Technical Reports Server (NTRS)

    Ellis, Erik L.; Butler, Ricky W.

    1987-01-01

    Presented is a statistical approach to measuring fault latency in a digital processor. The method relies on the use of physical fault injection where the duration of the fault injection can be controlled. Although a specific fault's latency period is never directly measured, the method indirectly determines the distribution of fault latency.

  15. The influence of motivational salience on saccade latencies.

    PubMed

    Rothkirch, Marcus; Ostendorf, Florian; Sax, Anne-Lene; Sterzer, Philipp

    2013-01-01

    Eye movements provide a direct link to study the allocation of overt attention to stimuli in the visual field. The initiation of saccades towards visual stimuli is known to be influenced by the bottom-up salience of stimuli as well as the motivational context of the task. Here, we asked whether the initiation of saccades is also influenced by the intrinsic motivational salience of a stimulus. Face stimuli were first associated with positive or negative motivational salience through instrumental learning. The same faces served as target stimuli in a subsequent saccade task, in which their motivational salience was no longer task-relevant. Participants performed either voluntary saccades, which required the selection of the saccade target out of two simultaneously presented stimuli (experiment 1), or reactive saccades, where only the target stimulus was presented (experiment 2). We found a specific effect of learned positive stimulus value on the latencies of voluntary saccades: For faces with high versus low positive motivational salience, saccadic latencies were significantly reduced. No such difference was observed for previously punished faces. In contrast, reactive saccades to both previously rewarded and punished faces were unaffected by learned stimulus value. Our findings show for the first time that saccadic preparation is susceptible to the acquired intrinsic motivational salience of visual stimuli. Based on the observation that only voluntary saccades but not reactive saccades were modulated, we conclude that the recruitment of neural processes for target identification is required to allow for an influence of motivational stimulus salience on saccadic preparation. PMID:23283417

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

    PubMed

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

    2010-01-01

    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. PMID:20730088

  17. Latency causes and reduction in optical metro networks

    NASA Astrophysics Data System (ADS)

    Bobrovs, Vjaceslavs; Spolitis, Sandis; Ivanovs, Girts

    2013-12-01

    The dramatic growth of transmitted information in fiber optical networks is leading to a concern about the network latency for high-speed reliable services like financial transactions, telemedicine, virtual and augmented reality, surveillance, and other applications. In order to ensure effective latency engineering, the delay variability needs to be accurately monitored and measured, in order to control it. This paper in brief describes causes of latency in fiber optical metro networks. Several available latency reduction techniques and solutions are also discussed, namely concerning usage of different chromatic dispersion compensation methods, low-latency amplifiers, optical fibers as well as other network elements.

  18. Enhancements to the multiple sleep latency test

    PubMed Central

    Meza-Vargas, Sonia; Giannouli, Eleni; Younes, Magdy

    2016-01-01

    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. PMID:27274327

  19. Serotonin shifts first-spike latencies of inferior colliculus neurons.

    PubMed

    Hurley, Laura M; Pollak, George D

    2005-08-24

    Many studies of neuromodulators have focused on changes in the magnitudes of neural responses, but fewer studies have examined neuromodulator effects on response latency. Across sensory systems, response latency is important for encoding not only the temporal structure but also the identity of stimuli. In the auditory system, latency is a fundamental response property that varies with many features of sound, including intensity, frequency, and duration. To determine the extent of neuromodulatory regulation of latency within the inferior colliculus (IC), a midbrain auditory nexus, the effects of iontophoretically applied serotonin on first-spike latencies were characterized in the IC of the Mexican free-tailed bat. Serotonin significantly altered the first-spike latencies in response to tones in 24% of IC neurons, usually increasing, but sometimes decreasing, latency. Serotonin-evoked changes in latency and spike count were not always correlated but sometimes occurred independently within individual neurons. Furthermore, in some neurons, the size of serotonin-evoked latency shifts depended on the frequency or intensity of the stimulus, as reported previously for serotonin-evoked changes in spike count. These results support the general conclusion that changes in latency are an important part of the neuromodulatory repertoire of serotonin within the auditory system and show that serotonin can change latency either in conjunction with broad changes in other aspects of neuronal excitability or in highly specific ways. PMID:16120790

  20. Latency correction of event-related potentials between different experimental protocols

    NASA Astrophysics Data System (ADS)

    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.

  1. Combinatorial Latency Reactivation for HIV-1 Subtypes and Variants▿ †

    PubMed Central

    Burnett, John C.; Lim, Kwang-il; Calafi, Arash; Rossi, John J.; Schaffer, David V.; Arkin, Adam P.

    2010-01-01

    The eradication of HIV-1 will likely require novel clinical approaches to purge the reservoir of latently infected cells from a patient. We hypothesize that this therapy should target a wide range of latent integration sites, act effectively against viral variants that have acquired mutations in their promoter regions, and function across multiple HIV-1 subtypes. By using primary CD4+ and Jurkat cell-based in vitro HIV-1 latency models, we observe that single-agent latency reactivation therapy is ineffective against most HIV-1 subtypes. However, we demonstrate that the combination of two clinically promising drugs—namely, prostratin and suberoylanilide hydroxamic acid (SAHA)—overcomes the limitations of single-agent approaches and can act synergistically for many HIV-1 subtypes, including A, B, C, D, and F. Finally, by identifying the proviral integration position of latent Jurkat cell clones, we demonstrate that this drug combination does not significantly enhance the expression of endogenous genes nearest to the proviral integration site, indicating that its effects may be selective. PMID:20357084

  2. KSHV LANA--the master regulator of KSHV latency.

    PubMed

    Uppal, Timsy; Banerjee, Sagarika; Sun, Zhiguo; Verma, Subhash C; Robertson, Erle S

    2014-12-01

    Kaposi's sarcoma associated herpesvirus (KSHV), like other human herpes viruses, establishes a biphasic life cycle referred to as dormant or latent, and productive or lytic phases. The latent phase is characterized by the persistence of viral episomes in a highly ordered chromatin structure and with the expression of a limited number of viral genes. Latency Associated Nuclear Antigen (LANA) is among the most abundantly expressed proteins during latency and is required for various nuclear functions including the recruitment of cellular machineries for viral DNA replication and segregation of the replicated genomes to daughter cells. LANA achieves these functions by recruiting cellular proteins including replication factors, chromatin modifying enzymes and cellular mitotic apparatus assembly. LANA directly binds to the terminal repeat region of the viral genome and associates with nucleosomal proteins to tether to the host chromosome. Binding of LANA to TR recruits the replication machinery, thereby initiating DNA replication within the TR. However, other regions of the viral genome can also initiate replication as determined by Single Molecule Analysis of the Replicated DNA (SMARD) approach. Recent, next generation sequence analysis of the viral transcriptome shows the expression of additional genes during latent phase. Here, we discuss the newly annotated latent genes and the role of major latent proteins in KSHV biology. PMID:25514370

  3. KSHV LANA—The Master Regulator of KSHV Latency

    PubMed Central

    Uppal, Timsy; Banerjee, Sagarika; Sun, Zhiguo; Verma, Subhash C.; Robertson, Erle S.

    2014-01-01

    Kaposi’s sarcoma associated herpesvirus (KSHV), like other human herpes viruses, establishes a biphasic life cycle referred to as dormant or latent, and productive or lytic phases. The latent phase is characterized by the persistence of viral episomes in a highly ordered chromatin structure and with the expression of a limited number of viral genes. Latency Associated Nuclear Antigen (LANA) is among the most abundantly expressed proteins during latency and is required for various nuclear functions including the recruitment of cellular machineries for viral DNA replication and segregation of the replicated genomes to daughter cells. LANA achieves these functions by recruiting cellular proteins including replication factors, chromatin modifying enzymes and cellular mitotic apparatus assembly. LANA directly binds to the terminal repeat region of the viral genome and associates with nucleosomal proteins to tether to the host chromosome. Binding of LANA to TR recruits the replication machinery, thereby initiating DNA replication within the TR. However, other regions of the viral genome can also initiate replication as determined by Single Molecule Analysis of the Replicated DNA (SMARD) approach. Recent, next generation sequence analysis of the viral transcriptome shows the expression of additional genes during latent phase. Here, we discuss the newly annotated latent genes and the role of major latent proteins in KSHV biology. PMID:25514370

  4. Equivalence Classes with Requirements for Short Response Latencies

    ERIC Educational Resources Information Center

    Tomanari, Gerson Y.; Sidman, Murray; Rubio, Adriana R.; Dube, William V.

    2006-01-01

    Five adult humans were tested for emergent conditional discriminations under rapid-responding contingencies. During four-comparison matching-to-sample baseline training (AB and AC), limited-hold contingencies for responding to samples and comparisons were gradually restricted to the shortest duration consistent with at least 95% accuracy and no…

  5. HIV-1 transcription and latency: an update

    PubMed Central

    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

  6. Measurement of the lateral thoracic reflex latency in ponies.

    PubMed

    Hahn, C N; Mayhew, I G; Washbourne, J R

    1998-01-01

    Lateral thoracic nerve reflex latencies values were measured in ponies using a simple, non-invasive technique. The reflex was elicited using an external triggering hammer attached to an electrodiagnostic unit. The resulting evoked, compound muscle action potentials were recorded with electrodes, which were placed over the 6th ribs or 11th rib level with the axilla. Two superimposed repeats of 4 signal-averaged sweeps of 50 or 100 milliseconds were recorded and the estimated reflex pathway was measured for each subject in order to calculate the reflex latencies and latency velocities. Mean left and right 6th rib peak latencies were not significantly different from each other (P = .609), but left 6th rib latencies were shorter than those recorded from the 11th rib (P < .0001), substantiating the existence of an indirect (central) pathway to the reflex. The calculated left and right 6th rib latency velocities were not significantly different from each other (P = .58) but left 6th rib latency velocities were different from left 11th rib (P = .009). The calculated latency velocities were within the broad range for corticospinal tract motor conduction velocities and comparable to magnetic motor evoked latency velocities. The use of lateral thoracic reflex latency measurements to objectively identify the site of spinal cord lesions is discussed. PMID:9686392

  7. Somatosensory spatial attention modulates amplitudes, latencies, and latency jitter of laser-evoked brain potentials

    PubMed Central

    Franz, Marcel; Nickel, Moritz M.; Ritter, Alexander; Miltner, Wolfgang H. R.

    2015-01-01

    Several studies provided evidence that the amplitudes of laser-evoked potentials (LEPs) are modulated by attention. However, previous reports were based on across-trial averaging of LEP responses at the expense of losing information about intertrial variability related to attentional modulation. The aim of this study was to investigate the effects of somatosensory spatial attention on single-trial parameters (i.e., amplitudes, latencies, and latency jitter) of LEP components (N2 and P2). Twelve subjects participated in a sustained spatial attention paradigm while noxious laser stimuli (left hand) and noxious electrical stimuli (right hand) were sequentially delivered to the dorsum of the respective hand with nonnoxious air puffs randomly interspersed within the sequence of noxious stimuli. Participants were instructed to mentally count all stimuli (i.e., noxious and nonnoxious) applied to the attended location. Laser stimuli, presented to the attended hand (ALS), elicited larger single-trial amplitudes of the N2 component compared with unattended laser stimuli (ULS). In contrast, single-trial amplitudes of the P2 component were not significantly affected by spatial attention. Single-trial latencies of the N2 and P2 were significantly smaller for ALS vs. ULS. Additionally, the across-trial latency jitter of the N2 component was reduced for ALS. Conversely, the latency jitter of the P2 component was smaller for ULS compared with ALS. With the use of single-trial analysis, the study provided new insights into brain dynamics of LEPs related to spatial attention. Our results indicate that single-trial parameters of LEP components are differentially modulated by spatial attention. PMID:25673731

  8. Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations.

    PubMed

    Laird, Gregory M; Bullen, C Korin; Rosenbloom, Daniel I S; Martin, Alyssa R; Hill, Alison L; Durand, Christine M; Siliciano, Janet D; Siliciano, Robert F

    2015-05-01

    Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels of latency reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, we compared 2-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation. Using the Bliss independence model to quantitate combined drug effects, we demonstrated that these combinations synergize to induce HIV-1 transcription. This robust latency reversal occurred without release of proinflammatory cytokines by rCD4s. To extend the clinical utility of our findings, we applied a mathematical model that estimates in vivo changes in plasma HIV-1 RNA from ex vivo measurements of virus production. Our study reconciles diverse findings from previous studies, establishes a quantitative experimental approach to evaluate combinatorial LRA efficacy, and presents a model to predict in vivo responses to LRAs. PMID:25822022

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

    PubMed

    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. PMID:26939403

  10. Low latency and persistent data storage

    DOEpatents

    Fitch, Blake G; Franceschini, Michele M; Jagmohan, Ashish; Takken, Todd

    2014-11-04

    Persistent data storage is provided by a computer program product that includes computer program code configured for receiving a low latency store command that includes write data. The write data is written to a first memory device that is implemented by a nonvolatile solid-state memory technology characterized by a first access speed. It is acknowledged that the write data has been successfully written to the first memory device. The write data is written to a second memory device that is implemented by a volatile memory technology. At least a portion of the data in the first memory device is written to a third memory device when a predetermined amount of data has been accumulated in the first memory device. The third memory device is implemented by a nonvolatile solid-state memory technology characterized by a second access speed that is slower than the first access speed.

  11. Low latency and persistent data storage

    DOEpatents

    Fitch, Blake G; Franceschini, Michele M; Jagmohan, Ashish; Takken, Todd E

    2014-02-18

    Persistent data storage is provided by a method that includes receiving a low latency store command that includes write data. The write data is written to a first memory device that is implemented by a nonvolatile solid-state memory technology characterized by a first access speed. It is acknowledged that the write data has been successfully written to the first memory device. The write data is written to a second memory device that is implemented by a volatile memory technology. At least a portion of the data in the first memory device is written to a third memory device when a predetermined amount of data has been accumulated in the first memory device. The third memory device is implemented by a nonvolatile solid-state memory technology characterized by a second access speed that is slower than the first access speed.

  12. Method of data communications with reduced latency

    SciTech Connect

    Blocksome, Michael A; Parker, Jeffrey J

    2013-11-05

    Data communications with reduced latency, including: writing, by a producer, a descriptor and message data into at least two descriptor slots of a descriptor buffer, the descriptor buffer comprising allocated computer memory segmented into descriptor slots, each descriptor slot having a fixed size, the descriptor buffer having a header pointer that identifies a next descriptor slot to be processed by a DMA controller, the descriptor buffer having a tail pointer that identifies a descriptor slot for entry of a next descriptor in the descriptor buffer; recording, by the producer, in the descriptor a value signifying that message data has been written into descriptor slots; and setting, by the producer, in dependence upon the recorded value, a tail pointer to point to a next open descriptor slot.

  13. Time Counts! Some Comments on System Latency in Head-Referenced Displays

    NASA Technical Reports Server (NTRS)

    Ellis, Stephen R.; Adelstein, Bernard D.

    2013-01-01

    System response latency is a prominent characteristic of human-computer interaction. Laggy systems are; however, not simply annoying but substantially reduce user productivity. The impact of latency on head referenced display systems, particularly head-mounted systems, is especially disturbing since not only can it interfere with dynamic registration in augmented reality displays but it also can in some cases indirectly contribute to motion sickness. We will summarize several experiments using standard psychophysical discrimination techniques that suggest what system latencies will be required to achieve perceptual stability for spatially referenced computer-generated imagery. In conclusion I will speculate about other system performance characteristics that I would hope to have for a dream augmented reality system.

  14. USCGC Healy science seawater system latency

    NASA Astrophysics Data System (ADS)

    Roberts, S. D.; Chayes, D. N.; Hiller, S. M.

    2008-12-01

    The U.S. Arctic research icebreaker USCGC Healy was delivered with the science seawater intake located near the bow. The sensors in the flow through science seawater system are located in the Biochem Lab about 128 meters aft with approximately 100 meters of pipe between the intake and the lab. This original intake and its plumbing were very prone to freezing up even in light ice conditions and was not designed to provide enough seawater to cool incubators. A new science seawater system was installed during the 2003- 2004 drydock. The intake for this system is located near Frame 95, approximately 85 meters aft of the bow and 8 meters below the water line. There are about 30 meters of pipe between the intake and the Biochem Lab. The new system incorporated a number of features including a centrifugal separator and slush stripping pumps which significantly improved the performance of the system in the presence of ice and substantially increased flow capability and included new plumbing to provide seawater on the bow for incubators. Using the time difference between the thermal features observed by an SBE 3 temperature sensor near the intake and the temperature from the SBE Thermosalinograph (SBE 21 and SBE 45) in the Biochem lab, we define a very broad range of time latencies that range from approximately 10 minutes to as much as 40 minutes when the system is not ingesting ice chips. The observed latency is correlated with changes in pumping rates, system pressure and episodic use of seawater for incubators and sample washing. Comparison of measured parameters between lowered CTDs and the Thermosalinograph indicate that while underway, flow around the hull causes surface water to reach the level of the intake. A modification to the existing flow through seawater system has been proposed that will substantially reduce the delay and improve reliability of the measured parameters when operating in ice. Technical support for science on the Healy is supported by the U

  15. LINEAR STRUCTURAL MODELS FOR RESPONSE AND LATENCY PERFORMANCE IN ARITHMETIC. PSYCHOLOGY SERIES, TECHNICAL REPORT NO. 100.

    ERIC Educational Resources Information Center

    SUPPES, PATRICK; AND OTHERS

    A LEARNING MODEL TO IDENTIFY FACTORS CONTRIBUTING TO THE DIFFICULTY OF A PROBLEM ITEM WAS SUPPORTED EMPIRICALLY, AND INDICATED THAT THE NUMBER OF STEPS REQUIRED TO SOLVE A PROBLEM WAS THE MOST IMPORTANT VARIABLE IN PREDICTING BOTH ERROR PROBABILITY AND RESPONSE LATENCY. THE MODEL, IN ORDER TO ESTABLISH DIFFERENTIAL PREDICTIONS OF DIFFICULTY IN…

  16. Working Memory Updating Latency Reflects the Cost of Switching between Maintenance and Updating Modes of Operation

    ERIC Educational Resources Information Center

    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…

  17. Effects of Prenominal Adjective Ordering on Children's Latencies and Errors in an Immediate Sentence Recall Task.

    ERIC Educational Resources Information Center

    Freedle, Roy; Hall, William S.

    A total of 34 children, ages 2 and a half to 6, were presented with sentences for imitation that either violated or honored a prenominal adjective ordering rule, which requires that size adjectives must precede color adjectives. Two response measures were evaluated in terms of these sentence types: latency to begin a sentence imitation and recall…

  18. Short latency cerebellar modulation of the basal ganglia

    PubMed Central

    Chen, Christopher H.; Fremont, Rachel; Arteaga-Bracho, Eduardo E.; Khodakhah, Kamran

    2014-01-01

    The graceful, purposeful motion of our body is an engineering feat which remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. Here we show in mice that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway. Under physiological conditions this short latency pathway is capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition this pathway relays aberrant cerebellar activity to the basal ganglia to cause dystonia. PMID:25402853

  19. Short latency cerebellar modulation of the basal ganglia.

    PubMed

    Chen, Christopher H; Fremont, Rachel; Arteaga-Bracho, Eduardo E; Khodakhah, Kamran

    2014-12-01

    The graceful, purposeful motion of our body is an engineering feat that remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow, multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. We found that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway in mice. Under physiological conditions, this short latency pathway was capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition, this pathway relayed aberrant cerebellar activity to the basal ganglia to cause dystonia. PMID:25402853

  20. Oscillations and latency in the clamped pupil light reflex

    NASA Astrophysics Data System (ADS)

    Milton, John G.; Ohira, Toru; Steck, Jeff; Crate, John; Longtin, Andre

    1993-11-01

    It is shown that the pupil latency can be estimated from pupil cycling measurements when the pupil light reflex is clamped with piecewise constant negative feedback. The solution of the mathematical model previously shown to describe these oscillations is utilized to develop a variety of strategies to estimate latency and to evaluate the effects of noise on these estimates. The results demonstrate that the pupil latency shows considerable variation.

  1. Calcium and the control of discrete wave latency in the ventral photoreceptor of Limulus.

    PubMed Central

    Martinez, J M; Srebro, R

    1976-01-01

    1. Discrete, transient depolarization (discrete waves) of the ventral photoreceptor of the horseshoe crab, Limulus, occur spontaneously in the dark adapted photoreceptor and are also evoked by light. They form the basic events which comprise the receptor potential. A brief, low energy flash of light evokes variable numbers of discrete waves which have variable latencies. Evidence suggesting that discrete wave latency reflects the kinetics of the chemical reactions of phototransduction is reviewed. 2. The concentration of extracellular Ca influences both the average discrete wave latency and its variability. Lowering extracellular Ca prolongs the latency and increases its variability. Increasing extracellular Ca has the opposite effect. 3. Changes in discrete wave latency caused by changes in extracellular Ca require 10--15 min to become fully manifest, whereas when the concentration of extracellular K is increased the photoreceptor achieves a steady-state depolarization in 10-15 sec. 4. Iontophoresis of the Ca-chelating agent EGTA into the photoreceptor increases both the average discrete wave latency and its variability. Iontophoresis of Ca-EGTA mixtures may either increase or decrease discrete wave latency and its variability depending upon the proportion of Ca mixed with EGTA. 5. It is suggested that the concentration of intracellular rather than extracellular ionized Ca is the prime factor indicating discrete wave latency. The effects of changing extracellular Ca can be explained if the photoreceptor is permeable to Ca in the dark and if it maintains a low intracellular Ca concentration by virtue of active metabolic processes (a pump-leak system). 6. Lowering the temperature of the photoreceptor also has the dual effect of increasing discrete wave latency and its variability. However, effects of lowering temperature and Ca simultaneously are greater than the sum of the two effects in individually. This suggests that Ca may be a reactant in the chemical process

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

    NASA Astrophysics Data System (ADS)

    Gang, Lu

    Wireless sensor networks are expected to be used in a wide range of applications from environment monitoring to event detection. The key challenge is to provide energy efficient communication; however, latency remains an important concern for many applications that require fast response. The central thesis of this work is that energy efficient medium access and sleep scheduling mechanisms can be designed without necessarily sacrificing application-specific latency performance. We validate this thesis through results from four case studies that cover various aspects of medium access and sleep scheduling design in wireless sensor networks. Our first effort, DMAC, is to design an adaptive low latency and energy efficient MAC for data gathering to reduce the sleep latency. We propose staggered schedule, duty cycle adaptation, data prediction and the use of more-to-send packets to enable seamless packet forwarding under varying traffic load and channel contentions. Simulation and experimental results show significant energy savings and latency reduction while ensuring high data reliability. The second research effort, DESS, investigates the problem of designing sleep schedules in arbitrary network communication topologies to minimize the worst case end-to-end latency (referred to as delay diameter). We develop a novel graph-theoretical formulation, derive and analyze optimal solutions for the tree and ring topologies and heuristics for arbitrary topologies. The third study addresses the problem of minimum latency joint scheduling and routing (MLSR). By constructing a novel delay graph, the optimal joint scheduling and routing can be solved by M node-disjoint paths algorithm under multiple channel model. We further extended the algorithm to handle dynamic traffic changes and topology changes. A heuristic solution is proposed for MLSR under single channel interference. In the fourth study, EEJSPC, we first formulate a fundamental optimization problem that provides tunable

  3. Understanding Factors That Modulate the Establishment of HIV Latency in Resting CD4+ T-Cells In Vitro

    PubMed Central

    Anderson, Jenny L.; Mota, Talia M.; Evans, Vanessa A.; Kumar, Nitasha; Rezaei, Simin D.; Cheong, Karey; Solomon, Ajantha; Wightman, Fiona; Cameron, Paul U.; Lewin, Sharon R.

    2016-01-01

    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. PMID:27383184

  4. Treating Excessively Slow Responding of a Young Man With Asperger Syndrome Using Differential Reinforcement of Short Response Latencies

    PubMed Central

    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 teach the participant to discriminate between math problems that could be answered rapidly and those that required more time for accurate performance. PMID:17970270

  5. Latency as a region contrast: Measuring ERP latency differences with Dynamic Time Warping.

    PubMed

    Zoumpoulaki, A; Alsufyani, A; Filetti, M; Brammer, M; Bowman, H

    2015-12-01

    Methods for measuring onset latency contrasts are evaluated against a new method utilizing the dynamic time warping (DTW) algorithm. This new method allows latency to be measured across a region instead of single point. We use computer simulations to compare the methods' power and Type I error rates under different scenarios. We perform per-participant analysis for different signal-to-noise ratios and two sizes of window (broad vs. narrow). In addition, the methods are tested in combination with single-participant and jackknife average waveforms for different effect sizes, at the group level. DTW performs better than the other methods, being less sensitive to noise as well as to placement and width of the window selected. PMID:26372033

  6. DART: A Microcomputer Program for Response Latency Analysis.

    ERIC Educational Resources Information Center

    Greene, John O.; Greene, Barry F.

    1987-01-01

    Discusses how chronometric measures such as the DART (Display And Response Timing) computer program, have become virtually indispensable in testing cognitive theories of human social behavior. Describes how the DART (1) provides a way to collect response latency data; and (2) allows measurement of response latencies to a set of user-specified,…

  7. Multiple sclerosis: symptom equivalent to delayed visual evoked potential latency.

    PubMed

    Stenager, E; Jensen, K

    1990-10-01

    An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison to that of patients who mastered this task. PMID:2275357

  8. Optimizing low latency LIGO-Virgo localization

    NASA Astrophysics Data System (ADS)

    Chen, Hsin-Yu; Holz, Daniel

    2015-04-01

    Fast and effective localization of gravitational wave (GW) events could play a crucial role in identifying possible electromagnetic counterparts, and thereby help usher in an era of GW multi-messenger astronomy. We discuss an algorithm for accurate and very low latency (<< 1 second) localization of GW sources using only the time of arrival and signal-to-noise ratio at each detector. The algorithm is independent of distances, masses, and waveform templates of the sources to leading order, and applies to all discrete sources detected by ground-based detector networks. For the two detector configuration (LIGO Hanford+Livingston) expected in late 2015 we find a median 50% localization of 150 deg2 for binary neutron stars (for SNR threshold of 12), consistent with previous findings. We explore the improvement in localization resulting from high SNR events, finding that the loudest out of the first four events reduces the median sky localization area by a factor of 1.8. We also discuss some strategies to optimize electromagnetic follow-up of GW events. We specifically explore the case of multi-messenger joint detections coming from independent (and possibly highly uncertain) localizations, such as for short gamma-ray bursts observed by Fermi GBM and neutrinos captured by IceCube.

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

    NASA Technical Reports Server (NTRS)

    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

  10. A primary neuron culture system for the study of herpes simplex virus latency and reactivation.

    PubMed

    Kobayashi, Mariko; Kim, Ju-Youn; Camarena, Vladimir; Roehm, Pamela C; Chao, Moses V; Wilson, Angus C; Mohr, Ian

    2012-01-01

    Herpes simplex virus type-1 (HSV-1) establishes a life-long latent infection in peripheral neurons. This latent reservoir is the source of recurrent reactivation events that ensure transmission and contribute to clinical disease. Current antivirals do not impact the latent reservoir and there are no vaccines. While the molecular details of lytic replication are well-characterized, mechanisms controlling latency in neurons remain elusive. Our present understanding of latency is derived from in vivo studies using small animal models, which have been indispensable for defining viral gene requirements and the role of immune responses. However, it is impossible to distinguish specific effects on the virus-neuron relationship from more general consequences of infection mediated by immune or non-neuronal support cells in live animals. In addition, animal experimentation is costly, time-consuming, and limited in terms of available options for manipulating host processes. To overcome these limitations, a neuron-only system is desperately needed that reproduces the in vivo characteristics of latency and reactivation but offers the benefits of tissue culture in terms of homogeneity and accessibility. Here we present an in vitro model utilizing cultured primary sympathetic neurons from rat superior cervical ganglia (SCG) (Figure 1) to study HSV-1 latency and reactivation that fits most if not all of the desired criteria. After eliminating non-neuronal cells, near-homogeneous TrkA(+) neuron cultures are infected with HSV-1 in the presence of acyclovir (ACV) to suppress lytic replication. Following ACV removal, non-productive HSV-1 infections that faithfully exhibit accepted hallmarks of latency are efficiently established. Notably, lytic mRNAs, proteins, and infectious virus become undetectable, even in the absence of selection, but latency-associated transcript (LAT) expression persists in neuronal nuclei. Viral genomes are maintained at an average copy number of 25 per neuron

  11. A Primary Neuron Culture System for the Study of Herpes Simplex Virus Latency and Reactivation

    PubMed Central

    Kobayashi, Mariko; Kim, Ju-Youn; Camarena, Vladimir; Roehm, Pamela C.; Chao, Moses V.; Wilson, Angus C.; Mohr, Ian

    2012-01-01

    Herpes simplex virus type-1 (HSV-1) establishes a life-long latent infection in peripheral neurons. This latent reservoir is the source of recurrent reactivation events that ensure transmission and contribute to clinical disease. Current antivirals do not impact the latent reservoir and there are no vaccines. While the molecular details of lytic replication are well-characterized, mechanisms controlling latency in neurons remain elusive. Our present understanding of latency is derived from in vivo studies using small animal models, which have been indispensable for defining viral gene requirements and the role of immune responses. However, it is impossible to distinguish specific effects on the virus-neuron relationship from more general consequences of infection mediated by immune or non-neuronal support cells in live animals. In addition, animal experimentation is costly, time-consuming, and limited in terms of available options for manipulating host processes. To overcome these limitations, a neuron-only system is desperately needed that reproduces the in vivo characteristics of latency and reactivation but offers the benefits of tissue culture in terms of homogeneity and accessibility. Here we present an in vitro model utilizing cultured primary sympathetic neurons from rat superior cervical ganglia (SCG) (Figure 1) to study HSV-1 latency and reactivation that fits most if not all of the desired criteria. After eliminating non-neuronal cells, near-homogeneous TrkA+ neuron cultures are infected with HSV-1 in the presence of acyclovir (ACV) to suppress lytic replication. Following ACV removal, non-productive HSV-1 infections that faithfully exhibit accepted hallmarks of latency are efficiently established. Notably, lytic mRNAs, proteins, and infectious virus become undetectable, even in the absence of selection, but latency-associated transcript (LAT) expression persists in neuronal nuclei. Viral genomes are maintained at an average copy number of 25 per neuron

  12. Normal values of patellar and ankle tendon reflex latencies.

    PubMed

    Frijns, C J; Laman, D M; van Duijn, M A; van Duijn, H

    1997-02-01

    The clinical value of latency measurement of tendon reflexes in neurological patients has been reported by several authors. However, normal values are not readily comparable. In the present study, latencies and amplitudes of patellar (PTR) and ankle tendon reflexes (ATR) were measured at rest and after facilitation in 102 normal controls. A manually operated reflex hammer, tipped with electrically conductive rubber, ensured an immediate start of the sweep of the oscilloscope. Latencies showed a significant correlation with height (r = 0.70 for PTR and r = 0.72 for ATR, P < 0.0001) and to a lesser degree with age (r = 0.16 and r = 0.30, P < 0.0001). While amplitudes were highly variable, rendering them less useful for diagnostic purposes, latencies showed minimal intra-individual variability (CV 1.5 and 0.8%, respectively). Correlation of ATR-latency with the H-reflex latency of the soleus muscle was very high (r = 0.97, P < 0.0001). Comparison with three other hammer types yielded corresponding results with a hammer supplied with a piezo-electric element; however, significantly shorter latencies were found with a hammer with a microswitch, and with another hammer with a spring-contact, due to a delay from the tap on the tendon until the start of the sweep of the monitor. PMID:9107465

  13. Factors influencing the latency of simple reaction time

    PubMed Central

    Woods, David L.; Wyma, John M.; Yund, E. William; Herron, Timothy J.; Reed, Bruce

    2015-01-01

    Simple reaction time (SRT), the minimal time needed to respond to a stimulus, is a basic measure of processing speed. SRTs were first measured by Francis Galton in the 19th century, who reported visual SRT latencies below 190 ms in young subjects. However, recent large-scale studies have reported substantially increased SRT latencies that differ markedly in different laboratories, in part due to timing delays introduced by the computer hardware and software used for SRT measurement. We developed a calibrated and temporally precise SRT test to analyze the factors that influence SRT latencies in a paradigm where visual stimuli were presented to the left or right hemifield at varying stimulus onset asynchronies (SOAs). Experiment 1 examined a community sample of 1469 subjects ranging in age from 18 to 65. Mean SRT latencies were short (231, 213 ms when corrected for hardware delays) and increased significantly with age (0.55 ms/year), but were unaffected by sex or education. As in previous studies, SRTs were prolonged at shorter SOAs and were slightly faster for stimuli presented in the visual field contralateral to the responding hand. Stimulus detection time (SDT) was estimated by subtracting movement initiation time, measured in a speeded finger tapping test, from SRTs. SDT latencies averaged 131 ms and were unaffected by age. Experiment 2 tested 189 subjects ranging in age from 18 to 82 years in a different laboratory using a larger range of SOAs. Both SRTs and SDTs were slightly prolonged (by 7 ms). SRT latencies increased with age while SDT latencies remained stable. Precise computer-based measurements of SRT latencies show that processing speed is as fast in contemporary populations as in the Victorian era, and that age-related increases in SRT latencies are due primarily to slowed motor output. PMID:25859198

  14. The early component of middle latency auditory-evoked potentials in the process of deviance detection.

    PubMed

    Li, Linfeng; Gong, Qin

    2016-07-01

    The aim of the present study was to investigate both the encoding mechanism and the process of deviance detection when deviant stimuli were presented in various patterns in an environment featuring repetitive sounds. In adults with normal hearing, middle latency responses were recorded within an oddball paradigm containing complex tones or speech sounds, wherein deviant stimuli featured different change patterns. For both complex tones and speech sounds, the Na and Pa components of middle latency responses showed an increase in the mean amplitude and a reduction in latency when comparing rare deviant stimuli with repetitive standard stimuli in a stimulation block. However, deviant stimuli with a rising frequency induced signals with smaller amplitudes than other deviant stimuli. The present findings indicate that deviant stimuli with different change patterns induce differing responses in the primary auditory cortex. In addition, the Pa components of speech sounds typically feature a longer latency and similar mean amplitude compared with complex tones, which suggests that the auditory system requires more complex processing for the analysis of speech sounds before processing in the auditory cortex. PMID:27203294

  15. Saccadic latency in deterministic environments: getting back on track after the unexpected happens.

    PubMed

    Anderson, Andrew J; Carpenter, Roger H S

    2010-01-01

    Saccadic latencies are commonly used to study decision mechanisms. For instance, in a random sequence, saccadic latency to a target depends on how frequently it has recently appeared. However, frequency is not the only factor that determines probability. Here we presented targets to the left or right, either in random sequences or in repeating patterns. Although the frequency of appearing on a given side was identical in each case, latencies for the low-frequency side were significantly shorter for repeating patterns than in random sequences, showing that the system can respond to the deterministic probabilities in such patterns. We then disrupted our patterns episodically, recommencing at a random starting position in the sequence. This significantly increased the latency, which remained high until the low-frequency target in the sequence reappeared, implying that the oculomotor system makes strategic use of low-frequency--but high-information--events to determine the phase of repeating sequences. The deterministic sequences of events in our patterns represent a simple model for the habitual sequences of actions commonly performed in daily life, which, when disrupted, require the engagement of a higher level problem-solving strategy to return us to our previous automated sequence as quickly as possible. PMID:21188783

  16. Differential Vertical Visual Latency as Determined with a Simultaneity Paradigm

    PubMed Central

    Patel, Shephali; Schwartz, Steven H.; Swanson, William H

    2010-01-01

    Behavioral studies, as well as anatomical and physiological data, suggest differences in functionality for inferior and superior visual fields. Previous investigations comparing latencies of the two fields have employed motor reaction times. This approach is of limited usefulness in elderly clinical populations where various degrees of motor impairment may be present. In this report, we describe a simultaneity paradigm that allows the determination of relative latencies without dependence on motor reaction times. A slightly, but statistically significant, shorter latency (3.9 +/− 5.9 msec) was found for the superior visual field. The results are not affected by age, and both within- and between-session variability are low. PMID:20034513

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

    PubMed

    Popov, V V; Supin AYa

    1991-12-01

    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. PMID:1816509

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

    PubMed

    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. PMID:26971946

  19. Lytic Promoters Express Protein during Herpes Simplex Virus Latency

    PubMed Central

    Russell, Tiffany A.; Tscharke, David C.

    2016-01-01

    Herpes simplex virus (HSV) has provided the prototype for viral latency with previously well-defined acute or lytic and latent phases. More recently, the deep quiescence of HSV latency has been questioned with evidence that lytic genes can be transcribed in this state. However, to date the only evidence that these transcripts might be translated has come from immunological studies that show activated T cells persist in the nervous system during latency. Here we use a highly sensitive Cre-marking model to show that lytic and latent phases are less clearly defined in two significant ways. First, around half of the HSV spread leading to latently infected sites occurred beyond the initial acute infection and second, we show direct evidence that lytic promoters can drive protein expression during latency. PMID:27348812

  20. The Role of Spike Temporal Latencies in Artificial Olfaction

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    Perdziak, Maciej; Witkowska, Dagmara; Gryncewicz, Wojciech; Przekoracka-Krawczyk, Anna; Ober, Jan

    2014-01-01

    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. Amblyopia is associated with abnormal visual experience (e.g., anisometropia) 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°) 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 ± 32 ms) 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 retina in subjects with anisometropic amblyopia. PMID:25352790

  2. Response latencies to postural disturbances in three species of teleostean fishes.

    PubMed

    Webb, Paul W

    2004-02-01

    Flow in aquatic systems is characterized by unsteadiness that creates destabilizing perturbations. Appropriate correction responses depend on response latency. The time between a disturbance induced by either removal of a flow refuge or striking various parts of the body with a narrow water jet was measured for three species, chosen as examples of modes in teleostean body/fin organization that are expected to affect stability. Creek chub Semotilus atromaculatus is representative of fusiform-bodied soft-rayed teleosts, smallmouth bass Micropterus dolomieu of fusiform-bodied spiny-rayed forms and bluegill Lepomis macrochirus of deep-bodied spiny-rayed forms. Observations were made at 23 degrees C. Loss of refuge resulted in a surge that fish corrected by starting to swim within 129+/-29 ms (mean +/- 2 S.E.M.) for chub, which was significantly shorter than minimal times of approximately 200 ms for bluegill and bass. Slips and heaves induced by water jets initially resulted in extension of the median and paired fins that would damp growth of the disturbance, but otherwise these disturbances were ignored. Yaws and pitches were more likely to cause fish to swim away from the stimulus, making corrections as they did so. There were no differences in latencies for slip, heave, yaw and pitch disturbances within each species, but latencies varied among species. For these disturbances, responses averaged 123+/-19 ms for chub, again significantly smaller than those of 201+/-24 ms for bass and 208+/-52 ms for bluegill. Values for the two centrarchids were not significantly different (P>0.08). The response latency for rolling disturbances did not differ among species but was significantly smaller than that for other disturbances, with an overall latency of 70+/-15 ms. The greater responsiveness to hydrostatic rolling instability is attributed to functions requiring an upright posture and differences among species in habitat preferences. PMID:14766954

  3. Evaluation of transducers for obtaining intraoperative short-latency auditory evoked potentials.

    PubMed

    Erwin, C W; Gulevich, S J

    1985-08-01

    Operative monitoring of short-latency auditory evoked potentials during posterior fossa surgery requires audio transducers of small physical size so as to not interfere with the operative field. There are many relatively inexpensive transducers in the commercial audio hifi market of appropriate size. Some produce suitable biological responses and tolerate long term use without failure. The authors describe factors to consider and methods used in testing such transducers. PMID:2410230

  4. Structural basis of protein phosphatase 2A stable latency

    PubMed Central

    Jiang, Li; Stanevich, Vitali; Satyshur, Kenneth A; Kong, Mei; Watkins, Guy R.; Wadzinski, Brian E.; Sengupta, Rituparna; Xing, Yongna

    2013-01-01

    The catalytic subunit of protein phosphatase 2A (PP2Ac) is stabilized in a latent form by α4, a regulatory protein essential for cell survival and biogenesis of all PP2A complexes. Here we report the structure of α4 bound to the N-terminal fragment of PP2Ac. This structure suggests that α4 binding to the full-length PP2Ac requires local unfolding near the active site, which perturbs the scaffold subunit binding site at the opposite surface via allosteric relay. These changes stabilize an inactive conformation of PP2Ac and convert oligomeric PP2A complexes to the α4 complex upon perturbation of the active site. The PP2Ac–α4 interface is essential for cell survival and sterically hinders a PP2A ubiquitination site, important for the stability of cellular PP2Ac. Our results show that α4 is a scavenger chaperone that binds to and stabilizes partially folded PP2Ac for stable latency, and reveal a mechanism by which α4 regulates cell survival, and biogenesis and surveillance of PP2A holoenzymes. PMID:23591866

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

    NASA Technical Reports Server (NTRS)

    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.

  6. Age-related effects of increasing postural challenge on eye movement onset latencies to visual targets.

    PubMed

    Jimenez, Sergio; Hollands, Mark; Palmisano, Stephen; Kim, Juno; Markoulli, Maria; McAndrew, Darryl; Stamenkovic, Alexander; Walsh, Joel; Bos, Sophie; Stapley, Paul J

    2016-06-01

    When a single light cue is given in the visual field, our eyes orient towards it with an average latency of 200 ms. If a second cue is presented at or around the time of the response to the first, a secondary eye movement occurs that represents a reorientation to the new target. While studies have shown that eye movement latencies to 'single-step' targets may or may not be lengthened with age, secondary eye movements (during 'double-step' displacements) are significantly delayed with increasing age. The aim of this study was to investigate whether the postural challenge posed simply by standing (as opposed to sitting) results in significantly longer eye movement latencies in older adults compared to the young. Ten young (<35 years) and 10 older healthy adults (>65 years) participated in the study. They were required to fixate upon a central target and move their eyes in response to 2 types of stimuli: (1) a single-step perturbation of target position either 15° to the right or left and (2) a double-step target displacement incorporating an initial target jump to the right or left by 15°, followed after 200 ms, by a shift of target position to the opposite side (e.g. +15° then -15°). All target displacement conditions were executed in sit and stand positions with the participant at the same distance from the targets. Eye movements were recorded using electro-oculography. Older adults did not show significantly longer eye movement latencies than the younger adults for single-step target displacements, and postural configuration (stand compared to sit) had no effect upon latencies for either group. We categorised double-step trials into those during which the second light changed after or before the onset of the eye shift to the first light. For the former category, young participants showed faster secondary eye shifts to the second light in the standing position, while the older adults did not. For the latter category of double-step trial, young participants

  7. Low-Latency Telerobotics from Mars Orbit: The Case for Synergy Between Science and Human Exploration

    NASA Technical Reports Server (NTRS)

    Valinia, A.; Garvin, J. B.; Vondrak, R.; Thronson, H.; Lester, D.; Schmidt, G.; Fong, T.; Wilcox, B.; Sellers, P.; White, N.

    2012-01-01

    Initial, science-directed human exploration of Mars will benefit from capabilities in which human explorers remain in orbit to control telerobotic systems on the surface (Figure 1). Low-latency, high-bandwidth telerobotics (LLT) from Mars orbit offers opportunities for what the terrestrial robotics community considers to be high-quality telepresence. Such telepresence would provide high quality sensory perception and situation awareness, and even capabilities for dexterous manipulation as required for adaptive, informed selection of scientific samples [1]. Astronauts on orbit in close communication proximity to a surface exploration site (in order to minimize communication latency) represent a capability that would extend human cognition to Mars (and potentially for other bodies such as asteroids, Venus, the Moon, etc.) without the challenges, expense, and risk of putting those humans on hazardous surfaces or within deep gravity wells. Such a strategy may be consistent with goals for a human space flight program that, are currently being developed within NASA.

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

    PubMed Central

    Fischer, Jörg; Milekovic, Tomislav; Schneider, Gerhard; Mehring, Carsten

    2014-01-01

    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. PMID:24478695

  9. An improved approximation ratio for the minimum latency problem

    SciTech Connect

    Goemans, M.; Kleinberg, J.

    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.

  10. Methods for UGV teleoperation with high latency communications

    NASA Astrophysics Data System (ADS)

    Witus, Gary; Hunt, Shawn; Janicki, Phil

    2011-05-01

    In this project, we developed and demonstrated complementary UGV control methods for teleoperation with highlatency communications. The methods included latency protection, predictive displays, and supervisory control. Latency protection mitigate against typical types of high-latency teleoperation input errors. The Phase I latency protection methods included filtering the joysick commands, limiting the commanded rates as a function of latency, and emergency stop when the operator commands and OCU navigation video were out of phase. Predictive displays indicate to the operator the current state of the UGV, i.e., the state after all of the latent commands are executed (latent commands are those that have been issued but whose effects do not yet appear in the OCU display). We implemented two alternative predictive display methods: augmented reality using iconography to indicate the effects of the latent commands, and virtual reality which warps the image to show the view to reflect the latent commands. Supervisory control allows the operator to specify simple, short-range objectives that the UGV can accomplish on its own, without advanced sensing, path planning, etc. We implemented an effective "point-and-go" supervisory control system. We successfully implemented and demonstrated these methods on a Packbot510 EOD robot (made by iRobot Corporation), currently being used in-theater.

  11. Network latency and operator performance in teleradiology applications.

    PubMed

    Stahl, J N; Tellis, W; Huang, H K

    2000-08-01

    Teleradiology applications often use an interactive conferencing mode with remote control mouse pointers. When a telephone is used for voice communication, latencies of the data network can create a temporal discrepancy between the position of the mouse pointer and the verbal communication. To assess the effects of this dissociation, we examined the performance of 5 test persons carrying out simple teleradiology tasks under varying simulated network conditions. When the network latency exceeded 400 milliseconds, the performance of the test persons dropped, and an increasing number of errors were made. This effect was the same for constant latencies, which can occur on the network path, and for variable delays caused by the Nagle algorithm, an internal buffering scheme used by the TCP/IP protocol. Because the Nagle algorithm used in typical TCP/IP implementations causes a latency of about 300 milliseconds even before a data packet is sent, any additional latency in the network of 100 milliseconds or more will result in a decreased operator performance in teleradiology applications. These conditions frequently occur on the public Internet or on overseas connections. For optimal performance, the authors recommend bypassing the Nagle algorithm in teleradiology applications. PMID:15359750

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

    PubMed

    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. PMID:23771428

  13. Tousled-like kinases modulate reactivation of gammaherpesviruses from latency.

    PubMed

    Dillon, Patrick J; Gregory, Sean M; Tamburro, Kristen; Sanders, Marcia K; Johnson, Gary L; Raab-Traub, Nancy; Dittmer, Dirk P; Damania, Blossom

    2013-02-13

    Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to human malignancies. The majority of tumor cells harbor latent virus, and a small percentage undergo spontaneous lytic replication. Both latency and lytic replication are important for viral pathogenesis and spread, but the cellular players involved in the switch between the two viral life-cycle phases are not clearly understood. We conducted a small interfering RNA (siRNA) screen targeting the cellular kinome and identified Tousled-like kinases (TLKs) as cellular kinases that control KSHV reactivation from latency. Upon treatment of latent KSHV-infected cells with siRNAs targeting TLKs, we saw robust viral reactivation. Knockdown of TLKs in latent KSHV-infected cells induced expression of viral lytic proteins and production of infectious virus. TLKs were also found to play a role in regulating reactivation from latency of another related oncogenic gammaherpesvirus, Epstein-Barr virus. Our results establish the TLKs as cellular repressors of gammaherpesvirus reactivation. PMID:23414760

  14. Scalla: Structured Cluster Architecture for Low Latency Access

    SciTech Connect

    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.

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

    PubMed

    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. PMID:17405124

  16. Therapeutics Targeting Protein Acetylation Perturb Latency of Human Viruses.

    PubMed

    Conrad, Ryan J; Ott, Melanie

    2016-03-18

    Persistent viral infections are widespread and represent significant public health burdens. Some viruses endure in a latent state by co-opting the host epigenetic machinery to manipulate viral gene expression. Small molecules targeting epigenetic pathways are now in the clinic for certain cancers and are considered as potential treatment strategies to reverse latency in HIV-infected individuals. In this review, we discuss how drugs interfering with one epigenetic pathway, protein acetylation, perturb latency of three families of pathogenic human viruses-retroviruses, herpesviruses, and papillomaviruses. PMID:26845514

  17. A collision-free with propagation latency WDMA protocol analysis

    NASA Astrophysics Data System (ADS)

    Pountourakis, I. E.; Baziana, P. A.

    2007-04-01

    The substantial role of propagation delay latency in WDM networks is examined in this paper in conjunction with a multi-channel control architecture (MCA) that reduces the processing overhead of control information for synchronous transmission in passive star topology. We exploit the peculiarity of propagation delay latency in WDM networks and its impact in the performance measures to introduce a simple multiple access algorithm avoiding data channel conflicts, aimed at improving of system utilization. Also we examine the effect of receiver collisions to performance measures evaluation developing analytic Markovian models for finite population.

  18. First low-latency LIGO+Virgo search for binary inspirals and their electromagnetic counterparts

    NASA Astrophysics Data System (ADS)

    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.; Kang, G.; Kanner, J. B.; Kasturi, R.; Katsavounidis, E.; Katzman, W.; Kaufer, H.; Kawabe, K.; Kawamura, S.; Kawazoe, F.; Kelley, D.; Kells, W.; Keppel, D. G.; Keresztes, Z.; Khalaidovski, A.; Khalili, F. Y.; Khazanov, E. A.; Kim, B. K.; Kim, C.; Kim, H.; Kim, K.; Kim, N.; Kim, Y. M.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Klimenko, S.; Kokeyama, K.; Kondrashov, V.; Koranda, S.; Korth, W. Z.; Kowalska, I.; Kozak, D.; Kranz, O.; Kringel, V.; Krishnamurthy, S.; Krishnan, B.; Królak, A.; Kuehn, G.; Kumar, R.; Kwee, P.; Lam, P. K.; Landry, M.; Lantz, B.; Lastzka, N.; Lawrie, C.; Lazzarini, A.; Leaci, P.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Leong, J. R.; Leonor, I.; Leroy, N.; Letendre, N.; Li, J.; Li, T. G. F.; Liguori, N.; Lindquist, P. E.; Liu, Y.; Liu, Z.; Lockerbie, N. A.; Lodhia, D.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J.; Luan, J.; Lubinski, M.; Lück, H.; Lundgren, A. P.; Macdonald, E.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Mageswaran, M.; Mailand, K.; Majorana, E.; Maksimovic, I.; Man, N.; Mandel, I.; Mandic, V.; Mantovani, M.; Marandi, A.; Marchesoni, F.; Marion, F.; Márka, S.; Márka, Z.; Markosyan, A.; Maros, E.; Marque, J.; Martelli, F.; Martin, I. W.; Martin, R. M.; Marx, J. N.; Mason, K.; Masserot, A.; Matichard, F.; Matone, L.; Matzner, R. A.; Mavalvala, N.; Mazzolo, G.; McCarthy, R.; McClelland, D. E.; McGuire, S. C.; McIntyre, G.; McIver, J.; McKechan, D. J. A.; McWilliams, S.; Meadors, G. D.; Mehmet, M.; Meier, T.; Melatos, A.; Melissinos, A. C.; Mendell, G.; Mercer, R. A.; Meshkov, S.; Messenger, C.; Meyer, M. S.; Miao, H.; Michel, C.; Milano, L.; Miller, J.; Minenkov, Y.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Miyakawa, O.; Moe, B.; Mohan, M.; Mohanty, S. D.; Mohapatra, S. R. P.; Moraru, D.; Moreno, G.; Morgado, N.; Morgia, A.; Mori, T.; Morriss, S. R.; Mosca, S.; Mossavi, K.; Mours, B.; Mow-Lowry, C. M.; Mueller, C. L.; Mueller, G.; Mukherjee, S.; Mullavey, A.; Müller-Ebhardt, H.; Munch, J.; Murphy, D.; Murray, P. G.; Mytidis, A.; Nash, T.; Naticchioni, L.; Necula, V.; Nelson, J.; Neri, I.; Newton, G.; Nguyen, T.; Nishizawa, A.; Nitz, A.; Nocera, F.; Nolting, D.; Normandin, M. E.; Nuttall, L.; Ochsner, E.; O'Dell, J.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; O'Reilly, B.; O'Shaughnessy, R.; Osthelder, C.; Ott, C. D.; Ottaway, D. J.; Ottens, R. S.; Overmier, H.; Owen, B. J.; Page, A.; Pagliaroli, G.; Palladino, L.; Palomba, C.; Pan, Y.; Pankow, C.; Paoletti, F.; Papa, M. A.; Parisi, M.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patel, P.; Pedraza, M.; Peiris, P.; Pekowsky, L.; Penn, S.; Perreca, A.; Persichetti, G.; Phelps, M.; Pichot, M.; Pickenpack, M.; Piergiovanni, F.; Pietka, M.; Pinard, L.; Pinto, I. M.; Pitkin, M.; Pletsch, H. J.; Plissi, M. V.; Poggiani, R.; Pöld, J.; Postiglione, F.; Prato, M.; Predoi, V.; Prestegard, T.; Price, L. R.; Prijatelj, M.; Principe, M.; Privitera, S.; Prix, R.; Prodi, G. A.; Prokhorov, L. G.; Puncken, O.; Punturo, M.; Puppo, P.; Quetschke, V.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Rácz, I.; Radkins, H.; Raffai, P.; Rakhmanov, M.; Rankins, B.; Rapagnani, P.; Raymond, V.; Re, V.; Redwine, K.; Reed, C. M.; Reed, T.; Regimbau, T.; Reid, S.; Reitze, D. H.; Ricci, F.; Riesen, R.; Riles, K.; Robertson, N. A.; Robinet, F.; Robinson, C.; Robinson, E. L.; Rocchi, A.; Roddy, S.; Rodriguez, C.; Rodruck, M.; Rolland, L.; Rollins, J. G.; Romano, J. D.; Romano, R.; Romie, J. H.; Rosińska, D.; Röver, C.; Rowan, S.; Rüdiger, A.; Ruggi, P.; Ryan, K.; Sainathan, P.; Salemi, F.; Sammut, L.; Sandberg, V.; Sannibale, V.; Santamaría, L.; Santiago-Prieto, I.; Santostasi, G.; Sassolas, B.; Sathyaprakash, B. S.; Sato, S.; Saulson, P. R.; Savage, R. L.; Schilling, R.; Schnabel, R.; Schofield, R. M. S.; Schreiber, E.; Schulz, B.; Schutz, B. F.; Schwinberg, P.; Scott, J.; Scott, S. M.; Seifert, F.; Sellers, D.; Sentenac, D.; Sergeev, A.; Shaddock, D. A.; Shaltev, M.; Shapiro, B.; Shawhan, P.; Shoemaker, D. H.; Sibley, A.; Siemens, X.; Sigg, D.; Singer, A.; Singer, L.; Sintes, A. M.; Skelton, G. R.; Slagmolen, B. J. J.; Slutsky, J.; Smith, J. R.; Smith, M. R.; Smith, R. J. E.; Smith-Lefebvre, N. D.; Somiya, K.; Sorazu, B.; Soto, J.; Speirits, F. C.; Sperandio, L.; Stefszky, M.; Stein, A. J.; Stein, L. C.; Steinert, E.; Steinlechner, J.; Steinlechner, S.; Steplewski, S.; Stochino, A.; Stone, R.; Strain, K. A.; Strigin, S. E.; Stroeer, A. S.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sung, M.; Susmithan, S.; Sutton, P. J.; Swinkels, B.; Tacca, M.; Taffarello, L.; Talukder, D.; Tanner, D. B.; Tarabrin, S. P.; Taylor, J. R.; Taylor, R.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Thüring, A.; Tokmakov, K. V.; Tomlinson, C.; Toncelli, A.; Tonelli, M.; Torre, O.; Torres, C.; Torrie, C. I.; Tournefier, E.; Travasso, F.; Traylor, G.; Tseng, K.; Ugolini, D.; Vahlbruch, H.; Vajente, G.; van den Brand, J. F. J.; Van Den Broeck, C.; van der Putten, S.; van Veggel, A. A.; Vass, S.; Vasuth, M.; Vaulin, R.; Vavoulidis, M.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Veltkamp, C.; Verkindt, D.; Vetrano, F.; Viceré, A.; Villar, A. E.; Vinet, J.-Y.; Vitale, S.; Vocca, H.; Vorvick, C.; Vyatchanin, S. P.; Wade, A.; Wade, L.; Wade, M.; Waldman, S. J.; Wallace, L.; Wan, Y.; Wang, M.; Wang, X.; Wang, Z.; Wanner, A.; Ward, R. L.; Was, M.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Wen, L.; Wessels, P.; West, M.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; White, D. J.; Whiting, B. F.; Wilkinson, C.; Willems, P. A.; Williams, L.; Williams, R.; Willke, B.; Winkelmann, L.; Winkler, W.; Wipf, C. C.; Wiseman, A. G.; Wittel, H.; Woan, G.; Wooley, R.; Worden, J.; Yakushin, I.; Yamamoto, H.; Yamamoto, K.; Yancey, C. C.; Yang, H.; Yeaton-Massey, D.; Yoshida, S.; Yu, P.; Yvert, M.; Zadrożny, A.; Zanolin, M.; Zendri, J.-P.; Zhang, F.; Zhang, L.; Zhang, W.; Zhao, C.; Zotov, N.; Zucker, M. E.; Zweizig, J.

    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.

  19. Modeling HIV-1 Latency in Primary T Cells Using a Replication-Competent Virus.

    PubMed

    Martins, Laura J; Bonczkowski, Pawel; Spivak, Adam M; De Spiegelaere, Ward; Novis, Camille L; DePaula-Silva, Ana Beatriz; Malatinkova, Eva; Typsteen, Wim; Bosque, Alberto; Vanderkerckhove, Linos; Planelles, Vicente

    2016-02-01

    HIV-1 latently infected cells in vivo can be found in extremely low frequencies. Therefore, in vitro cell culture models have been used extensively for the study of HIV-1 latency. Often, these in vitro systems utilize defective viruses. Defective viruses allow for synchronized infections and circumvent the use of antiretrovirals. In addition, replication-defective viruses cause minimal cytopathicity because they fail to spread and usually do not encode env or accessory genes. On the other hand, replication-competent viruses encode all or most viral genes and better recapitulate the nuances of the viral replication cycle. The study of latency with replication-competent viruses requires the use of antiretroviral drugs in culture, and this mirrors the use of antiretroviral treatment (ART) in vivo. We describe a model that utilizes cultured central memory CD4(+) T cells and replication-competent HIV-1. This method generates latently infected cells that can be reactivated using latency reversing agents in the presence of antiretroviral drugs. We also describe a method for the removal of productively infected cells prior to viral reactivation, which takes advantage of the downregulation of CD4 by HIV-1, and the use of a GFP-encoding virus for increased throughput. PMID:26171776

  20. Control of HIV Latency by Epigenetic and Non-Epigenetic Mechanisms

    PubMed Central

    Mbonye, Uri; Karn, Jonathan

    2011-01-01

    Intensive antiretroviral therapy successfully suppresses viral replication but is unable to eradicate the virus. HIV persists in a small number of resting memory T cells where HIV has been transcriptionally silenced. This review will focus on recent insights into the HIV transcriptional control mechanisms that provide the biochemical basis for understanding latency. There are no specific repressors of HIV transcription encoded by the virus, instead latency arises when the regulatory feedback mechanism driven by HIV Tat expression is disrupted. Small changes in transcriptional initiation, induced by epigenetic silencing, lead to profound restrictions in Tat levels and force the entry of proviruses into latency. In resting memory T cells, which carry the bulk of the latent viral pool, additional restrictions, especially the limiting cellular levels of the essential Tat cofactor P-TEFb and the transcription initiation factors NF-κB and NFAT ensure that the provirus remains silenced unless the host cell is activated. The detailed understanding of HIV transcription is providing a framework for devising new therapeutic strategies designed to purge the latent viral pool. Importantly, the recognition that there are multiple restrictions imposed on latent proviruses suggest that proviral reactivation will not be achieved when only a single reactivation step is targeted and that any optimal activation strategy will require both removal of epigenetic blocks and the activation of P-TEFb. PMID:22211660

  1. Kaposi's Sarcoma-Associated Herpesvirus Genome Replication, Partitioning, and Maintenance in Latency.

    PubMed

    Ohsaki, Eriko; Ueda, Keiji

    2012-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is thought to be an oncogenic member of the γ-herpesvirus subfamily. The virus usually establishes latency upon infection as a default infection pattern. The viral genome replicates according to the host cell cycle by recruiting the host cellular replication machinery. Among the latently expressing viral factors, LANA plays pivotal roles in viral genome replication, partitioning, and maintenance. LANA binds with two LANA-binding sites (LBS1/2) within a terminal repeat (TR) sequence and is indispensable for viral genome replication in latency. The nuclear matrix region seems to be important as a replication site, since LANA as well as cellular replication factors accumulate there and recruit the viral replication origin in latency (ori-P) by its binding activity to LBS. KSHV ori-P consists of LBS followed by a 32-bp GC-rich segment (32GC). Although it has been reported that LANA recruits cellular pre-replication complexes (pre-RC) such as origin recognition complexes (ORCs) to the ori-P through its interaction with ORCs, this mechanism does not account completely for the requirement of the 32GC. On the other hand, there are few reports about the partitioning and maintenance of the viral genome. LANA interacts with many kinds of chromosomal proteins, including Brd2/RING3, core histones, such as H2A/H2B and histone H1, and so on. The detailed molecular mechanisms by which LANA enables KSHV genome partitioning and maintenance still remain obscure. By integrating the findings reported thus far on KSHV genome replication, partitioning, and maintenance in latency, we will summarize what we know now, discuss what questions remain to be answered, and determine what needs to be done next to understand the mechanisms underlying viral replication, partitioning, and maintenance strategy. PMID:22291692

  2. Can central hexagon peak latency provide a clue to fixation within the mfERG.

    PubMed

    Hagan, R P; Small, A; Fisher, A C; Brown, M C

    2010-04-01

    The mfERG has proven to be a useful tool in determining central retinal and macular function. It is, however, reliant on good subject co-operation and fixation. This cannot always be guaranteed due to visual impairment or poor co-operation. Whilst a change in fixation is easy to identify with camera monitoring of the subject, a small eccentric fixation can be difficult to notice or quantify. Whilst the problem of fixation can be obviated by stimulating the retina directly with SLO (Scanning Laser Ophthalmoscope), this is expensive and a certain amount of expertize in optics is required to properly stimulate the retina. In this study, peak latency of response was investigated to see whether it changed across the retina and whether this measure could be used to help assess fixation. Eighteen normal eyes were stimulated using a 60 Hz CRT monitor with only 2 hexagons, one central and one peripheral. These hexagons were presented at three stimulation rates, fast (no filler frames between steps of the m-sequence) and slow (4 and 7 black filler frames between each step of the m-sequence), under all conditions significantly increased central hexagon latencies were noted. In a smaller experiment with 19 hexagons and only 4 subjects, it was noted a significant delay in latency was observed in ring 1 compared to ring 2 and 3 with central fixation, but not when the subjects fixed mid-peripheral and in the periphery to slow stimulation, showing that the central hexagon response was only delayed in the central hexagon when there was adequate fixation. This study suggests that latency could provide a clue to fixation particular at slow rates thereby improving the quality and confidence of recordings made clinically. PMID:19949833

  3. Shrapnel: Latency, Mourning and the Suicide of a Parent

    ERIC Educational Resources Information Center

    Bisagni, Francesco

    2012-01-01

    The aim of this paper is to describe some acute responses to the suicide of a parent, through the account of the analytic psychotherapy of a latency child who found the body of his dead father. The acute traumatic responses of the child show that the perceptual apparatus, time and space are subverted, while the functioning of the contact barrier…

  4. Resolution of Misconceptions of Latency and Adolescent Sicklers.

    ERIC Educational Resources Information Center

    Christy-Levine, Diane

    Misconceptions regarding sickle cell disease are qualitatively different among latency age patients as compared to adolescents. The evolution and resolution of these misconceptions determine the effectiveness of self-help programs for sickle cell patients. The Mount Sinai Hospital Sickle Cell Counseling Service is a coordinated center for sickle…

  5. Herpes simplex virus latency in isolated human neurons.

    PubMed Central

    Wigdahl, B; Smith, C A; Traglia, H M; Rapp, F

    1984-01-01

    Herpes simplex virus is most probably maintained in the ganglion neurons of the peripheral nervous system of humans in a latent form that can reactivate to produce recurrent disease. As an approximation of this cell-virus interaction, we have constructed a herpes simplex virus latency in vitro model system using human fetus sensory neurons as the host cell. Human fetus neurons were characterized as neuronal in origin by the detection of the neuropeptide substance P and the neuron-specific plasma membrane A2B5 antigen. Virus latency was established by blocking complete expression of the virus genome by treatment of infected human neurons with a combination of human leukocyte interferon and (E)-5-(2-bromovinyl)-2'-deoxyuridine for 7 days. After removal of inhibitors, virus latency was maintained for at least 9 days. This in vitro model will provide a system to analyze, in a primary human neuron, the state of the herpes simplex virus genome during establishment and maintenance of experimental latency. Images PMID:6091142

  6. Mars Surface Operations via Low-Latency Telerobotics from Phobos

    NASA Technical Reports Server (NTRS)

    Wright, Michael; Lupisella, Mark

    2016-01-01

    To help assess the feasibility and timing of Low-Latency Telerobotics (LLT) operations on Mars via a Phobos telecommand base, operations concepts (ops cons) and timelines for several representative sequences for Mars surface operations have been developed. A summary of these LLT sequences and timelines will be presented, along with associated assumptions, operational considerations, and challenges.

  7. Response Latency Detection of Lying on Personnel Tests.

    ERIC Educational Resources Information Center

    Holden, Ronald R.

    Recently, there has been a resurgence of interest in the use of response latencies in psychological assessment. Some research has suggested that response times associated with answering personality and integrity questionnaires may be useful in differentiating among honest responders and individuals who are lying. Using an experimental paradigm…

  8. [Circadian variation in the latency of auditory brainstem response].

    PubMed

    Murakami, S; Sotsu, M; Nakamura, N

    1992-07-01

    The auditory brainstem response (ABR) has been found to reflect many pathological conditions within the auditory system and brainstem. And now, many neurosurgeons are using it to monitor the integrity of the auditory pathway during neurosurgical procedures. It is said that ABR shows little variation from person to person or laboratory to laboratory, nor is it easily affected by anesthesia, level of consciousness, fluctuation of blood pressure or hypoxemia. On the other hand, previous studies have shown that component waves of the ABR increase in latency and decrease in amplitude with lowered temperature. We reported here that naturally occurring circadian variations in body temperature were correlated with similar changes in the latency of the ABR. Tympanic temperature (Tty), deep forehead temperature (Thd) and ABR were recorded every 3 hours during a 24-hour period for a total of 8 recording sessions from each of 6 healthy persons (2 males and 4 females, mean age 24.3 years). The subjects were free to come and go during the day but slept overnight in the laboratory. All subjects had circadian variations in each temperature on the order of one degree. Thd had a tendency to fluctuate and its range of difference from Tty was -0.5-0.4 degree C. There was a more significant negative correlation between the latency of the ABR and Tty than that of Thd. It has become apparent that ABR latency is affected by small temperature changes such as circadian variation. The rate of a latency change in the ABR was 0.15msec per degree (C).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1329888

  9. Immunogenic potential of latency associated antigens against Mycobacterium tuberculosis.

    PubMed

    Singh, Swati; Saraav, Iti; Sharma, Sadhna

    2014-02-01

    Tuberculosis remains a great health threat to the world among infectious diseases particularly with the advent of human immunodeficiency virus and emergence of drug resistant strains. In the light of the inconsistent efficacy imparted by the only currently available pre-exposure vaccine bacillus Calmette-Guerin BCG, the development of an improved TB vaccine is a very high international research priority. Vaccine candidates currently in clinical trials are also pre-exposure vaccines that aim to prevent active tuberculosis during an individual's lifetime. According to World Health Organization approximately a third of the world's population is latently infected with Mycobacterium tuberculosis. Dormancy or latency of Mycobacteria is associated with the formation of granuloma with poorly perfused interior leading to expression of genes which help them survive in this hostile environment. A group of about 50 genes belonging to the DosR regulon also known as latency antigens are expressed by Mycobacteria when they are persisting in the immuno-competent host. An understanding of the immunological effects produced by products of these latency induced genes may help in making a more potent vaccine. Incorporation of latency antigens into improved (live or subunit) vaccines may enhance the impact of these vaccines in which BCG priming can be followed by multisubunit protein boosting. These vaccines could act as post exposure vaccines for containment and prevention of latent TB activation. This heterologous boosting of BCG-primed immunity will be able to stimulate the known immune correlates of protective immunity against M. tuberculosis i.e. TH1 cells (CD4(+) and CD8(+) T cells) mediated immune responses with cytokines such as IFN-γ and TNF-α⋅ In our review we have analysed and compared the immunogenic potential of various latency-associated antigens of the DosR regulon in line with the current strategy of developing a recombinant post exposure booster vaccine. PMID

  10. Long-latency muscle activity reflects continuous, delayed sensorimotor feedback of task-level and not joint-level error

    PubMed Central

    Safavynia, Seyed A.

    2013-01-01

    In both the upper and lower limbs, evidence suggests that short-latency electromyographic (EMG) responses to mechanical perturbations are modulated based on muscle stretch or joint motion, whereas long-latency responses are modulated based on attainment of task-level goals, e.g., desired direction of limb movement. We hypothesized that long-latency responses are modulated continuously by task-level error feedback. Previously, we identified an error-based sensorimotor feedback transformation that describes the time course of EMG responses to ramp-and-hold perturbations during standing balance (Safavynia and Ting 2013; Welch and Ting 2008, 2009). Here, our goals were 1) to test the robustness of the sensorimotor transformation over a richer set of perturbation conditions and postural states; and 2) to explicitly test whether the sensorimotor transformation is based on task-level vs. joint-level error. We developed novel perturbation trains of acceleration pulses such that perturbations were applied when the body deviated from the desired, upright state while recovering from preceding perturbations. The entire time course of EMG responses (∼4 s) in an antagonistic muscle pair was reconstructed using a weighted sum of center of mass (CoM) kinematics preceding EMGs at long-latency delays (∼100 ms). Furthermore, CoM and joint kinematic trajectories became decorrelated during perturbation trains, allowing us to explicitly compare task-level vs. joint feedback in the same experimental condition. Reconstruction of EMGs was poorer using joint kinematics compared with CoM kinematics and required unphysiologically short (∼10 ms) delays. Thus continuous, long-latency feedback of task-level variables may be a common mechanism regulating long-latency responses in the upper and lower limbs. PMID:23803325

  11. Long-latency muscle activity reflects continuous, delayed sensorimotor feedback of task-level and not joint-level error.

    PubMed

    Safavynia, Seyed A; Ting, Lena H

    2013-09-01

    In both the upper and lower limbs, evidence suggests that short-latency electromyographic (EMG) responses to mechanical perturbations are modulated based on muscle stretch or joint motion, whereas long-latency responses are modulated based on attainment of task-level goals, e.g., desired direction of limb movement. We hypothesized that long-latency responses are modulated continuously by task-level error feedback. Previously, we identified an error-based sensorimotor feedback transformation that describes the time course of EMG responses to ramp-and-hold perturbations during standing balance (Safavynia and Ting 2013; Welch and Ting 2008, 2009). Here, our goals were 1) to test the robustness of the sensorimotor transformation over a richer set of perturbation conditions and postural states; and 2) to explicitly test whether the sensorimotor transformation is based on task-level vs. joint-level error. We developed novel perturbation trains of acceleration pulses such that perturbations were applied when the body deviated from the desired, upright state while recovering from preceding perturbations. The entire time course of EMG responses (∼4 s) in an antagonistic muscle pair was reconstructed using a weighted sum of center of mass (CoM) kinematics preceding EMGs at long-latency delays (∼100 ms). Furthermore, CoM and joint kinematic trajectories became decorrelated during perturbation trains, allowing us to explicitly compare task-level vs. joint feedback in the same experimental condition. Reconstruction of EMGs was poorer using joint kinematics compared with CoM kinematics and required unphysiologically short (∼10 ms) delays. Thus continuous, long-latency feedback of task-level variables may be a common mechanism regulating long-latency responses in the upper and lower limbs. PMID:23803325

  12. Recovery cycle times of inferior colliculus neurons in the awake bat measured with spike counts and latencies

    PubMed Central

    Sayegh, Riziq; Aubie, Brandon; Fazel-Pour, Siavosh; Faure, Paul A.

    2012-01-01

    Neural responses in the mammalian auditory midbrain (inferior colliculus; IC) arise from complex interactions of synaptic excitation, inhibition, and intrinsic properties of the cell. Temporally selective duration-tuned neurons (DTNs) in the IC are hypothesized to arise through the convergence of excitatory and inhibitory synaptic inputs offset in time. Synaptic inhibition can be inferred from extracellular recordings by presenting pairs of pulses (paired tone stimulation) and comparing the evoked responses of the cell to each pulse. We obtained single unit recordings from the IC of the awake big brown bat (Eptesicus fuscus) and used paired tone stimulation to measure the recovery cycle times of DTNs and non-temporally selective auditory neurons. By systematically varying the interpulse interval (IPI) of the paired tone stimulus, we determined the minimum IPI required for a neuron's spike count or its spike latency (first- or last-spike latency) in response to the second tone to recover to within ≥50% of the cell's baseline count or to within 1 SD of it's baseline latency in response to the first tone. Recovery times of shortpass DTNs were significantly shorter than those of bandpass DTNs, and recovery times of bandpass DTNs were longer than allpass neurons not selective for stimulus duration. Recovery times measured with spike counts were positively correlated with those measured with spike latencies. Recovery times were also correlated with first-spike latency (FSL). These findings, combined with previous studies on duration tuning in the IC, suggest that persistent inhibition is a defining characteristic of DTNs. Herein, we discuss measuring recovery times of neurons with spike counts and latencies. We also highlight how persistent inhibition could determine neural recovery times and serve as a potential mechanism underlying the precedence effect in humans. Finally, we explore implications of recovery times for DTNs in the context of bat hearing and

  13. AUTOMATED INSTRUCTION OF REMEDIAL ENGLISH, VOLUME II--RESPONSE LATENCY IN PROGRAMED LEARNING--LATENCY RELATED TO ERROR RATE.

    ERIC Educational Resources Information Center

    DOROUGH, C. DWIGHT; AND OTHERS

    FIVE CLASSES OF RESPONSE LATENCIES WERE CONSIDERED IN THE STUDY, WHICH EVOLVED FROM CRP 551 (ED 003 586). THEY WERE (1) READING, (2) ANSWERING, (3) SCORING AND TURNING TO THE NEXT FRAME OF MATERIAL, (4) READING PLUS ANSWERING, AND (5) TOTAL FRAME TIME (READING PLUS ANSWERING PLUS SCORING PLUS TURNING). THE SUBJECTS WERE 12 MALES AND 4 FEMALES…

  14. Reducing the latency of the Fractal Iterative Method to half an iteration

    NASA Astrophysics Data System (ADS)

    Béchet, Clémentine; Tallon, Michel

    2013-12-01

    The fractal iterative method for atmospheric tomography (FRiM-3D) has been introduced to solve the wavefront reconstruction at the dimensions of an ELT with a low-computational cost. Previous studies reported the requirement of only 3 iterations of the algorithm in order to provide the best adaptive optics (AO) performance. Nevertheless, any iterative method in adaptive optics suffer from the intrinsic latency induced by the fact that one iteration can start only once the previous one is completed. Iterations hardly match the low-latency requirement of the AO real-time computer. We present here a new approach to avoid iterations in the computation of the commands with FRiM-3D, thus allowing low-latency AO response even at the scale of the European ELT (E-ELT). The method highlights the importance of "warm-start" strategy in adaptive optics. To our knowledge, this particular way to use the "warm-start" has not been reported before. Futhermore, removing the requirement of iterating to compute the commands, the computational cost of the reconstruction with FRiM-3D can be simplified and at least reduced to half the computational cost of a classical iteration. Thanks to simulations of both single-conjugate and multi-conjugate AO for the E-ELT,with FRiM-3D on Octopus ESO simulator, we demonstrate the benefit of this approach. We finally enhance the robustness of this new implementation with respect to increasing measurement noise, wind speed and even modeling errors.

  15. Ultra-high speed and low latency broadband digital video transport

    NASA Astrophysics Data System (ADS)

    Stufflebeam, Joseph L.; Remley, Dennis M.; Sullivan, Anthony; Gurrola, Hector

    2004-07-01

    Various approaches for transporting digital video over Ethernet and SONET networks are presented. Commercial analog and digital frame grabbers are utilized, as well as software running under Microsoft Windows 2000/XP. No other specialized hardware is required. A network configuration using independent VLANs for video channels provides efficient transport for high bandwidth data. A framework is described for implementing both uncompressed and compressed streaming with standard and non-standard video. NTSC video is handled as well as other formats that include high resolution CMOS, high bit-depth infrared, and high frame rate parallel digital. End-to-end latencies of less than 200 msec are achieved.

  16. Blink reflex latency after exposure to trichloroethylene in well water

    SciTech Connect

    Feldman, R.G.; Chirico-Post, J.; Proctor, S.P.

    1988-03-01

    The electrophysiological measurement of the blink reflex (BR) can quantify the conduction latency in the reflex arc involving the Vth (trigeminal) and VIIth (facial) cranial nerves. We measured the electrophysiological BR in a population (N = 21), which had alleged chronic exposure to trichloroethylene (TCE) through the public drinking water at levels 30-80 times higher than the Environmental Protection Agency (EPA) Maximum Contamination Level (MCL). A highly significant difference was observed in the conduction latency means of the BR components (p less than .0001), when the study population was compared with laboratory controls (N = 27). This difference suggests a subclinical alteration of the Vth cranial nerve function due to chronic, environmental exposure to TCE.

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Molecular Basis of Latency in Pathogenic Human Viruses

    NASA Astrophysics Data System (ADS)

    Garcia-Blanco, Mariano A.; Cullen, Bryan R.

    1991-11-01

    Several human viruses are able to latently infect specific target cell populations in vivo. Analysis of the replication cycles of herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus suggests that the latent infections established by these human pathogens primarily result from a lack of host factors critical for the expression of viral early gene products. The subsequent activation of specific cellular transcription factors in response to extracellular stimuli can induce the expression of these viral regulatory proteins and lead to a burst of lytic viral replication. Latency in these eukaryotic viruses therefore contrasts with latency in bacteriophage, which is maintained primarily by the expression of virally encoded repressors of lytic replication.

  19. Mismatch Negativity Latency and Cognitive Function in Schizophrenia

    PubMed Central

    Kärgel, Christian; Sartory, Gudrun; Kariofillis, Daniela; Wiltfang, Jens; Müller, Bernhard W.

    2014-01-01

    Background The Mismatch Negativity (MMN) is an event-related potential (ERP) sensitive to early auditory deviance detection and has been shown to be reduced in schizophrenia patients. Moreover, MMN amplitude reduction to duration deviant tones was found to be related to functional outcomes particularly, to neuropsychological (working memory and verbal domains) and psychosocial measures. While MMN amplitude is thought to be correlated with deficits of early sensory processing, the functional significance of MMN latency remains unclear so far. The present study focused on the investigation of MMN in relation to neuropsychological function in schizophrenia. Method Forty schizophrenia patients and 16 healthy controls underwent a passive oddball paradigm (2400 binaural tones; 88% standards [1 kHz, 80 db, 80 ms], 11% frequency deviants [1.2 kHz], 11% duration deviants [40 ms]) and a neuropsychological test-battery. Patients were assessed with regard to clinical symptoms. Results Compared to healthy controls schizophrenia patients showed diminished MMN amplitude and shorter MMN latency to both deviants as well as an impaired neuropsychological test performance. Severity of positive symptoms was related to decreased MMN amplitude to duration deviants. Furthermore, enhanced verbal memory performance was associated with prolonged MMN latency to frequency deviants in patients. Conclusion The present study corroborates previous results of a diminished MMN amplitude and its association with positive symptoms in schizophrenia patients. Both, the findings of a shorter latency to duration and frequency deviants and the relationship of the latter with verbal memory in patients, emphasize the relevance of the temporal aspect of early auditory discrimination processing in schizophrenia. PMID:24740391

  20. HyspIRI Low Latency Concept and Benchmarks

    NASA Technical Reports Server (NTRS)

    Mandl, Dan

    2010-01-01

    Topics include HyspIRI low latency data ops concept, HyspIRI data flow, ongoing efforts, experiment with Web Coverage Processing Service (WCPS) approach to injecting new algorithms into SensorWeb, low fidelity HyspIRI IPM testbed, compute cloud testbed, open cloud testbed environment, Global Lambda Integrated Facility (GLIF) and OCC collaboration with Starlight, delay tolerant network (DTN) protocol benchmarking, and EO-1 configuration for preliminary DTN prototype.

  1. Short latency vestibular evoked potentials in the chicken embryo

    NASA Technical Reports Server (NTRS)

    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 < 6.0 ms) were scored and latencies and amplitudes quantified. Vestibular response latencies were significantly longer (P < 0.01) and amplitudes significantly smaller (P < 0.001) than those observed in 2-week-old birds. Mean response threshold for anesthetized embryos was -15.9dBre 1.0 g/ms, which was significantly higher (P < 0.03) than those observed in 2-week-old birds (-23.0dBre 1.0 g/ms). Latency/intensity functions (that is, slopes) were not significantly different between embryos and 2-week-old animals, but amplitude/intensity functions for embryos were significantly shallower than those for 2-week-old birds (P < 0.001). We presume that these differences reflect the refinement of sensory function that occurs following 19 to 20 days of incubation. The recording of vestibular evoked potentials provides an objective, direct and noninvasive measure of peripheral vestibular function in the 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.

  2. Auditory middle latency response in children with learning difficulties

    PubMed Central

    Frizzo, Ana Claudia Figueiredo; Issac, Myriam Lima; Pontes-Fernandes, Angela Cristina; Menezes, Pedro de Lemos; Funayama, Carolina Araújo Rodrigues

    2012-01-01

    Summary Introduction: This is an objective laboratory assessment of the central auditory systems of children with learning disabilities. Aim: To examine and determine the properties of the components of the Auditory Middle Latency Response in a sample of children with learning disabilities. Methods: This was a prospective, cross-sectional cohort study with quantitative, descriptive, and exploratory outcomes. We included 50 children aged 8–13 years of both genders with and without learning disorders. Those with disorders of known organic, environmental, or genetic causes were excluded. Results and Conclusions: The Na, Pa, and Nb waves were identified in all subjects. The ranges of the latency component values were as follows: Na = 9.8–32.3 ms, Pa = 19.0–51.4 ms, Nb = 30.0–64.3 ms (learning disorders group) and Na = 13.2–29.6 ms, Pa = 21.8–42.8 ms, Nb = 28.4–65.8 ms (healthy group). The values of the Na-Pa amplitude ranged from 0.3 to 6.8 ìV (learning disorders group) or 0.2–3.6 ìV (learning disorders group). Upon analysis, the functional characteristics of the groups were distinct: the left hemisphere Nb latency was longer in the study group than in the control group. Peculiarities of the electrophysiological measures were observed in the children with learning disorders. This study has provided information on the Auditory Middle Latency Response and can serve as a reference for other clinical and experimental studies in children with these disorders. PMID:25991954

  3. Using Arduino microcontroller boards to measure response latencies.

    PubMed

    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. PMID:23585023

  4. Saccade latency reveals episodic representation of object color.

    PubMed

    Gordon, Robert D

    2014-08-01

    While previous studies suggest that identity, but not color, plays a role in episodic object representation, such studies have typically used tasks in which only identity is relevant, raising the possibility that the results reflect task demands, rather than the general principles that underlie object representation. In the present study, participants viewed a preview display containing one (Experiments 1 and 2) or two (Experiment 3) letters, then viewed a target display containing a single letter, in either the same or a different location. Participants executed an immediate saccade to fixate the target; saccade latency served as the dependent variable. In all experiments, saccade latencies were longer to fixate a target appearing in its previewed location, consistent with a bias to attend to new objects rather than to objects for which episodic representations are being maintained in visual working memory. The results of Experiment 3 further demonstrate, however, that changing target color eliminates these latency differences. The results suggest that color and identity are part of episodic representation even when not task relevant and that examining biases in saccade execution may be a useful approach to studying episodic representation. PMID:24820158

  5. A Novel Mechanism of Latency in Matrix Metalloproteinases*

    PubMed Central

    López-Pelegrín, Mar; Ksiazek, Miroslaw; Karim, Abdulkarim Y.; Guevara, Tibisay; Arolas, Joan L.; Potempa, Jan; Gomis-Rüth, F. Xavier

    2015-01-01

    The matrix metalloproteinases (MMPs) are a family of secreted soluble or membrane-anchored multimodular peptidases regularly found in several paralogous copies in animals and plants, where they have multiple functions. The minimal consensus domain architecture comprises a signal peptide, a 60–90-residue globular prodomain with a conserved sequence motif including a cysteine engaged in “cysteine-switch” or “Velcro” mediated latency, and a catalytic domain. Karilysin, from the human periodontopathogen Tannerella forsythia, is the only bacterial MMP to have been characterized biochemically to date. It shares with eukaryotic forms the catalytic domain but none of the flanking domains. Instead of the consensus MMP prodomain, it features a 14-residue propeptide, the shortest reported for a metallopeptidase, which lacks cysteines. Here we determined the structure of a prokarilysin fragment encompassing the propeptide and the catalytic domain, and found that the former runs across the cleft in the opposite direction to a bound substrate and inhibits the latter through an “aspartate-switch” mechanism. This finding is reminiscent of latency maintenance in the otherwise unrelated astacin and fragilysin metallopeptidase families. In addition, in vivo and biochemical assays showed that the propeptide contributes to protein folding and stability. Our analysis of prokarilysin reveals a novel mechanism of latency and activation in MMPs. Finally, our findings support the view that the karilysin catalytic domain was co-opted by competent bacteria through horizontal gene transfer from a eukaryotic source, and later evolved in a specific bacterial environment. PMID:25555916

  6. A novel mechanism of latency in matrix metalloproteinases.

    PubMed

    López-Pelegrín, Mar; Ksiazek, Miroslaw; Karim, Abdulkarim Y; Guevara, Tibisay; Arolas, Joan L; Potempa, Jan; Gomis-Rüth, F Xavier

    2015-02-20

    The matrix metalloproteinases (MMPs) are a family of secreted soluble or membrane-anchored multimodular peptidases regularly found in several paralogous copies in animals and plants, where they have multiple functions. The minimal consensus domain architecture comprises a signal peptide, a 60-90-residue globular prodomain with a conserved sequence motif including a cysteine engaged in "cysteine-switch" or "Velcro" mediated latency, and a catalytic domain. Karilysin, from the human periodontopathogen Tannerella forsythia, is the only bacterial MMP to have been characterized biochemically to date. It shares with eukaryotic forms the catalytic domain but none of the flanking domains. Instead of the consensus MMP prodomain, it features a 14-residue propeptide, the shortest reported for a metallopeptidase, which lacks cysteines. Here we determined the structure of a prokarilysin fragment encompassing the propeptide and the catalytic domain, and found that the former runs across the cleft in the opposite direction to a bound substrate and inhibits the latter through an "aspartate-switch" mechanism. This finding is reminiscent of latency maintenance in the otherwise unrelated astacin and fragilysin metallopeptidase families. In addition, in vivo and biochemical assays showed that the propeptide contributes to protein folding and stability. Our analysis of prokarilysin reveals a novel mechanism of latency and activation in MMPs. Finally, our findings support the view that the karilysin catalytic domain was co-opted by competent bacteria through horizontal gene transfer from a eukaryotic source, and later evolved in a specific bacterial environment. PMID:25555916

  7. Saccade Latency Reveals Episodic Representation of Object Color

    PubMed Central

    Gordon, Robert D.

    2014-01-01

    While previous studies suggest that identity, but not color, plays a role in episodic object representation, such studies have typically used tasks in which only identity is relevant, raising the possibility that the results reflect task demands rather than the general principles that underlie object representation. In the present study, participants viewed a preview display containing one (Experiments 1 and 2) or two (Experiment 3) letters, then viewed a target display containing a single letter, in either the same or a different location. Participants executed an immediate saccade to fixate the target; saccade latency served as the dependent variable. In all experiments, saccade latencies were longer to fixate a target appearing in its previewed location, consistent with a bias to attend to new objects rather than to objects for which episodic representations are being maintained in visual working memory. The results of Experiment 3 further demonstrate, however, that changing target color eliminates these latency differences. The results suggest that color and identity are part of episodic representation even when not task relevant, and that examining biases in saccade execution may be a useful approach to studying episodic representation. PMID:24820158

  8. A Fast and Reliable Method for Simultaneous Waveform, Amplitude and Latency Estimation of Single-Trial EEG/MEG Data

    PubMed Central

    Weeda, Wouter D.; Grasman, Raoul P. P. P.; Waldorp, Lourens J.; van de Laar, Maria C.; van der Molen, Maurits W.; Huizenga, Hilde M.

    2012-01-01

    The amplitude and latency of single-trial EEG/MEG signals may provide valuable information concerning human brain functioning. In this article we propose a new method to reliably estimate single-trial amplitude and latency of EEG/MEG signals. The advantages of the method are fourfold. First, no a-priori specified template function is required. Second, the method allows for multiple signals that may vary independently in amplitude and/or latency. Third, the method is less sensitive to noise as it models data with a parsimonious set of basis functions. Finally, the method is very fast since it is based on an iterative linear least squares algorithm. A simulation study shows that the method yields reliable estimates under different levels of latency variation and signal-to-noise ratioÕs. Furthermore, it shows that the existence of multiple signals can be correctly determined. An application to empirical data from a choice reaction time study indicates that the method describes these data accurately. PMID:22761672

  9. Real-time imaging with radial GRAPPA: Implementation on a Heterogeneous Architecture for Low-Latency Reconstructions

    PubMed Central

    Saybasili, Haris; Herzka, Daniel A.; Seiberlich, Nicole; A.Griswold, Mark

    2014-01-01

    Combination of non-Cartesian trajectories with parallel MRI permits to attain unmatched acceleration rates when compared to traditional Cartesian MRI during real-time imaging.However, computationally demanding reconstructions of such imaging techniques, such as k-space domain radial generalized auto-calibrating partially parallel acquisitions (radial GRAPPA) and image domain conjugate gradient sensitivity encoding (CG-SENSE), lead to longer reconstruction times and unacceptable latency for online real-time MRI on conventional computational hardware. Though CG-SENSE has been shown to work with low-latency using a general purpose graphics processing unit (GPU), to the best of our knowledge, no such effort has been made for radial GRAPPA. radial GRAPPA reconstruction, which is robust even with highly undersampled acquisitions, is not iterative, requiring only significant computation during initial calibration while achieving good image quality for low-latency imaging applications. In this work, we present a very fast, low-latency, reconstruction framework based on a heterogeneous system using multi-core CPUs and GPUs. We demonstrate an implementation of radial GRAPPA that permits reconstruction times on par with or faster than acquisition of highly accelerated datasets in both cardiac and dynamic musculoskeletal imaging scenarios. Acquisition and reconstructions times are reported. PMID:24690453

  10. A Neuron-Specific Host MicroRNA Targets Herpes Simplex Virus-1 ICP0 Expression and Promotes Latency

    PubMed Central

    Pan, Dongli; Flores, Omar; Umbach, Jennifer L.; Pesola, Jean M.; Bentley, Peris; Rosato, Pamela C.; Leib, David A.; Cullen, Bryan R.; Coen, Donald M.

    2014-01-01

    Summary After infecting peripheral sites, herpes simplex virus (HSV) invades the nervous system and initiates latent infection in sensory neurons. Establishment and maintenance of HSV latency requires host survival, and entails repression of productive cycle (“lytic”) viral gene expression. We find that a neuron-specific microRNA, miR-138, represses expression of ICP0, a viral transactivator of lytic gene expression. A mutant HSV-1 (M138) with disrupted miR-138 target sites in ICP0 mRNA exhibits enhanced expression of ICP0 and other lytic proteins in infected neuronal cells in culture. Following corneal inoculation, M138-infected mice have higher levels of ICP0 and lytic transcripts in trigeminal ganglia during establishment of latency, and exhibit increased mortality and encephalitis symptoms. After full establishment of latency, the fraction of trigeminal ganglia harboring detectable lytic transcripts is greater in M138-infected mice. Thus, miR-138 is a neuronal factor that represses HSV-1 lytic gene expression, promoting host survival and viral latency. PMID:24721573

  11. Oxaliplatin antagonizes HIV-1 latency by activating NF-κB without causing global T cell activation

    SciTech Connect

    Zhu, Xiaoli; Liu, Sijie; Wang, Pengfei; Qu, Xiying; Wang, Xiaohui; Zeng, Hanxian; Chen, Huabiao; Zhu, Huanzhang

    2014-07-18

    Highlights: • The chemotherapeutic drug oxaliplatin reactivates latent HIV-1 in this cell line model of HIV-1 latency. • Reactivation is synergized when oxaliplatin is used in combination with valproic acid. • Oxaliplatin reactivates latent HIV-1 through activation of NF-kB and does not induce T cell activation. - Abstract: Reactivation of latent HIV-1 is a promising strategy for the clearance of the viral reservoirs. Because of the limitations of current agents, identification of new latency activators is urgently required. Using an established model of HIV-1 latency, we examined the effect of Oxaliplatin on latent HIV-1 reactivation. We showed that Oxaliplatin, alone or in combination with valproic acid (VPA), was able to reactivate HIV-1 without inducing global T cell activation. We also provided evidence that Oxaliplatin reactivated HIV-1 expression by inducing nuclear factor kappa B (NF-κB) nuclear translocation. Our results indicated that Oxaliplatin could be a potential drug candidate for anti-latency therapies.

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

    NASA Technical Reports Server (NTRS)

    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

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

    NASA Astrophysics Data System (ADS)

    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

  14. A Somatosensory Latency between the Thalamus and Cortex also Correlates with Level of Intelligence.

    ERIC Educational Resources Information Center

    Reed, T. Edward; Jensen, Arthur R.

    1993-01-01

    Results for sensory thalamocortical latency (3 somatosensory evoked potentials) for 205 college students agree with data that correlate a more extensive visual evoked potential latency with intelligence quotient. Findings suggest that the correlation occurs because the latency indexes cortical nerve conduction velocity. (SLD)

  15. Spatial auditory regularity encoding and prediction: Human middle-latency and long-latency auditory evoked potentials.

    PubMed

    Cornella, M; Bendixen, A; Grimm, S; Leung, S; Schröger, E; Escera, C

    2015-11-11

    By encoding acoustic regularities present in the environment, the human brain can generate predictions of what is likely to occur next. Recent studies suggest that deviations from encoded regularities are detected within 10-50ms after stimulus onset, as indicated by electrophysiological effects in the middle latency response (MLR) range. This is upstream of previously known long-latency (LLR) signatures of deviance detection such as the mismatch negativity (MMN) component. In the present study, we created predictable and unpredictable contexts to investigate MLR and LLR signatures of the encoding of spatial auditory regularities and the generation of predictions from these regularities. Chirps were monaurally delivered in an either regular (predictable: left-right-left-right) or a random (unpredictable left/right alternation or repetition) manner. Occasional stimulus omissions occurred in both types of sequences. Results showed that the Na component (peaking at 34ms after stimulus onset) was attenuated for regular relative to random chirps, albeit no differences were observed for stimulus omission responses in the same latency range. In the LLR range, larger chirp-and omission-evoked responses were elicited for the regular than for the random condition, and predictability effects were more prominent over the right hemisphere. We discuss our findings in the framework of a hierarchical organization of spatial regularity encoding. This article is part of a Special Issue entitled SI: Prediction and Attention. PMID:25912975

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

    NASA Technical Reports Server (NTRS)

    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.

  17. Development of a low-latency scalar communication routine on message-passing architectures

    SciTech Connect

    Pai, R.

    1994-01-11

    One of the most significant advances in computer systems over the past decade is parallel processing. To be scalable to a large number of processing nodes and to be able to support multiple levels and forms of parallelism and its flexible use, new parallel machines have to be multicomputer architectures that have general networking support and extremely low internode communication latencies. The performance of a program when ported to a parallel machine is limited mainly by the internode communication latencies of the machine. Therefore, the best parallel applications are those that seldom require communications which must be routed through the nodes. Thus the ratio of computation time to that of communication time is what determines, to a large extent, the performance metrics of an algorithm. The cost of synchronization and load imbalance appear secondary to that of the time required for internode communication and I/O, for communication intensive applications. This thesis is organized in chapters. The first chapter deals with the communication strategies in various message-passing computers. A taxonomy of inter-node communication strategies is presented in the second chapter and a comparison of the strategies in some existing machines is done. The implementation of communication in nCUBE Vertex O.S is explained in the third chapter. The fourth chapter deals with the communication routines in the Vertex O.S, and the last chapter explains the development and implementation of the scalar communication call. Finally some conclusions are presented.

  18. Working memory updating latency reflects the cost of switching between maintenance and updating modes of operation.

    PubMed

    Kessler, Yoav; Oberauer, Klaus

    2014-05-01

    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 the number of to-be-updated and to-be-maintained items, as well as their positions in the list, are reported. The pattern of latencies was best explained by a model assuming forward scanning of the list, updating modified items, and maintaining nonmodified items. Switching between updating and maintenance incurred a response time cost, which increased with overall set-size. The formation of new item-position associations accounted for an additional response time component. The finding of an update-switch cost provides novel behavioral support for a class of physiologically inspired computational models, in which updating and maintenance require 2 different states of WM. PMID:24446752

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

    PubMed Central

    Søgaard, Ole S.; Graversen, Mette E.; Leth, Steffen; Olesen, Rikke; Brinkmann, Christel R.; Nissen, Sara K.; Kjaer, Anne Sofie; Schleimann, Mariane H.; Denton, Paul W.; Hey-Cunningham, William J.; Koelsch, Kersten K.; Pantaleo, Giuseppe; Krogsgaard, Kim; Sommerfelt, Maja; Fromentin, Remi; Chomont, Nicolas; Rasmussen, Thomas A.; Østergaard, Lars; Tolstrup, Martin

    2015-01-01

    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. Trial Registration clinicaltrials.gov NTC02092116 PMID:26379282

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

    PubMed

    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. PMID:26997590

  1. The pontomesencephalic tegmentum delays the peak latency of the visual evoked potential in rats.

    PubMed

    Bringmann, A

    1995-12-29

    In previous experiments it was found that physostigmine application in unrestrained rats delayed the peak latency of the visual evoked potential (VEP). The present study was carried out to find the putative site that cholinergically mediates the latency delay of rat's VEP. After unilateral ibotenic acid lesions of the nucleus basalis magnocellularis (NBM) and the pedunculopontine tegmental nucleus (PPTg), respectively, the VEPs of freely moving rats were recorded in different behavioural states. While NBM lesion did not alter the behavioural modulation of the VEP latency, the PPTg lesion produced shorter VEP latencies in the occipital cortex of the lesioned hemisphere in high and moderate arousal states. The peak latency shortening was significant for exploratory sniffing. Physostigmine but not nicotine application abolished the shorter VEP latency. The results indicate a muscarinic mechanism within the pontomesencephalic tegmentum that ipsilaterally delayed the VEP latency in high and moderate but not in low arousal states. PMID:8787819

  2. Low-power low-latency MAC protocol for aeronautical applications

    NASA Astrophysics Data System (ADS)

    Sabater, Jordi; Kluge, Martin; Bovelli, Sergio; Schalk, Josef

    2007-05-01

    This paper describes asynchronous MAC (Medium Access Control) strategies based on the IEEE 802.15.4 physical layer for wireless aeronautical applications where low power and low latency are important requirements as well as security and data integrity. Sensor data is acquired and collected on request, by means of a mobile device, and later stored in a centralized database. In order to have the smallest power consumption the wireless sensor has to remain in deep sleep mode as long as possible and wake up and listen periodically for RF activity. If its unique ID is mentioned in the destination address field, the complete frame is received, processed and replied if necessary. If the detected packet is addressed to another sensor the reception will stop immediately and the wireless sensor will go into deep sleep mode again. Listening instead of sending actively does not 'pollute' the already crowded 2.45GHz spectrum, reduces collisions and increases security. The mobile data concentrator can not be synchronized with all the sensors installed in a distributed environment, therefore smart asynchronous data transmission strategies are needed to reduce latencies and increase throughput. For the considered application, sensors are independent of each other, simply share the medium and together with the data concentrator are organized in a star network topology. The centre of the star is the concentrator which is rarely in range. It coordinates and activates the wireless sensor nodes to collect the measured data.

  3. Early-latency categorical speech sound representations in the left inferior frontal gyrus.

    PubMed

    Alho, Jussi; Green, Brannon M; May, Patrick J C; Sams, Mikko; Tiitinen, Hannu; Rauschecker, Josef P; Jääskeläinen, Iiro P

    2016-04-01

    Efficient speech perception requires the mapping of highly variable acoustic signals to distinct phonetic categories. How the brain overcomes this many-to-one mapping problem has remained unresolved. To infer the cortical location, latency, and dependency on attention of categorical speech sound representations in the human brain, we measured stimulus-specific adaptation of neuromagnetic responses to sounds from a phonetic continuum. The participants attended to the sounds while performing a non-phonetic listening task and, in a separate recording condition, ignored the sounds while watching a silent film. Neural adaptation indicative of phoneme category selectivity was found only during the attentive condition in the pars opercularis (POp) of the left inferior frontal gyrus, where the degree of selectivity correlated with the ability of the participants to categorize the phonetic stimuli. Importantly, these category-specific representations were activated at an early latency of 115-140 ms, which is compatible with the speed of perceptual phonetic categorization. Further, concurrent functional connectivity was observed between POp and posterior auditory cortical areas. These novel findings suggest that when humans attend to speech, the left POp mediates phonetic categorization through integration of auditory and motor information via the dorsal auditory stream. PMID:26774614

  4. Relationship between gender role, anger expression, thermal discomfort and sleep onset latency in women

    PubMed Central

    von Arb, Mariella; Gompper, Britta; Meyer, Andrea H; Stutz, Elisabeth Zemp; Orgül, Selim; Flammer, Josef; Kräuchi, Kurt

    2009-01-01

    Background Women with thermal discomfort from cold extremities (hands and feet; TDCE) often suffer from prolonged sleep onset latency (SOL). Suppressed anger could contribute to the genesis of both TDCE and prolonged SOL. The aim of the study was to test the hypothesis whether stereotypic feminine gender socialization (SFGS) is related to anger suppression (experienced anger inwards, Anger-In), which in turn could affect TDCE and SOL. Methods 148 women, a sub-sample of a larger survey carried out in the Canton Basel-Stadt (Switzerland), sent back detailed postal questionnaires about SOL, TDCE, anger expression (STAXI, state -trait -anger -expression -inventory) and SFGS using a gender power inventory, estimating the degree of gender specific power expression explicitly within women by stereotypic feminine or male attribution. Statistics was performed by path analysis. Results A significant direct path was found from stereotypic feminine attribution to Anger-In and prolonged SOL. Additionally, a further indirect path from Anger-In via TDCE to SOL was found. In contrast, stereotypic male attribution was not related to Anger-In but was significantly associated with outwardly expressed anger. Limitations Self-reported data, retrospective cross-sectional survey, prospective studies are required including physiological measurements. Conclusion Stereotypic feminine gender socialization may play an important determinant for anger suppression, which subsequently can lead to thermal discomfort from cold extremities and prolonged sleep onset latency. PMID:19825177

  5. Long-latency evoked potentials to irrelevant, deviant stimuli

    NASA Technical Reports Server (NTRS)

    Snyder, E.; Hillyard, S. A.

    1976-01-01

    Occasional shifts of loudness in a repetitive train of clicks elicited a late-positive wave (P3a) in nonattending subjects which peaked at a mean latency of 258 msec and had a frontocentral scalp distribution; P3a was typically preceded by an 'N2' component at 196 msec. The P3a wave was distinguishable from the longer-latency (378 msec) parietocentrally distributed 'P3b' wave that was evoked by the same stimulus in an actively attending subject, thus confirming the findings of Squires et al. (1975). Infrequently presented single sounds did not produce large or consistent N2-P3a components; the critical condition for the generation of an N2-P3a wave seemed to be that the infrequent sounds represent a deviation (intensity increment or decrement) from a repetitive background. Furthermore, increasing the repetition rate of the background clicks drastically reduced N1-P2 amplitude but had little effect on the amplitude of N2-P3a. This suggests that N2-P3a is not simply a delayed N1-P2 'vertex potential', but rather reflects the operation of a 'mismatch' detector, which registers deviations from an ongoing auditory background.

  6. Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate.

    PubMed Central

    Coen, D M; Kosz-Vnenchak, M; Jacobson, J G; Leib, D A; Bogard, C L; Schaffer, P A; Tyler, K L; Knipe, D M

    1989-01-01

    Herpes simplex virus infection of mammalian hosts involves lytic replication at a primary site, such as the cornea, translocation by axonal transport to sensory ganglia and replication, and latent infection at a secondary site, ganglionic neurons. The virus-encoded thymidine kinase, which is a target for antiviral drugs such as acyclovir, is not essential for lytic replication yet evidently is required at the secondary site for replication and some phase of latent infection. To determine the specific stage in viral pathogenesis at which this enzyme is required, we constructed virus deletion mutants that were acyclovir resistant and exhibited no detectable thymidine kinase activity. After corneal inoculation of mice, the mutants replicated to high titers in the eye but were severely impaired for acute replication in trigeminal ganglia and failed to reactivate from ganglia upon cocultivation with permissive cells. Nevertheless, latency-associated transcripts were expressed in neuronal nuclei of ganglia from mutant-infected mice and superinfection of the ganglia with a second virus rescued the latent mutant virus. Thus, contrary to a widely accepted hypothesis, the thymidine kinase-negative mutants established latent infections, implying that neither thymidine kinase activity nor ganglionic replication is necessary for establishment of latency. Rather, thymidine kinase appears to be necessary for reactivation from latency. These results suggest that acyclovir-resistant viruses could establish latent infections in clinical settings and have implications for the use of genetically engineered herpesviruses to deliver foreign genes to neurons. Images PMID:2543985

  7. Latency reversal and viral clearance to cure HIV-1.

    PubMed

    Margolis, David M; Garcia, J Victor; Hazuda, Daria J; Haynes, Barton F

    2016-07-22

    Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication--a cure for AIDS. Paired testing of latency reversal and clearance strategies has begun, but additional obstacles to HIV eradication may emerge. Nevertheless, there is reason for optimism that advances in long-acting antiretroviral therapy and HIV prevention strategies will contribute to efforts in HIV cure research and that the implementation of these efforts will synergize to markedly blunt the effect of the HIV pandemic on society. PMID:27463679

  8. Fault latency in the memory - An experimental study on VAX 11/780

    NASA Technical Reports Server (NTRS)

    Chillarege, Ram; Iyer, Ravishankar K.

    1986-01-01

    Fault latency is the time between the physical occurrence of a fault and its corruption of data, causing an error. The measure of this time is difficult to obtain because the time of occurrence of a fault and the exact moment of generation of an error are not known. This paper describes an experiment to accurately study the fault latency in the memory subsystem. The experiment employs real memory data from a VAX 11/780 at the University of Illinois. Fault latency distributions are generated for s-a-0 and s-a-1 permanent fault models. Results show that the mean fault latency of a s-a-0 fault is nearly 5 times that of the s-a-1 fault. Large variations in fault latency are found for different regions in memory. An analysis of a variance model to quantify the relative influence of various workload measures on the evaluated latency is also given.

  9. Short latency compound action potentials from mammalian gravity receptor organs

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  10. Long latency auditory evoked potential in term and premature infants.

    PubMed

    Didoné, Dayane Domeneghini; Garcia, Michele Vargas; da Silveira, Aron Ferreira

    2014-01-01

    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. PMID:25992057

  11. Transcriptional control of HIV latency: Cellular signaling pathways, epigenetics, happenstance and the hope for a cure

    PubMed Central

    Mbonye, Uri; Karn, Jonathan

    2014-01-01

    Replication-competent latent HIV-1 proviruses that persist in the genomes of a very small subset of resting memory T cells in infected individuals under life-long antiretroviral therapy present a major barrier towards viral eradication. Multiple molecular mechanisms are required to repress the viral trans-activating factor Tat and disrupt the regulatory Tat feedback circuit leading to the establishment of the latent viral reservoir. In particular, latency is due to a combination of transcriptional silencing of proviruses via host epigenetic mechanisms and restrictions on the expression of P-TEFb, an essential co-factor for Tat. Induction of latent proviruses in the presence of antiretroviral therapy is expected to enable clearance of latently infected cells by viral cytopathic effects and host antiviral immune responses. An in-depth comprehensive understanding of the molecular control of HIV-1 transcription should inform the development of optimal combinatorial reactivation strategies that are intended to purge the latent viral reservoir. PMID:24565118

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Flexible, low-latency architecture for qubit control and measurement in circuit QED

    NASA Astrophysics Data System (ADS)

    Vlothuizen, Wouter; Deurloo, D.; Sterke, J. De; Vermeulen, R.; Schouten, R. N.; Dicarlo, Leo

    Increasing qubit numbers in circuit QED requires an extensible architecture for digital waveform generation of qubit control and measurement signals. For quantum error correction, the ability to select from a number of predetermined waveforms based on measurement results will become paramount. We present a room-temperature architecture with very low latency from measurement to waveform output. This modular FPGA-based system can generate both baseband and RF modulated signals using DACs clocked at 1 GHz. A backplane that interconnects several modules allows exchange of (measurement) information between modules and maintains deterministic timing across those modules. We replace the typical line based sequencer used in arbitrary waveform generators by a user programmable processor that treats waveforms and measurements as instructions added to a conventional CPU architecture. This allows for flexible coding of triggering, repetitions, delays and interactions between measurement and signal generation. We acknowledge funding from the Dutch Research Organization (NWO), an ERC Synergy Grant, and European project SCALEQIT.

  14. HTMT-class Latency Tolerant Parallel Architecture for Petaflops Scale Computation

    NASA Technical Reports Server (NTRS)

    Sterling, Thomas; Bergman, Larry

    2000-01-01

    semiconductor logic. Wave Division Multiplexing optical communications can approach a peak per fiber bandwidth of 1 Tbps and the new Data Vortex network topology employing this technology can connect tens of thousands of ports providing a bi-section bandwidth on the order of a Petabyte per second with latencies well below 100 nanoseconds, even under heavy loads. Processor-in-Memory (PIM) technology combines logic and memory on the same chip exposing the internal bandwidth of the memory row buffers at low latency. And holographic storage photorefractive storage technologies provide high-density memory with access a thousand times faster than conventional disk technologies. Together these technologies enable a new class of shared memory system architecture with a peak performance in the range of a Petaflops but size and power requirements comparable to today's largest Teraflops scale systems. To achieve high-sustained performance, HTMT combines an advanced multithreading processor architecture with a memory-driven coarse-grained latency management strategy called "percolation", yielding high efficiency while reducing the much of the parallel programming burden. This paper will present the basic system architecture characteristics made possible through this series of advanced technologies and then give a detailed description of the new percolation approach to runtime latency management.

  15. Digital pixel CMOS focal plane array with on-chip multiply accumulate units for low-latency image processing

    NASA Astrophysics Data System (ADS)

    Little, Jeffrey W.; Tyrrell, Brian M.; D'Onofrio, Richard; Berger, Paul J.; Fernandez-Cull, Christy

    2014-06-01

    A digital pixel CMOS focal plane array has been developed to enable low latency implementations of image processing systems such as centroid trackers, Shack-Hartman wavefront sensors, and Fitts correlation trackers through the use of in-pixel digital signal processing (DSP) and generic parallel pipelined multiply accumulate (MAC) units. Light intensity digitization occurs at the pixel level, enabling in-pixel DSP and noiseless data transfer from the pixel array to the peripheral processing units. The pipelined processing of row and column image data prior to off chip readout reduces the required output bandwidth of the image sensor, thus reducing the latency of computations necessary to implement various image processing systems. Data volume reductions of over 80% lead to sub 10μs latency for completing various tracking and sensor algorithms. This paper details the architecture of the pixel-processing imager (PPI) and presents some initial results from a prototype device fabricated in a standard 65nm CMOS process hybridized to a commercial off-the-shelf short-wave infrared (SWIR) detector array.

  16. Complexity optimization and high-throughput low-latency hardware implementation of a multi-electrode spike-sorting algorithm.

    PubMed

    Dragas, Jelena; Jackel, David; Hierlemann, Andreas; Franke, Felix

    2015-03-01

    Reliable real-time low-latency spike sorting with large data throughput is essential for studies of neural network dynamics and for brain-machine interfaces (BMIs), in which the stimulation of neural networks is based on the networks' most recent activity. However, the majority of existing multi-electrode spike-sorting algorithms are unsuited for processing high quantities of simultaneously recorded data. Recording from large neuronal networks using large high-density electrode sets (thousands of electrodes) imposes high demands on the data-processing hardware regarding computational complexity and data transmission bandwidth; this, in turn, entails demanding requirements in terms of chip area, memory resources and processing latency. This paper presents computational complexity optimization techniques, which facilitate the use of spike-sorting algorithms in large multi-electrode-based recording systems. The techniques are then applied to a previously published algorithm, on its own, unsuited for large electrode set recordings. Further, a real-time low-latency high-performance VLSI hardware architecture of the modified algorithm is presented, featuring a folded structure capable of processing the activity of hundreds of neurons simultaneously. The hardware is reconfigurable “on-the-fly” and adaptable to the nonstationarities of neuronal recordings. By transmitting exclusively spike time stamps and/or spike waveforms, its real-time processing offers the possibility of data bandwidth and data storage reduction. PMID:25415989

  17. Resting-State Subjective Experience and EEG Biomarkers Are Associated with Sleep-Onset Latency.

    PubMed

    Diaz, B Alexander; Hardstone, Richard; Mansvelder, Huibert D; Van Someren, Eus J W; Linkenkaer-Hansen, Klaus

    2016-01-01

    Difficulties initiating sleep are common in several disorders, including insomnia and attention deficit hyperactivity disorder. These disorders are prevalent, bearing significant societal and financial costs which require the consideration of new treatment strategies and a better understanding of the physiological and cognitive processes surrounding the time of preparing for sleep or falling asleep. Here, we search for neuro-cognitive associations in the resting state and examine their relevance for predicting sleep-onset latency using multi-level mixed models. Multiple EEG recordings were obtained from healthy male participants (N = 13) during a series of 5 min eyes-closed resting-state trials (in total, n = 223) followed by a period-varying in length up to 30 min-that either allowed subjects to transition into sleep ("sleep trials," n sleep = 144) or was ended while they were still awake ("wake trials," n wake = 79). After both eyes-closed rest, sleep and wake trials, subjective experience was assessed using the Amsterdam Resting-State Questionnaire (ARSQ). Our data revealed multiple associations between eyes-closed rest alpha and theta oscillations and ARSQ-dimensions Discontinuity of Mind, Self, Theory of Mind, Planning, and Sleepiness. The sleep trials showed that the transition toward the first sleep stage exclusively affected subjective experiences related to Theory of Mind, Planning, and Sleepiness. Importantly, sleep-onset latency was negatively associated both with eyes-closed rest ratings on the ARSQ dimension of Sleepiness and with the long-range temporal correlations of parietal theta oscillations derived by detrended fluctuation analysis (DFA). These results could be relevant to the development of personalized tools that help evaluate the success of falling asleep based on measures of resting-state cognition and EEG biomarkers. PMID:27148107

  18. Establishment of HSV1 Latency in Immunodeficient Mice Facilitates Efficient In Vivo Reactivation

    PubMed Central

    Ramakrishna, Chandran; Ferraioli, Adrianna; Calle, Aleth; Nguyen, Thanh K.; Openshaw, Harry; Lundberg, Patric S.; Lomonte, Patrick; Cantin, Edouard M.

    2015-01-01

    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. PMID:25760441

  19. Resting-State Subjective Experience and EEG Biomarkers Are Associated with Sleep-Onset Latency

    PubMed Central

    Diaz, B. Alexander; Hardstone, Richard; Mansvelder, Huibert D.; Van Someren, Eus J. W.; Linkenkaer-Hansen, Klaus

    2016-01-01

    Difficulties initiating sleep are common in several disorders, including insomnia and attention deficit hyperactivity disorder. These disorders are prevalent, bearing significant societal and financial costs which require the consideration of new treatment strategies and a better understanding of the physiological and cognitive processes surrounding the time of preparing for sleep or falling asleep. Here, we search for neuro-cognitive associations in the resting state and examine their relevance for predicting sleep-onset latency using multi-level mixed models. Multiple EEG recordings were obtained from healthy male participants (N = 13) during a series of 5 min eyes-closed resting-state trials (in total, n = 223) followed by a period–varying in length up to 30 min–that either allowed subjects to transition into sleep (“sleep trials,” nsleep = 144) or was ended while they were still awake (“wake trials,” nwake = 79). After both eyes-closed rest, sleep and wake trials, subjective experience was assessed using the Amsterdam Resting-State Questionnaire (ARSQ). Our data revealed multiple associations between eyes-closed rest alpha and theta oscillations and ARSQ-dimensions Discontinuity of Mind, Self, Theory of Mind, Planning, and Sleepiness. The sleep trials showed that the transition toward the first sleep stage exclusively affected subjective experiences related to Theory of Mind, Planning, and Sleepiness. Importantly, sleep-onset latency was negatively associated both with eyes-closed rest ratings on the ARSQ dimension of Sleepiness and with the long-range temporal correlations of parietal theta oscillations derived by detrended fluctuation analysis (DFA). These results could be relevant to the development of personalized tools that help evaluate the success of falling asleep based on measures of resting-state cognition and EEG biomarkers. PMID:27148107

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

    ERIC Educational Resources Information Center

    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…

  1. No file left behind - monitoring transfer latencies in PhEDEx

    NASA Astrophysics Data System (ADS)

    Chwalek, T.; Egeland, R.; Gutsche, O.; Huang, C.-H.; Kaselis, R.; Klute, M.; Magini, N.; Moscato, F.; Piperov, S.; Ratnikova, N.; Rossman, P.; Sanchez-Hernandez, A.; Sartirana, A.; Wildish, T.; Yang, M.; Xie, S.

    2012-12-01

    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-term evolution of transfer latencies, which are used as cumulative metrics to evaluate the performance of the transfer infrastructure, and to plan the global data placement strategy. In this contribution, we present the typical patterns of transfer latencies that may be identified with the latency monitor, and we show how we are able to detect the sources of latency arising from the underlying infrastructure (such as stuck files) which need operator intervention.

  2. The Influence of Non-Nociceptive Factors on Hot Plate Latency in Rats

    PubMed Central

    Gunn, Amanda; Bobeck, Erin N.; Weber, Ceri; Morgan, Michael M.

    2010-01-01

    The hot plate is a widely used test to assess nociception. The effect of non-nociceptive factors (weight, sex, activity, habituation, and repeated testing) on hot plate latency was examined. Comparison of body weight and hot plate latency revealed a small but significant inverse correlation (light rats had longer latencies). Habituating rats to the test room for 1 hr prior to testing did not decrease hot plate latency except for female rats tested on Days 2 - 4. Hot plate latency decreased with repeated daily testing, but this was not caused by a decrease in locomotor activity or learning to respond. Activity on the hot plate was consistent across all four trials, and prior exposure to a room temperature plate caused a similar decrease in latency as rats tested repeatedly on the hot plate. Despite this decrease in baseline hot plate latency, there was no difference in morphine antinociceptive potency. The present study shows that weight, habituation to the test room, and repeated testing can alter baseline hot plate latency, but these effects are small and have relatively little impact on morphine antinociception. PMID:20797920

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

    ERIC Educational Resources Information Center

    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. Discussion of AN Advanced LIGO Low-Latency Search for Compact Binary Gravitational Waves

    NASA Astrophysics Data System (ADS)

    Messick, Cody; LIGO Scientific Collaboration; Virgo Collaboration

    2016-03-01

    Advanced ligo completed its first observing run in january, marking the beginning of a new era in gravitational wave astronomy. Low-latency pipelines searched for gravitational waves from compact binary mergers during the observing run, uploading candidate events to a database within seconds. In my presentation, we will report on the low-latency gstlal-inspiral advanced ligo search.

  5. Does Neighborhood Density Influence Repetition Latency for Nonwords? Separating the Effects of Density and Duration

    ERIC Educational Resources Information Center

    Lipinski, J.; Gupta, P.

    2005-01-01

    Twelve experiments examined the effect of neighborhood density on repetition latency for nonwords. Previous reports have indicated that nonwords from high density neighborhoods are repeated with shorter latency than nonwords from low density neighborhoods (e.g., Vitevitch & Luce, 1998). Experiment 1 replicated these previously reported results;…

  6. Measurement of fault latency in a digital avionic miniprocessor

    NASA Technical Reports Server (NTRS)

    Mcgough, J. G.; Swern, F. L.

    1981-01-01

    The results of fault injection experiments utilizing a gate-level emulation of the central processor unit of the Bendix BDX-930 digital computer are presented. The failure detection coverage of comparison-monitoring and a typical avionics CPU self-test program was determined. The specific tasks and experiments included: (1) inject randomly selected gate-level and pin-level faults and emulate six software programs using comparison-monitoring to detect the faults; (2) based upon the derived empirical data develop and validate a model of fault latency that will forecast a software program's detecting ability; (3) given a typical avionics self-test program, inject randomly selected faults at both the gate-level and pin-level and determine the proportion of faults detected; (4) determine why faults were undetected; (5) recommend how the emulation can be extended to multiprocessor systems such as SIFT; and (6) determine the proportion of faults detected by a uniprocessor BIT (built-in-test) irrespective of self-test.

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

    PubMed

    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

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

    PubMed Central

    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

  9. FRELLED: FITS Realtime Explorer of Low Latency in Every Dimension

    NASA Astrophysics Data System (ADS)

    Taylor, Rhys P. W.

    2015-08-01

    FRELLED (FITS Realtime Explorer of Low Latency in Every Dimension) creates 3D images in real time from 3D FITS files and is written in Python for the 3D graphics suite Blender. Users can interactively generate masks around regions of arbitrary geometry and use them to catalog sources, hide regions, and perform basic analysis (e.g., image statistics within the selected region, generate contour plots, query NED and the SDSS). World coordinates are supported and multi-volume rendering is possible. FRELLED is designed for viewing HI data cubes and provides a number of tasks to commonly-used MIRIAD (ascl:1106.007) tasks (e.g. mbspect); however, many of its features are suitable for any type of data set. It also includes an n-body particle viewer with the ability to display 3D vector information as well as the ability to render time series movies of multiple FITS files and setup simple turntable rotation movies for single files.

  10. Nitrate reduction pathways in mycobacteria and their implications during latency.

    PubMed

    Khan, Arshad; Sarkar, Dhiman

    2012-02-01

    Mycobacterial persistence has gained a lot of attention with respect to developing novel antitubercular drugs, which could drastically reduce the duration of tuberculosis (TB) therapy. A better understanding of the physiology of Mycobacterium tuberculosis, and of the metabolic state of the bacillus during the latent period, is a primary need in finding drug targets against persistent TB. Recent biochemical and genetic studies of nitrate reduction in mycobacteria have revealed the roles of distinct proteins and enzymes involved in the pathway. The differential degree of nitrate reduction among pathogenic and non-pathogenic mycobacterial species, and its regulation during oxygen and nutrient limitation, suggest a link between nitrate reduction pathways and latency. The respiratory and assimilatory reduction of nitrate in mycobacteria may be interconnected to facilitate rapid adaptation to changing oxygen and/or nitrogen conditions, increasing metabolic flexibility for survival in the hostile host environment. This review summarizes the nitrate metabolic pathways operative in mycobacteria to provide an insight into the mechanisms that M. tuberculosis has evolved to adapt successfully to the host environment. PMID:22174380

  11. RESPONSE LATENCY AS AN INDEX OF RESPONSE STRENGTH DURING FUNCTIONAL ANALYSES OF PROBLEM BEHAVIOR

    PubMed Central

    Thomason-Sassi, Jessica L; Iwata, Brian A; Neidert, Pamela L; Roscoe, Eileen M

    2011-01-01

    Dependent variables in research on problem behavior typically are based on measures of response repetition, but these measures may be problematic when behavior poses high risk or when its occurrence terminates a session. We examined response latency as the index of behavior during assessment. In Experiment 1, we compared response rate and latency to the first response under acquisition and maintenance conditions. In Experiment 2, we compared data from existing functional analyses when graphed as rate versus latency. In Experiment 3, we compared results from pairs of independent functional analyses. Sessions in the first analysis were terminated following the first occurrence of behavior, whereas sessions in the second analysis lasted for 10 min. Results of all three studies showed an inverse relation between rate and latency, indicating that latency might be a useful measure of responding when repeated occurrences of behavior are undesirable or impractical to arrange. PMID:21541141

  12. Epstein-Barr virus latency type and spontaneous reactivation predict lytic induction levels.

    PubMed

    Phan, An T; Fernandez, Samantha G; Somberg, Jessica J; Keck, Kristin M; Miranda, Jj L

    2016-05-20

    The human Epstein-Barr virus (EBV) evades the immune system by entering a transcriptionally latent phase in B cells. EBV in tumor cells expresses distinct patterns of genes referred to as latency types. Viruses in tumor cells also display varying levels of lytic transcription resulting from spontaneous reactivation out of latency. We measured this dynamic range of lytic transcription with RNA deep sequencing and observed no correlation with EBV latency types among genetically different viruses, but type I cell lines reveal more spontaneous reactivation than isogenic type III cultures. We further determined that latency type and spontaneous reactivation levels predict the relative amount of induced reactivation generated by cytotoxic chemotherapy drugs. Our work has potential implications for personalizing medicine against EBV-transformed malignancies. Identifying latency type or measuring spontaneous reactivation may provide predictive power in treatment contexts where viral production should be either avoided or coerced. PMID:27091426

  13. Acquisition de donnees a haute resolution et faible latence dediee aux capteurs avioniques de position

    NASA Astrophysics Data System (ADS)

    Koubaa, Zied

    circuit (modulator) followed by digital filters. The complexity of the implementation, the processing delay and the output resolution are all susceptible to change depending on the architecture of these filters. Thus, the main problem while designing such a system arises in the opposing evolution of the resolution and latency parameters; the improvement or evolution of one, results in the destruction of the other. Therefore, our work aims to provide one or more method to optimize the latency caused by the CAN while maintaining the same resolution of the desired data (14 bits). This optimization takes into account the objective of integrating the DAP in modules of small size and low power consumption. This proposed solution was implemented in order to validate the design of the conception of the interface. We are also interested to achieve the proposed solution and validate our design. The obtained results will be evaluated after following the manufacturing strategy. The data acquisition unit is made up of two electronic components. The first component is an integrated circuit, which uses CMOS 0.13mum IBM technology and contains the analog part of CAN (SigmaDelta modulator). The second component is a Virtex-6 FPGA, which allows one to acquire the necessary digital processing required for the acquisition and conversion of the sensor signal. In the final version of the interface, our analog portion will be integrated with the analog portion of GSE in the same chip. The integrated digital logic in the (FPGA) role will thus provide digital data to the ESG module in order to generate the excitation signal.

  14. In vivo expression of human cytomegalovirus (HCMV) microRNAs during latency.

    PubMed

    Meshesha, Mesfin K; Bentwich, Zvi; Solomon, Semaria A; Avni, Yonat Shemer

    2016-01-01

    Viral encoded microRNAs play key roles in regulating gene expression and the life cycle of human herpes viruses. Latency is one of the hallmarks of the human cytomegalovirus (HCMV or HHV5) life cycle, and its control may have immense practical applications. The present study aims to identify HCMV encoded microRNAs during the latency phase of the virus. We used a highly sensitive real time PCR (RTPCR) assay that involves a pre-amplification step before RTPCR. It can detect HCMV encoded microRNAs (miRNAs) during latency in purified monocytes and PBMCs from HCMV IgG positive donors and in latently infected monocytic THP-1 cell lines. During the latency phase, only eight HCMV encoded microRNAs were detected in PBMCs, monocytes and in the THP-1 cells. Five originated from the UL region of the virus genome and three from the US region. Reactivation of the virus from latency, in monocytes obtained from the same donor, using dexamethasone restored the expression of all known HCMV encoded miRNAs including those that were absent during latency. We observed a shift in the abundance of the two arms of mir-US29 between the productive and latency stages of the viral life cycle, suggesting that the star "passenger" form of this microRNA is preferentially expressed during latency. As a whole, our study demonstrates that HCMV expresses during the latency phase, both in vivo and in vitro, only a subset of its microRNAs, which may indicate that they play an important role in maintenance and reactivation of latency. PMID:26302752

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

    PubMed

    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. PMID:26780798

  16. NPOESS' Key to Low Data Latency: SafetyNet(TM)

    NASA Astrophysics Data System (ADS)

    Koster, P. B.; Swearengen, J.; Jamilkowski, M. L.

    2008-12-01

    A key feature of the National Polar-orbiting Operational Environmental Satellite System (NPOESS) is the Northrop Grumman Space Technology patent-pending data collection architecture known as 'SafetyNetTM'. The centerpiece of SafetyNetTM is the system of fifteen globally-distributed ground receptors developed by Raytheon Company. These receptors or antennae will collect up to five times as much environmental data approxi-mately four times faster than current polar-orbiting weather satellites. Once collected, these data will be forwarded near-instantaneously to U.S. weather centrals via global fiber optic network for processing and production of data records for use in environmental prediction models. Key system design factors -- The NPOESS SafetyNetTM architecture provides: Frequent downlinks and maximizes contact duration (>100% margin) at low cost; Downlink bandwidth margin that allows all Stored Mission Data to be down linked to two separate receptors; and Minimal latency impacts from loss of multiple ground receptors. Other notable characteristics of SafetyNetTM: Simple, receive-only, Ka Band receptor design provides autonomous operations; Fifteen locations in ten countries; full-motion to track polar satellites; Reliable and timely collection, delivery and processing of quality data; 75% of NPOESS data products delivered to the US's weather centrals within 15 minutes; the rest in under 30 minutes. Presentation will show: A graphic of SafetyNetTM within the NPOESS program architecture; A depiction of the NPOESS data download scheme; A map of the worldwide SafetyNetTM receptor locations; A graph of the percent of NPOESS Environmental Data Records (EDRs) versus time from observation to delivery; A example chart of the NPOESS data downlink patterns to SafetyNetTM receptors; Example photos of SafetyNetTM receptor antennae and radomes.

  17. SafetyNet(TM) -- NPOESS's Low Data Latency Key

    NASA Astrophysics Data System (ADS)

    Swearengen, J.; Koster, P. B.; Jamilkowski, M. L.

    2008-12-01

    A key feature of the National Polar-orbiting Operational Environmental Satellite System (NPOESS) is the Northrop Grumman Space Technology patent-pending data collection architecture known as 'SafetyNetTM'. The centerpiece of SafetyNetTM is the system of fifteen globally-distributed ground receptors developed by Raytheon Company. These receptors or antennae will collect up to five times as much environmental data approximately four times faster than current polar-orbiting weather satellites. Once collected, these data will be forwarded near-instantaneously to U.S. weather centrals via global fiber optic network for processing and production of data records for use in environmental prediction models. Key system design factors: The NPOESS SafetyNetTM architecture provides: Frequent downlinks and maximizes contact duration (>100% margin) at low cost; Downlink bandwidth margin that allows all Stored Mission Data to be down linked to two separate receptors; and Minimal latency impacts from loss of multiple ground receptors. Other notable characteristics of SafetyNetTM: Simple, receive-only, Ka Band receptor design provides autonomous operations; Fifteen locations in ten countries; full-motion to track polar satellites; Reliable and timely collection, delivery and processing of quality data; 75% of NPOESS data products delivered to the US's weather centrals within 15 minutes; the rest in under 30 minutes. Presentation will show: A graphic of SafetyNetTM within the NPOESS program architecture; A depiction of the NPOESS data download scheme; A map of the worldwide SafetyNetTM receptor locations; A graph of the percent of NPOESS Environmental Data Records (EDRs) versus time from observation to delivery; A example chart of the NPOESS data downlink patterns to SafetyNetTM receptors; Example photos of SafetyNetTM receptor antennae and radomes.

  18. Downstream regulatory elements increase acute and latent herpes simplex virus type 2 latency-associated transcript expression but do not influence recurrence phenotype or establishment of latency.

    PubMed Central

    Yoshikawa, T; Stanberry, L R; Bourne, N; Krause, P R

    1996-01-01

    The role of putative promoter or activator sequences downstream of the herpes simplex virus type 2 latency-associated transcript (LAT) promoter and upstream of the LAT intron was investigated in vivo by constructing and evaluating mutant viruses with deletions in this region. The deletion of LAT promoter sequences upstream of the primary LAT transcript reduced levels of LAT expression during productive infections, compared with the LAT expression level of wild-type virus, and abolished LAT expression during latency. The deletion of the putative downstream regulatory elements reduced but did not eliminate LAT expression during productive and latent infections. The deletion of both regions almost completely eliminated acute LAT transcription, although additional acute LAT-region transcription directed by sequences upstream of either region was detected by reverse transcriptase PCR. The deletion of the downstream elements did not influence the ability of the virus to reactivate from latently infected guinea pigs relative to the ability of the wild-type virus to reactivate; thus, decreased LAT expression did not affect the frequency of recurrence. The deletion of both regions did not affect the ability of the virus to establish latency. We conclude that downstream regulatory elements are necessary for maximal acute LAT expression but do not constitute an independent promoter during latency and do not play an obvious role in the establishment of our reactivation from latency. PMID:8627672

  19. A Spatio-Temporal Framework for MEG/EEG Evoked Response Amplitude and Latency Variability Estimation

    PubMed Central

    Limpiti, Tulaya; Van Veen, Barry D.; Wakai, Ronald T.

    2009-01-01

    This paper presents a spatio-temporal framework for estimating single-trial response latencies and amplitudes from evoked response MEG/EEG data. Spatial and temporal bases are employed to capture the aspects of the evoked response that are consistent across trials. Trial amplitudes are assumed independent but have the same underlying normal distribution with unknown mean and variance. The trial latency is assumed to be deterministic but unknown. We assume the noise is spatially correlated with unknown covariance matrix. We introduce a generalized expectation-maximization algorithm called TriViAL (Trial Variability in Amplitude and Latency) which computes the maximum likelihood (ML) estimates of the amplitudes, latencies, basis coefficients, and noise covariance matrix. The proposed approach also performs ML source localization by scanning the TriViAL algorithm over spatial bases corresponding to different locations on the cortical surface. Source locations are identified as the locations corresponding to large likelihood values. The effectiveness of the TriViAL algorithm is demonstrated using simulated data and human evoked response experiments. The localization performance is validated using tactile stimulation of the finger. The efficacy of the algorithm in estimating latency variability is shown using the known dependence of the M100 auditory response latency to stimulus tone frequency. We also demonstrate that estimation of response amplitude is improved when latency is included in the signal model. PMID:19789097

  20. Age-Related Maturation of Wave V Latency of Auditory Brainstem Response in Children

    PubMed Central

    Bist, Sampan Singh; Kumar, Santosh

    2016-01-01

    Background and Objectives Auditory brainstem response (ABR) is a noninvasive measurement of a stimulus-locked, synchronous electrical event. ABR provides information concerning the functional integrity of brainstem nuclei. Age is a key factor in the interpretation of ABR peak latency among different age groups. Progressively with time it follows a "maturation pattern" during which latencies decrease. Wave V is very prominent and reliable for detection of threshold in children. The present study was performed to see the effect of age related auditory maturation on ABR wave V latency in children. Subjects and Methods The study involved 80 subjects ranging in age from birth to 12 years. The subjects were divided equally into eight age groups. ABR were elicited by an acoustic click stimuli, brainstem responses collected through electrode and recorded at the same time. Latency of wave V was acknowledged. Results Wave V latency decreased rapidly in early childhood, became slower after 3 years of age and completely matured by 12 years of age. There was no significant difference in latency of wave V between the ears with age. Conclusions There is a distinct maturation pattern of wave V latency in ABR for both ears. ABR is a reliable test to assess the functional maturation of wave V in children.

  1. Females Exhibit Shorter Paraspinal Reflex Latencies than Males in Response to Sudden Trunk Flexion Perturbations

    PubMed Central

    Miller, Emily M.; Slota, Gregory P.; Agnew, Michael J.; Madigan, Michael L.

    2010-01-01

    Background Females have a higher risk of experiencing low back pain or injury than males. One possible reason for this might be altered reflexes since longer paraspinal reflex latencies exist in injured patients versus healthy controls. Gender differences have been reported in paraspinal reflex latency, yet findings are inconsistent. The goal here was to investigate gender differences in paraspinal reflex latency, avoiding and accounting for potentially gender-confounding experimental factors. Methods Ten males and ten females underwent repeated trunk flexion perturbations. Paraspinal muscle activity and trunk kinematics were recorded to calculate reflex latency and maximum trunk flexion velocity. Two-way mixed model ANOVAs were used to determine the effects of gender on reflex latency and maximum trunk flexion velocity. Findings Reflex latency was 18.7% shorter in females than in males (P=0.02) when exposed to identical trunk perturbations, and did not vary by impulse (P=0.38). However, maximum trunk flexion velocity was 35.3% faster in females than males (P=0.01) when exposed to identical trunk perturbations, and increased with impulse (P<0.01). While controlling for differences in maximum trunk flexion velocity, reflex latency was 16.4% shorter in females than males (P=0.04). Implications The higher prevalence of low back pain and injury among females does not appear to result from slower paraspinal reflexes. PMID:20359800

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

    NASA Technical Reports Server (NTRS)

    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.

  3. Direct measurement of the system latency of gaze-contingent displays

    PubMed Central

    Woods, Russell L.

    2014-01-01

    Gaze-contingent displays combine a display device with an eyetracking system to rapidly update an image on the basis of the measured eye position. All such systems have a delay, the system latency, between a change in gaze location and the related change in the display. The system latency is the result of the delays contributed by the eyetracker, the display computer, and the display, and it is affected by the properties of each component, which may include variability. We present a direct, simple, and low-cost method to measure the system latency. The technique uses a device to briefly blind the eyetracker system (e.g., for video-based eyetrackers, a device with infrared light-emitting diodes (LED)), creating an eyetracker event that triggers a change to the display monitor. The time between these two events, as captured by a relatively low-cost consumer camera with high-speed video capability (1,000 Hz), is an accurate measurement of the system latency. With multiple measurements, the distribution of system latencies can be characterized. The same approach can be used to synchronize the eye position time series and a video recording of the visual stimuli that would be displayed in a particular gaze-contingent experiment. We present system latency assessments for several popular types of displays and discuss what values are acceptable for different applications, as well as how system latencies might be improved. PMID:23949955

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

    PubMed

    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. PMID:26485660

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

    NASA Technical Reports Server (NTRS)

    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.

  6. Particle filter with one-step randomly delayed measurements and unknown latency probability

    NASA Astrophysics Data System (ADS)

    Zhang, Yonggang; Huang, Yulong; Li, Ning; Zhao, Lin

    2016-01-01

    In this paper, a new particle filter is proposed to solve the nonlinear and non-Gaussian filtering problem when measurements are randomly delayed by one sampling time and the latency probability of the delay is unknown. In the proposed method, particles and their weights are updated in Bayesian filtering framework by considering the randomly delayed measurement model, and the latency probability is identified by maximum likelihood criterion. The superior performance of the proposed particle filter as compared with existing methods and the effectiveness of the proposed identification method of latency probability are both illustrated in two numerical examples concerning univariate non-stationary growth model and bearing only tracking.

  7. Saccades reduce latency and increase velocity of ocular accommodation.

    PubMed

    Schor, C M; Lott, L A; Pope, D; Graham, A D

    1999-11-01

    Horizontal vergence can be stimulated binocularly with disparity (disparity vergence) or monocularly with accommodation (accommodative vergence). The latter results from a neural cross-coupling that causes both horizontal vergence and accommodation to respond when either one is stimulated [Alpern, M., & Ellen, P. (1956). American Journal of Ophthalmology, 42, 289-303]. The velocity of disparity and accommodative vergence is enhanced when accompanied by saccades [Enright, J. T. (1984). Journal of Physiology (London) 350, 9-31; Enright, J. T. (1986). Journal of Physiology (London) 371, 69-89]. Based upon the coupling between accommodation and vergence, we predicted that accommodation should also be facilitated by saccades. An SRI Dual Purkinje Eyetracker was used to measure left and right eye position, and the accommodation of the left eye, in response to stimulation. Horizontal saccades were stimulated by targets separated by 2-6 degrees and accommodation was stimulated monocularly over a range of +/- 2 diopters (D). When saccades occurred within 0-400 ms following a monocular step stimulus to accommodation, latency of accommodation decreased and the associated accommodative-vergence response was synchronized with the saccade. Saccades also enhanced the velocity of accommodation and accommodative-vergence, and this facilitation increased with saccade amplitude. Transient vergence responses that are normally associated with saccades [Erkelens, C. J., Steinman, R. M., & Collewijn, H. (1989). Proceedings of the Royal Society of London B. Biological Sciences, 236, 441-465; Maxwell, J. S., & King, W. M. (1992). Journal of Neurophysiology, 68 (4), 1248-1260] did not affect accommodation when it was not stimulated by defocus. Because saccades and accommodation utilize separate plants and final common pathways, the synchronization of saccades and accommodation and the enhanced velocity of accommodation and accommodative-vergence must occur at more central sites

  8. NF-κB p50 Plays Distinct Roles in the Establishment and Control of Murine Gammaherpesvirus 68 Latency

    PubMed Central

    Krug, Laurie T.; Collins, Christopher M.; Gargano, Lisa M.; Speck, Samuel H.

    2009-01-01

    NF-κB signaling is critical to the survival and transformation of cells infected by the human gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. Here we have examined how elimination of the NF-κB transcription factor p50 from mice affects the life cycle of murine gammaherpesvirus 68 (MHV68). Notably, mice lacking p50 in every cell type were unable to establish a sufficiently robust immune response to control MHV68 infection, leading to high levels of latently infected B cells detected in the spleen and persistent virus replication in the lungs. The latter correlated with very low levels of virus-specific immunoglobulin G (IgG) in the infected p50−/− mice at day 48 postinfection. Because the confounding impact of the loss of p50 on the host response to MHV68 infection prevented a direct analysis of the role of this NF-κB family member on MHV68 latency in B cells, we generated and infected mixed p50+/+/p50−/− bone marrow chimeric mice. We show that the chimeric mice were able to control acute virus replication and exhibited normal levels of virus-specific IgG at 3 months postinfection, indicating the induction of a normal host immune response to MHV68 infection. However, in p50+/+/p50−/− chimeric mice the p50−/− B cells exhibited a significant defect compared to p50+/+ B cells in supporting MHV68 latency. In addition to identifying a role for p50 in the establishment of latency, we determined that the absence of p50 in a subset of the hematopoietic compartment led to persistent virus replication in the lungs of the chimeric mice, providing evidence that p50 is required for controlling virus reactivation. Taken together, these data demonstrate that p50 is required for immune control by the host and has distinct tissue-dependent roles in the regulation of murine gammaherpesvirus latency during chronic infection. PMID:19264770

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

    DOEpatents

    Farmwald, Paul M.

    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.

  10. Movement Adjustments Have Short Latencies Because There is No Need to Detect Anything.

    PubMed

    Smeets, Jeroen B; Oostwoud Wijdenes, Leonie; Brenner, Eli

    2016-04-01

    We can adjust an ongoing movement to a change in the target's position with a latency of about 100 ms, about half of the time that is needed to start a new movement in response to the same change in target position (reaction time). In this opinion paper, we discuss factors that could explain the difference in latency between initiating and adjusting a movement in response to target displacements. We consider the latency to be the sum of the durations of various stages in information processing. Many of these stages are identical for adjusting and initiating a movement; however, for movement initiation, it is essential to detect that something has changed to respond, whereas adjustments to movements can be based on updated position information without detecting that the position has changed. This explanation for the shorter latency for movement adjustments also explains why we can respond to changes that we do not detect. PMID:25674946

  11. Effect of helium-neon laser irradiation on peripheral sensory nerve latency

    SciTech Connect

    Snyder-Mackler, L.; Bork, C.E.

    1988-02-01

    The purpose of this randomized, double-blind study was to determine the effect of a helium-neon (He-Ne) laser on latency of peripheral sensory nerve. Forty healthy subjects with no history of right upper extremity pathological conditions were assigned to either a Laser or a Placebo Group. Six 1-cm2 blocks along a 12-cm segment of the subjects' right superficial radial nerve received 20-second applications of either the He-Ne laser or a placebo. We assessed differences between pretest and posttest latencies with t tests for correlated and independent samples. The Laser Group showed a statistically significant increase in latency that corresponded to a decrease in sensory nerve conduction velocity. Short-duration He-Ne laser application significantly increased the distal latency of the superficial radial nerve. This finding provides information about the mechanism of the reported pain-relieving effect of the He-Ne laser.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:26170050

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

    SciTech Connect

    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.

  15. Determinants of the establishment of human immunodeficiency virus type 1 latency.

    PubMed

    Duverger, Alexandra; Jones, Jennifer; May, Jori; Bibollet-Ruche, Frederic; Wagner, Frederic A; Cron, Randall Q; Kutsch, Olaf

    2009-04-01

    Recent research has emphasized the notion that human immunodeficiency virus type 1 (HIV-1) latency is controlled by a restrictive histone code at, or DNA methylation of, the integrated viral promoter (long terminal repeat [LTR]). The present concept of HIV-1 latency has essentially been patterned from the principles of cellular gene regulation. Here we introduce an experimental system that allows for the qualitative and quantitative kinetic study of latency establishment and maintenance at the population level. In this system, we find no evidence that HIV-1 latency establishment is the consequence of downregulation of initial active infection followed by the establishment of a restrictive histone code at the viral LTR. Latent infection was established following integration of the virus in the absence of viral gene expression (silent integration) and was a function of the NF-kappaB activation level in the host cell at the time of infection. In the absence of a role for epigenetic regulation, we demonstrate that transcriptional interference, a mechanism that has recently been suggested to add to the stabilization of HIV-1 latency, is the primary mechanism to govern latency maintenance. These findings provide direct experimental evidence that the high number of viral integration events (>90%) found in actively expressed genes of CD4(+) memory T cells from highly active antiretroviral therapy-suppressed patients represent indeed latent infection events and that transcriptional interference may be the primary mechanism to control HIV-1 latency in vivo. HIV-1 latency may thus not be governed by the principles of cellular gene regulation, and therapeutic strategies to deplete the pool of latently HIV-1-infected cells should be reconsidered. PMID:19144703

  16. Reducing the Maximum Latency of Selfish Ring Routing via Pairwise Cooperations

    NASA Astrophysics Data System (ADS)

    Chen, Xujin; Hu, Xiaodong; Ma, Weidong

    This paper studies the selfish routing game in ring networks with a load-dependent linear latency on each link. We adopt the asymmetric atomic routing model. Each player selfishly chooses a route to connect his source-destination pair, aiming at a lowest latency of his route, while the system objective is to minimize the maximum latency among all routes of players. Such a routing game always has a Nash equilibrium (NE) that is a "stable state" among all players, from which no player has the incentive to deviate unilaterally. Furthermore, 16 is the current best upper bound on its price of anarchy (PoA), the worst-case ratio between the maximum latencies in a NE and in a system optimum. In this paper we show that the PoA is at most 10.16 provided cooperations within pairs of players are allowed, where any two players could change their routes simultaneously if neither would experience a longer latency and at least one would experience a shorter latency.

  17. Operant control of response latency in monkeys: evidence for a central explanation1

    PubMed Central

    Saslow, Carol A.

    1968-01-01

    Two monkeys (M. mulatta) were trained to press a telegraph key after onset of a tone and release it quickly in response to a subsequent light or click stimulus occurring after a variable interval. After training first with a fixed time limit on response latency for key release and then with a continuously adjusting limit, reaction time to click was 160 msec and to light, about 200 msec. Temporal contingencies or “payoff bands” were then introduced which reinforced only responses with latencies which fell between two limits 50 msec apart. Feedback was given as to whether each latency was too slow, within the band, or too fast. A trained monkey could precisely center its latency distribution on any 50 msec-wide payoff band located from 200 to 600 msec after the stimulus, with from 60 to 80% of its responses achieving reinforcement. Distribution statistics were comparable to those of trained human subjects. Because such precise timing might be accomplished by a peripheral adjustment, such as changing the manner of holding the key, latency of electromyographic activation was measured in participating arm muscles in one monkey. Electromyographic activation preceded key release by a constant interval, regardless of response latency, indicating a more central mechanism for timing of brief intervals. PMID:4967111

  18. Impact of wave propagation delay on latency in optical communication systems

    NASA Astrophysics Data System (ADS)

    Kawanishi, Tetsuya; Kanno, Atsushi; Yoshida, Yuki; Kitayama, Ken-ichi

    2012-12-01

    Latency is an important figure to describe performance of transmission systems for particular applications, such as data transfer for earthquake early warning, transaction for financial businesses, interactive services such as online games, etc. Latency consists of delay due to signal processing at nodes and transmitters, and of signal propagation delay due to propagation of electromagnetic waves. The lower limit of the latency in transmission systems using conventional single mode fibers (SMFs) depends on wave propagation speed in the SMFs which is slower than c. Photonic crystal fibers, holly fibers and large core fibers can have low effective refractive indices, and can transfer light faster than in SMFs. In free-space optical systems, signals propagate with the speed c, so that the latency could be smaller than in optical fibers. For example, LEO satellites would transmit data faster than optical submarine cables, when the transmission distance is longer than a few thousand kilometers. This paper will discuss combination of various transmission media to reduce negative impact of the latency, as well as applications of low-latency systems.

  19. KSHV Latency Locus Cooperates with Myc to Drive Lymphoma in Mice

    PubMed Central

    Sin, Sang-Hoon; Kim, Yongbaek; Eason, Anthony; Dittmer, Dirk P.

    2015-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) has been linked to Kaposi sarcoma and B-cell malignancies. Mechanisms of KSHV-induced oncogenesis remain elusive, however, in part due to lack of reliable in vivo models. Recently, we showed that transgenic mice expressing the KSHV latent genes, including all viral microRNAs, developed splenic B cell hyperplasia with 100% penetrance, but only a fraction converted to B cell lymphomas, suggesting that cooperative oncogenic events were missing. Myc was chosen as a possible candidate, because Myc is deregulated in many B cell lymphomas. We crossed KSHV latency locus transgenic (latency) mice to Cα Myc transgenic (Myc) mice. By itself these Myc transgenic mice develop lymphomas only rarely. In the double transgenic mice (Myc/latency) we observed plasmacytosis, severe extramedullary hematopoiesis in spleen and liver, and increased proliferation of splenocytes. Myc/latency mice developed frank lymphoma at a higher rate than single transgenic latency or Myc mice. These data indicate that the KSHV latency locus cooperates with the deregulated Myc pathways to further lymphoma progression. PMID:26327622

  20. On the frequency dependence of the otoacoustic emission latency in hypoacoustic and normal ears

    NASA Astrophysics Data System (ADS)

    Sisto, R.; Moleti, A.

    2002-01-01

    Experimental measurements of the otoacoustic emission (OAE) latency of adult subjects have been obtained, as a function of frequency, by means of wavelet time-frequency analysis based on the iterative application of filter banks. The results are in agreement with previous OAE latency measurements by Tognola et al. [Hear. Res. 106, 112-122 (1997)], as regards both the latency values and the frequency dependence, and seem to be incompatible with the steep 1/f law that is predicted by scale-invariant full cochlear models. The latency-frequency relationship has been best fitted to a linear function of the cochlear physical distance, using the Greenwood map, and to an exponential function of the cochlear distance, for comparison with derived band ABR latency measurements. Two sets of ears [94 audiometrically normal and 42 impaired with high-frequency (f>3 kHz) hearing loss] have been separately analyzed. Significantly larger average latencies were found in the impaired ears in the mid-frequency range. Theoretical implications of these findings on the transmission of the traveling wave are discussed.

  1. Incorporating system latency associated with real-time target tracking radiotherapy in the dose prediction step

    NASA Astrophysics Data System (ADS)

    Roland, Teboh; Mavroidis, Panayiotis; Shi, Chengyu; Papanikolaou, Nikos

    2010-05-01

    System latency introduces geometric errors in the course of real-time target tracking radiotherapy. This effect can be minimized, for example by the use of predictive filters, but cannot be completely avoided. In this work, we present a convolution technique that can incorporate the effect as part of the treatment planning process. The method can be applied independently or in conjunction with the predictive filters to compensate for residual latency effects. The implementation was performed on TrackBeam (Initia Ltd, Israel), a prototype real-time target tracking system assembled and evaluated at our Cancer Institute. For the experimental system settings examined, a Gaussian distribution attributable to the TrackBeam latency was derived with σ = 3.7 mm. The TrackBeam latency, expressed as an average response time, was deduced to be 172 ms. Phantom investigations were further performed to verify the convolution technique. In addition, patient studies involving 4DCT volumes of previously treated lung cancer patients were performed to incorporate the latency effect in the dose prediction step. This also enabled us to effectively quantify the dosimetric and radiobiological impact of the TrackBeam and other higher latency effects on the clinical outcome of a real-time target tracking delivery.

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

    NASA Technical Reports Server (NTRS)

    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.

  3. Long-Latency Feedback Coordinates Upper-Limb and Hand Muscles during Object Manipulation Tasks123

    PubMed Central

    Thonnard, Jean-Louis; Scott, Stephen H.

    2016-01-01

    Suppose that someone bumps into your arm at a party while you are holding a glass of wine. Motion of the disturbed arm will engage rapid and goal-directed feedback responses in the upper-limb. Although such responses can rapidly counter the perturbation, it is also clearly desirable not to destabilize your grasp and/or spill the wine. Here we investigated how healthy humans maintain a stable grasp following perturbations by using a paradigm that requires spatial tuning of the motor response dependent on the location of a virtual target. Our results highlight a synchronized expression of target-directed feedback in shoulder and hand muscles occurring at ∼60 ms. Considering that conduction delays are longer for the more distal hand muscles, these results suggest that target-directed responses in hand muscles were initiated before those for the shoulder muscles. These results show that long-latency feedback can coordinate upper limb and hand muscles during object manipulation tasks. PMID:27022624

  4. Low latency breathing frequency detection and monitoring on a personal computer.

    PubMed

    Leskovsek, Matevz; Ahlin, Dragomira; Cancer, Rok; Hosta, Milan; Enova, Dusan; Pusenjak, Nika; Bunc, Matjaz

    2011-01-01

    We demonstrate a low latency respiratory/breathing frequency detection system that is fast (<5 ms), easy to operate, requires no batteries or external power supply and operates fully via computer-standard USB connection. Exercises in controlling ones breathing frequency, usually referred to as paced-breathing exercises, have shown positive effects in treating pulmonary diseases, cardiovascular diseases and stress/anxiety-related disorders. We developed a breathing frequency detection system which uses two pairs of microphones to detect exhalation activity, eliminate noise from the environment and stream the recording data via USB connection to a personal computer. It showed 97.1% reliability (10 subjects) when monitoring breathing activity in non-guided free breathing and 100% reliability (10 subjects) when monitoring breathing activity during interactive paced-breathing exercises. We also evaluated the breathing frequency detection systems noise elimination functionality which showed a reduction of 84.2 dB for stationary (white noise) and a reduction of 79.3 dB for non-stationary (hands clapping) noise. PMID:21767133

  5. Toxicity and in vitro activity of HIV-1 latency-reversing agents in primary CNS cells.

    PubMed

    Gray, Lachlan R; On, Hung; Roberts, Emma; Lu, Hao K; Moso, Michael A; Raison, Jacqueline A; Papaioannou, Catherine; Cheng, Wan-Jung; Ellett, Anne M; Jacobson, Jonathan C; Purcell, Damian F J; Wesselingh, Steve L; Gorry, Paul R; Lewin, Sharon R; Churchill, Melissa J

    2016-08-01

    Despite the success of combination antiretroviral therapy (cART), HIV persists in long lived latently infected cells in the blood and tissue, and treatment is required lifelong. Recent clinical studies have trialed latency-reversing agents (LRA) as a method to eliminate latently infected cells; however, the effects of LRA on the central nervous system (CNS), a well-known site of virus persistence on cART, are unknown. In this study, we evaluated the toxicity and potency of a panel of commonly used and well-known LRA (panobinostat, romidepsin, vorinostat, chaetocin, disulfiram, hexamethylene bisacetamide [HMBA], and JQ-1) in primary fetal astrocytes (PFA) as well as monocyte-derived macrophages as a cellular model for brain perivascular macrophages. We show that most LRA are non-toxic in these cells at therapeutic concentrations. Additionally, romidepsin, JQ-1, and panobinostat were the most potent at inducing viral transcription, with greater magnitude observed in PFA. In contrast, vorinostat, chaetocin, disulfiram, and HMBA all demonstrated little or no induction of viral transcription. Together, these data suggest that some LRA could potentially activate transcription in latently infected cells in the CNS. We recommend that future trials of LRA also examine the effects of these agents on the CNS via examination of cerebrospinal fluid. PMID:26727904

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Changes in P3b Latency and Amplitude Reflect Expertise Acquisition in a Football Visuomotor Learning Task

    PubMed Central

    Morgan, Kyle K.; Luu, Phan; Tucker, Don M.

    2016-01-01

    Learning is not a unitary phenomenon. Rather, learning progresses through stages, with the stages reflecting different challenges that require the support of specific cognitive processes that reflect the functions of different brain networks. A theory of general learning proposes that learning can be divided into early and late stages controlled by corticolimbic networks located in frontal and posterior brain regions, respectively. Recent human studies using dense-array EEG (dEEG) support these results by showing progressive increases in P3b amplitude (an Event Related Potential with estimated sources in posterior cingulate cortex and hippocampus) as participants acquire a new visuomotor skill. In the present study, the P3b was used to track the learning and performance of participants as they identify defensive football formations and make an appropriate response. Participants acquired the task over three days, and P3b latency and amplitude significantly changed when participants learned the task. As participants demonstrated further proficiency with extensive training, amplitude and latency changes in the P3b continued to closely mirror performance improvements. Source localization results across all days suggest that an important source generator of the P3b is located in the posterior cingulate cortex. Results from the study support prior findings and further suggest that the careful analysis of covert learning mechanisms and their underlying electrical signatures are a robust index of task competency. PMID:27111898

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

    NASA Astrophysics Data System (ADS)

    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

  9. Technologies for low-bandwidth high-latency unmanned ground vehicle control

    NASA Astrophysics Data System (ADS)

    Pace, Teresa; Cogan, Ken; Hunt, Lee; Restine, Paul

    2014-05-01

    Automation technology has evolved at a rapid pace in recent years; however, many real-world problems require contextual understanding, problem solving, and other forms of higher-order thinking that extends beyond the capabilities of robots for the foreseeable future. This limits the complexity of automation which can be supplied to modern unmanned ground robots (UGV) and necessitates human-in-the-loop monitoring and control for some portions of missions. In order for the human operator to make decisions and provide tasking during key portions of the mission, existing solutions first derive significant information from a potentially dense reconstruction of the scene utilizing LIDAR, video, and other onboard sensors. A dense reconstruction contains too much data for real-time transmission over a modern wireless data link, so the robot electronics must first condense the scene representation prior to transmission. The control station receives this condensed scene representations and provides visual information to the human operator; the human operator then provides tele-operation commands in real-time to the robot. This paper discusses approaches to dense scene reduction of the data required to transmit to a human-in-the loop as well as the challenges associated with them. In addition, the complex and unstructured nature of real-world environments increases the need for tele-operation. Furthermore, many environments reduce the bandwidth and increase the latency of the link. Ultimately, worsening conditions will cause the tele-operation control process to break down, rendering the robot ineffective. In a worst-case scenario, extreme conditions causing a complete loss-of-communications could result in mission failure and loss of the vehicle.

  10. Viewing time effects revisited: prolonged response latencies for sexually attractive targets under restricted task conditions.

    PubMed

    Imhoff, Roland; Schmidt, Alexander F; Nordsiek, Uta; Luzar, Charlotte; Young, Andrew W; Banse, Rainer

    2010-12-01

    Sexually attractive stimuli are watched longer than unattractive stimuli. The processes underlying this robust and reliable viewing time effect are presently not well understood. In the present research comprising four experiments (total N = 250), four classes of potential explanations are proposed and the derived implications were experimentally tested. Contrary to explanations based on either deliberate delay or attentional adhesion to sexually attractive stimuli, prolonged response latencies were also found under restricted task conditions. Sexually preferred targets elicited longer response latencies in a self-paced evaluation task when stimulus pictures were presented for 750 ms (Experiment 1) or for 500 ms and followed by a pattern mask (Experiment 2). Prolonged latencies for sexually preferred targets were also observed when sexual attractiveness was rated in a speeded binary decision task with a response window of 1000 ms (Experiment 3). Eventually, it was shown that the response latency effect in the speeded binary choice task was still preserved when only the heads of target individuals were presented instead of the bodies (Experiment 4). Mate identification and schematic processes are discussed as the remaining plausible mechanisms for prolonged response latencies for sexually attractive targets under restricted conditions. PMID:20198414

  11. Middle latency auditory evoked responses in normal term infants: a longitudinal study.

    PubMed

    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. PMID:2739875

  12. Toll-interacting protein inhibits HIV-1 infection and regulates viral latency.

    PubMed

    Li, Chuan; Kuang, Wen-Dong; Qu, Di; Wang, Jian-Hua

    2016-06-24

    HIV-1 latency is mainly characterized by a reversible silencing of long-terminal repeat (LTR)-driven transcription of provirus. The existing of repressive factors has been described to contribute to transcription silencing of HIV-1. Toll-interacting protein (Tollip) has been identified as a repressor of Toll like receptors (TLR)-mediated signaling. Our previous study has found that Tollip inhibited NF-κB-dependent HIV-1 promoter LTR-driven transcription, indicating the potential role of Tollip in governing viral latency. In this study, by using HIV-1 latently infected Jurkat T-cell and central memory CD4(+) T-cells, we demonstrate the role of Tollip in regulating HIV-1 latency, as the knock-down of Tollip promoted HIV-1 reactivation from both HIV-1 latently infected Jurkat CD4(+) T cells and primary central memory T cells (TCM). Moreover, we found that the activities of LTRs derived from multiple HIV-1 subtypes could be repressed by Tollip; Knock-down of Tollip promoted HIV-1 transcription and infection in CD4(+) T cells. Our data indicate a key role of Tollip in suppressing HIV-1 infection and regulating viral latency, which provides a potential host target for combating HIV-1 infection and latency. PMID:27181351

  13. The utility of a 5th nap in multiple sleep latency test

    PubMed Central

    Lykouras, Dimosthenis; Rees, Kate

    2016-01-01

    Background This is the first study that aimed to look specifically at the utility of the 5th nap in the multiple sleep latency test (MSLT), a test used to assist in the diagnosis of narcolepsy. Methods Data was retrospectively collected from the Sleep Disorders Centre of a Tertiary Hospital on patients that had a 5th nap during their MSLT from the 08th November 2011 to 12th November 2014. Results Fifty-three patients had a 5th nap performed out of 378 MSLT studies. In 16% of cases a diagnosis of narcolepsy was given directly due to the inclusion of the 5th nap on the MSLT. Here a 5th nap allowed diagnostic criteria of mean sleep latency <8 minutes and >2 SOREMPS to be met. In 53% of cases the mean sleep latency increased due to 5th nap inclusion; the mean sleep latency of the first four naps was 5.6 vs. 6.7 after inclusion of the 5th nap. Conclusions The 5th nap is not often performed within the MSLT studies. Our study shows that only a few patients may benefit from a 5th nap opportunity which also led to increase of the mean sleep latency at the expense of extra time, cost, labour and increased patient anxiety. PMID:26904269

  14. Dynamics of HIV Latency and Reactivation in a Primary CD4+ T Cell Model

    PubMed Central

    Muñoz, Miguel; Martinez, Raquel; Bartha, István; Cavassini, Matthias; Thorball, Christian; Fellay, Jacques; Beerenwinkel, Niko; Ciuffi, Angela; Telenti, Amalio

    2014-01-01

    HIV latency is a major obstacle to curing infection. Current strategies to eradicate HIV aim at increasing transcription of the latent provirus. In the present study we observed that latently infected CD4+ T cells from HIV-infected individuals failed to produce viral particles upon ex vivo exposure to SAHA (vorinostat), despite effective inhibition of histone deacetylases. To identify steps that were not susceptible to the action of SAHA or other latency reverting agents, we used a primary CD4+ T cell model, joint host and viral RNA sequencing, and a viral-encoded reporter. This model served to investigate the characteristics of latently infected cells, the dynamics of HIV latency, and the process of reactivation induced by various stimuli. During latency, we observed persistence of viral transcripts but only limited viral translation. Similarly, the reactivating agents SAHA and disulfiram successfully increased viral transcription, but failed to effectively enhance viral translation, mirroring the ex vivo data. This study highlights the importance of post-transcriptional blocks as one mechanism leading to HIV latency that needs to be relieved in order to purge the viral reservoir. PMID:24875931

  15. Fine mapping of the latency-related gene of herpes simplex virus type 1: alternative splicing produces distinct latency-related RNAs containing open reading frames

    SciTech Connect

    Wechsler, S.L.; Nesburn, A.B.; Watson, R.; Slanina, S.M.; Ghiasi, H.

    1988-11-01

    The latency-related (LR) gene of herpes simplex virus type 1 (HSV-1) is transcriptionally active during HSV-1 latency, producing at least two LR-RNAs. The LR gene partially overlaps the immediate-early gene ICP0 and is transcribed in the opposite direction from ICP0, producing LR-RNAs that are complementary (antisense) to ICP0 mRNA. The LR gene is thought to be involved in HSV-1 latency. The authors report here the time mapping and partial sequence analysis of this HSV-1 LR gene. /sup 32/P-labeled genomic DNA restriction fragments and synthetic oligonucleotides were used as probes for in situ hybridizations and Northern (RNA) blot hybridizations of RNA from trigeminal ganglia of rabbits latently infected with HSV-1. The two most abundant LR-RNAs appeared to share their 5' and 3' ends and to be produced by alternative splicing. These LR-RNAs were approximately 2 and 1.3 to 1.5 kilobases in length and were designated LR-RNA 1 and LF-RNA 2, respectively. LR-RNA 1 appeared to have at least one intron removed, while LR-RNA 2 appeared to have at least two introns removed. The LR-RNAs contained two potential long open reading frames, suggesting the possibility that one or more of the LR-RNAs may be a functional mRNA.

  16. Fast response electromagnetic follow-ups from low latency GW triggers

    NASA Astrophysics Data System (ADS)

    Howell, E. J.; Chu, Q.; Rowlinson, A.; Gao, H.; Zhang, B.; Tingay, S. J.; Boër, M.; Wen, L.

    2016-05-01

    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 γ-ray. We show that while challenging, breakthrough multi-messenger science is possible through low latency pipelines.

  17. Two varieties of long-latency positive waves evoked by unpredictable auditory stimuli in man

    NASA Technical Reports Server (NTRS)

    Squires, N. K.; Squires, K. C.; Hillyard, S. A.

    1975-01-01

    Two distinct late-positive components of the scalp-recorded auditory evoked potential were identified which differed in their latency, scalp topography and psychological correlates. The earlier component (latency about 240 msec) was elicited by infrequent, unpredictable shifts of either intensity or frequency in a train of tone pips, whether the subject was ignoring or attending. The later component (latency about 350 msec) occurred only when the subject was actively attending to the tones; it was evoked by the infrequent, unpredictable stimulus shifts, regardless of whether the subject was counting that stimulus or the more frequently occurring stimulus. Both of these distinct psychophysiological entities have previously been collectively referred to as 'P-3' or 'P-300' in the literature.

  18. Latency of the nictitating membrane response to periocular electrostimulation in unanesthetized rabbits.

    PubMed

    Moore, J W; Desmond, J E

    1982-06-01

    The latency of the nictitating membrane response (NMR) in rabbit (Oryctolagus cuniculus) to periocular electro-stimulation is a negative exponential function of stimulus current with an asymptote of approximately 17 msec. The NMR was recorded by means of a precision low-torque potentiometer like that employed in previous studies of NMR latency, and the criterion of response initiation employed here was similar to that employed in studies of classical conditioning in this preparation. Using estimates from physiological studies on surgically acute preparations, the minimum latency of the NMR of 17 msec can be decomposed as follows: 4 msec to fire motoneurons of the accessory abducens nucleus; 9 msec for conduction, synaptic transmission, and recruitment of retractor bulbi muscle fibers; 4 msec for the nictitating membrane to initiate its sweep after eyeball retraction. The implications of these estimates for chronic unit-recording studies of the conditioned NMR are discussed. PMID:7111447

  19. Long noncoding RNA NRON contributes to HIV-1 latency by specifically inducing tat protein degradation

    PubMed Central

    Li, Jun; Chen, Cancan; Ma, Xiancai; Geng, Guannan; Liu, Bingfeng; Zhang, Yijun; Zhang, Shaoyang; Zhong, Fudi; Liu, Chao; Yin, Yue; Cai, Weiping; Zhang, Hui

    2016-01-01

    Long noncoding RNAs (lncRNAs) play multiple key regulatory roles in various cellular pathways. However, their functions in HIV-1 latent infection remain largely unknown. Here we show that a lncRNA named NRON, which is highly expressed in resting CD4+ T lymphocytes, could be involved in HIV-1 latency by specifically inducing Tat protein degradation. Our results suggest that NRON lncRNA potently suppresses the viral transcription by decreasing the cellular abundance of viral transactivator protein Tat. NRON directly links Tat to the ubiquitin/proteasome components including CUL4B and PSMD11, thus facilitating Tat degradation. Depletion of NRON, especially in combination with a histone deacetylase (HDAC) inhibitor, significantly reactivates the viral production from the HIV-1-latently infected primary CD4+ T lymphocytes. Our data indicate that lncRNAs play a role in HIV-1 latency and their manipulation could be a novel approach for developing latency-reversing agents. PMID:27291871

  20. Sensor Spatial Distortion, Visual Latency, and Update Rate Effects on 3D Tracking in Virtual Environments

    NASA Technical Reports Server (NTRS)

    Ellis, S. R.; Adelstein, B. D.; Baumeler, S.; Jense, G. J.; Jacoby, R. H.; Trejo, Leonard (Technical Monitor)

    1998-01-01

    Several common defects that we have sought to minimize in immersing virtual environments are: static sensor spatial distortion, visual latency, and low update rates. Human performance within our environments during large amplitude 3D tracking was assessed by objective and subjective methods in the presence and absence of these defects. Results show that 1) removal of our relatively small spatial sensor distortion had minor effects on the tracking activity, 2) an Adapted Cooper-Harper controllability scale proved the most sensitive subjective indicator of the degradation of dynamic fidelity caused by increasing latency and decreasing frame rates, and 3) performance, as measured by normalized RMS tracking error or subjective impressions, was more markedly influenced by changing visual latency than by update rate.

  1. Epstein-Barr virus growth/latency III program alters cellular microRNA expression

    SciTech Connect

    Cameron, Jennifer E. Fewell, Claire Yin, Qinyan McBride, Jane Wang Xia Lin Zhen

    2008-12-20

    The Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cancers. Initial EBV infection alters lymphocyte gene expression, inducing cellular proliferation and differentiation as the virus transitions through consecutive latency transcription programs. Cellular microRNAs (miRNAs) are important regulators of signaling pathways and are implicated in carcinogenesis. The extent to which EBV exploits cellular miRNAs is unknown. Using micro-array analysis and quantitative PCR, we demonstrate differential expression of cellular miRNAs in type III versus type I EBV latency including elevated expression of miR-21, miR-23a, miR-24, miR-27a, miR-34a, miR-146a and b, and miR-155. In contrast, miR-28 expression was found to be lower in type III latency. The EBV-mediated regulation of cellular miRNAs may contribute to EBV signaling and associated cancers.

  2. PI-ping - Benchmark Tool for Testing Latencies and Throughput in Operating Systems

    NASA Astrophysics Data System (ADS)

    Abaffy, J.; Krajčovič, T.

    In this paper we present a benchmark tool called PI-ping that can be used to compare real-time performance of operating systems. It uses two types of processes that are common in operating systems - interactive tasks demanding low latencies and also processes demanding high CPU utilization. Most operating systems have to perform well in both conditions and the goal is to achieve the highest throughput when keeping the latencies within a reasonable interval. PI-ping measures the latencies of an interactive process when the system is under heavy computational load. Using PI-ping benchmark tool we are able to compare different operating systems and we attest the functionality of it using two very common operating systems - Linux and FreeBSD.

  3. Studies of HIV-1 latency in an ex vivo model that uses primary central memory T cells

    PubMed Central

    Bosque, Alberto; Planelles, Vicente

    2010-01-01

    HIV-1 latency is considered the last hurdle toward viral eradication in the presence of antiretroviral therapy. Studies of viral latency in vivo are complicated by the low frequency of latently infected cells found in HIV-1 patients. To be able to study the signaling pathways and viral determinants of latency and reactivation, we have developed a novel method that generates high numbers of latently HIV-1 infected cells, which are derived from human primary CD4+ T lymphocytes. This method allows for the study of different aspects of HIV-1 latency, such as the transcription factors needed for viral reactivation and the signaling pathways involved. In this review, we describe in detail an experimental protocol for the generation of HIV-1 latency using human primary CD4+ T cells. We also present the salient points of other latency models in the field, along with key findings arising from each model. PMID:20970502

  4. Not only amblyopic but also dominant eye in subjects with strabismus show increased saccadic latency.

    PubMed

    Perdziak, Maciej; Witkowska, Dagmara K; Gryncewicz, Wojciech; Ober, Jan K

    2016-08-01

    Amblyopia is a developmental disorder of vision usually associated with the presence of strabismus and/or anisometropia during early childhood. Subject literature has shown that both the amblyopic and fellow eyes (especially in strabismic subjects) may manifest a variety of perceptual and oculomotor deficits. Previous studies using simple saccadic responses (pro-saccades) showed an increased saccadic latency only for the amblyopic eye viewing conditions. So far, there have appeared no saccadic latency studies in strabismic amblyopia for more complex volitional saccades. In order to maximize the contribution of the central retina in the process of saccade initiation, we decided to use delayed saccadic responses in order to test the hypothesis about saccadic latency increase in both eyes in strabismic amblyopes. The results from our study have shown that saccadic latency is increased both in the dominant and amblyopic eyes. In addition, the amblyopic eye in the strabismic group showed greater increase in saccadic latency compared to an amblyopic eye in the anisometropic group from our previous study. The observed increase in saccadic reaction time for the dominant eye is novel and provides further evidence that the visual pathway associated with the dominant eye might be also impaired in strabismic amblyopia. Since an abnormal binocular input during visual system development may affect gaze stability in both eyes, we speculate that unsteady fixation accompanied with subtle perceptual deficits contribute to an increase in saccadic latency that is observed in the dominant eye. Moreover, it appears that the cortical processes related to saccade decisions are delayed both for amblyopic and fellow eyes in strabismic subjects. PMID:27559718

  5. Ablation of STAT3 in the B Cell Compartment Restricts Gammaherpesvirus Latency In Vivo

    PubMed Central

    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

  6. Improvement of FPGA control via high speed but high latency interfaces

    NASA Astrophysics Data System (ADS)

    Zabołotny, Wojciech M.

    2015-09-01

    In last years, the throughput of interfaces used in computer systems to control extension boards or external hardware has increased significantly. Unfortunately, those interfaces have also significant round-trip latency. This fact seriously impairs the efficiency of those control algorithms, which require a tight handshake. In such algorithms, the communication consists of a sequence of write and read operations, where read result (the handshake status) must be checked before the next write command is issued. This problem can be solved by the implementation of an intelligent controller in the controlled hardware. This controller should execute high-level commands locally performing all necessary handshake operations. Unfortunately, such a complex and highly specialized controller would consume a significant amount of FPGA resources. This paper presents an alternative approach which uses a highly simplified versatile controller implemented in FPGA. This simple controller may improve the efficiency of certain, relatively broad class of control algorithms. The proposed controller accepts a set of simple commands, which describe the write operations, read operations, and simple test operations. The control algorithm is described as a sequence of those operations. If the controlled hardware works correctly, all tests are passed, and the controller only notifies the host about successful completion. In case if certain handshake test fails, the host is notified about the position of the failed test and type of failure. That allows the controlling software to investigate and cure the problem. The controller may be also used in a standard mode, where status or result of each command is returned immediately and may be checked before the next command is issued. The paper also proposes a simple method for writing of software, which uses the new controller. This method allows to implement the control procedures that are very similar to those using traditional controllers. That

  7. Human Papillomavirus Type 18 cis-Elements Crucial for Segregation and Latency.

    PubMed

    Ustav, Mart; Castaneda, Fernando Rodriguez; Reinson, Tormi; Männik, Andres; Ustav, Mart

    2015-01-01

    Stable maintenance replication is characteristic of the latency phase of HPV infection, during which the viral genomes are actively maintained as extrachromosomal genetic elements in infected proliferating basal keratinocytes. Active replication in the S-phase and segregation of the genome into daughter cells in mitosis are required for stable maintenance replication. Most of our knowledge about papillomavirus genome segregation has come from studies of bovine papillomavirus type 1 (BPV-1), which have demonstrated that the E2 protein cooperates with cellular trans-factors and that E2 binding sites act as cis-regulatory elements in the viral genome that are essential for the segregation process. However, the genomic organization of the regulatory region in HPVs, and the properties of the viral proteins are different from those of their BPV-1 counterparts. We have designed a segregation assay for HPV-18 and used it to demonstrate that the E2 protein performs segregation in combination with at least two E2 binding sites. The cooperative binding of the E2 protein to two E2 binding sites is a major determinant of HPV-18 genome segregation, as demonstrated by the change in spacing between adjacent binding sites #1 and #2 in the HPV-18 Upstream Regulatory Region (URR). Duplication or triplication of the natural 4 bp 5'-CGGG-3' spacer between the E2 binding sites increased the cooperative binding of the E2 molecules as well as E2-dependent segregation. Removal of any spacing between these sites eliminated cooperative binding of the E2 protein and disabled segregation of the URR and HPV-18 genome. Transfer of these configurations of the E2 binding sites into viral genomes confirmed the role of the E2 protein and binding sites #1 and #2 in the segregation process. Additional analysis demonstrated that these sites also play an important role in the transcriptional regulation of viral gene expression from different HPV-18 promoters. PMID:26288015

  8. Human Papillomavirus Type 18 cis-Elements Crucial for Segregation and Latency

    PubMed Central

    Ustav, Mart; Castaneda, Fernando Rodriguez; Reinson, Tormi; Männik, Andres; Ustav, Mart

    2015-01-01

    Stable maintenance replication is characteristic of the latency phase of HPV infection, during which the viral genomes are actively maintained as extrachromosomal genetic elements in infected proliferating basal keratinocytes. Active replication in the S-phase and segregation of the genome into daughter cells in mitosis are required for stable maintenance replication. Most of our knowledge about papillomavirus genome segregation has come from studies of bovine papillomavirus type 1 (BPV-1), which have demonstrated that the E2 protein cooperates with cellular trans-factors and that E2 binding sites act as cis-regulatory elements in the viral genome that are essential for the segregation process. However, the genomic organization of the regulatory region in HPVs, and the properties of the viral proteins are different from those of their BPV-1 counterparts. We have designed a segregation assay for HPV-18 and used it to demonstrate that the E2 protein performs segregation in combination with at least two E2 binding sites. The cooperative binding of the E2 protein to two E2 binding sites is a major determinant of HPV-18 genome segregation, as demonstrated by the change in spacing between adjacent binding sites #1 and #2 in the HPV-18 Upstream Regulatory Region (URR). Duplication or triplication of the natural 4 bp 5’-CGGG-3’ spacer between the E2 binding sites increased the cooperative binding of the E2 molecules as well as E2-dependent segregation. Removal of any spacing between these sites eliminated cooperative binding of the E2 protein and disabled segregation of the URR and HPV-18 genome. Transfer of these configurations of the E2 binding sites into viral genomes confirmed the role of the E2 protein and binding sites #1 and #2 in the segregation process. Additional analysis demonstrated that these sites also play an important role in the transcriptional regulation of viral gene expression from different HPV-18 promoters. PMID:26288015

  9. Effects of age, signal level, and signal rate on the auditory middle latency response.

    PubMed

    Tucker, D A; Ruth, R A

    1996-04-01

    The effects of age, signal rate, and signal level on the maturing auditory middle latency response (AMLR) were evaluated in 50 normal-hearing subjects ranging in age from 2 days to 35 years. Ipsilateral and contralateral AMLR waveforms were recorded in newborns (n = 10), children (n = 10), preteens (n = 10), teens (n = 10), and adults (n = 10). The AMLR Pa waveform was obtained in 70 to 100 percent of all subjects. The variables of age, signal level, and site of recording significantly affected Pa peak amplitude and absolute latency. However, stimulus rate did not significantly affect the response. PMID:8652873

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

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

    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.

  12. Translational Compensation of a Frameshift Mutation Affecting Herpes Simplex Virus Thymidine Kinase Is Sufficient To Permit Reactivation from Latency

    PubMed Central

    Griffiths, Anthony; Chen, Shun-Hua; Horsburgh, Brian C.; Coen, Donald M.

    2003-01-01

    Herpes simplex virus thymidine kinase is important for reactivation of virus from its latent state and is a target for the antiviral drug acyclovir. Most acyclovir-resistant isolates have mutations in the thymidine kinase gene; however, how these mutations confer clinically relevant resistance is unclear. Reactivation from explanted mouse ganglia was previously observed with a patient-derived drug-resistant isolate carrying a single guanine insertion within a run of guanines in the thymidine kinase gene. Despite this mutation, low levels of active enzyme were synthesized following an unusual ribosomal frameshift. Here we report that a virus, generated from a pretherapy isolate from the same patient, engineered to lack thymidine kinase activity, was competent for reactivation. This suggested that the clinical isolate contains alleles of other genes that permit reactivation in the absence of thymidine kinase. Therefore, to establish whether thymidine kinase synthesized via a ribosomal frameshift was sufficient for reactivation under conditions where reactivation requires this enzyme, we introduced the mutation into the well-characterized strain KOS. This mutant virus reactivated from latency, albeit less efficiently than KOS. Plaque autoradiography revealed three phenotypes of reactivating viruses: uniformly low thymidine kinase activity, mixed high and low activity, and uniformly high activity. We generated a recombinant thymidine kinase-null virus from a reactivating virus expressing uniformly low activity. This virus did not reactivate, confirming that mutations in other genes that would influence reactivation had not arisen. Therefore, in strains that require thymidine kinase for reactivation from latency, low levels of enzyme synthesized via a ribosomal frameshift can suffice. PMID:12663777

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

    NASA Technical Reports Server (NTRS)

    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

  14. Relationship between Size Summation Properties, Contrast Sensitivity and Response Latency in the Dorsomedial and Middle Temporal Areas of the Primate Extrastriate Cortex

    PubMed Central

    Lui, Leo L.; Bourne, James A.; Rosa, Marcello G. P.

    2013-01-01

    Analysis of the physiological properties of single neurons in visual cortex has demonstrated that both the extent of their receptive fields and the latency of their responses depend on stimulus contrast. Here, we explore the question of whether there are also systematic relationships between these response properties across different cells in a neuronal population. Single unit recordings were obtained from the middle temporal (MT) and dorsomedial (DM) extrastriate areas of anaesthetized marmoset monkeys. For each cell, spatial integration properties (length and width summation, as well as the presence of end- and side-inhibition within 15° of the receptive field centre) were determined using gratings of optimal direction of motion and spatial and temporal frequencies, at 60% contrast. Following this, contrast sensitivity was assessed using gratings of near-optimal length and width. In both areas, we found a relationship between spatial integration and contrast sensitivity properties: cells that summated over smaller areas of the visual field, and cells that displayed response inhibition at larger stimulus sizes, tended to show higher contrast sensitivity. In a sample of MT neurons, we found that cells showing longer latency responses also tended to summate over larger expanses of visual space in comparison with neurons that had shorter latencies. In addition, longer-latency neurons also tended to show less obvious surround inhibition. Interestingly, all of these effects were stronger and more consistent with respect to the selectivity for stimulus width and strength of side-inhibition than for length selectivity and end-inhibition. The results are partially consistent with a hierarchical model whereby more extensive receptive fields require convergence of information from larger pools of “feedforward” afferent neurons to reach near-optimal responses. They also suggest that a common gain normalization mechanism within MT and DM is involved, the spatial extent

  15. Modeling adenovirus latency in human lymphocyte cell lines.

    PubMed

    Zhang, Yange; Huang, Wen; Ornelles, David A; Gooding, Linda R

    2010-09-01

    Species C adenovirus establishes a latent infection in lymphocytes of the tonsils and adenoids. To understand how this lytic virus is maintained in these cells, four human lymphocytic cell lines that support the entire virus life cycle were examined. The T-cell line Jurkat ceased proliferation and died shortly after virus infection. BJAB, Ramos (B cells), and KE37 (T cells) continued to divide at nearly normal rates while replicating the virus genome. Viral genome numbers peaked and then declined in BJAB cells below one genome per cell at 130 to 150 days postinfection. Ramos and KE37 cells maintained the virus genome at over 100 copies per cell over a comparable period of time. BJAB cells maintained the viral DNA as a monomeric episome. All three persistently infected cells lost expression of the cell surface coxsackie and adenovirus receptor (CAR) within 24 h postinfection, and CAR expression remained low for at least 340 days postinfection. CAR loss proceeded via a two-stage process. First, an initial loss of cell surface staining for CAR required virus late gene expression and a CAR-binding fiber protein even while CAR protein and mRNA levels remained high. Second, CAR mRNA disappeared at around 30 days postinfection and remained low even after virus DNA was lost from the cells. At late times postinfection (day 180), BJAB cells could not be reinfected with adenovirus, even when CAR was reintroduced to the cells via retroviral transduction, suggesting that the expression of multiple genes had been stably altered in these cells following infection. PMID:20573817

  16. Estimating Testing Time: The Effects of Item Characteristics on Response Latency.

    ERIC Educational Resources Information Center

    Halkitis, Perry N.; And Others

    The relationship between test item characteristics and testing time was studied for a computer-administered licensing examination. One objective of the study was to develop a model to predict testing time on the basis of known item characteristics. Response latencies (i.e., the amount of time taken by examinees to read, review, and answer items)…

  17. An Investigation of the Effect of Network Latency on Pedagogic Efficacy: A Comparison of Disciplines

    ERIC Educational Resources Information Center

    Bush, H. Francis; Squire, James; Sullivan, Gerald; Walsh, Vonda; English, Anthony; Bolen, Rosie

    2008-01-01

    E-learning has become a mainstream educational opportunity, as noted in "U.S. News & World Report." Further, differences among college students have been documented in various disciplines. An experiment was conducted to determine the effects of network latency on pedagogical efficacy based on the students who were classified as in…

  18. Neuromagnetic Oscillations Predict Evoked-Response Latency Delays and Core Language Deficits in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    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.

    2015-01-01

    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…

  19. Effects of dynamic synapses on noise-delayed response latency of a single neuron.

    PubMed

    Uzuntarla, M; Ozer, M; Ileri, U; Calim, A; Torres, J J

    2015-12-01

    The noise-delayed decay (NDD) phenomenon emerges when the first-spike latency of a periodically forced stochastic neuron exhibits a maximum for a particular range of noise intensity. Here, we investigate the latency response dynamics of a single Hodgkin-Huxley neuron that is subject to both a suprathreshold periodic stimulus and a background activity arriving through dynamic synapses. We study the first-spike latency response as a function of the presynaptic firing rate f. This constitutes a more realistic scenario than previous works, since f provides a suitable biophysically realistic parameter to control the level of activity in actual neural systems. We first report on the emergence of classical NDD behavior as a function of f for the limit of static synapses. Second, we show that when short-term depression and facilitation mechanisms are included at the synapses, different NDD features can be found due to their modulatory effect on synaptic current fluctuations. For example, an intriguing double NDD (DNDD) behavior occurs for different sets of relevant synaptic parameters. Moreover, depending on the balance between synaptic depression and synaptic facilitation, single NDD or DNDD can prevail, in such a way that synaptic facilitation favors the emergence of DNDD whereas synaptic depression favors the existence of single NDD. Here we report the existence of the DNDD effect in the response latency dynamics of a neuron. PMID:26764730

  20. Auditory Middle Latency Responses in Chronic Smokers Compared to Nonsmokers: Differential Effects of Stimulus and Age

    ERIC Educational Resources Information Center

    Ramkissoon, Ishara; Beverly, Brenda L.

    2014-01-01

    Purpose: Effects of clicks and tonebursts on early and late auditory middle latency response (AMLR) components were evaluated in young and older cigarette smokers and nonsmokers. Method: Participants ( n = 49) were categorized by smoking and age into 4 groups: (a) older smokers, (b) older nonsmokers, (c) young smokers, and (d) young nonsmokers.…

  1. Does Latency in Recording Data Make a Difference? Confirming the Accuracy of Teachers' Data

    ERIC Educational Resources Information Center

    Taber-Doughty, Teresa; Jasper, Andrea D.

    2012-01-01

    The effects of latency on the accuracy of data recorded by three special education teachers were examined in this study. Teachers recorded data on the target behaviors of three students with varying disabilities. The accuracy of data recorded was assessed during three time periods: immediately after the target behavior occurred, at the end of the…

  2. Auditory Middle Latency Response and Phonological Awareness in Students with Learning Disabilities

    PubMed Central

    Romero, Ana Carla Leite; Funayama, Carolina Araújo Rodrigues; Capellini, Simone Aparecida; Frizzo, Ana Claudia Figueiredo

    2015-01-01

    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. PMID:26491479

  3. Response Latency in Survey Research: A Strategy for Detection and Avoidance of Satisficing Behaviors

    ERIC Educational Resources Information Center

    Wanich, Wipada

    2010-01-01

    Response latency has been widely used as a cognitive method to investigate how respondents answer survey questions and also as a method to identify problems with survey questions (e.g., flawed or poorly worded questions) or errors associated with respondents' behaviors (e.g., faking). However, little attention has been paid to using response…

  4. Choice Latency as a Cue for Children's Subjective Confidence in the Correctness of Their Answers

    ERIC Educational Resources Information Center

    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…

  5. Flash Memory Reliability: Read, Program, and Erase Latency Versus Endurance Cycling

    NASA Technical Reports Server (NTRS)

    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.

  6. Light and Movement: Making Contact with a Traumatised and Embattled Latency Girl

    ERIC Educational Resources Information Center

    Allnutt, Louise

    2010-01-01

    This paper shows a child psychotherapist learning and developing her technique as she attempts to make contact with a child who is extremely hard to reach. It is based on the first two years of three-times-weekly intensive psychotherapy of a latency girl who had little faith in a helpful therapeutic relationship. Her defences against such a…

  7. Theta oscillation coupled spike latencies yield computational vigour in a mammalian sensory system

    PubMed Central

    Margrie, Troy W; Schaefer, Andreas T

    2003-01-01

    Theoretical work carried out almost a decade ago proposed that subthreshold oscillations in membrane potential could be used to convert synaptic current strength into a code reliant on action potential (AP) latencies. Using whole-cell recordings we present experimental evidence for the occurrence of prominent network-driven subthreshold theta oscillations in mitral cells of the mouse olfactory bulb. Activity induced by both injected current and sensory input was accurately reflected in initial AP latency from the beginning of each oscillation cycle. In a network model we found that an AP latency code rather than AP number or instantaneous firing rate provided computational speed and high resolution, and was easily implemented. This coding strategy was also found to be invariant to the total input current as long as the relative input intensities to glomeruli remained constant. However, it was highly sensitive to changes in the ratios of the input currents and improved by lateral inhibitory mechanisms. Since the AP latency-based coding scheme was dependent on the subthreshold oscillation we conclude that the theta rhythm serves a functional role in temporally reformatting the strengths and patterns of synaptic input in this sensory system. PMID:12527724

  8. Act quickly, decide later: long-latency visual processing underlies perceptual decisions but not reflexive behavior.

    PubMed

    Jolij, Jacob; Scholte, H Steven; van Gaal, Simon; Hodgson, Timothy L; Lamme, Victor A F

    2011-12-01

    Humans largely guide their behavior by their visual representation of the world. Recent studies have shown that visual information can trigger behavior within 150 msec, suggesting that visually guided responses to external events, in fact, precede conscious awareness of those events. However, is such a view correct? By using a texture discrimination task, we show that the brain relies on long-latency visual processing in order to guide perceptual decisions. Decreasing stimulus saliency leads to selective changes in long-latency visually evoked potential components reflecting scene segmentation. These latency changes are accompanied by almost equal changes in simple RTs and points of subjective simultaneity. Furthermore, we find a strong correlation between individual RTs and the latencies of scene segmentation related components in the visually evoked potentials, showing that the processes underlying these late brain potentials are critical in triggering a response. However, using the same texture stimuli in an antisaccade task, we found that reflexive, but erroneous, prosaccades, but not antisaccades, can be triggered by earlier visual processes. In other words: The brain can act quickly, but decides late. Differences between our study and earlier findings suggesting that action precedes conscious awareness can be explained by assuming that task demands determine whether a fast and unconscious, or a slower and conscious, representation is used to initiate a visually guided response. PMID:21557644

  9. Effects of dynamic synapses on noise-delayed response latency of a single neuron

    NASA Astrophysics Data System (ADS)

    Uzuntarla, M.; Ozer, M.; Ileri, U.; Calim, A.; Torres, J. J.

    2015-12-01

    The noise-delayed decay (NDD) phenomenon emerges when the first-spike latency of a periodically forced stochastic neuron exhibits a maximum for a particular range of noise intensity. Here, we investigate the latency response dynamics of a single Hodgkin-Huxley neuron that is subject to both a suprathreshold periodic stimulus and a background activity arriving through dynamic synapses. We study the first-spike latency response as a function of the presynaptic firing rate f . This constitutes a more realistic scenario than previous works, since f provides a suitable biophysically realistic parameter to control the level of activity in actual neural systems. We first report on the emergence of classical NDD behavior as a function of f for the limit of static synapses. Second, we show that when short-term depression and facilitation mechanisms are included at the synapses, different NDD features can be found due to their modulatory effect on synaptic current fluctuations. For example, an intriguing double NDD (DNDD) behavior occurs for different sets of relevant synaptic parameters. Moreover, depending on the balance between synaptic depression and synaptic facilitation, single NDD or DNDD can prevail, in such a way that synaptic facilitation favors the emergence of DNDD whereas synaptic depression favors the existence of single NDD. Here we report the existence of the DNDD effect in the response latency dynamics of a neuron.

  10. Equal latency contours for bottlenose dolphins (Tursiops truncatus) and California sea lions (Zalophus californianus).

    PubMed

    Mulsow, Jason; Schlundt, Carolyn E; Brandt, Lacey; Finneran, James J

    2015-11-01

    Loudness perception by non-human animals is difficult to study directly. Previous research efforts have instead focused on estimating loudness perception using simple reaction time (RT) data. These data are used to generate equal latency contours that serve as a proxy for equal loudness contours. To aid the design of auditory weighting functions for marine mammals, equal latency contours were generated using RT data for two marine mammal species that are representative of broader functional hearing groups: the bottlenose dolphin (under water) and California sea lion (in air). In all cases, median RT decreased with increasing tone sound pressure level (SPL). The equal latency contours corresponding to near-threshold SPLs were similar to audiograms for both species. The sea lion contours showed some compression at frequencies below 1 kHz; however, a similar pattern was not apparent in the more variable data for dolphins. Equal latency contours for SPLs greater than approximately 40 dB above threshold diverged from predicted equal loudness contours, likely due to the asymptotic nature of RT at the highest tested SPLs. The results suggest that auditory threshold data, potentially augmented with compression at low frequencies, may provide a useful way forward when designing auditory weighting functions for marine mammals. PMID:26627745

  11. Histone modifications induced by MDV infection at early cytolytic and latency phases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  12. Using Pre and Post Low-"p" Latency to Assess Behavioral Momentum: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Lee, David L.; Belfiore, Phillip J.; Ferko, Doreen; Hua, Youjia; Carranza, Mandy; Hildebrand, Katie

    2006-01-01

    Delivering high-probability (high-p) request sequences is an effective method to increase compliance across settings. To date, researchers have used frequency of compliance and latency to initiate low-probability (low-p) requests to document these effects. Both measures focus on events just prior to and during the low-p task. In these two studies…

  13. Fuzzy Logic based Handoff Latency Reduction Mechanism in Layer 2 of Heterogeneous Mobile IPv6 Networks

    NASA Astrophysics Data System (ADS)

    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.

  14. The effect of joint instability on latency and recruitment order of the shoulder muscles.

    PubMed

    Santos, Marcio J; Belangero, William Dias; Almeida, Gil L

    2007-04-01

    Several shoulder dysfunctions are generally characterized as Shoulder Impingement Syndrome (SIS). Specifically, glenohumeral instability (GI) has been viewed as a primary cause of SIS in young individuals, mainly in overhead athletics. Past studies have associated GI with modifications in latency, recruitment order and/or EMG activity. However, it is not clear if pain and/or joint instability can account for these observed changes. The aim of this investigation was to analyze the effect of glenohumeral instability on the latencies and recruitment order of the superficial muscles of the glenohumeral and scapulothoracic joints in swimmers without pain symptom. Eight individuals with and eight without history of Shoulder Impingement Syndrome performed bilateral and simultaneous shoulder elevations at three different distances. The shoulder kinematics and EMG activities of glenohumeral and scapulothoracic muscles were registered. Results showed that subjects of both groups performed the task with similar latencies and recruitment order of the muscle activities. We conclude that shoulder instability does not necessarily affect the latencies and recruitment order of the shoulder muscles during the elevation of the shoulder in the scapular plane. Pain and other factors may be involved in the kinematics and electromyographic alterations demonstrated in other experiments. PMID:16546403

  15. Length of Latency with Preterm Premature Rupture of Membranes before 32 Weeks’ Gestation

    PubMed Central

    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

  16. H-reflex latency in uremic neuropathy: correlation with NCV and clinical findings.

    PubMed

    Halar, E M; Brozovich, F V; Milutinovic, J; Inouye, V L; Becker, V M

    1979-04-01

    Sixty-two uremic patients on dialysis of varying durations were tested bilaterally for posterior tibial nerve H-reflex latency, at 3-month intervals. Bilateral nerve conduction velocities (NCVs) of the peroneal, tibial, and sural nerves were concomitantly determined in all subjects. Proprioception sense, vibration perception threshold at the great toes, and deep tendon reflexes at the knee and ankle were determined in all subjects on the day of electrodiagnostic testing. The sensitivity of the H-reflex latency in detection of the onset and severity of uremic neuropathy was assessed. H-reflex latency changes were compared to NCV and clinical test results. The following was found: (1) of the parameters studied, the H-reflex latency appeared to be the most sensitive indicator of early uremic polyneuropathies, (2) electrodiagnostic tests were more sensitive to the onset of neuropathies than the clinical testing parameters studied, and (3) the sural sensory nerve appeared to be involved earlier than peroneal and tibial motor nerves in neuropathies studied. PMID:224838

  17. Faster Orientation Latencies Toward Native Language in Two-Month-Old Infants.

    ERIC Educational Resources Information Center

    Dehaene-Lambertz, G.; Houston, D.

    1998-01-01

    Assessed the amount of linguistic information needed by 2-year-old infants to recognize whether or not a sentence belongs to their native language. A cross-linguistic study of French and American 2-month-old infants was conducted, measuring the latency of the first ocular saccade toward a loudspeaker playing short French and English utterances.…

  18. HSV carrying WT REST establishes latency but reactivates only if the synthesis of REST is suppressed.

    PubMed

    Zhou, Guoying; Du, Te; Roizman, Bernard

    2013-02-01

    HSVs transit from vigorous replication at the portal of entry into the body to a latent state in sensory neurons in which only noncoding (e.g., latency-associated transcript) and micro-RNAs are expressed. In productive infection, viral genes must be sequentially derepressed at two checkpoints. A leading role in the repression of viral genes is carried out by histone deacetylase (HDAC)/corepressor element-1 silencing transcription factor (CoREST)/lysinespecific demethylase1(LSD1)/RE1-silencing transcription factor (REST) repressor complex (HCLR). Previously, we reported that to define the role of the components of the HCLR complex in the establishment of latency, we constructed recombinant virus (R112) carrying a dominant-negative REST that bound response elements in DNA but could not recruit repressive proteins. This recombinant virus was unable to establish latency. In the current studies, we constructed a virus (R111) carrying WT REST with a WT genome. We report the following findings: (a) R111 readily established latent infection in trigeminal ganglia; however, although the amounts of viral DNAs in latently infected neurons were similar to those of WT virus, the levels of latency-associated transcript and micro-RNAs were 50- to 100-fold lower; (b) R111 did not spontaneously reactivate in ganglionic organ cultures; however, viral genes were expressed if the synthesis of REST was blocked by cycloheximide; and (c) histone deacetylase inhibitors reactivated the WT parent but not the R111 recombinant virus. The results suggest that REST plays a transient role in the establishment of latency but not in reactivation and suggest the existence of at least two phases at both establishment and reactivation. PMID:23341636

  19. IRF-7, a new interferon regulatory factor associated with Epstein-Barr virus latency.

    PubMed Central

    Zhang, L; Pagano, J S

    1997-01-01

    The Epstein-Barr virus (EBV) BamHI Q promoter (Qp) is the only promoter used for the transcription of Epstein-Barr virus nuclear antigen 1 (EBNA-1) mRNA in cells in the most restricted (type I) latent infection state. However, Qp is inactive in type III latency. With the use of the yeast one-hybrid system, a new cellular gene has been identified that encodes proteins which bind to sequence in Qp. The deduced amino acid sequence of the gene has significant homology to the interferon regulatory factors (IRFs). This new gene and products including two splicing variants are designated IRF-7A, IRF-7B, and IRF-7C. The expression of IRF-7 is predominantly in spleen, thymus, and peripheral blood leukocytes (PBL). IRF-7 proteins were identified in primary PBL with specific antiserum against IRF-7B protein. IRF-7s can bind to interferon-stimulated response element (ISRE) sequence and repress transcriptional activation by both interferon and IRF-1. Additionally, a functional viral ISRE sequence, 5'-GCGAAAACGAAAGT-3', has been identified in Qp. Finally, the expression of IRF-7 is consistently high in type III latency cells and almost undetectable in type I latency, corresponding to the activity of endogenous Qp in these latency states and the ability of the IRF-7 proteins to repress Qp-reporter constructs. The identification of a functional viral ISRE and association of IRF-7 with type III latency may be relevant to the mechanism of regulation of Qp. PMID:9315633

  20. Brain Targeted Transcranial Administration of Diazepam and Shortening of Sleep Latency in Healthy Human Volunteers

    PubMed Central

    Pathirana, W.; Gunasekera, S. M.; Constantine, G. R.; Perera, Sanja; Perera, B. M.; Kamaladiwela, R.

    2011-01-01

    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. Transcranial brain targeted

  1. Instruction-dependent modulation of the long-latency stretch reflex is associated with indicators of startle

    PubMed Central

    Ravichandran, Vengateswaran J.; Honeycutt, Claire F.; Shemmell, Jonathan; Perreault, Eric J.

    2013-01-01

    Long-latency responses elicited by postural perturbation are modulated by how a subject is instructed to respond to the perturbation, yet the neural pathways responsible for this modulation remain unclear. The goal of this study was to determine if instruction-dependent modulation is associated with activity in brainstem pathways contributing to startle. Our hypothesis was that elbow perturbations can evoked startle, indicated by activity in the sternocleidomastoid muscle (SCM). Perturbation responses were compared to those elicited by a loud acoustic stimulus, known to elicit startle. Postural perturbations and startling acoustic stimuli both evoked SCM activity, but only when a ballistic elbow extension movement was planned. Both stimuli triggered SCM activity with the same probability. When SCM activity was present, there was an associated early onset of triceps EMG, as required for the planned movement. This early EMG onset occurred at a time often attributed to long-latency stretch reflexes (75-100ms). The nature of the perturbation-triggered EMG (excitatory or inhibitory) was independent of the perturbation direction (flexion or extension) indicating that it was not a feedback response appropriate for returning the limb to its original position. The net EMG response to perturbations delivered after a movement had been planned could be explained as the sum of a stretch reflex opposing the perturbation and a startle-evoked response associated with the prepared movement. These results demonstrate that rapid perturbations can trigger early release of a planned ballistic movement, and that this release is associated with activity in the brainstem pathways contributing to startle reflexes. PMID:23811739

  2. Treating Excessively Slow Responding of a Young Man with Asperger Syndrome Using Differential Reinforcement of Short Response Latencies

    ERIC Educational Resources Information Center

    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…

  3. The interaction between anxiety sensitivity and cigarette smoking level in relation to sleep onset latency among adolescent cigarette smokers.

    PubMed

    Bilsky, Sarah A; Feldner, Matthew T; Knapp, Ashley A; Babson, Kimberly A; Leen-Feldner, Ellen W

    2016-08-01

    Cigarette smoking during adolescence is linked to a number of sleep disturbances and has been consistently linked to sleep onset latency among adults. However, little research has examined factors that may influence the relation between cigarette smoking level and sleep onset latency among adolescents. One factor that may be particularly important in this regard is anxiety sensitivity (AS). The current study examined whether cigarette smoking level interacted with AS in its association with sleep onset latency among 94 adolescent (Mage = 15.72) cigarette smokers. As hypothesized, AS interacted with smoking level to relate to sleep onset latency, even after controlling for age and gender. This relation was specific to sleep onset latency as opposed to other types of sleep disturbances, and that adolescents who smoked at higher levels tended to go to sleep later and wake up later than adolescents who smoked at relatively lower levels. PMID:27351343

  4. A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

    PubMed Central

    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

  5. Identification of B Cells as a Major Site for Cyprinid Herpesvirus 3 Latency

    PubMed Central

    Reed, Aimee N.; Izume, Satoko; Dolan, Brian P.; LaPatra, Scott; Kent, Michael; Dong, Jing

    2014-01-01

    ABSTRACT Cyprinid herpesvirus 3 (CyHV-3), commonly known as koi herpesvirus (KHV), is a member of the Alloherpesviridae, and is a recently discovered emerging herpesvirus that is highly pathogenic for koi and common carp. Our previous study demonstrated that CyHV-3 becomes latent in peripheral white blood cells (WBC). In this study, CyHV-3 latency was further investigated in IgM+ WBC. The presence of the CyHV-3 genome in IgM+ WBC was about 20-fold greater than in IgM− WBC. To determine whether CyHV-3 expressed genes during latency, transcription from all eight open reading frames (ORFs) in the terminal repeat was investigated in IgM+ WBC from koi with latent CyHV-3 infection. Only a spliced ORF6 transcript was found to be abundantly expressed in IgM+ WBC from CyHV-3 latently infected koi. The spliced ORF6 transcript was also detected in vitro during productive infection as early as 1 day postinfection. The ORF6 transcript from in vitro infection begins at −127 bp upstream of the ATG codon and ends +188 bp downstream of the stop codon, +20 bp downstream of the polyadenylation signal. The hypothetical protein of ORF6 contains a consensus sequence with homology to a conserved domain of EBNA-3B and ICP4 from Epstein-Barr virus and herpes simplex virus 1, respectively, both members of the Herpesviridae. This is the first report of latent CyHV-3 in B cells and identification of gene transcription during latency for a member of the Alloherpesviridae. IMPORTANCE This is the first demonstration that a member of the Alloherpesviridae, cyprinid herpesvirus 3 (CyHV-3), establishes a latent infection in the B cells of its host, Cyprinus carpio. In addition, this is the first report of identification of gene transcription during latency for a member of Herpesvirales outside Herpesviridae. This is also the first report that the hypothetical protein of latent transcript of CyHV-3 contains a consensus sequence with homology to a conserved domain of EBNA-3B from Epstein

  6. A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation.

    PubMed

    Kennedy, Peter G E; Rovnak, Joel; Badani, Hussain; Cohrs, Randall J

    2015-07-01

    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 increasing

  7. Advances in high-speed low-latency communications for nanopositioning in advanced microscopy

    NASA Astrophysics Data System (ADS)

    Jordan, Scott C.

    2012-06-01

    We present a comparison of classical and recently developed communications interfacing technologies relevant to scanned imaging. We adopt an applications perspective, with a focus on interfacing techniques as enablers for enhanced resolution, speed, stability, information density or similar benefits. A wealth of such applications have emerged, ranging from nanoscale-stabilized force microscopy yielding 100X resolution improvement thanks to leveraging the latest in interfacing capabilities, to novel approaches in analog interfacing which improve data density and DAC resolution by several orders of magnitude. Our intent is to provide tools to understand, select and implement advanced interfacing to take applications to the next level. We have entered an era in which new interfacing techniques are enablers, in their own right, for novel imaging techniques. For example, clever leveraging of new interfacing technologies has yielded nanoscale stabilization and atomic-force microscopy (AFM) resolution enhancement. To assist in choosing and implementing interfacing strategies that maximize performance and enable new capabilities, we review available interfaces such as USB2, GPIB and Ethernet against the specific needs of positioning for the scanned-imaging community. We spotlight recent developments such as LabVIEW FPGA, which allows non-specialists to quickly devise custom logic and interfaces of unprecedentedly high performance and parallelism. Notable applications are reviewed, including a clever amalgamation of AFM and optical tweezers and a picometer-scaleaccuracy interferometer devised for ultrafine positioning validation. We note the Serial Peripheral Interface (SPI), emerging as a high-speed/low-latency instrumentation interface. The utility of instrument-specific parallel (PIO) and TTL sync/trigger (DIO) interfaces is also discussed. Requirements of tracking and autofocus are reviewed against the time-critical needs of typical applications (to avoid, for example

  8. HIV-1 Latency: An Update of Molecular Mechanisms and Therapeutic Strategies

    PubMed Central

    Battistini, Angela; Sgarbanti, Marco

    2014-01-01

    The major obstacle towards HIV-1 eradication is the life-long persistence of the virus in reservoirs of latently infected cells. In these cells the proviral DNA is integrated in the host’s genome but it does not actively replicate, becoming invisible to the host immune system and unaffected by existing antiviral drugs. Rebound of viremia and recovery of systemic infection that follows interruption of therapy, necessitates life-long treatments with problems of compliance, toxicity, and untenable costs, especially in developing countries where the infection hits worst. Extensive research efforts have led to the proposal and preliminary testing of several anti-latency compounds, however, overall, eradication strategies have had, so far, limited clinical success while posing several risks for patients. This review will briefly summarize the more recent advances in the elucidation of mechanisms that regulates the establishment/maintenance of latency and therapeutic strategies currently under evaluation in order to eradicate HIV persistence. PMID:24736215

  9. Low-latency analysis pipeline for compact binary coalescences in the advanced gravitational wave detector era

    NASA Astrophysics Data System (ADS)

    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.

  10. Reducing latency of a child's responding to instructions by means of a token system1

    PubMed Central

    Fjellstedt, Nancy; Sulzer-Azároff, Beth

    1973-01-01

    The response latency of following directions by an 8-yr-old boy from a class for emotionally disturbed children was modified by the contingent application of a token system. To demonstrate reinforcer effectiveness, a multiple baseline approach was used. Measures were obtained for the time elapsed between the presentation of verbal directions and five performances: (1) entering the experimental room, (2) putting toys away, (3) beginning academic work, (4) putting toys away again, and (5) returning to the classroom and completing preparations for leaving school. These five measures were placed on the token system at three different times. The results demonstrated that four of the five performances were clearly affected by the token system as their response latency for following directions decreased substantially. PMID:16795384

  11. A Type of Low-Latency Data Gathering Method with Multi-Sink for Sensor Networks.

    PubMed

    Sha, Chao; Qiu, Jian-Mei; Li, Shu-Yan; Qiang, Meng-Ye; Wang, Ru-Chuan

    2016-01-01

    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. PMID:27338401

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

    PubMed Central

    Ramchurn, Anusha; de Fockert, Jan W.; Mason, Luke; Darling, Stephen; Bunce, David

    2014-01-01

    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. PMID:25120458

  13. A Type of Low-Latency Data Gathering Method with Multi-Sink for Sensor Networks

    PubMed Central

    Sha, Chao; Qiu, Jian-mei; Li, Shu-yan; Qiang, Meng-ye; Wang, Ru-chuan

    2016-01-01

    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. PMID:27338401

  14. Design and performance of a high resolution, low latency stripline beam position monitor system

    NASA Astrophysics Data System (ADS)

    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.

  15. Non-coding RNAs: novel players in chromatin-regulation during viral latency.

    PubMed

    Eilebrecht, Sebastian; Schwartz, Christian; Rohr, Olivier

    2013-08-01

    Chromatin structure plays an essential role during gene expression regulation not only in the case of the host cellular genome, but also during the viral life cycle. Epigenetic chromatin marks thereby define, whether a gene promoter is accessible for the transcription machinery or whether a repressive heterochromatin state is established. The heterochromatin-mediated repression of lytic viral genes results in viral latency, enabling the virus to persist dormant without being recognized by the host immune system, but keeping the potential for reactivation. Arising new systems biology approaches are starting to uncover an unexpected multiplicity and variety of non-coding (nc)RNAs playing important roles during chromatin structure control, likely constituting a novel layer in epigenetic regulation. In this review we give an overview of chromatin-regulatory viral and host cellular ncRNAs and their links to viral latency. PMID:23660570

  16. Correlated biased random walk with latency in one and two dimensions: Asserting patterned and unpredictable movement

    NASA Astrophysics Data System (ADS)

    Rodriguez-Horta, E.; Estevez-Rams, E.; Lora-Serrano, R.; Fernández, B. Aragón

    2016-09-01

    The correlated biased random walk with latency in one and two dimensions is discussed with regard to the portion of irreducible random movement and structured movement. It is shown how a quantitative analysis can be carried out by using computational mechanics. The stochastic matrix for both dynamics are reported. Latency introduces new states in the finite state machine description of the system in both dimensions, allowing for a full nearest neighbor coordination in the two dimensional case. Complexity analysis is used to characterize the movement, independently of the set of control parameters, making it suitable for the discussion of other random walk models. The complexity map of the system dynamics is reported for the two dimensional case.

  17. Saltatory conduction revealed by unidimensional latency-topography of peripheral nerve impulse.

    PubMed

    Homma, S; Mizote, M; Nakajima, Y

    1983-09-01

    The ventral or dorsal root of the rat was placed on 12 electrodes arranged side by side at 0.4 mm intervals. Impulse conduction along the fiber was displayed using unidimensional latency-topography, which corresponds to the relation between latency and electrode distance. The relation revealed step-like displacement, which implies saltatory conduction of the impulse. Since the distance between the plateaux correspond to internodal length, the conduction velocity could be calculated from the length and the time differences between plateaux. It was found from 36 observations that : (i) mean internodal length was 0.92 +/- 0.13 mm (range 0.70--1.25 mm); (ii) mean conduction velocity was 76.1 +/- 20.7 m/s; and (iii) the correlation coefficient of conduction velocity and internodal length was statistically significant at r = 0.38 (P less than 0.025), so the longer the internodal length, the higher the conduction velocity. PMID:6633955

  18. Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

    PubMed Central

    Coppola, Mariateresa; van den Eeden, Susan J. F.; Wilson, Louis; Franken, Kees L. M. C.; Ottenhoff, Tom H. M.

    2015-01-01

    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. PMID:26202436

  19. Short latency vestibular evoked potentials in the Japanese quail (Coturnix coturnix japonica)

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

    Short-latency vestibular-evoked potentials to pulsed linear acceleration were characterized in the quail. Responses occurred within 8 ms following the onset of stimuli and were composed of a series of positive and negative peaks. The latencies and amplitudes of the first four peaks were quantitatively characterized. Mean latencies at 1.0 g ms-1 ranged from 1265 +/- 208 microseconds (P1, N = 18) to 4802 +/- 441 microseconds (N4, N = 13). Amplitudes ranged from 3.72 +/- 1.51 microV (P1/N1, N = 18) to 1.49 +/- 0.77 microV (P3/N3, N = 16). Latency-intensity (LI) slopes ranged from -38.7 +/- 7.3 microseconds dB-1 (P1, N = 18) to -71.6 +/- 21.9 microseconds dB-1 (N3, N = 15) and amplitude-intensity (AI) slopes ranged from 0.20 +/- 0.08 microV dB-1 (P1/N1, N = 18) to 0.07 +/- 0.04 microV dB-1 (P3/N3, N = 11). The mean response threshold across all animals was -21.83 +/- 3.34 dB re: 1.0 g ms-1 (N = 18). Responses remained after cochlear extirpation showing that they could not depend critically on cochlear activity. Responses were eliminated by destruction of the vestibular end organs, thus showing that responses depended critically and specifically on the vestibular system. The results demonstrate that the responses are vestibular and the findings provide a scientific basis for using vestibular responses to evaluate vestibular function through ontogeny and senescence in the quail.

  20. Is Latency to Test Deadline a Predictor of Student Test Performance?

    ERIC Educational Resources Information Center

    Landrum, R. Eric; Gurung, Regan A. R.

    2013-01-01

    When students are given a period or window of time to take an exam, is taking an exam earlier in the window (high latency to deadline) related to test scores? In Study 1, students (n = 236) were given windows of time to take online each of 13 quizzes and 4 exams. In Study 2, students (n = 251) similarly took 4 exams online within a test window. In…

  1. Statistical analysis of censored motion sickness latency data using the two-parameter Weibull distribution

    NASA Technical Reports Server (NTRS)

    Park, Won J.; Crampton, George H.

    1988-01-01

    The suitability of the two-parameter Weibull distribution for describing highly censored cat motion sickness latency data was evaluated by estimating the parameters with the maximum likelihood method and testing for goodness of fit with the Kolmogorov-Smirnov statistic. A procedure for determining confidence levels and testing for significance of the difference between Weibull parameters is described. Computer programs for these procedures may be obtained from an archival source.

  2. Short-latency crossed responses in the human biceps femoris muscle

    PubMed Central

    Stevenson, Andrew J T; Kamavuako, Ernest N; Geertsen, Svend S; Farina, Dario; Mrachacz-Kersting, Natalie

    2015-01-01

    Interlimb reflexes contribute to the central neural co-ordination between different limbs in both humans and animals. Although commissural interneurons have only been directly identified in animals, spinally-mediated interlimb reflexes have been discovered in a number of human lower limb muscles, indicating their existence in humans. The present study aimed 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-contraction in the cBF. Following iKnee extension joint rotations, an inhibitory reflex was observed in the surface electromyographic (EMG) activity of the cBF, whereas a facilitatory reflex was observed in the cBF following iKnee flexion joint rotations. The onset latency of both cBF reflexes was 44 ms, which is too fast for a transcortical pathway to contribute. The cBF inhibitory and facilitatory reflexes followed the automatic gain control principle, with the size of the response increasing as the level of background pre-contraction in the cBF muscle increased. In addition to the surface EMG, both short-latency inhibitory and facilitatory cBF reflexes were recorded directly at the motor unit level by i.m. EMG, and the same population of cBF motor units that were inhibited following iKnee extension joint rotations were facilitated following iKnee flexion joint rotations. Therefore, parallel interneuronal pathways (probably involving commissural interneurons) from ipsilateral afferents to common motoneurons in the contralateral leg can probably explain the perturbation direction-dependent reversal in the sign of the short-latency cBF reflex. PMID:25970767

  3. Emotion moderates the association between HTR2A (rs6313) genotype and antisaccade latency.

    PubMed

    Mills, Mark; Wieda, Olivia; Stoltenberg, Scott F; Dodd, Michael D

    2016-09-01

    The serotonin system is heavily involved in cognitive and emotional control processes. Previous work has typically investigated this system's role in control processes separately for cognitive and emotional domains, yet it has become clear the two are linked. The present study, therefore, examined whether variation in a serotonin receptor gene (HTR2A, rs6313) moderated effects of emotion on inhibitory control. An emotional antisaccade task was used in which participants looked toward (prosaccade) or away (antisaccade) from a target presented to the left or right of a happy, angry, or neutral face. Overall, antisaccade latencies were slower for rs6313 C allele homozygotes than T allele carriers, with no effect of genotype on prosaccade latencies. Thus, C allele homozygotes showed relatively weak inhibitory control but intact reflexive control. Importantly, the emotional stimulus was either present during target presentation (overlap trials) or absent (gap trials). The gap effect (slowed latency in overlap versus gap trials) in antisaccade trials was larger with angry versus neutral faces in C allele homozygotes. This impairing effect of negative valence on inhibitory control was larger in C allele homozygotes than T allele carriers, suggesting that angry faces disrupted/competed with the control processes needed to generate an antisaccade to a greater degree in these individuals. The genotype difference in the negative valence effect on antisaccade latency was attenuated when trial N-1 was an antisaccade, indicating top-down regulation of emotional influence. This effect was reduced in C/C versus T/_ individuals, suggesting a weaker capacity to downregulate emotional processing of task-irrelevant stimuli. PMID:27161551

  4. Low-latency digital frequency synthesizer using the residue number system

    NASA Technical Reports Server (NTRS)

    Chren, William A., Jr.

    1993-01-01

    A low-latency frequency synthesizer using the Direct Digital Synthesis (DDS) technique has been designed. Called the Residue Assisted Frequency Synthesizer (RAFS), it exhibits frequency switching times which are reduced by more than 50 percent below previously published designs. The switching speed advantage is made possible by the use of the Residue Number System, which allows the pipeline lengths in the Phase Accumulator and other circuitry to be reduced significantly.

  5. Complex Interplay of the UL136 Isoforms Balances Cytomegalovirus Replication and Latency

    PubMed Central

    Caviness, Katie; Bughio, Farah; Crawford, Lindsey B.; Streblow, Daniel N.; Nelson, Jay A.; Caposio, Patrizia

    2016-01-01

    ABSTRACT Human cytomegalovirus (HCMV), a betaherpesvirus, persists indefinitely in the human host through poorly understood mechanisms. The UL136 gene is carried within a genetic locus important to HCMV latency termed the UL133/8 locus, which also carries UL133, UL135, and UL138. Previously, we demonstrated that UL136 is expressed as five protein isoforms ranging from 33-kDa to 19-kDa, arising from alternative transcription and, likely, translation initiation mechanisms. We previously showed that the UL136 isoforms are largely dispensable for virus infection in fibroblasts, a model for productive virus replication. In our current work, UL136 has emerged as a complex regulator of HCMV infection in multiple contexts of infection relevant to HCMV persistence: in an endothelial cell (EC) model of chronic infection, in a CD34+ hematopoietic progenitor cell (HPC) model of latency, and in an in vivo NOD-scid IL2Rγcnull humanized (huNSG) mouse model for latency. The 33- and 26-kDa isoforms promote replication, while the 23- and 19-kDa isoforms suppress replication in ECs, in CD34+ HPCs, and in huNSG mice. The role of the 25-kDa isoform is context dependent and influences the activity of the other isoforms. These isoforms localize throughout the secretory pathway, and loss of the 33- and 26-kDa UL136 isoforms results in virus maturation defects in ECs. This work reveals an intriguing functional interplay between protein isoforms that impacts virus replication, latency, and dissemination, contributing to the overall role of the UL133/8 locus in HCMV infection. PMID:26933055

  6. High-frame-rate low-latency hardware-in-the-loop image generation: an illustration of the particle method and DIME

    NASA Astrophysics Data System (ADS)

    Cantle, Allan J.; Devlin, Malachy; Lord, Eric; Chamberlain, Richard

    2000-07-01

    New computing architectures based on the DIME standard have been previously introduced which allow for processing of high frame rate imaging systems which may also need low latency capability, a common requirement for HWIL systems. This paper is presented in two sections: To achieve future realism in image generation systems for hardware-in-the-loop (HWIL) testing a significant increase in processing power is required, but additionally a suitable architecture is essential to provide low latency response on the data flow. Nallatech previously introduced DIME as a novel platform for HWIL systems which is capable of handling sub-frame latencies and greater than 100 Hz frame rates. We will demonstrate the system operating on traditional complex imaging problems, such as large convolution masks of 13 X 13 and also on new image generation techniques such as the particle method which is being developed by Matra British Aerospace Dynamics UK (MBDUK). MBDUK are proceeding on upgrading existing HWIL image generation systems for real-time particle models, to higher frame rates and increased complexity. Using Nallatech's latest DIME based architectures, models containing thousands of individual particles can be created at frame rates over 100 Hz and a resolution of 1024 X 1024 oversampled 4 times. This is possible because particle models exhibit high levels of parallelism ideal for exploiting the architecture of an FPGA. This paper will demonstrate the versatility of these particle models to create highly realistic signatures in terms of spatial dynamics and IR signature. Particle models are ideal for simulating dynamic objects such as flares, exhaust plumes, fires and explosions.

  7. Autophagy Genes Enhance Murine Gammaherpesvirus 68 Reactivation from Latency by Preventing Virus-Induced Systemic Inflammation.

    PubMed

    Park, Sunmin; Buck, Michael D; Desai, Chandni; Zhang, Xin; Loginicheva, Ekaterina; Martinez, Jennifer; Freeman, Michael L; Saitoh, Tatsuya; Akira, Shizuo; Guan, Jun-Lin; He, You-Wen; Blackman, Marcia A; Handley, Scott A; Levine, Beth; Green, Douglas R; Reese, Tiffany A; Artyomov, Maxim N; Virgin, Herbert W

    2016-01-13

    Host genes that regulate systemic inflammation upon chronic viral infection are incompletely understood. Murine gammaherpesvirus 68 (MHV68) infection is characterized by latency in macrophages, and reactivation is inhibited by interferon-γ (IFN-γ). Using a lysozyme-M-cre (LysMcre) expression system, we show that deletion of autophagy-related (Atg) genes Fip200, beclin 1, Atg14, Atg16l1, Atg7, Atg3, and Atg5, in the myeloid compartment, inhibited MHV68 reactivation in macrophages. Atg5 deficiency did not alter reactivation from B cells, and effects on reactivation from macrophages were not explained by alterations in productive viral replication or the establishment of latency. Rather, chronic MHV68 infection triggered increased systemic inflammation, increased T cell production of IFN-γ, and an IFN-γ-induced transcriptional signature in macrophages from Atg gene-deficient mice. The Atg5-related reactivation defect was partially reversed by neutralization of IFN-γ. Thus Atg genes in myeloid cells dampen virus-induced systemic inflammation, creating an environment that fosters efficient MHV68 reactivation from latency. PMID:26764599

  8. Restructuring a software based MPEG-4 video decoder for short latency hardware acceleration

    NASA Astrophysics Data System (ADS)

    Boutellier, Jani; Silvén, Olli; Erdelyi, Tamas

    2007-02-01

    The multimedia capabilities of emerging high-end battery powered mobile devices rely on monolithic hardware accelerators with long latencies to minimize interrupt and software overheads. When compared to pure software implementations, monolithic hardware accelerator solutions need an order of magnitude less power. However, they are rather inflexible and difficult to modify to provide support for multiple coding standards. A more flexible alternative is to employ finer grained short latency accelerators that implement the individual coding functions. Unfortunately, with this approach the software overheads can become very high, if interrupts are used for synchronizing the software and hardware. Preferably, the cost of hardware accelerator interfacing should be at the same level with software functions. In this paper we study the benefits attainable from such an approach. As a case study we restructure a MPEG-4 video decoder in a manner that enables the simultaneous decoding of multiple bit streams using short latency hardware accelerators. The approach takes multiple video bit streams as input and produces a multiplexed stream that is used to control the hardware accelerators without interrupts. The decoding processes of each stream can be considered as threads that share the same hardware resources. Software simulations predict that the energy efficiency of the approach would be significantly better than for a pure software implementation.

  9. Shift of the Muscular Inhibition Latency during On-Line Acquisition of Anticipatory Postural Adjustments

    PubMed Central

    Barlaam, Fanny; Vaugoyeau, Marianne; Fortin, Carole; Assaiante, Christine; Schmitz, Christina

    2016-01-01

    During action, Anticipatory Postural Adjustments (APAs) cancel the consequences of a movement on postural stabilization. Their muscular expression is characterized by early changes in the activity of the postural muscles, before the movement begins. To explore the mechanisms enabling the acquisition of APAs, a learning paradigm was designed in which the voluntary lifting of a load with one hand triggered the unloading of another load suspended below the contralateral forearm. The aim of this study was to investigate changes in the muscular expression that uncovers the progressive learning of new APAs. A trial-by-trial analysis of kinematic and electromyographic signals recorded on the right arm was conducted in twelve adults through six sessions of learning. Kinematic results reported an enhancement of the postural stabilization across learning. The main EMG pattern found during learning consisted of a flexor inhibition, where latency was shifted towards an earlier occurrence in parallel with the improvement of the postural performance. A linear regression analysis conducted between the inhibition latency and the maximal amplitude of elbow rotation showed that the earlier the inhibition onset, the better the postural stabilization. This study revealed that the progressive shift of the postural flexor inhibition latency could be considered as a reliable neurophysiological marker of the progressive learning of new APAs. Importantly, this marker could be used to track motor learning abnormalities in pathology. We relate our findings to the update of a forward predictive model of action, defined as a system that predicts beforehand the consequences of the action on posture. PMID:27192604

  10. From Motion to Photons in 80 Microseconds: Towards Minimal Latency for Virtual and Augmented Reality.

    PubMed

    Lincoln, Peter; Blate, Alex; Singh, Montek; Whitted, Turner; State, Andrei; Lastra, Anselmo; Fuchs, Henry

    2016-04-01

    We describe an augmented reality, optical see-through display based on a DMD chip with an extremely fast (16 kHz) binary update rate. We combine the techniques of post-rendering 2-D offsets and just-in-time tracking updates with a novel modulation technique for turning binary pixels into perceived gray scale. These processing elements, implemented in an FPGA, are physically mounted along with the optical display elements in a head tracked rig through which users view synthetic imagery superimposed on their real environment. The combination of mechanical tracking at near-zero latency with reconfigurable display processing has given us a measured average of 80 µs of end-to-end latency (from head motion to change in photons from the display) and also a versatile test platform for extremely-low-latency display systems. We have used it to examine the trade-offs between image quality and cost (i.e. power and logical complexity) and have found that quality can be maintained with a fairly simple display modulation scheme. PMID:26780797

  11. Low-Latency Teleoperations for Human Exploration and Evolvable Mars Campaign

    NASA Technical Reports Server (NTRS)

    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.

  12. PEALL4: a 4-channel, 12-bit, 40-MSPS, Power Efficient and Low Latency SAR ADC

    NASA Astrophysics Data System (ADS)

    Rarbi, F.; Dzahini, D.; Gallin-Martel, L.; Bouvier, J.; Zeloufi, M.; Trocme, B.; Gabaldon Ruiz, C.

    2015-01-01

    The PEALL4 chip is a Power Efficient And Low Latency 4-channels, 12-bit and 40-MSPS successive approximation register (SAR) ADC. It was designed featuring a very short latency time in the context of ATLAS Liquid Argon Calorimeter phase I upgrade. Moreover this design could be a good option for ATLAS phase II and other High Energy Physics (HEP) projects. The full functionality of the converter is achieved by an embedded high-speed clock frequency conversion generated by the ADC itself. The design and testing results of the PEALL4 chip implemented in a commercial 130nm CMOS process are presented. The size of this 4-channel ADC with embedded voltage references and sLVS output serializer is 2.8x3.4 mm2. The chip presents a short latency time less than 25 ns defined from the very beginning of the sampling to the last conversion bit made available. A total power consumption below 27mW per channel is measured including the reference buffer and the sLVS serializer.

  13. Measurement-based analysis of error latency. [in computer operating system

    NASA Technical Reports Server (NTRS)

    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.

  14. Human Space Exploration and Human Space Flight: Latency and the Cognitive Scale of the Universe

    NASA Technical Reports Server (NTRS)

    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.

  15. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems

    PubMed Central

    Bialek, Julia K.; Dunay, Gábor A.; Voges, Maike; Schäfer, Carola; Spohn, Michael; Stucka, Rolf; Hauber, Joachim; Lange, Ulrike C.

    2016-01-01

    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. PMID:27341108

  16. Functional and physical interaction between p53 and BZLF1: implications for Epstein-Barr virus latency.

    PubMed Central

    Zhang, Q; Gutsch, D; Kenney, S

    1994-01-01

    The p53 tumor suppressor protein, which is commonly mutated in human cancers, has been shown to interact directly with virally encoded from papillomavirus, adenovirus, and simian virus 40. The disruption of p53 function may be required for efficient replication of certain viruses and may also play a role in the development of virally induced malignancies. Infection with Epstein-Barr virus (EBV) has been associated with the development of B-cell lymphomas and nasopharyngeal carcinoma. Here we show that the EBV immediate-early protein, BZLF1 (Z), which is responsible for initiating the switch from latent to lytic infection, can interact directly in vitro and in vivo with the tumor suppressor protein, p53. This interaction requires the coiled-coil dimerization domain of the Z protein and the carboxy-terminal portion of p53. Overexpression of wild-type p53 inhibits the ability of Z to disrupt viral latency. Likewise, Z inhibits p53-dependent transactivation in lymphoid cells. The direct interaction between Z and p53 may play a role in regulating the switch from latent to lytic viral infection. Images PMID:8114724

  17. A hundred years of latency: from Freudian psychosexual theory to dynamic systems nonlinear development in middle childhood.

    PubMed

    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. PMID:24737202

  18. Quantifying risk over the life course - latency, age-related susceptibility, and other time-varying exposure metrics.

    PubMed

    Wang, Molin; Liao, Xiaomei; Laden, Francine; Spiegelman, Donna

    2016-06-15

    Identification of the latency period and age-related susceptibility, if any, is an important aspect of assessing risks of environmental, nutritional, and occupational exposures. We consider estimation and inference for latency and age-related susceptibility in relative risk and excess risk models. We focus on likelihood-based methods for point and interval estimation of the latency period and age-related windows of susceptibility coupled with several commonly considered exposure metrics. The method is illustrated in a study of the timing of the effects of constituents of air pollution on mortality in the Nurses' Health Study. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26750582

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

    NASA Technical Reports Server (NTRS)

    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

  20. A Gammaherpesvirus Noncoding RNA Is Essential for Hematogenous Dissemination and Establishment of Peripheral Latency

    PubMed Central

    Feldman, Emily R.; Kara, Mehmet; Oko, Lauren M.; Grau, Katrina R.; Krueger, Brian J.; Zhang, Junjie; Feng, Pinghui; van Dyk, Linda F.; Renne, Rolf

    2016-01-01

    ABSTRACT Recent intense investigations have uncovered important functions for a diverse array of novel noncoding RNA (ncRNA) species, including microRNAs (miRNAs) and long noncoding RNAs. Not surprisingly, viruses from multiple families have evolved to encode their own regulatory RNAs; however, the specific in vivo functions of these ncRNAs are largely unknown. The human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) are highly ubiquitous pathogens that are associated with the development of a wide range of malignancies, including Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, and Kaposi’s sarcoma. Like EBV and KSHV, murine gammaherpesvirus 68 (MHV68) establishes lifelong latency in B cells and is associated with lymphoproliferative disease and lymphoma. Similar to the EBV-encoded small RNA (EBER)-1 and -2, MHV68 encodes eight 200- to 250-nucleotide polymerase III-transcribed ncRNAs called TMERs (tRNA-miRNA-encoded RNAs), which are highly expressed in latently infected cells and lymphoproliferative disease. To define the in vivo contribution of TMERs to MHV68 biology, we generated a panel of individual TMER mutant viruses. Through comprehensive in vivo analyses, we identified TMER4 as a key mediator of virus dissemination. The TMER4 mutant virus replicated normally in lungs and spread with normal kinetics and distribution to lung-draining lymph nodes, but it was significantly attenuated for infection of circulating blood cells and for latency establishment at peripheral sites. Notably, TMER4 stem-loops but not miRNAs were essential for wild-type TMER4 activity. Thus, these findings revealed a crucial miRNA-independent function of the TMER4 ncRNA in MHV68 hematogenous dissemination and latency establishment. IMPORTANCE Noncoding RNAs (ncRNAs) represent an intriguing and diverse class of molecules that are now recognized for their participation in a wide array of cellular processes. Viruses

  1. Modulation of amplitude and latency of motor evoked potential by direction of transcranial magnetic stimulation

    NASA Astrophysics Data System (ADS)

    Sato, Aya; Torii, Tetsuya; Iwahashi, Masakuni; Itoh, Yuji; Iramina, Keiji

    2014-05-01

    The present study analyzed the effects of monophasic magnetic stimulation to the motor cortex. The effects of magnetic stimulation were evaluated by analyzing the motor evoked potentials (MEPs). The amplitude and latency of MEPs on the abductor pollicis brevis muscle were used to evaluate the effects of repetitive magnetic stimulation. A figure eight-shaped flat coil was used to stimulate the region over the primary motor cortex. The intensity of magnetic stimulation was 120% of the resting motor threshold, and the frequency of magnetic stimulation was 0.1 Hz. In addition, the direction of the current in the brain was posterior-anterior (PA) or anterior-posterior (AP). The latency of MEP was compared with PA and AP on initial magnetic stimulation. The results demonstrated that a stimulus in the AP direction increased the latency of the MEP by approximately 2.5 ms. MEP amplitude was also compared with PA and AP during 60 magnetic stimulations. The results showed that a stimulus in the PA direction gradually increased the amplitude of the MEP. However, a stimulus in the AP direction did not modulate the MEP amplitude. The average MEP amplitude induced from every 10 magnetic pulses was normalized by the average amplitude of the first 10 stimuli. These results demonstrated that the normalized MEP amplitude increased up to approximately 150%. In terms of pyramidal neuron indirect waves (I waves), magnetic stimulation inducing current flowing backward to the anterior preferentially elicited an I1 wave, and current flowing forward to the posterior elicited an I3 wave. It has been reported that the latency of the I3 wave is approximately 2.5 ms longer than the I1 wave elicitation, so the resulting difference in latency may be caused by this phenomenon. It has also been reported that there is no alteration of MEP amplitude at a frequency of 0.1 Hz. However, this study suggested that the modulation of MEP amplitude depends on stimulation strength and stimulation direction.

  2. Advances in high-throughput speed, low-latency communication for embedded instrumentation ( 7th Annual SFAF Meeting, 2012)

    ScienceCinema

    Jordan, Scott [Physik Instrumente

    2013-02-11

    Scott Jordan on "Advances in high-throughput speed, low-latency communication for embedded instrumentation" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

  3. A Paradox of Syntactic Priming: Why Response Tendencies Show Priming for Passives, and Response Latencies Show Priming for Actives

    PubMed Central

    Segaert, Katrien; Menenti, Laura; Weber, Kirsten; Hagoort, Peter

    2011-01-01

    Speakers tend to repeat syntactic structures across sentences, a phenomenon called syntactic priming. Although it has been suggested that repeating syntactic structures should result in speeded responses, previous research has focused on effects in response tendencies. We investigated syntactic priming effects simultaneously in response tendencies and response latencies for active and passive transitive sentences in a picture description task. In Experiment 1, there were priming effects in response tendencies for passives and in response latencies for actives. However, when participants' pre-existing preference for actives was altered in Experiment 2, syntactic priming occurred for both actives and passives in response tendencies as well as in response latencies. This is the first investigation of the effects of structure frequency on both response tendencies and latencies in syntactic priming. We discuss the implications of these data for current theories of syntactic processing. PMID:22022352

  4. Advances in high-throughput speed, low-latency communication for embedded instrumentation ( 7th Annual SFAF Meeting, 2012)

    SciTech Connect

    Jordan, Scott

    2012-06-01

    Scott Jordan on "Advances in high-throughput speed, low-latency communication for embedded instrumentation" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

  5. Toxoplasma gondii exposure affects neural processing speed as measured by acoustic startle latency in schizophrenia and controls

    PubMed Central

    Pearce, Bradley D.; Hubbard, Sydney; Rivera, Hilda N.; Wilkins, Patricia P.; Fisch, Marylynn C.; Hopkins, Myfanwy H.; Hasenkamp, Wendy; Gross, Robin; Bliwise, Nancy; Jones, Jeffrey L.; Duncan, Erica

    2013-01-01

    The prevalence of Toxoplasma gondii (TOXO) infection in schizophrenia (SCZ) is elevated compared to controls (odds ratio=2.73). TOXO infection is associated with psychomotor slowing in rodents and non-psychiatric humans. Latency of the acoustic startle response, an index of neural processing speed, is the time it takes for a startling stimulus to elicit the reflexive response through a three-synapse subcortical circuit. We report a significant slowing of latency in TOXO seropositive SCZ vs. seronegative SCZ, and in TOXO seropositive controls vs. seronegative controls. Latency was likewise slower in SCZ subjects than in controls. These findings indicate a slowing of neural processing speed with chronic TOXO infection; the slowest startle latency was seen in the TOXO seropositive SCZ group. PMID:23953218

  6. Mid-latency auditory evoked potential response revealed as an evidence of neural plasticity in blinnd individuals.

    PubMed

    Muthusamy, Anbarasi; Gajendran, Rajkumar; Rao B, Vishwanatha

    2014-01-01

    There is a general impression that visually blind individuals show an exceptionally better perception of other sensory modalities such as hearing, touch and smell sensations. In this study, we intended to compare the mid-latency auditory evoked potential response (MLAEP) or Middle latency Response (MLR) to get an idea of the activity pattern of auditory thalamus and cortex between 30 visually handicapped subjects and 30 normal sighted subjects. The results showed a decrease in many of the MLR wave latencies, but highly significant for the wave Pa (P value <0.002). This fact can be reflected as an evidence of existence of cross-modal neuroplasticity. We also inferred that there are significant gender differences with latencies shorter in males than females (P value <0.02) in the blind subjects group which could be attributed to their rehabilitation training. PMID:25509959

  7. A Network of Hydrophobic Residues Impeding Helix αC Rotation Maintains Latency of Kinase Gcn2, Which Phosphorylates the α Subunit of Translation Initiation Factor 2▿

    PubMed Central

    Gárriz, Andrés; Qiu, Hongfang; Dey, Madhusudan; Seo, Eun-Joo; Dever, Thomas E.; Hinnebusch, Alan G.

    2009-01-01

    Kinase Gcn2 is activated by amino acid starvation and downregulates translation initiation by phosphorylating the α subunit of translation initiation factor 2 (eIF2α). The Gcn2 kinase domain (KD) is inert and must be activated by tRNA binding to the adjacent regulatory domain. Previous work indicated that Saccharomyces cerevisiae Gcn2 latency results from inflexibility of the hinge connecting the N and C lobes and a partially obstructed ATP-binding site in the KD. Here, we provide strong evidence that a network of hydrophobic interactions centered on Leu-856 also promotes latency by constraining helix αC rotation in the KD in a manner relieved during amino acid starvation by tRNA binding and autophosphorylation of Thr-882 in the activation loop. Thus, we show that mutationally disrupting the hydrophobic network in various ways constitutively activates eIF2α phosphorylation in vivo and bypasses the requirement for a key tRNA binding motif (m2) and Thr-882 in Gcn2. In particular, replacing Leu-856 with any nonhydrophobic residue activates Gcn2, while substitutions with various hydrophobic residues maintain kinase latency. We further provide strong evidence that parallel, back-to-back dimerization of the KD is a step on the Gcn2 activation pathway promoted by tRNA binding and autophosphorylation. Remarkably, mutations that disrupt the L856 hydrophobic network or enhance hinge flexibility eliminate the need for the conserved salt bridge at the parallel dimer interface, implying that KD dimerization facilitates the reorientation of αC and remodeling of the active site for enhanced ATP binding and catalysis. We propose that hinge remodeling, parallel dimerization, and reorientation of αC are mutually reinforcing conformational transitions stimulated by tRNA binding and secured by the ensuing autophosphorylation of T882 for stable kinase activation. PMID:19114556

  8. Middle Latency Auditory Evoked Potential (MLAEP) in Workers with and without Tinnitus who are Exposed to Occupational Noise

    PubMed Central

    dos Santos Filha, Valdete Alves Valentins; Samelli, Alessandra Giannella; Matas, Carla Gentile

    2015-01-01

    Background Tinnitus is an important occupational health concern, but few studies have focused on the central auditory pathways of workers with a history of occupational noise exposure. Thus, we analyzed the central auditory pathways of workers with a history of occupational noise exposure who had normal hearing threshold, and compared middle latency auditory evoked potential in those with and without noise-induced tinnitus. Material/Methods Sixty individuals (30 with and 30 without tinnitus) underwent the following procedures: anamnesis, immittance measures, pure-tone air conduction thresholds at all frequencies between 0.25–8 kHz, and middle latency auditory evoked potentials. Results Quantitative analysis of latencies and amplitudes of middle latency auditory evoked potential showed no significant differences between the groups with and without tinnitus. In the qualitative analysis, we found that both groups showed increased middle latency auditory evoked potential latencies. The study group had more alterations of the “both” type regarding the Na-Pa amplitude, while the control group had more “electrode effect” alterations, but these alterations were not significantly different when compared to controls. Conclusions Individuals with normal hearing with or without tinnitus who are exposed to occupational noise have altered middle latency auditory evoked potential, suggesting impairment of the auditory pathways in cortical and subcortical regions. Although differences did not reach significance, individuals with tinnitus seemed to have more abnormalities in components of the middle latency auditory evoked potential when compared to individuals without tinnitus, suggesting alterations in the generation and transmission of neuroelectrical impulses along the auditory pathway. PMID:26358094

  9. Temporal, but not Directional, Prior Knowledge Shortens Muscle Reflex Latency in Response to Sudden Transition of Support Surface During Walking.

    PubMed

    Shinya, Masahiro; Kawashima, Noritaka; Nakazawa, Kimitaka

    2016-01-01

    The central nervous system takes advantage of prior knowledge about potential upcoming perturbations for modulating postural reflexes. There are two distinct aspects of prior knowledge: spatial and temporal. This study investigated how each of spatial and temporal prior knowledge contributes to the shortening of muscle response latency. Eleven participants walked on a split-belt treadmill and perturbed by sudden acceleration or deceleration of the right belt at right foot contact. Spatial prior knowledge was given by instruction of possible direction (e.g., only acceleration) of upcoming perturbation at the beginning of an experimental session. Temporal prior knowledge was given to subjects by warning tones at foot contact during three consecutive strides before the perturbation. In response to acceleration perturbation, reflexive muscle activity was observed in soleus (SOL) and gastrocnemius (GAS) muscles. Onset latency of the GAS response was shorter (72 ms vs. 58 ms) when subjects knew the timing of the upcoming perturbation, whereas the latency was independent of directional prior knowledge. SOL onset latency (44 ms) was not influenced by directional nor temporal prior knowledge. Although spinal neural circuit that mediates short-latency reflex was not influenced by the prior knowledge, excitability in supra-spinal neural circuit that mediates medium- and long-latency reflex might be enhanced by knowing the timing of the upcoming perturbation. PMID:26903838

  10. Analysis of latency time and its determinants in asbestos related malignant mesothelioma cases of the Italian register.

    PubMed

    Marinaccio, Alessandro; Binazzi, Alessandra; Cauzillo, Gabriella; Cavone, Domenica; Zotti, Renata De; Ferrante, Pierpaolo; Gennaro, Valerio; Gorini, Giuseppe; Menegozzo, Massimo; Mensi, Carolina; Merler, Enzo; Mirabelli, Dario; Montanaro, Fabio; Musti, Marina; Pannelli, Franco; Romanelli, Antonio; Scarselli, Alberto; Tumino, Rosario

    2007-12-01

    Italy was an important producer of raw asbestos until 1992 (when it was banned) and it is now experiencing severe public health consequences due to large-scale industrial use of asbestos in shipbuilding and repair, asbestos-cement production, railways, buildings, chemicals and many other industrial sectors. Latency of malignant mesothelioma generally shows a large variability and the relationship with the modality of asbestos exposure is still not fully clarified. We present an analysis of latency period among the case list collected by the Italian mesothelioma register (ReNaM) in the period of diagnosis 1993-2001 (2544 malignant mesothelioma (MM) cases with asbestos exposure history). Exposure is assessed retrospectively by interview. Statistical univariate analyses were performed to estimate median and variability measures of latency time by anatomical site, gender and diagnosis period. The role of diagnostic confidence level, the morphology of the tumour and the modalities of asbestos exposure were verified in a regression multivariate model. We found a median latency period of 44.6 years increasing in recent years with a linear trend. Anatomical site, gender and morphology were not relevant for MM latency time whereas a shorter latency period was documented among occupationally exposed subjects (43 years) with respect to environmentally and household exposed ones (48 years). PMID:17980576

  11. Temporal, but not Directional, Prior Knowledge Shortens Muscle Reflex Latency in Response to Sudden Transition of Support Surface During Walking

    PubMed Central

    Shinya, Masahiro; Kawashima, Noritaka; Nakazawa, Kimitaka

    2016-01-01

    The central nervous system takes advantage of prior knowledge about potential upcoming perturbations for modulating postural reflexes. There are two distinct aspects of prior knowledge: spatial and temporal. This study investigated how each of spatial and temporal prior knowledge contributes to the shortening of muscle response latency. Eleven participants walked on a split-belt treadmill and perturbed by sudden acceleration or deceleration of the right belt at right foot contact. Spatial prior knowledge was given by instruction of possible direction (e.g., only acceleration) of upcoming perturbation at the beginning of an experimental session. Temporal prior knowledge was given to subjects by warning tones at foot contact during three consecutive strides before the perturbation. In response to acceleration perturbation, reflexive muscle activity was observed in soleus (SOL) and gastrocnemius (GAS) muscles. Onset latency of the GAS response was shorter (72 ms vs. 58 ms) when subjects knew the timing of the upcoming perturbation, whereas the latency was independent of directional prior knowledge. SOL onset latency (44 ms) was not influenced by directional nor temporal prior knowledge. Although spinal neural circuit that mediates short-latency reflex was not influenced by the prior knowledge, excitability in supra-spinal neural circuit that mediates medium- and long-latency reflex might be enhanced by knowing the timing of the upcoming perturbation. PMID:26903838

  12. Effect of MLC tracking latency on conformal volumetric modulated arc therapy (VMAT) plans in 4D stereotactic lung treatment

    PubMed Central

    Bedford, James L.; Fast, Martin F.; Nill, Simeon; McDonald, Fiona M.A.; Ahmed, Merina; Hansen, Vibeke N.; Oelfke, Uwe

    2015-01-01

    Background and purpose The latency of a multileaf collimator (MLC) tracking system used to overcome respiratory motion causes misalignment of the treatment beam with respect to the gross tumour volume, which may result in reduced target coverage. This study investigates the magnitude of this effect. Material and methods Simulated superior–inferior breathing motion was used to construct histograms of isocentre offset with respect to the gross tumour volume (GTV) for a variety of tracking latencies. Dose distributions for conformal volumetric modulated arc therapy (VMAT) arcs were then calculated at a range of offsets and summed according to these displacement histograms. The results were verified by delivering the plans to a Delta4 phantom on a motion platform. Results In the absence of an internal target margin, a tracking latency of 150 ms reduces the GTV D95% by approximately 2%. With a margin of 2 mm, the same drop in dose occurs for a tracking latency of 450 ms. Lung V13Gy is unaffected by a range of latencies. These results are supported by the phantom measurements. Conclusions Assuming that internal motion can be modelled by a rigid translation of the patient, MLC tracking of conformal VMAT can be effectively accomplished in the absence of an internal target margin for substantial breathing motion (4 s period and 20 mm peak–peak amplitude) so long as the system latency is less than 150 ms. PMID:26277856

  13. Relating the Variability of Tone-Burst Otoacoustic Emission and Auditory Brainstem Response Latencies to the Underlying Cochlear Mechanics

    PubMed Central

    Verhulst, Sarah; Shera, Christopher A.

    2016-01-01

    Forward and reverse cochlear latency and its relation to the frequency tuning of the auditory filters can be assessed using tone bursts (TBs). Otoacoustic emissions (TBOAEs) estimate the cochlear roundtrip time, while auditory brainstem responses (ABRs) to the same stimuli aim at measuring the auditory filter buildup time. Latency ratios are generally close to two and controversy exists about the relationship of this ratio to cochlear mechanics. We explored why the two methods provide different estimates of filter buildup time, and ratios with large inter-subject variability, using a time-domain model for OAEs and ABRs. We compared latencies for twenty models, in which all parameters but the cochlear irregularities responsible for reflection-source OAEs were identical, and found that TBOAE latencies were much more variable than ABR latencies. Multiple reflection-sources generated within the evoking stimulus bandwidth were found to shape the TBOAE envelope and complicate the interpretation of TBOAE latency and TBOAE/ABR ratios in terms of auditory filter tuning. PMID:27175040

  14. Relating the variability of tone-burst otoacoustic emission and auditory brainstem response latencies to the underlying cochlear mechanics

    NASA Astrophysics Data System (ADS)

    Verhulst, Sarah; Shera, Christopher A.

    2015-12-01

    Forward and reverse cochlear latency and its relation to the frequency tuning of the auditory filters can be assessed using tone bursts (TBs). Otoacoustic emissions (TBOAEs) estimate the cochlear roundtrip time, while auditory brainstem responses (ABRs) to the same stimuli aim at measuring the auditory filter buildup time. Latency ratios are generally close to two and controversy exists about the relationship of this ratio to cochlear mechanics. We explored why the two methods provide different estimates of filter buildup time, and ratios with large inter-subject variability, using a time-domain model for OAEs and ABRs. We compared latencies for twenty models, in which all parameters but the cochlear irregularities responsible for reflection-source OAEs were identical, and found that TBOAE latencies were much more variable than ABR latencies. Multiple reflection-sources generated within the evoking stimulus bandwidth were found to shape the TBOAE envelope and complicate the interpretation of TBOAE latency and TBOAE/ABR ratios in terms of auditory filter tuning.

  15. BASALT 1: Extravehicular Activity Science Operations Concepts under Communication Latency and Bandwidth Constraints at Craters of the Moon, Idaho

    NASA Technical Reports Server (NTRS)

    Chappell, Steven P.; Beaton, Kara; Miller, Matthew J.; Lim, Darlene S. S.; Abercromby, Andrew F. J.

    2017-01-01

    conservative and affordable flight data rate, and a higher bandwidth case (5.0 Mb/s uplink, 10.0 Mb/s downlink), representing an upgraded human mission capability that would require additional infrastructure and technology development. In all conditions, two EVA crewmembers communicated with two intravehicular (IV) crewmembers with high bandwidth and near-zero communication latency, simulating communication among crewmembers on Mars. EVA crewmembers wore simulated EVA informatics backpacks including communication systems, position tracking, hand-held field spectrometers, cameras, and sample collection tools. Bidirectional communication between crewmembers ("Mars") and a Mission Support Center ("Earth"), staffed by a team of science and operations experts, was subject to the aforementioned latency and bandwidth constraints. This paper presents the synthesized results of the BASALT 1 deployment with respect to ConOps and capabilities assessment. Evaluation of the ConOps and capabilities was accomplished through a combination of network analytical data, completion of scientific objectives, ethnographic observations, planned versus actual timeline data, and collection of subjective ratings and comments using the same methodology employed during multiple previous NASA analog tests. In addition to assessing the acceptability of the ConOps and capabilities from scientific and operational perspectives, the extent to which specific capabilities enabled or enhanced the science operations was also evaluated. These data will provide a basis for prioritization of capability development for future BASALT deployments and, ultimately, future human exploration missions.

  16. Structural Basis for Latency and Function of Immune Inhibitor A Metallopeptidase, a Modulator of the Bacillus anthracis Secretome.

    PubMed

    Arolas, Joan L; Goulas, Theodoros; Pomerantsev, Andrei P; Leppla, Stephen H; Gomis-Rüth, F Xavier

    2016-01-01

    Immune inhibitor A(InhA)-type metallopeptidases are potential virulence factors secreted by members of the Bacillus cereus group. Two paralogs from anthrax-causing Bacillus anthracis (BaInhA1 and BaInhA2) were shown to degrade host tissue proteins with broad substrate specificity. Analysis of their activation mechanism and the crystal structure of a zymogenic BaInhA2 variant revealed a ∼750-residue four-domain structure featuring a pro-peptide, a catalytic domain, a domain reminiscent of viral envelope glycoproteins, and a MAM domain grafted into the latter. This domain, previously found only in eukaryotes, is required for proper protein expression in B. anthracis and evinces certain flexibility. Latency is uniquely modulated by the N-terminal segment of the pro-peptide, which binds the catalytic zinc through its α-amino group and occupies the primed side of the active-site cleft. The present results further our understanding of the modus operandi of an anthrax secretome regulator. PMID:26745529

  17. Proteasome inhibitors act as bifunctional antagonists of human immunodeficiency virus type 1 latency and replication

    PubMed Central

    2013-01-01

    Background Existing highly active antiretroviral therapy (HAART) effectively controls viral replication in human immunodeficiency virus type 1 (HIV-1) infected individuals but cannot completely eradicate the infection, at least in part due to the persistence of latently infected cells. One strategy that is being actively pursued to eliminate the latent aspect of HIV-1 infection involves therapies combining latency antagonists with HAART. However, discordant pharmacokinetics between these types of drugs can potentially create sites of active viral replication within certain tissues that might be impervious to HAART. Results A preliminary reverse genetic screen indicated that the proteasome might be involved in the maintenance of the latent state. This prompted testing to determine the effects of proteasome inhibitors (PIs) on latently infected cells. Experiments demonstrated that PIs effectively activated latent HIV-1 in several model systems, including primary T cell models, thereby defining PIs as a new class of HIV-1 latency antagonists. Expanding upon experiments from previous reports, it was also confirmed that PIs inhibit viral replication. Moreover, it was possible to show that PIs act as bifunctional antagonists of HIV-1. The data indicate that PIs activate latent provirus and subsequently decrease viral titers and promote the production of defective virions from activated cells. Conclusions These results represent a proof-of-concept that bifunctional antagonists of HIV-1 can be developed and have the capacity to ensure precise tissue overlap of anti-latency and anti-replication functions, which is of significant importance in the consideration of future drug therapies aimed at viral clearance. PMID:24156270

  18. Opposing Regulation of the EGF Receptor: A Molecular Switch Controlling Cytomegalovirus Latency and Replication

    PubMed Central

    Zeltzer, Sebastian; Reitsma, Justin; Petrucelli, Alex; Umashankar, Mahadevaiah; Rak, Mike; Zagallo, Patricia; Schroeder, Joyce; Terhune, Scott; Goodrum, Felicia

    2016-01-01

    Herpesviruses persist indefinitely in their host through complex and poorly defined interactions that mediate latent, chronic or productive states of infection. Human cytomegalovirus (CMV or HCMV), a ubiquitous β-herpesvirus, coordinates the expression of two viral genes, UL135 and UL138, which have opposing roles in regulating viral replication. UL135 promotes reactivation from latency and virus replication, in part, by overcoming replication-suppressive effects of UL138. The mechanism by which UL135 and UL138 oppose one another is not known. We identified viral and host proteins interacting with UL138 protein (pUL138) to begin to define the mechanisms by which pUL135 and pUL138 function. We show that pUL135 and pUL138 regulate the viral cycle by targeting that same receptor tyrosine kinase (RTK) epidermal growth factor receptor (EGFR). EGFR is a major homeostatic regulator involved in cellular proliferation, differentiation, and survival, making it an ideal target for viral manipulation during infection. pUL135 promotes internalization and turnover of EGFR from the cell surface, whereas pUL138 preserves surface expression and activation of EGFR. We show that activated EGFR is sequestered within the infection-induced, juxtanuclear viral assembly compartment and is unresponsive to stress. Intriguingly, these findings suggest that CMV insulates active EGFR in the cell and that pUL135 and pUL138 function to fine-tune EGFR levels at the cell surface to allow the infected cell to respond to extracellular cues. Consistent with the role of pUL135 in promoting replication, inhibition of EGFR or the downstream phosphoinositide 3-kinase (PI3K) favors reactivation from latency and replication. We propose a model whereby pUL135 and pUL138 together with EGFR comprise a molecular switch that regulates states of latency and replication in HCMV infection by regulating EGFR trafficking to fine tune EGFR signaling. PMID:27218650

  19. Characterising the association of latency with α(1)-antitrypsin polymerisation using a novel monoclonal antibody.

    PubMed

    Tan, Lu; Perez, Juan; Mela, Marianna; Miranda, Elena; Burling, Keith A; Rouhani, Farshid N; DeMeo, Dawn L; Haq, Imran; Irving, James A; Ordóñez, Adriana; Dickens, Jennifer A; Brantly, Mark; Marciniak, Stefan J; Alexander, Graeme J M; Gooptu, Bibek; Lomas, David A

    2015-01-01

    α1-Antitrypsin is primarily synthesised in the liver, circulates to the lung and protects pulmonary tissues from proteolytic damage. The Z mutant (Glu342Lys) undergoes inactivating conformational change and polymerises. Polymers are retained within the hepatocyte endoplasmic reticulum (ER) in homozygous (PiZZ) individuals, predisposing the individuals to hepatic cirrhosis and emphysema. Latency is an analogous process of inactivating, intra-molecular conformational change and may co-occur with polymerisation. However, the relationship between latency and polymerisation remained unexplored in the absence of a suitable probe. We have developed a novel monoclonal antibody specific for latent α1-antitrypsin and used it in combination with a polymer-specific antibody, to assess the association of both conformers in vitro, in disease and during augmentation therapy. In vitro kinetics analysis showed polymerisation dominated the pathway but latency could be promoted by stabilising monomeric α1-antitrypsin. Polymers were extensively produced in hepatocytes and a cell line expressing Z α1-antitrypsin but the latent protein was not detected despite manipulation of the secretory pathway. However, α1-antitrypsin augmentation therapy contains latent α1-antitrypsin, as did the plasma of 63/274 PiZZ individuals treated with augmentation therapy but 0/264 who were not receiving this medication (p<10(-14)). We conclude that latent α1-antitrypsin is a by-product of the polymerisation pathway, that the intracellular folding environment is resistant to formation of the latent conformer but that augmentation therapy introduces latent α1-antitrypsin into the circulation. A suite of monoclonal antibodies and methodologies developed in this study can characterise α1-antitrypsin folding and conformational transitions, and screen methods to improve augmentation therapy. PMID:25462157

  20. Characterising the association of latency with α1-antitrypsin polymerisation using a novel monoclonal antibody

    PubMed Central

    Tan, Lu; Perez, Juan; Mela, Marianna; Miranda, Elena; Burling, Keith A; Rouhani, Farshid N; DeMeo, Dawn L; Haq, Imran; Irving, James A; Ordóñez, Adriana; Dickens, Jennifer A; Brantly, Mark; Marciniak, Stefan J; Alexander, Graeme J M; Gooptu, Bibek; Lomas, David A

    2015-01-01

    α1-Antitrypsin is primarily synthesised in the liver, circulates to the lung and protects pulmonary tissues from proteolytic damage. The Z mutant (Glu342Lys) undergoes inactivating conformational change and polymerises. Polymers are retained within the hepatocyte endoplasmic reticulum (ER) in homozygous (PiZZ) individuals, predisposing the individuals to hepatic cirrhosis and emphysema. Latency is an analogous process of inactivating, intra-molecular conformational change and may co-occur with polymerisation. However, the relationship between latency and polymerisation remained unexplored in the absence of a suitable probe. We have developed a novel monoclonal antibody specific for latent α1-antitrypsin and used it in combination with a polymer-specific antibody, to assess the association of both conformers in vitro, in disease and during augmentation therapy. In vitro kinetics analysis showed polymerisation dominated the pathway but latency could be promoted by stabilising monomeric α1-antitrypsin. Polymers were extensively produced in hepatocytes and a cell line expressing Z α1-antitrypsin but the latent protein was not detected despite manipulation of the secretory pathway. However, α1-antitrypsin augmentation therapy contains latent α1-antitrypsin, as did the plasma of 63/274 PiZZ individuals treated with augmentation therapy but 0/264 who were not receiving this medication (p < 10−14). We conclude that latent α1-antitrypsin is a by-product of the polymerisation pathway, that the intracellular folding environment is resistant to formation of the latent conformer but that augmentation therapy introduces latent α1-antitrypsin into the circulation. A suite of monoclonal antibodies and methodologies developed in this study can characterise α1-antitrypsin folding and conformational transitions, and screen methods to improve augmentation therapy. PMID:25462157

  1. Relationship between latency of brainstem auditory-evoked potentials and head size in dogs.

    PubMed

    Meij, B P; Venker-van Haagen, A J; van den Brom, W E

    1992-12-01

    Cranium and brainstem dimensions were measured in 32 postmortem dog heads. Positive correlations were found between cranium length (CL) and brainstem length (BL) (r = 0.87), between cranium width (CW) and brainstem width (BW) (r = 0.83), and between cranium distance (CD = CL+CW/2) and brainstem distance (BD = BL+BW/2) (r = 0.91). Positive correlation coefficients were also found between CL and CW (r = 0.90), and between BL and BW (r = 0.85). It was concluded that head size accurately reflected brainstem size. A least squares estimation of the brainstem distance (BD) from CL and CW values was BD = 10.9 + 0.16 (CL+CW/2) (BD, CL and CW in mm). Brainstem auditory evoked potentials (BAEPs) and cranium dimensions were measured in 43 dogs (86 ears) with different head size, body size, sex and age. Wave form, absolute and interpeak latencies and correlation coefficients, relating latencies to cranium dimensions and body weight, were analysed. CL, CW, and CD were positively correlated with body weight (r = 0.93, 0.70 and 0.93, respectively), and CL, CW, and CD were correlated with age (r = 0.33, 0.52, and 0.40, respectively). BAEPs consisted of five distinct positive peaks (I to V). Secondary positive peaks following peaks I and II were seen in 60% (I') and 90% (II') of the recordings. Late waves were recorded in 90% (VI), 50% (VII), and 25% (VIII) of the recordings. Latencies increased with decreasing stimulus intensity level (from 90 dB to 10 dB hearing level, HL), especially for peaks I, II, V, and the I-V interpeak interval.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1485399

  2. The temporal resolution of neural codes: does response latency have a unique role?

    PubMed Central

    Oram, M W; Xiao, D; Dritschel, B; Payne, K R

    2002-01-01

    This article reviews the nature of the neural code in non-human primate cortex and assesses the potential for neurons to carry two or more signals simultaneously. Neurophysiological recordings from visual and motor systems indicate that the evidence for a role for precisely timed spikes relative to other spike times (ca. 1-10 ms resolution) is inconclusive. This indicates that the visual system does not carry a signal that identifies whether the responses were elicited when the stimulus was attended or not. Simulations show that the absence of such a signal reduces, but does not eliminate, the increased discrimination between stimuli that are attended compared with when the stimuli are unattended. The increased accuracy asymptotes with increased gain control, indicating limited benefit from increasing attention. The absence of a signal identifying the attentional state under which stimuli were viewed can produce the greatest discrimination between attended and unattended stimuli. Furthermore, the greatest reduction in discrimination errors occurs for a limited range of gain control, again indicating that attention effects are limited. By contrast to precisely timed patterns of spikes where the timing is relative to other spikes, response latency provides a fine temporal resolution signal (ca. 10 ms resolution) that carries information that is unavailable from coarse temporal response measures. Changes in response latency and changes in response magnitude can give rise to different predictions for the patterns of reaction times. The predictions are verified, and it is shown that the standard method for distinguishing executive and slave processes is only valid if the representations of interest, as evidenced by the neural code, are known. Overall, the data indicate that the signalling evident in neural signals is restricted to the spike count and the precise times of spikes relative to stimulus onset (response latency). These coding issues have implications for our

  3. Vestibular short latency responses to pulsed linear acceleration in unanesthetized animals

    NASA Technical Reports Server (NTRS)

    Jones, T. A.

    1992-01-01

    Linear acceleration transients were used to elicit vestibular compound action potentials in non-invasively prepared, unanesthetized animals for the first time (chicks, Gallus domesticus, n = 33). Responses were composed of a series of up to 8 dominant peaks occurring within 8 msec of the stimulus. Response amplitudes for 1.0 g stimulus ranged from 1 to 10 microV. A late, slow, triphasic, anesthesia-labile component was identified as a dominant response feature in unanesthetized animals. Amplitudes increased and latencies decreased as stimulus intensity was increased (MANOVA P less than 0.05). Linear regression slope ranges were: amplitudes = 1.0-5.0 microV/g; latencies = -300 to -1100 microseconds/g. Thresholds for single polarity stimuli (0.035 +/- 0.022 g, n = 11) were significantly lower than those of alternating polarity (0.074 +/- 0.028 g, n = 18, P less than 0.001). Bilateral labyrinthectomy eliminated responses whereas bilateral extirpation of cochleae did not significantly change response thresholds. Intense acoustic masking (100/104 dB SL) produced no effect in 2 animals, but did produce small to moderate effects on response amplitudes in 7 others. Changes were attributed to effects on vestibular end organs. Results of unilateral labyrinth blockade (tetrodotoxin) suggest that P1 and N1 preferentially reflect ipsilateral eighth nerve compound action potentials whereas components beyond approximately 2 msec reflect activity from vestibular neurons that depend on both labyrinths. The results demonstrate that short latency vestibular compound action potentials can be measured in unanesthetized, non-invasively prepared animals.

  4. Opposing Regulation of the EGF Receptor: A Molecular Switch Controlling Cytomegalovirus Latency and Replication.

    PubMed

    Buehler, Jason; Zeltzer, Sebastian; Reitsma, Justin; Petrucelli, Alex; Umashankar, Mahadevaiah; Rak, Mike; Zagallo, Patricia; Schroeder, Joyce; Terhune, Scott; Goodrum, Felicia

    2016-05-01

    Herpesviruses persist indefinitely in their host through complex and poorly defined interactions that mediate latent, chronic or productive states of infection. Human cytomegalovirus (CMV or HCMV), a ubiquitous β-herpesvirus, coordinates the expression of two viral genes, UL135 and UL138, which have opposing roles in regulating viral replication. UL135 promotes reactivation from latency and virus replication, in part, by overcoming replication-suppressive effects of UL138. The mechanism by which UL135 and UL138 oppose one another is not known. We identified viral and host proteins interacting with UL138 protein (pUL138) to begin to define the mechanisms by which pUL135 and pUL138 function. We show that pUL135 and pUL138 regulate the viral cycle by targeting that same receptor tyrosine kinase (RTK) epidermal growth factor receptor (EGFR). EGFR is a major homeostatic regulator involved in cellular proliferation, differentiation, and survival, making it an ideal target for viral manipulation during infection. pUL135 promotes internalization and turnover of EGFR from the cell surface, whereas pUL138 preserves surface expression and activation of EGFR. We show that activated EGFR is sequestered within the infection-induced, juxtanuclear viral assembly compartment and is unresponsive to stress. Intriguingly, these findings suggest that CMV insulates active EGFR in the cell and that pUL135 and pUL138 function to fine-tune EGFR levels at the cell surface to allow the infected cell to respond to extracellular cues. Consistent with the role of pUL135 in promoting replication, inhibition of EGFR or the downstream phosphoinositide 3-kinase (PI3K) favors reactivation from latency and replication. We propose a model whereby pUL135 and pUL138 together with EGFR comprise a molecular switch that regulates states of latency and replication in HCMV infection by regulating EGFR trafficking to fine tune EGFR signaling. PMID:27218650

  5. Human short-latency ocular vergence responses produced by interocular velocity differences.

    PubMed

    Sheliga, B M; Quaia, C; FitzGibbon, E J; Cumming, B G

    2016-08-01

    We studied human short-latency vergence eye movements to a novel stimulus that produces interocular velocity differences without a changing disparity signal. Sinusoidal luminance gratings moved in opposite directions (left vs. right; up vs. down) in the two eyes. The grating seen by each eye underwent ¼-wavelength shifts with each image update. This arrangement eliminated changing disparity cues, since the phase difference between the eyes alternated between 0° and 180°. We nevertheless observed robust short-latency vergence responses (VRs), whose sign was consistent with the interocular velocity differences (IOVDs), indicating that the IOVD cue in isolation can evoke short-latency VRs. The IOVD cue was effective only when the images seen by the two eyes overlapped in space. We observed equally robust VRs for opposite horizontal motions (left in one eye, right in the other) and opposite vertical motions (up in one eye, down in the other). Whereas the former are naturally generated by objects moving in depth, the latter are not part of our normal experience. To our knowledge, this is the first demonstration of a behavioral consequence of vertical IOVD. This may reflect the fact that some neurons in area MT are sensitive to these motion signals (Czuba, Huk, Cormack, & Kohn, 2014). VRs were the strongest for spatial frequencies in the range of 0.35-1 c/°, much higher than the optimal spatial frequencies for evoking ocular-following responses observed during frontoparallel motion. This suggests that the two motion signals are detected by different neuronal populations. We also produced IOVD using moving uncorrelated one-dimensional white-noise stimuli. In this case the most effective stimuli have low speed, as predicted if the drive originates in neurons tuned to high spatial frequencies (Sheliga, Quaia, FitzGibbon, & Cumming, 2016). PMID:27548089

  6. [Multiple sleep latency test, maintenance of wakefulness test and suggestive immobilization test].

    PubMed

    Tanaka, Haruhito

    2015-06-01

    In clinical practice, assessment usually involves self-report; however, objective measures are available. The multiple sleep latency test(MSLT) is performed during the main period of wakefulness and is designed to determine a patient's propensity to fall asleep. To be valid, the MSLT should be performed the day after nocturnal polysomnography (PSG). It is the standard test for the assessment of objective sleepiness and diagnosis of narcolepsy, that is a mean sleep latency equal to or under 8 minutes and equal to or greater than two sleep onset REM periods (SOREMPs). As opposed to the MSLT, the maintenance of wakefulness test (MWT) is designed to test the patient's ability to stay awake. The MWT is a 40-minutes protocol consisting of four trials separated by 2-hour intervals and is performed in much the same way as the MSLT. The MWT may be indicated in assessment of individuals in whom the inability to remain awake constitutes a safety issue, or in patients with narcolepsy or idiopathic hypersomnia to assess response to treatment with medications. There is little evidence linking mean sleep latency on the MWT with risk of accidents in real world circumstances. The suggestive immobilization test(SIT) was designed during which sensor and motor symptoms of restless legs syndrome are quantified during a period of immobility taking place in the evening before PSG. The patient is instructed to avoid moving voluntary for the entire duration of the test, which is designed to last 1 hour. The subjective leg discomfort evaluation and periodic leg movement by surface electromyograms from right and left anterior tibialis support diagnosis for restless legs syndrome. Many factors, such as clinical setting, pretest condition or aging effects etc. can alter the findings of the test and considerable clinical judgment is needed to avoid an error in interpretation. Above those three sleep-wake related tests provide us useful information. PMID:26065128

  7. Broncholaveolar lavage to detect cytomegalovirus infection, latency, and reactivation in immune competent hosts.

    PubMed

    Mansfield, Sara; Dwivedi, Varun; Byrd, Sara; Trgovcich, Joanne; Griessl, Marion; Gutknecht, Michael; Cook, Charles H

    2016-08-01

    Roughly 1/3rd of immune competent patients will reactivate latent cytomegalovirus (CMV) during critical illness. There are no standard methods to detect reactivation, and some investigators have postulated that presence of DNA in BAL fluid is indicative of viral replication. To test this hypothesis, we used a murine model that allows inclusion of matched healthy controls which is not possible in human studies. BALB/c mice infected with Smith-murine CMV or PBS (mock) had BAL evaluated 7, 14, or 21 days after acute infections, during latency, or during bacterial sepsis. Plaque assay, PCR, and rtPCR were performed on BALs and concomitantly obtained lung tissue. BAL cellular compositions, including tetramer evaluation of CMV-specific T cells were evaluated by flow cytometry. CMV DNA were detected in BAL at all time-points during acute infection, becoming undetectable in all mice during latency, then were detected again during bacterial sepsis, peaking 3 weeks after onset. mCMV specific T-cells were most numerous in BAL after acute viral infections, decreasing to low levels during latency, then fluctuating during bacterial sepsis. Specifically, mCMV-specific T-cells contracted at sepsis onset, expanding 2-4 weeks post-sepsis, presumably in response to increased viral loads at that time point. Altogether, our results support the use of BAL PCR for the diagnosis of CMV replication in immune competent hosts. Additionally, we demonstrate dynamic changes in CMV-specific T cells that occur in BAL during CMV infection and during sepsis induced viral reactivation. J. Med. Virol. 88:1408-1416, 2016. © 2016 Wiley Periodicals, Inc. PMID:26762116

  8. Human short-latency ocular vergence responses produced by interocular velocity differences

    PubMed Central

    Sheliga, B. M.; Quaia, C.; FitzGibbon, E. J.; Cumming, B. G.

    2016-01-01

    We studied human short-latency vergence eye movements to a novel stimulus that produces interocular velocity differences without a changing disparity signal. Sinusoidal luminance gratings moved in opposite directions (left vs. right; up vs. down) in the two eyes. The grating seen by each eye underwent ¼-wavelength shifts with each image update. This arrangement eliminated changing disparity cues, since the phase difference between the eyes alternated between 0° and 180°. We nevertheless observed robust short-latency vergence responses (VRs), whose sign was consistent with the interocular velocity differences (IOVDs), indicating that the IOVD cue in isolation can evoke short-latency VRs. The IOVD cue was effective only when the images seen by the two eyes overlapped in space. We observed equally robust VRs for opposite horizontal motions (left in one eye, right in the other) and opposite vertical motions (up in one eye, down in the other). Whereas the former are naturally generated by objects moving in depth, the latter are not part of our normal experience. To our knowledge, this is the first demonstration of a behavioral consequence of vertical IOVD. This may reflect the fact that some neurons in area MT are sensitive to these motion signals (Czuba, Huk, Cormack, & Kohn, 2014). VRs were the strongest for spatial frequencies in the range of 0.35–1 c/°, much higher than the optimal spatial frequencies for evoking ocular-following responses observed during frontoparallel motion. This suggests that the two motion signals are detected by different neuronal populations. We also produced IOVD using moving uncorrelated one-dimensional white-noise stimuli. In this case the most effective stimuli have low speed, as predicted if the drive originates in neurons tuned to high spatial frequencies (Sheliga, Quaia, FitzGibbon, & Cumming, 2016). PMID:27548089

  9. The adequate stimulus for avian short latency vestibular responses to linear translation

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

    Transient linear acceleration stimuli have been shown to elicit eighth nerve vestibular compound action potentials in birds and mammals. The present study was undertaken to better define the nature of the adequate stimulus for neurons generating the response in the chicken (Gallus domesticus). In particular, the study evaluated the question of whether the neurons studied are most sensitive to the maximum level of linear acceleration achieved or to the rate of change in acceleration (da/dt, or jerk). To do this, vestibular response thresholds were measured as a function of stimulus onset slope. Traditional computer signal averaging was used to record responses to pulsed linear acceleration stimuli. Stimulus onset slope was systematically varied. Acceleration thresholds decreased with increasing stimulus onset slope (decreasing stimulus rise time). When stimuli were expressed in units of jerk (g/ms), thresholds were virtually constant for all stimulus rise times. Moreover, stimuli having identical jerk magnitudes but widely varying peak acceleration levels produced virtually identical responses. Vestibular response thresholds, latencies and amplitudes appear to be determined strictly by stimulus jerk magnitudes. Stimulus attributes such as peak acceleration or rise time alone do not provide sufficient information to predict response parameter quantities. Indeed, the major response parameters were shown to be virtually independent of peak acceleration levels or rise time when these stimulus features were isolated and considered separately. It is concluded that the neurons generating short latency vestibular evoked potentials do so as "jerk encoders" in the chicken. Primary afferents classified as "irregular", and which traditionally fall into the broad category of "dynamic" or "phasic" neurons, would seem to be the most likely candidates for the neural generators of short latency vestibular compound action potentials.

  10. Spatial attention boosts short-latency neural responses in human visual cortex.

    PubMed

    Mishra, Jyoti; Martínez, Antígona; Schroeder, Charles E; Hillyard, Steven A

    2012-01-16

    In a previous study of visual-spatial attention, Martinez et al. (2007) replicated the well-known finding that stimuli at attended locations elicit enlarged early components in the averaged event-related potential (ERP), which were localized to extrastriate visual cortex. The mechanisms that underlie these attention-related ERP modulations in the latency range of 80-200 ms, however, remain unclear. The main question is whether attention produces increased ERP amplitudes in time-domain averages by augmenting stimulus-triggered neural activity, or alternatively, by increasing the phase-locking of ongoing EEG oscillations to the attended stimuli. We compared these alternative mechanisms using Morlet wavelet decompositions of event-related EEG changes. By analyzing single-trial spectral amplitudes in the theta (4-8 Hz) and alpha (8-12 Hz) bands, which were the dominant frequencies of the early ERP components, it was found that stimuli at attended locations elicited enhanced neural responses in the theta band in the P1 (88-120 ms) and N1 (148-184 ms) latency ranges that were additive with the ongoing EEG. In the alpha band there was evidence for both increased additive neural activity and increased phase-synchronization of the EEG following attended stimuli, but systematic correlations between pre- and post-stimulus alpha activity were more consistent with an additive mechanism. These findings provide the strongest evidence to date in humans that short-latency neural activity elicited by stimuli within the spotlight of spatial attention is boosted or amplified at early stages of processing in extrastriate visual cortex. PMID:21983181

  11. Intracellular-activated Notch1 can reactivate Kaposi's sarcoma-associated herpesvirus from latency

    SciTech Connect

    Lan, Ke; Murakami, Masanao; Choudhuri, Tathagata; Kuppers, Daniel A.; Robertson, Erle S. . E-mail: erle@mail.med.upenn.edu

    2006-08-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a predominantly latent infection in the infected host. Importantly, during latency, only a small number of viral encoded genes are expressed. This viral gene expression pattern contributes to the establishment of long-term infection as well as the ability of the virus to evade the immune system. Previous studies have been shown that the replication and transcription activator (RTA) encoded by ORF50 activates it downstream genes and initiates viral lytic reactivation through functional interaction with RBP-J{kappa}, the major downstream effector of the Notch signaling pathway. This indicates that RTA can usurp the conserved Notch signaling pathway and mimic the activities of intracellular Notch1 to modulate gene expression. In this report, we show that the activated intracellular domain of Notch1 (ICN) is aberrantly accumulated in KSHV latently infected pleural effusion lymphoma (PEL) cells. ICN activated the RTA promoter in a dose-dependent manner, and forced expression of ICN in latently infected KSHV-positive cells initiated full blown lytic replication with the production of infectious viral progeny. However, latency-associated nuclear antigen (LANA) which is predominantly expressed during latency can specifically down-modulate ICN-mediated transactivation of RTA and so control KSHV for lytic reactivation. These results demonstrate that LANA can inhibit viral lytic replication by antagonizing ICN function and suggest that LANA is a critical component of the regulatory control mechanism for switching between viral latent and lytic replication by directly interacting with effectors of the conserved cellular Notch1 pathway.

  12. Human brain cortical correlates of short-latency afferent inhibition: a combined EEG-TMS study.

    PubMed

    Ferreri, Florinda; Ponzo, David; Hukkanen, Taina; Mervaala, Esa; Könönen, Mervi; Pasqualetti, Patrizio; Vecchio, Fabrizio; Rossini, Paolo Maria; Määttä, Sara

    2012-07-01

    When linking in time electrical stimulation of the peripheral nerve with transcranial magnetic stimulation (TMS), the excitability of the motor cortex can be modulated to evoke clear inhibition, as reflected by the amplitude decrement in the motor-evoked potentials (MEPs). This specific property, designated short-latency afferent inhibition (SAI), occurs when the nerve-TMS interstimulus interval (ISI) is approximately 25 ms and is considered to be a corticothalamic phenomenon. The aim of the present study was to use the electroencephalographic (EEG) responses to navigated-TMS coregistration to better characterize the neuronal circuits underlying SAI. The present experimental set included magnetic resonance imaging (MRI)-navigated TMS and 60-channel TMS-compatible EEG devices. TMS-evoked EEG responses and MEPs were analyzed in eight healthy volunteers; ISIs between median nerve and cortical stimulation were determined relative to the latency of the individual N20 component of the somatosensory-evoked potential (SEP) obtained after stimulation of the median nerve. ISIs from the latency of the N20 plus 3 ms and N20 plus 10 ms were investigated. In all experimental conditions, TMS-evoked EEG responses were characterized by a sequence of negative deflections peaking at approximately 7, 44, and 100 ms alternating with positive peaks at approximately 30, 60, and 180 ms post-TMS. Moreover, ISI N20+3 ms modulated both EEG-evoked activity and MEPs. In particular, it inhibited MEP amplitudes, attenuated cortical P60 and N100 responses, and induced motor cortex beta rhythm selective decrement of phase locking. The findings of the present experiment suggest the cortical origin of SAI that could result from the cortico-cortical activation of GABAergic-mediated inhibition onto the corticospinal neurons modulated by cholinergic activation able to reducing intralaminar inhibition and promoting intracolumnar inhibition. PMID:22457460

  13. Study and Simulation of Enhancements for TCP Performance Over Noisy High Latency Links

    NASA Technical Reports Server (NTRS)

    Partridge, Craig

    1999-01-01

    The goal of this study is to better understand how TCP behaves over noisy, high-latency links such as satellite links and propose improvements to TCP implementations such that TCP might better handle such links. This report is comprised of a series of smaller reports, presentations and recommendations. Included in these documents are a summary of the TCP enhancement techniques for large windows, protect against wrap around (PAWS), use of selective acknowledgements (SACK), increasing TCP's initial window and recommendations to implement TCP pacing.

  14. Universal fantasy in latency: Separation, attachment and sexuality in Julio Cortázar's Bestiary.

    PubMed

    Shustorovich, Ellen; Weinstein, Lissa

    2010-12-01

    This paper joins recent efforts to build a conceptual bridge between psychoanalysis and attachment theory. A psychoanalytic reading of Julio Cortázar's Bestiary, a story about a young girl sent away for a summer vacation, is used to conceptualize the relationship between attachment and sexuality during latency. Middle childhood is seen as a pivotal period when cognitive maturation, internalization of parental figures, increasing independence and importance of those outside the family make fantasy the central adaptive mode of functioning. As such, the literature on attachment, which focuses on observed events, has to be supplemented with investigations of the actively created fantasies of that age period. PMID:21133908

  15. Global analysis on a class of multi-group SEIR model with latency and relapse.

    PubMed

    Wang, Jinliang; Shu, Hongying

    2016-02-01

    In this paper, we investigate the global dynamics of a multi-group SEIR epidemic model, allowing heterogeneity of the host population, delay in latency and delay due to relapse distribution for the human population. Our results indicate that when certain restrictions on nonlinear growth rate and incidence are fulfilled, the basic reproduction number R0 plays the key role of a global threshold parameter in the sense that the long-time behaviors of the model depend only on R0. The proofs of the main results utilize the persistence theory in dynamical systems, Lyapunov functionals guided by graph-theoretical approach. PMID:26776266

  16. Herpes simplex virus infection: part I--Biology, clinical presentation and latency.

    PubMed

    Yarom, N; Buchner, A; Dayan, D

    2005-01-01

    Oro-facial manifestations of herpes simplex virus (HSV) infections are very common, and include primary herpetic gingivo-stomatitis, recurrent herpes labialis and recurrent intra-oral herpes. Recent research in molecular biology has advanced our knowledge of the HSV pathogenesis and behavior. Understanding the exact mechanism of HSV latency and reactivation enables improvement of drug therapy and prevention strategies of HSV infections. The aim of this review is to update the recent development in the biological and clinical research related to HSV infection, focusing on oral and perioral lesions. PMID:15786655

  17. Influence of ND10 Components on Epigenetic Determinants of Early KSHV Latency Establishment

    PubMed Central

    Dobner, Thomas; Tessmer, Uwe; Grundhoff, Adam

    2014-01-01

    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 suggest that KSHV

  18. Effect of LED light stimulation on sleep latency in night shift people

    NASA Astrophysics Data System (ADS)

    Wu, Jih-Huah; Chang, Yang-Chyuan; Chiu, Hui-Ling; Fang, Wei; Shan, Yi-Chia; Chen, Ming-Jie; Chang, Yu-Ting

    2014-05-01

    Sleep problems are getting worse and worse in modern world. They have a severe impact on psychological and physical health, as well as social performances. From our previous study, the brainwave α rhythm, θ wave and β wave were affected by radiating the palm of the subjects with low-level laser array. In addition, from other study, the LED array stimulator (LEDAS) also has the similar effects. In the present study, LED light was used to radiate the left palm of the subjects too, and the effects were assessed with the multiple sleep latency test (MSLT) and heart-rate variability (HRV) analysis. The results revealed that it doesn't have significant meaning between these two groups. However, the tendency of the sleep latency (SL) in the LED group was shorter than that in the control group. In addition, the autonomic nervous system (ANS) analysis showed that the sympathetic nervous system was getting larger in the LED group than that in the control group, and total ANS activity were mainly getting larger in the LED group. We infer that this LED stimulation could reduce SL and balance ANS activity of the night-shift people. In the future, the further study will be conducted on normal subjects.

  19. SMAC: A soft MAC to reduce control overhead and latency in CDMA-based AMI networks

    DOE PAGESBeta

    Garlapati, Shravan; Kuruganti, Teja; Buehrer, Michael R.; Reed, Jeffrey H.

    2015-10-26

    The utilization of state-of-the-art 3G cellular CDMA technologies in a utility owned AMI network results in a large amount of control traffic relative to data traffic, increases the average packet delay and hence are not an appropriate choice for smart grid distribution applications. Like the CDG, we consider a utility owned cellular like CDMA network for smart grid distribution applications and classify the distribution smart grid data as scheduled data and random data. Also, we propose SMAC protocol, which changes its mode of operation based on the type of the data being collected to reduce the data collection latency andmore » control overhead when compared to 3G cellular CDMA2000 MAC. The reduction in the data collection latency and control overhead aids in increasing the number of smart meters served by a base station within the periodic data collection interval, which further reduces the number of base stations needed by a utility or reduces the bandwidth needed to collect data from all the smart meters. The reduction in the number of base stations and/or the reduction in the data transmission bandwidth reduces the CAPital EXpenditure (CAPEX) and OPerational EXpenditure (OPEX) of the AMI network. Finally, the proposed SMAC protocol is analyzed using markov chain, analytical expressions for average throughput and average packet delay are derived, and simulation results are also provided to verify the analysis.« less

  20. Increased latencies to initiate cocaine self-administration following laterodorsal tegmental nucleus lesions

    PubMed Central

    Steidl, Stephan; Cardiff, Katherine M.; Wise, Roy A.

    2015-01-01

    Cholinergic input to the ventral tegmental area (VTA), origin of the mesocorticolimbic dopamine system that is critical for cocaine reward, is important for both cocaine seeking and cocaine taking. The laterodorsal tegmental nucleus (LDTg) provides one of the two major sources of excitatory cholinergic input to the VTA, but little is known of the role of the LDTg in cocaine reward. LDTg cholinergic cells express urotensin-II receptors and here we used local microinjections of a conjugate of the endogenous ligand for these receptors with diphtheria toxin (Dtx::UII) to lesion the cholinergic cells of the LDTg in rats previously trained to self-administer cocaine (1 mg/kg/infusion, i.v.). Lesioned rats showed long latencies to initiate cocaine self-administration after treatment with the toxin, which resulted in a reduction in cocaine intake per session. Priming injections reduced latencies to initiate responding for cocaine in lesioned rats, and once they began to respond the rats regulated their moment-to-moment cocaine intake within normal limits. Thus we conclude that while LDTg cholinergic cell loss does not significantly alter the rewarding effects of cocaine, LDTg lesions can reduce the rat’s responsiveness to cocaine-predictive stimuli. PMID:25746513

  1. Speeding up the brain: when spatial facilitation translates into latency shortening

    PubMed Central

    Paradis, Anne-Lise; Morel, Shasha; Seriès, Peggy; Lorenceau, Jean

    2012-01-01

    Waves of activity following a focal stimulation are reliably observed to spread across the cortical tissue. The origin of these waves remains unclear and the underlying mechanisms and function are still debated. In this study, we ask whether waves of activity modulate the magnetoencephalography (MEG) signals recorded in humans during visual stimulation with Gabor patches sequentially flashed along a vertical path, eliciting a perception of vertical apparent motion. Building upon the functional properties of long-rang horizontal connections, proposed to contribute to spreading activity, we specifically probe the amplitude and latency of MEG responses as a function of Gabor contrast and orientation. The results indicate that in the left hemisphere the response amplitude is enhanced and the half height response latency is shortened for co-aligned Gabor as compared to misaligned Gabor patches at a low but not at a high contrast. Building upon these findings, we develop a biologically plausible computational model that performs a “spike time alignment” of the responses to elongated contours with varying contrast, endowing them with a phase advance relative to misaligned contours. PMID:23267321

  2. Drive latencies in hypoglossal motoneurons indicate developmental change in the brainstem respiratory network

    NASA Astrophysics Data System (ADS)

    Fietkiewicz, Christopher; Loparo, Kenneth A.; Wilson, Christopher G.

    2011-10-01

    The respiratory rhythm originates and diverges from the brainstem to drive thousands of motoneurons that are responsible for control of the diaphragm, intercostals and upper airway. These motoneurons are known to have a wide range of phase relationships, even within a single motoneuron pool. The proposed source of this rhythm, the preBötzinger complex (preBötC), responds to an array of developmental changes in the first days post-birth, specifically at postnatal day 3 (P3). We hypothesize that such developmental changes in the preBötC have a direct effect on motoneuron phase relationships and should be detectable around age P3. To test our hypothesis, we obtained single- and dual-voltage-clamp recordings of hypoglossal motoneurons in an in vitro slice preparation. We introduce a novel approach to analyzing the phase relationships between motoneurons by using cross-correlation analysis to determine the drive latencies. This analysis reveals that the distribution of drive latencies undergoes a significant change at or before age P3. We use a computational model of the in vitro slice to demonstrate the observed phase differences and hypothesize that network heterogeneity alone may not be sufficient to explain them. Through simulations, we show the effects on the preBötC of different network characteristics such as clustering and common inputs.

  3. Daytime Sleepiness in Adults With ADHD: A Pilot Trial With a Multiple Sleep Latency Test.

    PubMed

    Sobanski, Esther; Alm, Barbara; Hennig, Oliver; Riemann, Dieter; Feige, Bernd; Schredl, Michael

    2014-04-17

    Objective: To evaluate sleep latency (SL) during the multiple sleep latency test (MSLT) and subjective daytime sleepiness in adult ADHD and controls. Method: Subjective daytime sleepiness was assessed by Epworth Sleepiness Scale (ESS) in 27 unmedicated adults with ADHD and in 182 controls. Thirteen ADHD patients and 26 controls underwent MSLT after one night of polysomnography (PSG). Results: Mean MSLT-SL was 10.6 ± 4.8 min in ADHD and 12.2 ± 4.2 min in controls (n.s.). Mean ESS score was 9.3 ± 4.9 points in ADHD and 6.9 ± 3.4 points in controls (p < .005). MSLT-SL and ESS scores correlated inversely by trend (r = -.45, p < .1) but not with ADHD symptoms or ADHD subtype. Conclusion: Adults with ADHD do not differ from controls in mean MSLT-SL but experience increased subjective daytime sleepiness. Patients with subjective higher daytime tiredness fell asleep faster during MSLT. PMID:24743976

  4. SMAC: A soft MAC to reduce control overhead and latency in CDMA-based AMI networks

    SciTech Connect

    Garlapati, Shravan; Kuruganti, Teja; Buehrer, Michael R.; Reed, Jeffrey H.

    2015-10-26

    The utilization of state-of-the-art 3G cellular CDMA technologies in a utility owned AMI network results in a large amount of control traffic relative to data traffic, increases the average packet delay and hence are not an appropriate choice for smart grid distribution applications. Like the CDG, we consider a utility owned cellular like CDMA network for smart grid distribution applications and classify the distribution smart grid data as scheduled data and random data. Also, we propose SMAC protocol, which changes its mode of operation based on the type of the data being collected to reduce the data collection latency and control overhead when compared to 3G cellular CDMA2000 MAC. The reduction in the data collection latency and control overhead aids in increasing the number of smart meters served by a base station within the periodic data collection interval, which further reduces the number of base stations needed by a utility or reduces the bandwidth needed to collect data from all the smart meters. The reduction in the number of base stations and/or the reduction in the data transmission bandwidth reduces the CAPital EXpenditure (CAPEX) and OPerational EXpenditure (OPEX) of the AMI network. Finally, the proposed SMAC protocol is analyzed using markov chain, analytical expressions for average throughput and average packet delay are derived, and simulation results are also provided to verify the analysis.

  5. In vitro activation of human herpesviruses 6 and 7 from latency.

    PubMed Central

    Katsafanas, G C; Schirmer, E C; Wyatt, L S; Frenkel, N

    1996-01-01

    Human herpesviruses 6 and 7 (HHV-6 and HHV-7) are prevalent lymphotropic viruses that infect more than 80% of children at infancy or during early childhood. Infection ranges from asymptomatic to severe disease. HHV-6B causes exanthem subitum. The virus can be recovered from peripheral blood mononuclear cells during the acute phase of exanthem subitum, but the host remains latently infected throughout life. In immunocompromised patients undergoing kidney, liver, or bone marrow transplantation latent HHV-6B is reactivated, at times causing severe or fatal disease. Here, we describe the establishment of an in vitro system for reactivation of HHV-6B and HHV-7 from latency. HHV-7 is reactivated from latently infected peripheral blood mononuclear cells by T-cell activation. HHV-6B could not be reactivated under similar conditions; however, the latent HHV-6B could be recovered after the cells were infected with HHV-7. Once reactivated, the HHV-6B genomes became prominent and the HHV-7 disappeared. We conclude that HHV-7 can provide a transacting function(s) mediating HHV-6 reactivating from latency. Understanding the activation process is critical for the development of treatments to control the activation of latent viruses so as to avoid these sometimes life threatening infections in transplant recipients. Images Fig. 2 Fig. 3 Fig. 5 PMID:8790409

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

    PubMed Central

    Kurtzer, Isaac L.

    2015-01-01

    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 (SLR) 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 (LLR) (around 50–100 ms) which acts more rapidly than voluntary reactions but shares some supraspinal pathways and functional capabilities. In particular, the LLR accounts for the arm’s biomechanical properties rather than only responding to local muscle stretch like the SLR. This paper will review how the LLR 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 (RF) contribute to the LLR 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. PMID:25688187

  7. A Unique SUMO-2-Interacting Motif within LANA Is Essential for KSHV Latency

    PubMed Central

    Cai, Qiliang; Cai, Shen; Zhu, Caixia; Verma, Suhbash C.; Choi, Ji-Young; Robertson, Erle S.

    2013-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) stabilizes hypoxia-inducible factor α (HIF-1α) during latent infection, and HIF-1α reactivates lytic replication under hypoxic stress. However, the mechanism utilized by KSHV to block lytic reactivation with the accumulation of HIF-1α in latency remains unclear. Here, we report that LANA encoded by KSHV contains a unique SUMO-interacting motif (LANASIM) which is specific for interaction with SUMO-2 and facilitates LANA SUMOylation at lysine 1140. Proteomic and co-immunoprecipitation analysis further reveal that the SUMO-2 modified transcription repressor KAP1 is a critical factor recruited by LANASIM. Deletion of LANASIM led to functional loss of both LANA-mediated viral episome maintenance and lytic gene silencing. Moreover, hypoxia reduced KAP1 SUMOylation and resulted in dissociation of both KAP1 and Sin3A repressors from LANASIM-associated complex. Therefore, the LANASIM motif plays an essential role in KSHV latency and is a potential drug target against KSHV-associated cancers. PMID:24278015

  8. Behavioral correlates of the decision process in a dynamic environment: post-choice latencies reflect relative value and choice evaluation

    PubMed Central

    Fam, Justine; Westbrook, Fred; Arabzadeh, Ehsan

    2015-01-01

    One characteristic of natural environments is that outcomes vary across time. Animals need to adapt to these environmental changes and adjust their choices accordingly. In this experiment, we investigated the sensitivity with which rats could detect, and adapt to, multiple changes in the environment. Rats chose between two spouts which delivered 5% sucrose rewards with distinct probabilities. Across three phases, reward probabilities changed in size (large or small) and direction (increase or decrease). A discrete trial-structure was used, which allowed the choice process to be decomposed into three distinct response latency measures (choice execution latency, spout sampling duration, and trial-initiation latency). We found that a large decrease in reward probabilities rapidly produced the greatest change in choice proportions. The time taken to execute a choice reflected the differences in reward probabilities across the two spouts in some cases, but also reflected training history. By contrast, the amount of time rats spent responding at reward spouts in anticipation of reward consistently reflected the relative likelihood of reward across the two spouts and not the absolute probability of reward. The latency to initiate the subsequent trial reflected choice evaluation. These three response latencies thus indexed key behavioral correlates of the choice process as it unfolds in time. We discuss how this paradigm can be used to assess the corresponding neural correlates of decision-making. PMID:26483649

  9. LGIT In Vitro Latency Model in Primary and T Cell Lines to Test HIV-1 Reactivation Compounds.

    PubMed

    Jung, Ulrike; Takahashi, Mayumi; Rossi, John J; Burnett, John C

    2016-01-01

    Persistent latent HIV-1 reservoirs pose a major barrier for combinatorial antiretroviral therapy (cART) to achieve eradication of the virus. A variety of mechanisms likely contribute to HIV-1 persistence, including establishment of post-integration latency in resting CD4+ T-lymphocytes, the proliferation of these latently infected cells, and the induced or spontaneous reactivation of latent virus. To elucidate the mechanisms of latency and to investigate therapeutic strategies for reactivating and purging the latent reservoir, investigators have developed in vitro models of HIV-1 latency using primary CD4+ T-lymphocytes and CD4+ T-cell lines. Several types of in vitro latency models range from replication-competent to single-round, replication-deficient viruses exhibiting different degrees of viral genomic deletion. Working under the hypothesis that HIV-1 post-integration latency is directly linked to HIV-1 promoter activity, which can be obscured by additional proteins expressed during replication, we focus here on the creation of latently infected primary human T-cells and cell lines through the single-round, replication deficient HIV-1 LGIT model. In this model the long terminal repeat (LTR) of the HIV-1 virus drives a cassette of GFP-IRES-Tat that allows testing of reactivating components and initiates a positive feedback loop through Tat expression. PMID:26714717

  10. Use of Stimulus-frequency Otoacoustic Emission Latency and Level to Investigate Cochlear Mechanics in Human Earsa)

    PubMed Central

    Schairer, Kim S.; Ellison, John C.; Fitzpatrick, Denis; Keefe, Douglas H.

    2006-01-01

    Stimulus frequency otoacoustic emission (SFOAE) sound pressure level (SPL) and latency were measured at probe frequencies from 500 to 4000 Hz and probe levels from 40 to 70 dB SPL in 16 normal-hearing adult ears. The main goal was to use SFOAE latency estimates to better understand possible source mechanisms such as linear coherent reflection, nonlinear distortion, and reverse transmission via the cochlear fluid, and how those sources might change as a function of stimulus level. Another goal was to use SFOAE latencies to noninvasively estimate cochlear tuning. SFOAEs were dominated by the reflection source at low stimulus levels, consistent with previous research, but neither nonlinear distortion nor fluid compression become the dominant source even at the highest stimulus level. At each stimulus level, the SFOAE latency was an approximately constant number of periods from 1000 to 4000 Hz, consistent with cochlear scaling symmetry. SFOAE latency decreased with increasing stimulus level in an approximately frequency-independent manner. Tuning estimates were constant above 1000 Hz, consistent with simultaneous masking data, but in contrast to previous estimates from SFOAEs. PMID:16938978

  11. The effect of CD4 receptor downregulation and its downstream signaling molecules on HIV-1 latency

    SciTech Connect

    Kim, Kyung-Chang; Kim, Hyeon Guk; Roh, Tae-Young; Park, Jihwan; Jung, Kyung-Min; Lee, Joo-Shil; Choi, Sang-Yun; Kim, Sung Soon; Choi, Byeong-Sun

    2011-01-14

    Research highlights: {yields} CD4 receptors were downregulated on the surface of HIV-1 latently infected cells. {yields} CD4 downstream signaling molecules were suppressed in HIV-1 latently infected cells. {yields} HIV-1 progeny can be reactivated by induction of T-cell activation signal molecules. {yields} H3K4me3 and H3K9ac were highly enriched in CD4 downstream signaling molecules. {yields} HIV-1 latency can be maintained by the reduction of downstream signaling molecules. -- Abstract: HIV-1 can establish a latent infection in memory CD4 + T cells to evade the host immune response. CD4 molecules can act not only as the HIV-1 receptor for entry but also as the trigger in an intracellular signaling cascade for T-cell activation and proliferation via protein tyrosine kinases. Novel chronic HIV-1-infected A3.01-derived (NCHA) cells were used to examine the involvement of CD4 downstream signaling in HIV-1 latency. CD4 receptors in NCHA cells were dramatically downregulated on its surface but were slightly decreased in whole-cell lysates. The expression levels of CD4 downstream signaling molecules, including P56{sup Lck}, ZAP-70, LAT, and c-Jun, were sharply decreased in NCHA cells. The lowered histone modifications of H3K4me3 and H3K9ac correlated with the downregulation of P56{sup Lck}, ZAP-70, and LAT in NCHA cells. AP-1 binding activity was also reduced in NCHA cells. LAT and c-Jun suppressed in NCHA cells were highly induced after PMA treatment. In epigenetic analysis, other signal transduction molecules which are associated with active and/or latent HIV-1 infection showed normal states in HIV-1 latently infected cells compared to A3.01 cells. In conclusion, we demonstrated that the HIV-1 latent state is sustained by the reduction of downstream signaling molecules via the downregulation of CD4 and the attenuated activity of transcription factor as AP-1. The HIV-1 latency model via T-cell deactivation may provide some clues for the development of the new

  12. Modeling latency code processing in the electric sense: from the biological template to its VLSI implementation.

    PubMed

    Engelmann, Jacob; Walther, Tim; Grant, Kirsty; Chicca, Elisabetta; Gómez-Sena, Leonel

    2016-01-01

    Understanding the coding of sensory information under the temporal constraints of natural behavior is not yet well resolved. There is a growing consensus that spike timing or latency coding can maximally exploit the timing of neural events to make fast computing elements and that such mechanisms are essential to information processing functions in the brain. The electric sense of mormyrid fish provides a convenient biological model where this coding scheme can be studied. The sensory input is a physically ordered spatial pattern of current densities, which is coded in the precise timing of primary afferent spikes. The neural circuits of the processing pathway are well known and the system exhibits the best known illustration of corollary discharge, which provides the reference to decoding the sensory afferent latency pattern. A theoretical model has been constructed from available electrophysiological and neuroanatomical data to integrate the principal traits of the neural processing structure and to study sensory interaction with motor-command-driven corollary discharge signals. This has been used to explore neural coding strategies at successive stages in the network and to examine the simulated network capacity to reproduce output neuron responses. The model shows that the network has the ability to resolve primary afferent spike timing differences in the sub-millisecond range, and that this depends on the coincidence of sensory and corollary discharge-driven gating signals. In the integrative and output stages of the network, corollary discharge sets up a proactive background filter, providing temporally structured excitation and inhibition within the network whose balance is then modulated locally by sensory input. This complements the initial gating mechanism and contributes to amplification of the input pattern of latencies, conferring network hyperacuity. These mechanisms give the system a robust capacity to extract behaviorally meaningful features of the

  13. A 2.5-Kilobase Deletion Containing a Cluster of Nine MicroRNAs in the Latency-Associated-Transcript Locus of the Pseudorabies Virus Affects the Host Response of Porcine Trigeminal Ganglia during Established Latency

    PubMed Central

    Mahjoub, Nada; Dhorne-Pollet, Sophie; Fuchs, Walter; Endale Ahanda, Marie-Laure; Lange, Elke; Klupp, Barbara; Arya, Anoop; Loveland, Jane E.; Lefevre, François; Mettenleiter, Thomas C.

    2014-01-01

    ABSTRACT The alphaherpesvirus pseudorabies virus (PrV) establishes latency primarily in neurons of trigeminal ganglia when only the transcription of the latency-associated transcript (LAT) locus is detected. Eleven microRNAs (miRNAs) cluster within the LAT, suggesting a role in establishment and/or maintenance of latency. We generated a mutant (M) PrV deleted of nine miRNA genes which displayed properties that were almost identical to those of the parental PrV wild type (WT) during propagation in vitro. Fifteen pigs were experimentally infected with either WT or M virus or were mock infected. Similar levels of virus excretion and host antibody response were observed in all infected animals. At 62 days postinfection, trigeminal ganglia were excised and profiled by deep sequencing and quantitative RT-PCR. Latency was established in all infected animals without evidence of viral reactivation, demonstrating that miRNAs are not essential for this process. Lower levels of the large latency transcript (LLT) were found in ganglia infected by M PrV than in those infected by WT PrV. All PrV miRNAs were expressed, with highest expression observed for prv-miR-LLT1, prv-miR-LLT2 (in WT ganglia), and prv-miR-LLT10 (in both WT and M ganglia). No evidence of differentially expressed porcine miRNAs was found. Fifty-four porcine genes were differentially expressed between WT, M, and control ganglia. Both viruses triggered a strong host immune response, but in M ganglia gene upregulation was prevalent. Pathway analyses indicated that several biofunctions, including those related to cell-mediated immune response and the migration of dendritic cells, were impaired in M ganglia. These findings are consistent with a function of the LAT locus in the modulation of host response for maintaining a latent state. IMPORTANCE This study provides a thorough reference on the establishment of latency by PrV in its natural host, the pig. Our results corroborate the evidence obtained from the study

  14. Visual and somatosensory evoked potentials and F-wave latency measurements in hereditary neuropathy with liability to pressure palsies.

    PubMed

    Strenge, H; Soyka, D; Tackmann, W

    1982-01-01

    Pattern shift visual evoked potentials (VEPs), cervical and cortical somatosensory evoked responses (SEPs) and motor conduction velocities studied by F-wave latency measurements were investigated in two family members with hereditary neuropathy with liability to pressure palsies (HN-PP). In both cases in VEPs and SEP conduction times N13-N20 were normal. A bilateral pathological increase of latencies of early SEP components, N9-N13 transit times and F-wave latencies revealed a lesion in the proximal parts of the median nerves close to the spinal cord in the older patient. These abnormalities emphasize the close relationship of HN-PP with hereditary polyradiculopathy (Mayer 1975). PMID:6174708

  15. Use of the response-latency paradigm for eliciting and evaluating women's responses to the threat of date rape.

    PubMed

    Anderson, RaeAnn E; Cahill, Shawn P

    2014-01-01

    This study evaluates the novel use of the response-latency paradigm to elicit women's hypothetical behavioral responses to the threat of acquaintance rape. There were 146 college women recruited and randomly assigned to 4 study conditions. In 3 of the conditions, the threat to which participants responded was experimentally controlled; in the fourth control condition, participants selected the level of threat themselves, following standard procedure of the response-latency paradigm. Results indicated that participant's responses became more intense as threat levels increased; this relationship was not moderated by whether the threat was controlled by the experimenter or the participant. These results indicate the response-latency paradigm is useful for eliciting and evaluating women's hypothetical responses to the threat of acquaintance rape to learn more about this process. PMID:24834746

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

    NASA Technical Reports Server (NTRS)

    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.

  17. The influence of job familiarity and impression management on self-report measure scale scores and response latencies.

    PubMed

    Vasilopoulos, N L; Reilly, R R; Leaman, J A

    2000-02-01

    Two studies were conducted to examine the effects of job familiarity and impression management on response latencies and scale scores for measures of personality and situational judgment. In a laboratory study using university students and a field study using U.S. Border Patrol Agent applicants, impression management was generally associated with faster personality item responses when job familiarity was high and with slower responses when job familiarity was low. Both impression management and job familiarity were associated with personality item responses that were more likely to lead to a job offer. The field study revealed a similar pattern of results for situational judgment scale response latencies, although only impression management was associated with item responses that were more likely to lead to a job offer. The implications for using response latencies to detect impression management on self-report measures are discussed. PMID:10740956

  18. Does pilates exercise increase physical activity, quality of life, latency, and sleep quantity in middle-aged people?

    PubMed

    García-Soidán, J L; Giraldez, V Arufe; Cachón Zagalaz, J; Lara-Sánchez, A J

    2014-12-01

    This prospective study assessed the effects of a 12-wk. exercise program based on the Pilates method (2 one-hr. sessions per week) on 99 sedentary middle-aged volunteers (M age = 47.6 yr., SD = 0.8), using an accelerometry, the Pittsburgh Sleep Quality Index, and the SF-36 questionnaire to measure changes in physical activity, quality of life, sleep latency, and quantity. The variables (quality of life, sleep latency, and quantity) were compared before and after applying the Pilates program. All of the physical and emotional components of the SF-36 questionnaire showed significant improvement, and the latency and sleep quantity also showed significant increases. The results indicate that Pilates is an accessible, interesting exercise program that can generate important changes in middle age. PMID:25456245

  19. Hiding the Disk and Network Latency of Out-of-Core Visualization

    NASA Technical Reports Server (NTRS)

    Ellsworth, David

    2001-01-01

    This paper describes an algorithm that improves the performance of application-controlled demand paging for out-of-core visualization by hiding the latency of reading data from both local disks or disks on remote servers. The performance improvements come from better overlapping the computation with the page reading process, and by performing multiple page reads in parallel. The paper includes measurements that show that the new multithreaded paging algorithm decreases the time needed to compute visualizations by one third when using one processor and reading data from local disk. The time needed when using one processor and reading data from remote disk decreased by two thirds. Visualization runs using data from remote disk actually ran faster than ones using data from local disk because the remote runs were able to make use of the remote server's high performance disk array.

  20. FRELLED : The FITS Realtime Explorer of Low Latency in Every Dimension

    NASA Astrophysics Data System (ADS)

    Taylor, Rhys

    2013-01-01

    I present the FITS Realtime Explorer of Low Latency in Every Dimension (FRELLED). Using the graphics engine of the open-source program, "Blender", FRELLED enables users to view 3-dimensional FITS files from any angle in realtime. The user can freely rotate, pan, zoom, and toggle perspective and orthographic rendering while the image is instantaneously updated. Objects found can be easily masked and catalogued, and a 2D version is available. FRELLED was developed as part of the Arecibo Galaxy Environment Survey (AGES), a neutral hydrogen survey where visual source extraction is essential. Using FRELLED, data cubes can be searched approximately 30 times faster than using existing FITS viewers, with no loss of completeness or reliability in the resulting catalogues. While it is currently designed for HI surveys, FRELLED can be adapted for use with data at other wavelengths.

  1. Identification and characterization of latency-associated peptide-expressing γδ T cells

    PubMed Central

    Rezende, Rafael M.; da Cunha, Andre P.; Kuhn, Chantal; Rubino, Stephen; M'Hamdi, Hanane; Gabriely, Galina; Vandeventer, Tyler; Liu, Shirong; Cialic, Ron; Pinheiro-Rosa, Natalia; Oliveira, Rafael P.; Gaublomme, Jellert T.; Obholzer, Nikolaus; Kozubek, James; Pochet, Nathalie; Faria, Ana M. C.; Weiner, Howard L.

    2015-01-01

    γδ T cells are a subset of lymphocytes specialized in protecting the host against pathogens and tumours. Here we describe a subset of regulatory γδ T cells that express the latency-associated peptide (LAP), a membrane-bound TGF-β1. Thymic CD27+IFN-γ+CCR9+α4β7+TCRγδ+ cells migrate to the periphery, particularly to Peyer's patches and small intestine lamina propria, where they upregulate LAP, downregulate IFN-γ via ATF-3 expression and acquire a regulatory phenotype. TCRγδ+LAP+ cells express antigen presentation molecules and function as antigen presenting cells that induce CD4+Foxp3+ regulatory T cells, although TCRγδ+LAP+ cells do not themselves express Foxp3. Identification of TCRγδ+LAP+ regulatory cells provides an avenue for understanding immune regulation and biologic processes linked to intestinal function and disease. PMID:26644347

  2. A low-latency Glitch Classification Algorithm Based in Waveform Morphology

    NASA Astrophysics Data System (ADS)

    Gabbard, Hunter; Mukherjee, Soma; Stone, Robert

    2016-03-01

    We present a novel and efficient algorithm for classification of signals that arise in gravitational wave channels of the Laser Interferometer Gravitational Wave Observatory (LIGO). Using data from LIGO's sixth science run (S6), we developed a new glitch classification algorithm based mainly on the morphology of the waveform as well as several other parameters (signal-to-noise ratio (SNR), duration, bandwidth, etc.). This is done using two novel methods, Kohonen Self Organizing Feature Maps (SOMs), and discrete wavelet transform coefficients. This study shows the feasibility of utilizing unsupervised machine learning techniques (SOMs) in order to display a multidimensional trigger set in a low-latency two dimensional format. UTRGV NSF REU Program.

  3. Herpes simplex virus latency-associated transcript is a stable intron.

    PubMed Central

    Farrell, M J; Dobson, A T; Feldman, L T

    1991-01-01

    The latency-associated transcript (LAT) is the major viral transcript detected by in situ hybridization of mouse and human sensory ganglia latently infected with herpes simplex virus type 1. The last 750 bases of LAT are complementary to infected-cell polypeptide 0, a herpes simplex virus type 1 immediate-early gene that encodes a transactivating protein that may facilitate re-activation of the virus from the latent state. Several laboratories have shown that LAT accumulates in the nucleus and is not polyadenylylated. Recently, we showed that the promoter for LAT lies 688 bases upstream from its 5' end. We report here that LAT is actually a uniquely stable intron. Furthermore, LAT effectively inhibits transactivation of gene expression by infected-cell polypeptide 0 in transient transfection assays. Images PMID:1846963

  4. Latency Hiding in Dynamic Partitioning and Load Balancing of Grid Computing Applications

    NASA Technical Reports Server (NTRS)

    Das, Sajal K.; Harvey, Daniel J.; Biswas, Rupak

    2001-01-01

    The Information Power Grid (IPG) concept developed by NASA is aimed to provide a metacomputing platform for large-scale distributed computations, by hiding the intricacies of highly heterogeneous environment and yet maintaining adequate security. In this paper, we propose a latency-tolerant partitioning scheme that dynamically balances processor workloads on the.IPG, and minimizes data movement and runtime communication. By simulating an unsteady adaptive mesh application on a wide area network, we study the performance of our load balancer under the Globus environment. The number of IPG nodes, the number of processors per node, and the interconnected speeds are parameterized to derive conditions under which the IPG would be suitable for parallel distributed processing of such applications. Experimental results demonstrate that effective solution are achieved when the IPG nodes are connected by a high-speed asynchronous interconnection network.

  5. Evaluating long-latency auditory evoked potentials in the diagnosis of cortical hearing loss in children

    PubMed Central

    Lopez-Soto, Teresa; Postigo-Madueno, Amparo; Nunez-Abades, Pedro

    2016-01-01

    In centrally related hearing loss, there is no apparent damage in the auditory system, but the patient is unable to hear sounds. In patients with cortical hearing loss (and in the absence of communication deficit, either total or partial, as in agnosia or aphasia), some attention-related or language-based disorders may lead to a wrong diagnosis of hearing impairment. The authors present two patients (8 and 11 years old) with no anatomical damage to the ear, the absence of neurological damage or trauma, but immature cortical auditory evoked potentials. Both patients presented a clinical history of multiple diagnoses over several years. Because the most visible symptom was moderate hearing loss, the patients were recurrently referred to audiological testing, with no improvement. This report describes the use of long-latency evoked potentials to determine cases of cortical hearing loss, where hearing impairment is a consequence of underdevelopment at the central nervous system. PMID:27006780

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

    PubMed

    Rahayu, Retno; Ohsaki, Eriko; Omori, Hiroko; Ueda, Keiji

    2016-09-01

    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. PMID:27254595

  7. Establishment and maintenance of HIV latency: model systems and opportunities for intervention

    PubMed Central

    Marsden, Matthew D; Zack, Jerome A

    2011-01-01

    HAART has succeeded in reducing morbidity and mortality rates in patients infected with HIV. However, a small amount of replication-competent HIV can persist during HAART, allowing the virus to re-emerge if therapy is ceased. One significant source of this persistent virus is a pool of long-lived, latently infected CD4+ T cells. This article outlines what is known about how this reservoir is established and maintained, and describes the model systems that have provided insights into the molecular mechanisms governing HIV latency. The therapeutic approaches for eliminating latent cells that have been attempted are also discussed, including how improvements in understanding of these persistent HIV reservoirs are being used to develop enhanced methods for their depletion. PMID:21318097

  8. Identification and characterization of latency-associated peptide-expressing γδ T cells.

    PubMed

    Rezende, Rafael M; da Cunha, Andre P; Kuhn, Chantal; Rubino, Stephen; M'Hamdi, Hanane; Gabriely, Galina; Vandeventer, Tyler; Liu, Shirong; Cialic, Ron; Pinheiro-Rosa, Natalia; Oliveira, Rafael P; Gaublomme, Jellert T; Obholzer, Nikolaus; Kozubek, James; Pochet, Nathalie; Faria, Ana M C; Weiner, Howard L

    2015-01-01

    γδ T cells are a subset of lymphocytes specialized in protecting the host against pathogens and tumours. Here we describe a subset of regulatory γδ T cells that express the latency-associated peptide (LAP), a membrane-bound TGF-β1. Thymic CD27+IFN-γ+CCR9+α4β7+TCRγδ+ cells migrate to the periphery, particularly to Peyer's patches and small intestine lamina propria, where they upregulate LAP, downregulate IFN-γ via ATF-3 expression and acquire a regulatory phenotype. TCRγδ+LAP+ cells express antigen presentation molecules and function as antigen presenting cells that induce CD4+Foxp3+ regulatory T cells, although TCRγδ+LAP+ cells do not themselves express Foxp3. Identification of TCRγδ+LAP+ regulatory cells provides an avenue for understanding immune regulation and biologic processes linked to intestinal function and disease. PMID:26644347

  9. Systematic Errors in Low-latency Gravitational Wave Parameter Estimation Impact Electromagnetic Follow-up Observations

    NASA Astrophysics Data System (ADS)

    Littenberg, Tyson B.; Farr, Ben; Coughlin, Scott; Kalogera, Vicky

    2016-03-01

    Among the most eagerly anticipated opportunities made possible by Advanced LIGO/Virgo are multimessenger observations of compact mergers. Optical counterparts may be short-lived so rapid characterization of gravitational wave (GW) events is paramount for discovering electromagnetic signatures. One way to meet the demand for rapid GW parameter estimation is to trade off accuracy for speed, using waveform models with simplified treatment of the compact objects’ spin. We report on the systematic errors in GW parameter estimation suffered when using different spin approximations to recover generic signals. Component mass measurements can be biased by \\gt 5σ using simple-precession waveforms and in excess of 20σ when non-spinning templates are employed. This suggests that electromagnetic observing campaigns should not take a strict approach to selecting which LIGO/Virgo candidates warrant follow-up observations based on low-latency mass estimates. For sky localization, we find that searched areas are up to a factor of ∼ 2 larger for non-spinning analyses, and are systematically larger for any of the simplified waveforms considered in our analysis. Distance biases for the non-precessing waveforms can be in excess of 100% and are largest when the spin angular momenta are in the orbital plane of the binary. We confirm that spin-aligned waveforms should be used for low-latency parameter estimation at the minimum. Including simple precession, though more computationally costly, mitigates biases except for signals with extreme precession effects. Our results shine a spotlight on the critical need for development of computationally inexpensive precessing waveforms and/or massively parallel algorithms for parameter estimation.

  10. Contralateral Noise Stimulation Delays P300 Latency in School-Aged Children

    PubMed Central

    Ubiali, Thalita; Sanfins, Milaine Dominici; Borges, Leticia Reis; Colella-Santos, Maria Francisca

    2016-01-01

    Background and Objective The auditory cortex modulates auditory afferents through the olivocochlear system, which innervates the outer hair cells and the afferent neurons under the inner hair cells in the cochlea. Most of the studies that investigated the efferent activity in humans focused on evaluating the suppression of the otoacoustic emissions by stimulating the contralateral ear with noise, which assesses the activation of the medial olivocochlear bundle. The neurophysiology and the mechanisms involving efferent activity on higher regions of the auditory pathway, however, are still unknown. Also, the lack of studies investigating the effects of noise on human auditory cortex, especially in peadiatric population, points to the need for recording the late auditory potentials in noise conditions. Assessing the auditory efferents in schoolaged children is highly important due to some of its attributed functions such as selective attention and signal detection in noise, which are important abilities related to the development of language and academic skills. For this reason, the aim of the present study was to evaluate the effects of noise on P300 responses of children with normal hearing. Methods P300 was recorded in 27 children aged from 8 to 14 years with normal hearing in two conditions: with and whitout contralateral white noise stimulation. Results P300 latencies were significantly longer at the presence of contralateral noise. No significant changes were observed for the amplitude values. Conclusion Contralateral white noise stimulation delayed P300 latency in a group of school-aged children with normal hearing. These results suggest a possible influence of the medial olivocochlear activation on P300 responses under noise condition. PMID:26849224

  11. Chromatin structure regulates human cytomegalovirus gene expression during latency, reactivation and lytic infection.

    PubMed

    Sinclair, John

    2010-01-01

    Infection of cells with human cytomegalovirus (HCMV) has two potential outcomes. For instance, infection of fibroblasts results in extensive viral gene expression, viral DNA replication and release of progeny virus. In contrast, in undifferentiated myeloid cells, the lytic transcription programme of HCMV is effectively suppressed and cells undergo latent infection. It is now accepted that the suppression of viral lytic gene expression observed during latency in myeloid cells is a result of the inability of undifferentiated cell types to support robust viral immediate early (IE) gene expression--crucial genes responsible for driving the lytic cycle. The repression of IE gene expression in undifferentiated myeloid cells, at least in part, results from specific post-translational modifications of histones associated with the viral major immediate early promoter (MIEP). In cells of the early myeloid lineage, the histone modifications present on the MIEP impart on it a repressive chromatin structure preventing transcriptional activity. Reactivation of HCMV lytic infection is correlated to changes in histone modifications around the MIEP resulting in a chromatin structure conducive to transcriptional activity. These changes are intimately linked with the differentiation of myeloid cells - a phenomenon known to reactivate latent virus in vivo. Chromatin structure of the viral MIEP, therefore, plays a crucial role in latency and reactivation of this persistent human herpesvirus. Whether chromatin-mediated regulation of viral lytic gene expression also occurs, is only beginning to be addressed. However, recent work suggests that all classes of lytic HCMV promoters are subjected to regulation by post-translational modification of their associated histones throughout the time course of infection. Incoming viral genomes appear to be the targets of intrinsic cellular defence mechanisms which attempt to silence viral gene expression through chromatinisation. Viral functions

  12. Origin of the facial long latency responses elicited by magnetic stimulation.

    PubMed

    Rimpiläinen, I

    1994-04-01

    With magnetic stimulation (MS) it is possible to elicit bilateral long latency facial motor responses (LLRs). Due to a relatively wide magnetic field, the site of neural activation may take place in many different structures. The purpose of this study was to determine the site of origin of facial LLRs. The motor long latency responses were recorded bilaterally on the naso-labial folds (NLFs) with reference electrodes on the nose, and on some subjects also with reference electrodes on the chin. The stimulating coil was placed in the right parietal area. LLRs obtained with MS were compared to LLRs elicited electrically at the right stylomastoid foramen, supraorbital foramen, as well as cutaneous sensory area V1 of the trigeminal nerve. In addition, right sided high intensity electrical stimuli, paired magnetic stimulation and electrical stimulation with interstimulus intervals ranging from 0 to 80 msec were also applied for comparison. LLRs recorded with reference to the nose were always elicitable with MS as well as with the other stimulation procedures. The responses elicited with MS did not differ from those elicited electrically at various extracranial stimulation sites. With paired stimuli the second LLRs were inhibited by the preceding stimulation, whether given magnetically or electrically. In subjects with elicitable LLRs with chin references, the responses were always bilateral. Based on the similar characteristics with extracranial electrical stimuli, bilateral distribution of the responses, and inhibition of the second response with paired stimuli, it is concluded that the neural origin of LLRs to MS is in the extracranial trigeminal or facial nerve branches. PMID:7512918

  13. Sleep Perception in Obstructive Sleep Apnea: A Study Using Polysomnography and the Multiple Sleep Latency Test

    PubMed Central

    Nam, Hyunwoo; Lim, Jae-Sung; Kim, Jun-Soon; Lee, Keon-Joo; Koo, Dae Lim

    2016-01-01

    Background and Purpose Discrepancies between objectively measured sleep and subjective sleep perception in patients with insomnia have been reported. However, few studies have investigated sleep-state misperception in patients with obstructive sleep apnea (OSA). We designed this study to 1) delineate the factors that could affect this discrepancy and 2) infer an underlying mechanism in patients with OSA. Methods We recruited patients who visited our sleep clinic for the evaluation of their snoring and/or observed OSA. Participants completed a structured questionnaire and underwent overnight polysomnography. On the following day, five sessions of the multiple sleep latency test (MSLT) were applied. We divided the patients into two groups: normal sleep perception and abnormal perception. The abnormal-perception group included patients whose perceived total sleep time was less than 80% of that measured in polysomnography. Results Fifty OSA patients were enrolled from a university hospital sleep clinic. Excessive daytime sleepiness, periodic limb movement index (PLMI), and the presence of dreaming were positively associated with poor sleep perception. REM sleep near the sleep termination exerted important effects. Respiratory disturbance parameters were not related to sleep perception. There was a prolongation in the sleep latency in the first session of the MSLT and we suspected that a delayed sleep phase occurred in poor-sleep perceivers. Conclusions As an objectively good sleep does not match the subjective good-sleep perception in OSA, physicians should keep in mind that OSA patients who perceive that they have slept well does not mean that their OSA is less severe. PMID:27074296

  14. OTRA-THS MAC to reduce Power Outage Data Collection Latency in a smart meter network

    SciTech Connect

    Garlapati, Shravan K; Kuruganti, Phani Teja; Buehrer, Richard M; Reed, Jeffrey H

    2014-01-01

    The deployment of advanced metering infrastructure by the electric utilities poses unique communication challenges, particularly as the number of meters per aggregator increases. During a power outage, a smart meter tries to report it instantaneously to the electric utility. In a densely populated residential/industrial locality, it is possible that a large number of smart meters simultaneously try to get access to the communication network to report the power outage. If the number of smart meters is very high of the order of tens of thousands (metropolitan areas), the power outage data flooding can lead to Random Access CHannel (RACH) congestion. Several utilities are considering the use of cellular network for smart meter communications. In 3G/4G cellular networks, RACH congestion not only leads to collisions, retransmissions and increased RACH delays, but also has the potential to disrupt the dedicated traffic flow by increasing the interference levels (3G CDMA). In order to overcome this problem, in this paper we propose a Time Hierarchical Scheme (THS) that reduces the intensity of power outage data flooding and power outage reporting delay by 6/7th, and 17/18th when compared to their respective values without THS. Also, we propose an Optimum Transmission Rate Adaptive (OTRA) MAC to optimize the latency in power outage data collection. The analysis and simulation results presented in this paper show that both the OTRA and THS features of the proposed MAC results in a Power Outage Data Collection Latency (PODCL) that is 1/10th of the 4G LTE PODCL.

  15. Neuroanatomic localization of priming effects for famous faces with latency-corrected event-related potentials.

    PubMed

    Kashyap, Rajan; Ouyang, Guang; Sommer, Werner; Zhou, Changsong

    2016-02-01

    The late components of event-related brain potentials (ERPs) pose a difficult problem in source localization. One of the reasons is the smearing of these components in conventional averaging because of trial-to-trial latency-variability. The smearing problem may be addressed by reconstructing the ERPs after latency synchronization with the Residue Iteration Decomposition (RIDE) method. Here we assessed whether the benefits of RIDE at the surface level also improve source localization of RIDE-reconstructed ERPs (RERPs) measured in a face priming paradigm. Separate source models for conventionally averaged ERPs and RERPs were derived and sources were localized for both early and late components. Jackknife averaging on the data was used to reduce the residual variance during source localization compared to conventional source model fitting on individual subject data. Distances between corresponding sources of both ERP and RERP models were measured to check consistency in both source models. Sources for activity around P100, N170, early repetition effect (ERE/N250r) and late repetition effect (LRE/N400) were reported and priming effects in these sources were evaluated for six time windows. Significant improvement in priming effect of the late sources was found from the RERP source model, especially in the Medio-Temporal Lobe, Prefrontal Cortex, and Anterior Temporal Lobe. Consistent with previous studies, we found early priming effects in the right hemisphere and late priming effects in the left hemisphere. Also, the priming effects in right hemisphere outnumbered the left hemisphere, signifying dominance of right hemisphere in face recognition. In conclusion, RIDE reconstructed ERPs promise a comprehensive understanding of the time-resolved dynamics the late sources play during face recognition. PMID:26683085

  16. Drug Testing in Children with Excessive Daytime Sleepiness During Multiple Sleep Latency Testing

    PubMed Central

    Katz, Eliot S.; Maski, Kiran; Jenkins, Amanda J.

    2014-01-01

    Study Objective: To determine the incidence of positive drug screens in children undergoing a multiple sleep latency test (MSLT) for evaluation of excessive daytime sleepiness (EDS). Methods: A retrospective analysis was performed in children evaluated at the Boston Children's Hospital Sleep Center between 1998 and 2013 who underwent MSLT for EDS with a concurrent urine and/or serum drug screen. Results: A total of 210 MSLTs were accompanied by drug testing. Children were 12.7 ± 3.7 years old (mean ± SD), 43% were female, and 24% had narcolepsy. Positive tests were obtained in 32% for caffeine, 5% for prescription medications, and 4% for over-the-counter drugs. No drugs of abuse were identified. Children testing positive for caffeine were older (13.8 ± 3.5 vs. 12.4 ± 3.7) and more likely female (59% vs. 36%), but did not differ in MSLT or overnight polysomnographic parameters compared to children without caffeine detected. Overall, only 14% had specific documentation regarding caffeine intake, though 90% were referred from a sleep clinic. Of the children testing positive for caffeine, 5% acknowledged use, 3% denied use, and 92% did not have a documented caffeine intake history during their sleep clinic visit. Conclusions: Routine drug testing for drugs of abuse during an MSLT for EDS yielded no positive results over a 15-year period, indicating that this routine practice is unnecessary in our pediatric population without specific concerns. However, objective evidence for caffeine exposure was found in 32% of tested children undergoing an MSLT. Sleep physicians rarely documented the caffeine intake history during clinic visits for EDS. Citation: Katz ES, Maski K, Jenkins AJ. Drug testing in children with excessive daytime sleepiness during multiple sleep latency testing. J Clin Sleep Med 2014;10(8):897-901. PMID:25126037

  17. Involvement of histone methyltransferase GLP in HIV-1 latency through catalysis of H3K9 dimethylation

    SciTech Connect

    Ding, Donglin; Qu, Xiying; Li, Lin; Zhou, Xin; Liu, Sijie; Lin, Shiguan; Wang, Pengfei; Liu, Shaohui; Kong, Chuijin; Wang, Xiaohui; Liu, Lin; Zhu, Huanzhang

    2013-06-05

    Understanding the mechanism of HIV-1 latency is crucial to eradication of the viral reservoir in HIV-1-infected individuals. However, the role of histone methyltransferase (HMT) G9a-like protein (GLP) in HIV-1 latency is still unclear. In the present work, we established four clonal cell lines containing HIV-1 vector. We found that the integration sites of most clonal cell lines favored active gene regions. However, we also observed hypomethylation of CpG of HIV 5′LTR in all four clonal cell lines. Additionally, 5′-deoxy-5′-methylthioadenosine (MTA), a broad-spectrum histone methyltransferase inhibitor, was used to examine the role of histone methylation in HIV-1 latency. MTA was found to decrease the level of H3K9 dimethylation, causing reactivation of latent HIV-1 in C11 cells. GLP knockdown by small interfering RNA clearly induced HIV-1 LTR expression. Results suggest that GLP may play a significant role in the maintenance of HIV-1 latency by catalyzing dimethylation of H3K9. - Highlights: ► We have established an in vitro model of HIV-1 latency. ► The integration sites of most clonal cell lines favor in active gene regions. ► Hypomethylation occurs in CpG islands of HIV 5′LTR in all four clonal cell lines. ► MTA can reactivate latent HIV-1 by decreasing the level of H3K9 me2 in C11 cells. ► HMT GLP may play a significant role in the maintenance of HIV-1 latency.

  18. Canine Sense and Sensibility: Tipping Points and Response Latency Variability as an Optimism Index in a Canine Judgement Bias Assessment

    PubMed Central

    Starling, Melissa J.; Branson, Nicholas; Cody, Denis; Starling, Timothy R.; McGreevy, Paul D.

    2014-01-01

    Recent advances in animal welfare science used judgement bias, a type of cognitive bias, as a means to objectively measure an animal's affective state. It is postulated that animals showing heightened expectation of positive outcomes may be categorised optimistic, while those showing heightened expectations of negative outcomes may be considered pessimistic. This study pioneers the use of a portable, automated apparatus to train and test the judgement bias of dogs. Dogs were trained in a discrimination task in which they learned to touch a target after a tone associated with a lactose-free milk reward and abstain from touching the target after a tone associated with water. Their judgement bias was then probed by presenting tones between those learned in the discrimination task and measuring their latency to respond by touching the target. A Cox's Proportional Hazards model was used to analyse censored response latency data. Dog and Cue both had a highly significant effect on latency and risk of touching a target. This indicates that judgement bias both exists in dogs and differs between dogs. Test number also had a significant effect, indicating that dogs were less likely to touch the target over successive tests. Detailed examination of the response latencies revealed tipping points where average latency increased by 100% or more, giving an indication of where dogs began to treat ambiguous cues as predicting more negative outcomes than positive ones. Variability scores were calculated to provide an index of optimism using average latency and standard deviation at cues after the tipping point. The use of a mathematical approach to assessing judgement bias data in animal studies offers a more detailed interpretation than traditional statistical analyses. This study provides proof of concept for the use of an automated apparatus for measuring cognitive bias in dogs. PMID:25229458

  19. Canine sense and sensibility: tipping points and response latency variability as an optimism index in a canine judgement bias assessment.

    PubMed

    Starling, Melissa J; Branson, Nicholas; Cody, Denis; Starling, Timothy R; McGreevy, Paul D

    2014-01-01

    Recent advances in animal welfare science used judgement bias, a type of cognitive bias, as a means to objectively measure an animal's affective state. It is postulated that animals showing heightened expectation of positive outcomes may be categorised optimistic, while those showing heightened expectations of negative outcomes may be considered pessimistic. This study pioneers the use of a portable, automated apparatus to train and test the judgement bias of dogs. Dogs were trained in a discrimination task in which they learned to touch a target after a tone associated with a lactose-free milk reward and abstain from touching the target after a tone associated with water. Their judgement bias was then probed by presenting tones between those learned in the discrimination task and measuring their latency to respond by touching the target. A Cox's Proportional Hazards model was used to analyse censored response latency data. Dog and Cue both had a highly significant effect on latency and risk of touching a target. This indicates that judgement bias both exists in dogs and differs between dogs. Test number also had a significant effect, indicating that dogs were less likely to touch the target over successive tests. Detailed examination of the response latencies revealed tipping points where average latency increased by 100% or more, giving an indication of where dogs began to treat ambiguous cues as predicting more negative outcomes than positive ones. Variability scores were calculated to provide an index of optimism using average latency and standard deviation at cues after the tipping point. The use of a mathematical approach to assessing judgement bias data in animal studies offers a more detailed interpretation than traditional statistical analyses. This study provides proof of concept for the use of an automated apparatus for measuring cognitive bias in dogs. PMID:25229458

  20. A 348-base-pair region in the latency-associated transcript facilitates herpes simplex virus type 1 reactivation.

    PubMed Central

    Bloom, D C; Hill, J M; Devi-Rao, G; Wagner, E K; Feldman, L T; Stevens, J G

    1996-01-01

    Latency-associated transcript (LAT) promoter deletion mutants of herpes simplex virus type 1 have a reduced capacity to reactivate following adrenergic induction in the rabbit eye model. We have mapped a reactivation phenotype within LAT and describe the construction of recombinants in which poly(A) addition sites have been placed at intervals within the LAT region to form truncated LAT transcripts. These mutants localize the induced reactivation phenotype to the 5' end of LAT. To further define this region, we constructed a recombinant containing a 348-bp deletion located 217 bp downstream of the transcription start site of the 8.5-kb LAT. This virus, 17delta348, expresses LAT but exhibits a significantly reduced ability to reactivate following epinephrine iontophoresis into the cornea. Quantitative DNA PCR analysis reveals that 17delta 348 establishes a latent infection within rabbit trigeminal ganglia with the same efficiency as does either the rescuant or wild-type virus. The region deleted in 17delta348 encodes three potential translational initiators (ATGs) which we have mutated and demonstrated to be dispensable for epinephrine-induced reactivation. In addition, three smaller deletions within this region have been constructed and were shown to reactivate at wild-type (parent) frequencies. These studies indicate that an undefined portion of the 348-bp region is required to facilitate induced reactivation. Sequence analysis of this 348-bp region revealed a CpG island which extends into the LAT promoter and which possesses homology to conserved elements within the mouse and human XIST transcript encoded on the X chromosome. Possible implications of these elements in the regulation of LAT expression are discussed. PMID:8642650

  1. Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes.

    PubMed

    You, Jianxin; Srinivasan, Viswanathan; Denis, Gerald V; Harrington, William J; Ballestas, Mary E; Kaye, Kenneth M; Howley, Peter M

    2006-09-01

    The latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) is required for viral episome maintenance in host cells during latent infection. Two regions of the protein have been implicated in tethering LANA/viral episomes to the host mitotic chromosomes, and LANA chromosome-binding sites are subjects of high interest. Because previous studies had identified bromodomain protein Brd4 as the mitotic chromosome anchor for the bovine papillomavirus E2 protein, which tethers the viral episomes to host mitotic chromosomes (J. You, J. L. Croyle, A. Nishimura, K. Ozato, and P. M. Howley, Cell 117:349-360, 2004, and J. You, M. R. Schweiger, and P. M. Howley, J. Virol. 79:14956-14961, 2005), we examined whether KSHV LANA interacts with Brd4. We found that LANA binds Brd4 in vivo and in vitro and that the binding is mediated by a direct protein-protein interaction between the ET (extraterminal) domain of Brd4 and a carboxyl-terminal region of LANA previously implicated in chromosome binding. Brd4 associates with mitotic chromosomes throughout mitosis and demonstrates a strong colocalization with LANA and the KSHV episomes on host mitotic chromosomes. Although another bromodomain protein, RING3/Brd2, binds to LANA in a similar fashion in vitro, it is largely excluded from the mitotic chromosomes in KSHV-uninfected cells and is partially recruited to the chromosomes in KSHV-infected cells. These data identify Brd4 as an interacting protein for the carboxyl terminus of LANA on mitotic chromosomes and suggest distinct functional roles for the two bromodomain proteins RING3/Brd2 and Brd4 in LANA binding. Additionally, because Brd4 has recently been shown to have a role in transcription, we examined whether Brd4 can regulate the CDK2 promoter, which can be transactivated by LANA. PMID:16940503

  2. Effect of macular ablation on frequency and latency of motion-induced emesis in the squirrel monkey

    NASA Technical Reports Server (NTRS)

    Brizzee, Kenneth R.; Igarashi, Makoto

    1986-01-01

    Three previously motion-emetic sensitive squirrel monkeys were rendered refractory to a standard motion-emetic regimen by a two-stage utriculosacculectomy procedure which preserved the cristae ampullares of semicircular canals. Three nonoperated control squirrel monkeys tested on the same motion-emetic regimen time schedule as the operated animals remained motion-emetic sensitive with regard to incidence, frequency, and latency of motion-induced emetic responses. Following a sham surgical procedure (stapedectomy) performed on two of the latter animals and one additional new animal, the emetic incidence decreased from 100 to 89 percent, but the frequency and latency were not altered significantly.

  3. Epstein-Barr virus (EBV) association and latency profile in pediatric Burkitt's lymphoma: experience of a single institution in Argentina.

    PubMed

    Lara, Julia; Cohen, Melina; De Matteo, Elena; Aversa, Luis; Preciado, Maria Victoria; Chabay, Paola

    2014-05-01

    The aim of this study is to characterize EBV expression and latency pattern in pediatric Burkitt's lymphoma in a single institution in Argentina. EBV-encoded RNA or protein was analyzed in 27 patients. EBERs was expressed in 37% of patients (29% of immunocompetent and 100% of immunosuppressed patients). EBV-positive cases were observed exclusively in patients younger than 5 years old. EBV association with immunocompetent patients exhibits the sporadic pattern in region under study, while its presence in patients infected with HIV was higher than described previously. EBV latency I profile was present in most of the patients, except for two immunosuppressed patients who displayed LMP1 expression. PMID:24027016

  4. Evidence for a contribution of the motor cortex to the long-latency stretch reflex of the human thumb.

    PubMed Central

    Capaday, C; Forget, R; Fraser, R; Lamarre, Y

    1991-01-01

    1. In normal subjects, transcranial magnetic stimulation of the hand region of the motor cortex evokes motor responses only in contralateral hand muscles at a latency of about 19-24 ms. In contrast, stimulation of the motor cortex of three mirror movement subjects evoked, nearly simultaneously, motor responses in hand muscles on both sides of the body at latencies similar to those of normal subjects. In these subjects no other neuroanatomical pathways appear to be abnormally directed across the mid-line. Thus, their mirror movements are probably due to a projection of the corticospinal tract to homologous motoneurone pools on each side of the body. 2. We reasoned that if the motor cortex contributes to the generation of long-latency stretch reflex responses then in these mirror movement subjects stretching a muscle on one side of the body should produce long-latency reflex responses in the ipsilateral and the homologous contralateral muscle. 3. To test this idea experiments were done on normal human subjects and on the subjects with mirror movements. The electromyographic (EMG) activity of the flexor pollicis longus muscle (FPL) on each side of the body was recorded. Stretch of the distal phalanx of the thumb of one hand produced a series of distinct reflex EMG responses in the ipsilateral FPL. The earliest response, when present, began at 25 ms (S.D. = 3.5 ms) and was followed by responses at 40 (S.D. = 3.9 ms) and 56 ms (S.D. = 4.3 ms). There was no difference, either in timing or intensity, between the ipsilateral FPL EMG responses of normal subjects and those of the mirror movement subjects. 4. No response of any kind was observed in the contralateral (unstretched) FPL of normal subjects. In contrast, we observed in all three mirror movement subjects EMG responses in the contralateral (unstretched) FPL beginning at 45-50 ms. The latency of this response is considerably shorter than the fastest voluntary kinaesthetic reaction time, which was on average 130 ms (S

  5. The latency information theory revolution, part II: its statistical physics bridges and the discovery of the time dual of thermodynamics

    NASA Astrophysics Data System (ADS)

    Feria, Erlan H.

    2010-04-01

    Statistical physics bridges for latency information theory (LIT) are revealed in this second paper of a three paper series that include the discovery of the time dual of thermodynamics. LIT is the universal guidance theory for efficient system designs that has inherently surfaced from the confluence of five ideas. They are: 1) The source entropy and channel capacity performance bounds of Shannon's mathematical theory of communication; 2) The latency time (LT) certainty of Einstein's relativity theory; 3) The information space (IS) uncertainty of Heisenberg's quantum physics; 4) The black hole Hawking radiation and its Boltzmann thermodynamics entropy S in SI J/K; and 5) The author's 1978 conjecture of a structural-physical LT-certainty/IS-uncertainty duality for stochastic control. LIT is characterized by a four quadrants revolution with two mathematical-intelligence quadrants and two physical-life ones. Each quadrant of LIT is assumed to be physically independent of the others and guides its designs with an entropy if it is IS-uncertain and an ectropy if it is LT-certain. While LIT's physical-life quadrants I and III address the efficient use of life time by physical signal movers and of life space by physical signal retainers, respectively, its mathematicalintelligence quadrants II and IV address the efficient use of intelligence space by mathematical signal sources and of processing time by mathematical signal processors, respectively. Seven results are stated next that relate to the revelation of statistical physics bridges for LIT. They are: 1) Thermodynamics, a special case of statistical physics, has a time dual named lingerdynamics; 2) Lingerdynamics has a dimensionless lingerdynamics-ectropy Z that is the LT-certainty dual of a dimensionless thermodynamics-entropy, and like thermodynamics has four physical laws that drive the Universe; 3) S advances a bridge between quadrant II's source-entropy H in bit units and quadrant III's retainer-entropy N in SI m2

  6. User Needs and Assessing the Impact of Low Latency NASA Earth Observation Data Availability on Societal Benefit

    NASA Technical Reports Server (NTRS)

    Brown, Molly E.; Carroll, Mark L.; Escobar, Vanessa M.

    2014-01-01

    Since the advent of NASA's Earth Observing System, knowledge of the practical benefits of Earth science data has grown considerably. The community using NASA Earth science observations in applications has grown significantly, with increasing sophistication to serve national interests. Data latency, or how quickly communities receive science observations after acquisition, can have a direct impact on the applications and usability of the information. This study was conducted to determine how users are incorporating NASA data into applications and operational processes to benefit society beyond scientific research, as well as to determine the need for data latency of less than 12 h. The results of the analysis clearly show the significant benefit to society of serving the needs of the agricultural, emergency response, environmental monitoring and weather communities who use rapidly delivered, accurate Earth science data. The study also showed the potential of expanding the communities who use low latency NASA science data products to provide new ways of transforming data into information. These benefits can be achieved with a clear and consistent NASA policy on product latency.

  7. Some Effects of Variations in Response Time Latency on Speech Rate, Interruptions, and Fluency in Children's Speech.

    ERIC Educational Resources Information Center

    Newman, Linda L.; Smit, Ann B.

    1989-01-01

    The study examined adult-child interactions during conversation with respect to the effects of adult paralinguistic speech variations on the speech production of four four-year-old children. Analysis indicated that each child's response time latency (RTL) was significantly longer when the experimenter's RTL was longer. (Author/DB)

  8. In vitro system using human neurons demonstrates that varicella-zoster vaccine virus is impaired for reactivation, but not latency.

    PubMed

    Sadaoka, Tomohiko; Depledge, Daniel P; Rajbhandari, Labchan; Venkatesan, Arun; Breuer, Judith; Cohen, Jeffrey I

    2016-04-26

    Varicella-zoster virus (VZV) establishes latency in human sensory and cranial nerve ganglia during primary infection (varicella), and the virus can reactivate and cause zoster after primary infection. The mechanism of how the virus establishes and maintains latency and how it reactivates is poorly understood, largely due to the lack of robust models. We found that axonal infection of neurons derived from hESCs in a microfluidic device with cell-free parental Oka (POka) VZV resulted in latent infection with inability to detect several viral mRNAs by reverse transcriptase-quantitative PCR, no production of infectious virus, and maintenance of the viral DNA genome in endless configuration, consistent with an episome configuration. With deep sequencing, however, multiple viral mRNAs were detected. Treatment of the latently infected neurons with Ab to NGF resulted in production of infectious virus in about 25% of the latently infected cultures. Axonal infection of neurons with vaccine Oka (VOka) VZV resulted in a latent infection similar to infection with POka; however, in contrast to POka, VOka-infected neurons were markedly impaired for reactivation after treatment with Ab to NGF. In addition, viral transcription was markedly reduced in neurons latently infected with VOka compared with POka. Our in vitro system recapitulates both VZV latency and reactivation in vivo and may be used to study viral vaccines for their ability to establish latency and reactivate. PMID:27078099

  9. Recall Latencies, Confidence, and Output Positions of True and False Memories: Implications for Recall and Metamemory Theories

    ERIC Educational Resources Information Center

    Jou, Jerwen

    2008-01-01

    Recall latency, recall accuracy rate, and recall confidence were examined in free recall as a function of recall output serial position using a modified Deese-Roediger-McDermott paradigm to test a strength-based theory against the dual-retrieval process theory of recall output sequence. The strength theory predicts the item output sequence to be…

  10. Atypical Long-Latency Auditory Event-Related Potentials in a Subset of Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Bishop, Dorothy V. M.; Hardiman, Mervyn; Uwer, Ruth; von Suchodoletz, Waldemar

    2007-01-01

    It has been proposed that specific language impairment (SLI) is the consequence of low-level abnormalities in auditory perception. However, studies of long-latency auditory ERPs in children with SLI have generated inconsistent findings. A possible reason for this inconsistency is the heterogeneity of SLI. The intraclass correlation (ICC) has been…

  11. The Effect of Perceived Child Anxiety Status on Parental Latency to Intervene with Anxious and Nonanxious Youth

    ERIC Educational Resources Information Center

    Aschenbrand, Sasha G.; Kendall, Philip C.

    2012-01-01

    Objective: We examined the effect of perceived child anxiety status on parental latency to intervene with anxious and nonanxious youth. Method: Parents (68) of anxiety-disordered (PAD) and nonanxiety-disordered (PNAD; 56) children participated. Participants listened and responded to an audio vignette of a parent-child interaction: Half were told…

  12. The Effects of Onset and Offset Warning and Post-Target Stimuli on the Saccade Latency of Children and Adults.

    ERIC Educational Resources Information Center

    Ross, Susan M.; Ross, Leonard E.

    1983-01-01

    Two studies involving children (mean age of 10 years) and adults investigated the effects of visual stimulus onsets and offsets on the latency of saccades to peripheral targets. Results were interpreted as indicating that, while stimulus intake processes have a greater interference effect on children's eye movements, oculomotor processes are…

  13. Using a Multicomponent Adapted Power Card Strategy to Decrease Latency during Interactivity Transitions for Three Children with Developmental Disabilities

    ERIC Educational Resources Information Center

    Angell, Maureen E.; Nicholson, Joanna K.; Watts, Emily H.; Blum, Craig

    2011-01-01

    An adapted Power Card strategy was examined to determine effectiveness in decreasing latency in responding to teacher cues to initiate interactivity transitions in the classroom among three students, aged 10 to 11 years, with developmental disabilities (i.e., one with autism and two with intellectual disability). The Power Card strategy, a form of…

  14. Temporal dynamics of choice behavior in rats and humans: an examination of pre- and post-choice latencies

    PubMed Central

    Fam, Justine; Westbrook, Fred; Arabzadeh, Ehsan

    2016-01-01

    Identifying similarities and differences in choice behavior across species is informative about how basic mechanisms give rise to more complex processes. In the present study, we compared pre- and post-choice latencies between rats and humans under two paradigms. In Experiment 1, we used a cued choice paradigm where subjects were presented with a cue that directed them as to which of two options to respond for rewards. In Experiment 2, subjects were free to choose between two options in order to procure rewards. In both Experiments rewards were delivered with distinct probabilities. The trial structure used in these experiments allowed the choice process to be decomposed into pre- and post-choice processes. Overall, post-choice latencies reflected the difference in reward probability between the two options, where latencies for the option with higher probability of reward were longer than those for the option with lower probability of reward. An interesting difference between rats and humans was observed: the choice behavior for humans, but not rats, was sensitive to the free-choice aspect of the tasks, such that in free-choice trials post-choice latencies no longer reflected the difference in reward probabilities between the two options. PMID:26862000

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

    NASA Astrophysics Data System (ADS)

    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.

  16. An animal model of slot machine gambling: the effect of structural characteristics on response latency and persistence.

    PubMed

    Peters, Heather; Hunt, Maree; Harper, David

    2010-12-01

    Despite the prevalence of problem gamblers and the ethical issues involved in studying gambling behavior with humans, few animal models of gambling have been developed. When designing an animal model it is necessary to determine if behavior in the paradigm is similar to human gambling. In human studies, response latencies following winning trials and near win trials are greater than those following clear losses. Weatherly and Derenne (Anal Gambl Behav 1:79-89, 2007) investigated whether this pattern was found with rats working in an animal analogue of slot machine gambling. They found a similar pattern of response latencies but the subjects' behavior did not come under control of the visual stimuli signalling the different outcomes. The animal model of slot machine gambling we used addressed procedural issues in Weatherly and Derenne's model and examined whether reinforcer magnitude and the presence of near win trials influenced response latency and resistance to extinction. Response latencies of the six female Norway Hooded rats varied as a function of reinforcer magnitude and the presence of near-win trials. These results are consistent with prior research and with the idea that near win trials serve as conditional reinforcers. PMID:20217196

  17. Word Retrieval Latencies as a Function of Frequency and Age-of-Acquisition Priming, Repeated Trials, and Individual Differences.

    ERIC Educational Resources Information Center

    Carroll, John B.

    In three immediately succeeding trials, 45 young adults named 50 pictures of objects as rapidly as possible; word retrieval latencies were measured for each item. Before each trial, one experimental group was given information as to the word frequency (WF) level of the items' names. The other experimental group was given information as to the…

  18. Effects of Planning and Goal Setting on Reducing Latency to Task Engagement for Struggling Readers in Middle School

    ERIC Educational Resources Information Center

    Stevenson, Nathan A.

    2016-01-01

    The current study examined the effect of a planning and goal-setting intervention in reducing latency to task engagement. This study used a multiple baseline design across participants for two seventh-grade and two eighth-grade students in a remedial reading class. The behavioral intervention was administered in small groups at the start of each…

  19. Experimental evidence for the basal generation place of the short-latency transient-evoked otoacoustic emissions.

    PubMed

    Moleti, A; Sisto, R; Lucertini, M

    2014-05-01

    Time-frequency analysis of the transient-evoked otoacoustic emission response was performed on a population of subjects affected by sensory-neural hearing loss characterized by a sharp audiometric profile, caused by firearm noise exposure (42 ears), and on a control population of normal-hearing subjects (84 ears). Time-frequency filtering permitted a careful evaluation of the relation between the audiometric profile and the spectral shape of the long- and short-latency otoacoustic components. Both filtered spectra closely follow the shape of the audiometric profile, with a frequency shift between them. The typical frequency shift was evaluated by averaging the otoacoustic spectra and the audiograms among groups of ears with the same cutoff frequency. Assuming that the otoacoustic emission source function depends on the local effectiveness of the cochlear amplifier, this experimental evidence suggests that the short-latency response is generated at a cochlear place displaced towards the base by about 0.5-1 mm with respect to the generation place of the long-latency component. The analysis of the control group demonstrates that, below 4 kHz, the observed effect is not dependent on the data acquisition and analysis procedure. These results confirm previous theoretical estimates and independent experimental evidence based on the measured latency difference between the two components. PMID:24815267

  20. Somatosensory cortical efferent neurons of the awake rabbit: latencies to activation via supra--and subthreshold receptive fields.

    PubMed

    Swadlow, H A; Hicks, T P

    1996-04-01

    1. Latencies to peripheral sensory stimulation were examined in four classes of antidromically identified efferent neurons in the primary somatosensory cortex (S1) of awake rabbits. Both suprathreshold responses (action potentials) and subthreshold responses were examined. Subthreshold responses were examined by monitoring the thresholds of efferent neurons to juxtasomal current pulses (JSCPs) delivered through the recording microelectrode (usually 1-3 microA). Through the use of this method, excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) were manifested as decreases and increases in threshold, respectively. Efferent populations examined included callosal (CC) neurons, ipsilateral corticocortical (C-IC) neurons, and descending corticofugal neurons of layer 5 (CF-5) and layer 6 (CF-6). Very brief air puffs (rise and fall times 0.6 ms) were delivered to the receptor periphery via a high-speed solenoid valve. 2. Whereas all CF-5 neurons had demonstrable suprathreshold excitatory and/or inhibitory responses to peripheral stimulation, most CC, C-IC, and CF-6 neurons did not. CC and CF-6 neurons that yielded no suprathreshold response to the stimulus had lower axonal conduction velocities than those that did respond (P < 0.0001 in both cases). However, subthreshold receptive fields could be demonstrated in many of the otherwise unresponsive CC (81%), C-IC (88%), and CF-6 (43%) neurons. The subthreshold responses usually consisted of an initial excitatory component (a decrease in the threshold to the JSCP) and a subsequent long-duration (> 80 ms) inhibitory component. A few neurons (1 CC, 1 C-IC, and 5 CF-6) showed an initial short latency inhibitory response in the absence of any excitatory component. 3. Some CC and C-IC neurons yielded supra- and/or subthreshold responses to peripheral stimulation at latencies of 6.1-7 ms. All such neurons were found at intermediate cortical depths (thought to correspond to deep layer 2

  1. Asynchronous RTK precise DGNSS positioning method for deriving a low-latency high-rate output

    NASA Astrophysics Data System (ADS)

    Liang, Zhang; Hanfeng, Lv; Dingjie, Wang; Yanqing, Hou; Jie, Wu

    2015-07-01

    Low-latency high-rate (1 Hz) precise real-time kinematic (RTK) can be applied in high-speed scenarios such as aircraft automatic landing, precise agriculture and intelligent vehicle. The classic synchronous RTK (SRTK) precise differential GNSS (DGNSS) positioning technology, however, is not able to obtain a low-latency high-rate output for the rover receiver because of long data link transmission time delays (DLTTD) from the reference receiver. To overcome the long DLTTD, this paper proposes an asynchronous real-time kinematic (ARTK) method using asynchronous observations from two receivers. The asynchronous observation model (AOM) is developed based on undifferenced carrier phase observation equations of the two receivers at different epochs with short baseline. The ephemeris error and atmosphere delay are the possible main error sources on positioning accuracy in this model, and they are analyzed theoretically. In a short DLTTD and during a period of quiet ionosphere activity, the main error sources decreasing positioning accuracy are satellite orbital errors: the "inverted ephemeris error" and the integration of satellite velocity error which increase linearly along with DLTTD. The cycle slip of asynchronous double-differencing carrier phase is detected by TurboEdit method and repaired by the additional ambiguity parameter method. The AOM can deal with synchronous observation model (SOM) and achieve precise positioning solution with synchronous observations as well, since the SOM is only a specific case of AOM. The proposed method not only can reduce the cost of data collection and transmission, but can also support the mobile phone network data link transfer mode for the data of the reference receiver. This method can avoid data synchronizing process besides ambiguity initialization step, which is very convenient for real-time navigation of vehicles. The static and kinematic experiment results show that this method achieves 20 Hz or even higher rate output in

  2. Precise evaluation of GNSS position and latency errors in dynamic agricultural applications

    NASA Astrophysics Data System (ADS)

    Sama, Michael Patrick

    A method for precisely synchronizing an external serial data stream to the pulseper- second (PPS) output signal from a global navigation satellite-based system (GNSS) receiver was investigated. A signal timing device was designed that used a digital signal processor (DSP) with serial inputs and input captures to generate time stamps for asynchronous serial data based on an 58593.75 Hz internal timer. All temporal measurements were made directly in hardware to eliminate software latency. The resolution of the system was 17.1 is, which translated to less than one millimeter of horizontal position error at travel speeds typical of most agricultural operations. The dynamic error of a TTS was determined using a rotary test fixture. Tests were performed at angular velocities ranging from 0 to 3.72 rad/s and a radius of 0.635 m. Average latency from the TTS was shown to be consistently near 0.252 s for all angular velocities and less variable when using a reflector based machine target versus a prism target. Sight distance from the target to the TTS was shown to have very little effect on accuracy between 4 and 30 m. The TTS was determined to be a limited as a position reference for dynamic GNSS and vehicle auto-guidance testing based on angular velocity. The dynamic error of a GNSS receiver was determined using the rotary test fixture and modeled as discrete probability density functions for varying angular velocities and filter levels. GNSS position and fixture data were recorded for angular velocities of 0.824, 1.423, 2.018, 2.618, and 3.222 rad/s at a 1 m radius. Filter levels were adjusted to four available settings including; no filter, normal filter, high filter, and max filter. Each data set contained 4 hours of continuous operation and was replicated three times. Results showed that higher angular velocities increased the variability of the distribution of error while not having a significant effect on average error. The distribution of error tended to change

  3. The rate and latency of star formation in dense, massive clumps in the Milky Way

    NASA Astrophysics Data System (ADS)

    Heyer, M.; Gutermuth, R.; Urquhart, J. S.; Csengeri, T.; Wienen, M.; Leurini, S.; Menten, K.; Wyrowski, F.

    2016-04-01

    Context. Newborn stars form within the localized, high density regions of molecular clouds. The sequence and rate at which stars form in dense clumps and the dependence on local and global environments are key factors in developing descriptions of stellar production in galaxies. Aims: We seek to observationally constrain the rate and latency of star formation in dense massive clumps that are distributed throughout the Galaxy and to compare these results to proposed prescriptions for stellar production. Methods: A sample of 24 μm-based Class I protostars are linked to dust clumps that are embedded within molecular clouds selected from the APEX Telescope Large Area Survey of the Galaxy. We determine the fraction of star-forming clumps, f∗, that imposes a constraint on the latency of star formation in units of a clump's lifetime. Protostellar masses are estimated from models of circumstellar environments of young stellar objects from which star formation rates are derived. Physical properties of the clumps are calculated from 870 μm dust continuum emission and NH3 line emission. Results: Linear correlations are identified between the star formation rate surface density, ΣSFR, and the quantities ΣH2/τff and ΣH2/τcross, suggesting that star formation is regulated at the local scales of molecular clouds. The measured fraction of star forming clumps is 23%. Accounting for star formation within clumps that are excluded from our sample due to 24 μm saturation, this fraction can be as high as 31%, which is similar to previous results. Dense, massive clumps form primarily low mass (<1-2 M⊙) stars with emergent 24 μm fluxes below our sensitivity limit or are incapable of forming any stars for the initial 70% of their lifetimes. The low fraction of star forming clumps in the Galactic center relative to those located in the disk of the Milky Way is verified. Full Tables 2-4 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130

  4. miR-190 is upregulated in Epstein-Barr Virus type I latency and modulates cellular mRNAs involved in cell survival and viral reactivation.

    PubMed

    Cramer, Elizabeth M; Shao, Ying; Wang, Yan; Yuan, Yan

    2014-09-01

    Epstein-Barr Virus (EBV) is a prevalent human pathogen infecting over 90% of the population. Much of the success of the virus is attributed to its ability to maintain latency. The detailed mechanisms underlying the establishment and maintenance of EBV latency remain poorly understood. A microRNA profiling study revealed differential expression of many cellular miRNAs between types I and III latency cells, suggesting cellular miRNAs may play roles in regulating EBV latency. mir-190 is the most differentially up-regulated miRNA in type I latency cells as compared with type III latency cells and the up-regulation appears to be attributed to EBER RNAs that express in higher levels in type I latency cells than type III cells. With the aide of a lentiviral overexpression system and microarray analysis, several cellular mRNAs are identified as potential targets of mir-190. By targeting TP53INP1, miR-190 enhances cell survival by preventing apoptosis and relieving G0/G1 cell cycle arrest. Additionally, miR-190 down-regulates NR4A3, a cellular immediate-early gene for EBV reactivation, and inhibits the expression of the viral immediate-early gene bzlf1 and viral lytic DNA replication. Taken together, our data revealed a mechanism that EBV utilizes a cellular microRNA to promote host cell survival and prevent virus from entering lytic life cycle for latency maintenance. PMID:25086243

  5. Unsupervised, low latency anomaly detection of algorithmically generated domain names by generative probabilistic modeling.

    PubMed

    Raghuram, Jayaram; Miller, David J; Kesidis, George

    2014-07-01

    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. PMID:25685511

  6. Unsupervised, low latency anomaly detection of algorithmically generated domain names by generative probabilistic modeling

    PubMed Central

    Raghuram, Jayaram; Miller, David J.; Kesidis, George

    2014-01-01

    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. PMID:25685511

  7. How is the serial order of a spatial sequence represented? Insights from transposition latencies.

    PubMed

    Hurlstone, Mark J; Hitch, Graham J

    2015-03-01

    How is the serial order of a spatial sequence represented in short-term memory (STM)? Previous research by Farrell and Lewandowsky (Farrell & Lewandowsky, 2004; Lewandowsky & Farrell, 2008) has shown that 5 alternative mechanisms for the representation of serial order can be distinguished on the basis of their predictions concerning the response times accompanying transposition errors. We report 3 experiments involving the output-timed serial recall of sequences of seen spatial locations that tested these predictions. The results of all 3 experiments revealed that transposition latencies are a negative function of transposition displacement, but with a reduction in the slope of the function for postponement, compared with anticipation errors. This empirical pattern is consistent with that observed in serial recall of verbal sequences reported by Farrell and Lewandowsky (2004), and with the predictions of a competitive queuing mechanism, within which serial order is represented via a primacy gradient of activations over items combined with associations between items and positional markers, and with suppression of items following recall. The results provide the first clear evidence that spatial and verbal STM rely on some common mechanisms and principles for the representation of serial order. PMID:25436478

  8. Wanderings of a DNA enzymologist: from DNA polymerase to viral latency.

    PubMed

    Lehman, I Robert

    2006-01-01

    I am a member of what has been called, perhaps too grandiosely, "The Greatest Generation." I grew up during the Great Depression and served in the U.S. Army during World War II. Because of my military service and the benefits of the GI Bill, I was able to attend college and, later, graduate school. Early in my graduate studies, I became fascinated with enzymes and the biochemical reactions that they catalyze. This fascination has never left me during the 50 years I have been a "DNA enzymologist." I was fortunate to have had as a mentor Arthur Kornberg, one of the great biochemists of the twentieth century, and a splendid group of postdocs and graduate students. I have studied DNA polymerases, DNA nucleases, DNA ligases, and DNA recombinases, enzymes that are critical to our understanding of DNA replication, repair, and recombination. Most recently, I have been studying herpes virus replication and inadvertently wandered into an entirely new area-viral latency. PMID:16756482

  9. Neuromagnetic Oscillations Predict Evoked-Response Latency Delays and Core Language Deficits in Autism Spectrum Disorders

    PubMed Central

    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.

    2016-01-01

    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. PMID:23963591

  10. The Effect of Mood on Sleep Onset Latency and REM Sleep in Interepisode Bipolar Disorder

    PubMed Central

    Talbot, Lisa S.; Hairston, Ilana S.; Eidelman, Polina; Gruber, June; Harvey, Allison G.

    2014-01-01

    The present study investigates whether interepisode mood regulation impairment contributes to disturbances in sleep onset latency (SOL) and rapid eye movement (REM) sleep. Individuals with interepisode bipolar disorder (n = 28) and healthy controls (n = 28) slept in the laboratory for 2 baseline nights, a happy mood induction night, and a sad mood induction night. There was a significant interaction whereby on the happy mood induction night the bipolar group exhibited significantly longer SOL than did the control group, while there was no difference on the baseline nights. In addition, control participants exhibited shorter SOL on the happy mood induction night compared to the baseline nights, a finding that was not observed in the bipolar group. On the sad mood induction night, participants in both groups had shorter SOL and increased REM density when compared to the baseline nights. Bipolar participants exhibited heightened REM density compared to control participants on both nights. These results raise the possibility that regulation of positive stimuli may be a contributor to difficulties with SOL, while hyperactivity may be characteristic of REM sleep. PMID:19685943

  11. Low Latency DESDynI Data Products for Disaster Response, Resource Management and Other Applications

    NASA Technical Reports Server (NTRS)

    Doubleday, Joshua R.; Chien, Steve A.; Lou, Yunling

    2011-01-01

    We are developing onboard processor technology targeted at the L-band SAR instrument onboard the planned DESDynI mission to enable formation of SAR images onboard opening possibilities for near-real-time data products to augment full data streams. Several image processing and/or interpretation techniques are being explored as possible direct-broadcast products for use by agencies in need of low-latency data, responsible for disaster mitigation and assessment, resource management, agricultural development, shipping, etc. Data collected through UAVSAR (L-band) serves as surrogate to the future DESDynI instrument. We have explored surface water extent as a tool for flooding response, and disturbance images on polarimetric backscatter of repeat pass imagery potentially useful for structural collapse (earthquake), mud/land/debris-slides etc. We have also explored building vegetation and snow/ice classifiers, via support vector machines utilizing quad-pol backscatter, cross-pol phase, and a number of derivatives (radar vegetation index, dielectric estimates, etc.). We share our qualitative and quantitative results thus far.

  12. Study of the scapular muscle latency and deactivation time in people with and without shoulder impingement.

    PubMed

    Phadke, Vandana; Ludewig, Paula M

    2013-04-01

    Changes in muscle activities are commonly associated with shoulder impingement and theoretically caused by changes in motor program strategies. The purpose of this study was to assess for differences in latencies and deactivation times of scapular muscles between subjects with and without shoulder impingement. Twenty-five healthy subjects and 24 subjects with impingement symptoms were recruited. Glenohumeral kinematic data and myoelectric activities using surface electrodes from upper trapezius (UT), lower trapezius (LT), serratus anterior (SA) and anterior fibers of deltoid were collected as subjects raised and lowered their arm in response to a visual cue. Data were collected during unloaded, loaded and after repetitive arm raising motion conditions. The variables were analyzed using 2 or 3 way mixed model ANOVAs. Subjects with impingement demonstrated significantly earlier contraction of UT while raising in the unloaded condition and an earlier deactivation of SA across all conditions during lowering of the arm. All subjects exhibited an earlier activation and delayed deactivation of LT and SA in conditions with a weight held in hand. The subjects with impingement showed some significant differences to indicate possible differences in motor control strategies. Rehabilitation measures should consider appropriate training measures to improve movement patterns and muscle control. PMID:23137918

  13. A short latency between radiation exposure from nuclear plants and cancer in young children.

    PubMed

    Mangano, Joseph J

    2006-01-01

    Previous reports document a short latency of cancer onset in young children exposed to low doses of radioactivity. The standard mortality ratio (SMR) for cancer in children dying before age ten rose in the period 6-10 years after the Three Mile Island and Chernobyl accidents in populations most exposed to fallout. SMRs near most nuclear power plants were elevated 6-10 years after startup, particularly for leukemia. Cancer incidence in children under age ten living near New York and New Jersey nuclear plants increased 4-5 years after increases in average strontium-90 in baby teeth, and declined 4-5 years after Sr-90 averages dropped. The assumption that Sr-90 and childhood cancer are correlated is best supported for a supralinear dose-response, meaning the greatest per-dose risks are at the lowest doses. Findings document that the very young are especially susceptible to adverse effects of radiation exposure, even at relatively low doses. PMID:16524167

  14. Decreased attentional responsivity during sleep deprivation: orienting response latency, amplitude, and habituation.

    PubMed

    McCarthy, M E; Waters, W F

    1997-02-01

    Ever increasing societal demands for uninterrupted work are causing unparalleled amounts of sleep deprivation among workers. Sleep deprivation has been linked to safety problems ranging from medical misdiagnosis to industrial and vehicular accidents. Microsleeps (very brief intrusions of sleep into wakefulness) are usually cited as the cause of the performance decrements during sleep deprivation. Changes in a more basic physiological phenomenon, attentional shift, were hypothesized to be additional factors in performance declines. The current study examined the effects of 36 hours of sleep deprivation on the electrodermal-orienting response (OR), a measure of attentional shift or capture. Subjects were 71 male undergraduate students, who were divided into sleep deprivation and control (non-sleep deprivation) groups. The expected negative effects of sleep deprivation on performance were noted in increased reaction times and increased variability in the sleep-deprived group on attention-demanding cognitive tasks. OR latency was found to be significantly delayed after sleep deprivation, OR amplitude was significantly decreased, and habituation of the OR was significantly faster during sleep deprivation. These findings indicate impaired attention, the first revealing slowed shift of attention to novel stimuli, the second indicating decreased attentional allocation to stimuli, and the third revealing more rapid loss of attention to repeated stimuli. These phenomena may be factors in the impaired cognitive performance seen during sleep deprivation. PMID:9143071

  15. Pure-tone masking profiles for human auditory brainstem and middle latency responses.

    PubMed

    Mackersie, C; Down, K E; Stapells, D R

    1993-02-01

    Several studies have compared the frequency selectivity of waves I and V of the auditory brainstem response (ABR) in humans, however little is known about the frequency selectivity of the middle latency response (MLR). Simultaneous recordings of ABRs and MLRs to 60 dB peSPL 2000-Hz probe tones were obtained in the presence of 0.5, 1.0, 1.41, 2.0, 2.83 and 4.0 kHz maskers presented at 40, 60, and 80 dB SPL. ABR/MLR iso-intensity masking profiles showing the percentage of the unmasked amplitudes as a function of frequency were constructed for ABR peak V-Vn and MLR peaks Na-Pa and Nb-Pb at each masker intensity. No significant differences were found between the frequency selectivity of the ABR and MLR, and the effects of masking on the amplitudes of these responses were similar. These results are consistent with the suggestion that frequency tuning is similar up to the level of the primary auditory cortex. PMID:8458760

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

    PubMed

    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. PMID:23963591

  17. GOCE rapid science orbits: Achieving sub-dm orbit precision with minimal latency

    NASA Astrophysics Data System (ADS)

    van den Ijssel, Jose; Visser, Pieter N. A. M.; van Helleputte, Tom; Bock, Heike

    For the GOCE satellite a Rapid Science Orbit (RSO) chain has been implemented to produce daily orbits with a 1-day latency and an accuracy of around 10 cm, in order to support satellite operations. The RSO will be used as input for external calibration and geodetic preprocessing of the gradiometer data and for quick-look gravity field modeling. The RSO chain provides as a baseline two orbit products, a reduced-dynamic and a kinematic solution. The reduced-dynamic RSO solution is computed using the NASA/GSFC GEODYN s/w package and is based on a triple differenced approach, using ionospheric-free GPS phase measurements along with rapid GPS orbits provided by the International GNSS Service. The kinematic RSO solution is computed using the DLR GHOST s/w package, and is based on a zero differenced approach, using rapid GPS orbits and clocks computed by the Center for Orbit Determination in Europe. An overview of both RSO POD strategies will be presented, together with results obtained using about one year of GOCE data. Special attention will be given to the handling of the clock behaviour of the GOCE GPS receiver, which is not steered to GPS time and can show large drifts of up to 10 msec. In addition, the estimated non-gravitational accelerations resulting from the RSO computations will be compared with the gradiometer common-mode accelerations, during different modes of the drag-free control system.

  18. Low latency, high bandwidth data communications between compute nodes in a parallel computer

    DOEpatents

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

    2010-11-02

    Methods, parallel computers, and computer program products are disclosed for low latency, high bandwidth data communications between compute nodes in a parallel computer. Embodiments include receiving, by an origin direct memory access (`DMA`) engine of an origin compute node, data for transfer to a target compute node; sending, by the origin DMA engine of the origin compute node to a target DMA engine on the target compute node, a request to send (`RTS`) message; transferring, by the origin DMA engine, a predetermined portion of the data to the target compute node using memory FIFO operation; determining, by the origin DMA engine whether an acknowledgement of the RTS message has been received from the target DMA engine; if the an acknowledgement of the RTS message has not been received, transferring, by the origin DMA engine, another predetermined portion of the data to the target compute node using a memory FIFO operation; and if the acknowledgement of the RTS message has been received by the origin DMA engine, transferring, by the origin DMA engine, any remaining portion of the data to the target compute node using a direct put operation.

  19. Activity in V4 reflects the direction, but not the latency, of saccades during visual search.

    PubMed

    Gee, Angela L; Ipata, Anna E; Goldberg, Michael E

    2010-10-01

    We constantly make eye movements to bring objects of interest onto the fovea for more detailed processing. Activity in area V4, a prestriate visual area, is enhanced at the location corresponding to the target of an eye movement. However, the precise role of activity in V4 in relation to these saccades and the modulation of other cortical areas in the oculomotor system remains unknown. V4 could be a source of visual feature information used to select the eye movement, or alternatively, it could reflect the locus of spatial attention. To test these hypotheses, we trained monkeys on a visual search task in which they were free to move their eyes. We found that activity in area V4 reflected the direction of the upcoming saccade but did not predict the latency of the saccade in contrast to activity in the lateral intraparietal area (LIP). We suggest that the signals in V4, unlike those in LIP, are not directly involved in the generation of the saccade itself but rather are more closely linked to visual perception and attention. Although V4 and LIP have different roles in spatial attention and preparing eye movements, they likely perform complimentary processes during visual search. PMID:20610790

  20. A novel role of SIRT1 in gammaherpesvirus latency and replication.

    PubMed

    He, Meilan; Gao, Shou-Jiang

    2014-01-01

    Viruses often hijack cellular functions to facilitate their infection and replication. SIRT1, one of the most widely studied sirtuins, functions as both metabolic sensor and transcriptional regulator. SIRT1 has broad cellular functions including metabolic homeostasis, stress response, tumorigenesis and autophagy. The role of SIRT1 in the life cycle of viruses remains unclear. Like all herpesviruses, oncogenic gammaherpesvirus KSHV has both latent and lytic phases. In a recent study, we have shown that SIRT1 binds to the promoter and silence the expression of KSHV replication and transcription activator (RTA), a key activator of viral lytic replication. Chemical inhibition or knock down of SIRT1 is sufficient to initiate the lytic replication program by increasing active histone H3 trimethyl Lys4 (H3K4me3) mark and decreasing repressive histone H3 trimethyl Lys27 (H3K27me3) mark in the RTA promoter. SIRT1 also interacts with RTA and inhibits RTA transactivation of its own promoter and those of downstream target genes. Our findings reveal that SIRT1 regulates KSHV latency by inhibiting different stages of viral lytic replication, and link a metabolic sensor and transcriptional regulator SIRT1 to KSHV life cycle. PMID:25485577

  1. The utility of respiratory inductance plethysmography in REM sleep scoring during multiple sleep latency testing.

    PubMed

    Drakatos, Panagis; Higgins, Sean; Duncan, Iain; Bridle, Kate; Briscoe, Sam; Leschziner, Guy D; Kent, Brian D; Williams, Adrian J

    2016-08-01

    Rapid eye movement sleep (REM) presents with a characteristic erratic breathing pattern. We investigated the feasibility of using respiration, derived from respiratory inductance plethysmography (RIP), in conjunction with chin electromyography, electrocardiography and pulse oximetry to facilitate the identification of REM sleep (RespREM) during nocturnal polysomnography (NPSG) and Multiple Sleep Latency Testing (MSLT). The Cohen's weighted kappa for the presence of REM and its duration in 20 consecutive NPSGs, using RespREM and compared to the current guidelines, ranged between 0.74-0.93 and 0.68-0.73 respectively for 5 scorers. The respective intraclass correlation coefficients were above 0.89. In 97.7% of the Sleep-Onset-REM-Periods (SOREMPs) during 41 consecutive MSLTs with preserved RIP, the RespREM was present and in 46.6% it coincided with the REM onset, while in the majority of the remainder RespREM preceded conventional REM onset. The erratic breathing pattern during REM, derived from RIP, is present and easily recognisable during SOREMPs in the MSLTs and may serve as a useful adjunctive measurement in identifying REM sleep. PMID:27141851

  2. Absence of the Uracil DNA Glycosylase of Murine Gammaherpesvirus 68 Impairs Replication and Delays the Establishment of Latency In Vivo

    PubMed Central

    Minkah, Nana; Macaluso, Marc; Oldenburg, Darby G.; Paden, Clinton R.; White, Douglas W.; McBride, Kevin M.

    2015-01-01

    ABSTRACT Uracil DNA glycosylases (UNG) are highly conserved proteins that preserve DNA fidelity by catalyzing the removal of mutagenic uracils. All herpesviruses encode a viral UNG (vUNG), and yet the role of the vUNG in a pathogenic course of gammaherpesvirus infection is not known. First, we demonstrated that the vUNG of murine gammaherpesvirus 68 (MHV68) retains the enzymatic function of host UNG in an in vitro class switch recombination assay. Next, we generated a recombinant MHV68 with a stop codon in ORF46/UNG (ΔUNG) that led to loss of UNG activity in infected cells and a replication defect in primary fibroblasts. Acute replication of MHV68ΔUNG in the lungs of infected mice was reduced 100-fold and was accompanied by a substantial delay in the establishment of splenic latency. Latency was largely, yet not fully, restored by an increase in virus inoculum or by altering the route of infection. MHV68 reactivation from latent splenocytes was not altered in the absence of the vUNG. A survey of host UNG activity in cells and tissues targeted by MHV68 indicated that the lung tissue has a lower level of enzymatic UNG activity than the spleen. Taken together, these results indicate that the vUNG plays a critical role in the replication of MHV68 in tissues with limited host UNG activity and this vUNG-dependent expansion, in turn, influences the kinetics of latency establishment in distal reservoirs. IMPORTANCE Herpesviruses establish chronic lifelong infections using a strategy of replicative expansion, dissemination to latent reservoirs, and subsequent reactivation for transmission and spread. We examined the role of the viral uracil DNA glycosylase, a protein conserved among all herpesviruses, in replication and latency of murine gammaherpesvirus 68. We report that the viral UNG of this murine pathogen retains catalytic activity and influences replication in culture. The viral UNG was impaired for productive replication in the lung. This defect in expansion at the

  3. MEP Latencies Predict the Neuromodulatory Effect of cTBS Delivered to the Ipsilateral and Contralateral Sensorimotor Cortex

    PubMed Central

    Huang, Gan; Mouraux, André

    2015-01-01

    Background Recently, it was shown that the highly variable after-effect of continuous theta-burst stimulation (cTBS) of the primary motor cortex (M1) can be predicted by the latency of motor-evoked potentials (MEPs) recorded before cTBS. This suggests that at least part of this inter-individual variability is driven by differences in the neuronal populations preferentially activated by transcranial magnetic stimulation (TMS). Methods Here, we recorded MEPs, TMS-evoked brain potentials (TEPs) and somatosensory-evoked potentials (SEPs) to investigate the effects of cTBS delivered over the primary sensorimotor cortex on both the ipsilateral and contralateral M1, and the ipsilateral and contralateral primary somatosensory cortex (S1). Results We confirm that the after-effects of cTBS can be predicted by the latency of MEPs recorded before cTBS. Over the hemisphere onto which cTBS was delivered, short-latency MEPs at baseline were associated with an increase of MEP magnitude (i.e. an excitatory effect of cTBS) whereas late-latency MEPs were associated with reduced MEPs (i.e. an inhibitory effect of cTBS). This relationship was reversed over the contralateral hemisphere, indicating opposite effects of cTBS on the responsiveness of the ipsilateral and contralateral M1. Baseline MEP latencies also predicted changes in the magnitude of the N100 wave of TEPs elicited by stimulation of the ipsilateral and contralateral hemisphere, indicating that this TEP component is specifically dependent on the state of M1. Finally, there was a reverse relationship between MEP latency and the effects of cTBS on the SEP waveforms (50–130 ms), indicating that after-effects of cTBS on S1 are opposite to those on M1. Conclusion Taken together, our results confirm that the variable after-effects of cTBS can be explained by differences in the neuronal populations activated by TMS. Furthermore, our results show that this variability also determines remote effects of cTBS in S1 and the

  4. The herpes simplex virus type 1 regulatory protein ICP0 enhances virus replication during acute infection and reactivation from latency.

    PubMed Central

    Cai, W; Astor, T L; Liptak, L M; Cho, C; Coen, D M; Schaffer, P A

    1993-01-01

    ICP0 is a potent activator of herpes simplex virus type 1 gene expression in transient assays and in productive infection. A role for ICP0 in reactivation from latency in vivo has also been suggested on the basis of the observation that viruses with mutations in both copies of the diploid gene for ICP0 reactivate less efficiently than wild-type virus. Because the ICP0 gene is contained entirely within the coding sequences for the latency-associated transcripts (LATs), ICP0 mutants also contain mutations in LAT coding sequences. This overlap raises the question of whether mutations in ICP0 or the LATs, which have also been implicated in reactivation, are responsible for the reduced reactivation frequencies characteristic of ICP0 mutants. Two approaches were taken to examine more definitively the role of ICP0 in the establishment and reactivation of latency. First, a series of ICP0 nonsense, insertion, and deletion mutant viruses that exhibit graded levels of ICP0-specific transactivating activity were tested for parameters of the establishment and reactivation of latency in a mouse ocular model. Although these mutants are ICP0 LAT double mutants, all nonsense mutants induced the synthesis of near-wild-type levels of the 2-kb LAT, demonstrating that the nonsense linker did not disrupt the synthesis of this LAT species. All mutants replicated less efficiently than the wild-type virus in mouse eyes and ganglia during the acute phase of infection. The replication efficiencies of the mutants at these sites corresponded well with the ICP0 transactivating activities of individual mutant peptides in transient expression assays. All mutants exhibited reduced reactivation frequencies relative to those of wild-type virus, and reactivation frequencies, like replication efficiencies in eyes and ganglia, correlated well with the level of ICP0 transactivating activity exhibited by individual mutant peptides. The amount of DNA of the different mutants varied in latently infected

  5. Low Latency Workflow Scheduling and an Application of Hyperspectral Brightness Temperatures

    NASA Astrophysics Data System (ADS)

    Nguyen, P. T.; Chapman, D. R.; Halem, M.

    2012-12-01

    New system analytics for Big Data computing holds the promise of major scientific breakthroughs and discoveries from the exploration and mining of the massive data sets becoming available to the science community. However, such data intensive scientific applications face severe challenges in accessing, managing and analyzing petabytes of data. While the Hadoop MapReduce environment has been successfully applied to data intensive problems arising in business, there are still many scientific problem domains where limitations in the functionality of MapReduce systems prevent its wide adoption by those communities. This is mainly because MapReduce does not readily support the unique science discipline needs such as special science data formats, graphic and computational data analysis tools, maintaining high degrees of computational accuracies, and interfacing with application's existing components across heterogeneous computing processors. We address some of these limitations by exploiting the MapReduce programming model for satellite data intensive scientific problems and address scalability, reliability, scheduling, and data management issues when dealing with climate data records and their complex observational challenges. In addition, we will present techniques to support the unique Earth science discipline needs such as dealing with special science data formats (HDF and NetCDF). We have developed a Hadoop task scheduling algorithm that improves latency by 2x for a scientific workflow including the gridding of the EOS AIRS hyperspectral Brightness Temperatures (BT). This workflow processing algorithm has been tested at the Multicore Computing Center private Hadoop based Intel Nehalem cluster, as well as in a virtual mode under the Open Source Eucalyptus cloud. The 55TB AIRS hyperspectral L1b Brightness Temperature record has been gridded at the resolution of 0.5x1.0 degrees, and we have computed a 0.9 annual anti-correlation to the El Nino Southern oscillation in

  6. A short latency vestibular evoked potential (VsEP) produced by bone-conducted acoustic stimulation

    NASA Astrophysics Data System (ADS)

    McAngus Todd, Neil P.; Rosengren, Sally M.; Colebatch, James G.

    2003-12-01

    In this paper data are presented from an experiment which provides evidence for the existence of a short latency, acoustically evoked potential of probable vestibular origin. The experiment was conducted in two phases using bone-conducted acoustic stimulation. In the first phase subjects were stimulated with 6-ms, 500-Hz tone bursts in order to obtain the threshold VT for vestibular evoked myogenic potentials (VEMP). It was confirmed that the difference between bone-conducted auditory and acoustic vestibular thresholds was slightly over 30 dB. The estimated threshold was then used as a reference value in the second part of the experiment to stimulate subjects over a range of intensities from -6 to +18 dB (re:VT). Averaged EEG recordings were made with eight Ag/AgCl electrodes placed on the scalp at Fpz, F3, F4, F7, F8, Cz, T3, and T4 according to the 10-20 system. Below VT auditory midlatency responses (MLRs) were observed. Above VT two additional potentials appeared: a positivity at about 10 ms (P10) which was maximal at Cz, and a negativity at about 15 ms (N15) which was maximal at Fpz. Extrapolation of the growth functions for the P10 and N15 indicated a threshold close to VT, consistent with a vestibular origin of these potentials. Given the low threshold of vestibular acoustic sensitivity it is possible that this mode may make a contribution to the detection of and affective responses to loud low frequency sounds. The evoked potentials may also have application as a noninvasive and nontraumatic test of vestibular projections to the cortex.

  7. Saccadic latency is modulated by emotional content of spatially filtered face stimuli.

    PubMed

    Bannerman, Rachel L; Hibbard, Paul B; Chalmers, Kirsty; Sahraie, Arash

    2012-12-01

    Models of attention and emotion assign a special status to the processing of threat. While evidence for threat-related attentional bias in highly anxious individuals is robust, effects in the normal population are mixed. An important explanation for the absence of threat-related attentional bias in nonanxious individuals may relate to the spatial frequency components of stimuli. Here we report behavioral data from two experiments examining the relationship between spatial frequency components of emotional and neutral faces and fast saccadic orienting behavior. In Experiment 1 participants had to saccade toward a single face, filtered to include mostly low, high or broad spatial frequencies (LSF, HSF or BSF), posing a fearful, happy or neutral expression presented for 20 ms in the periphery. At BSF a general emotional effect was found whereby saccadic responses were faster for fearful and happy faces relative to neutral, with no significant differences between fearful and happy faces. At LSF both fearful and happy faces had shorter saccadic latencies in comparison to neutral, demonstrating an emotional bias consistent with the BSF data. However, at LSF fearful faces resulted in significantly faster saccades than happy faces indicating that this bias was stronger for threat-related faces. There was no difference in saccadic responses between any emotions at HSF. Experiment 2 showed that the emotional bias diminished for inverted stimuli suggesting that the results were not attributable to low-level image properties. The findings suggest an overall advantage in the oculomotor system for orientation to emotional stimuli and at LSF in particular, a significantly faster localization of threat conveyed by the face stimuli in all individuals. PMID:22775132

  8. Central and peripheral components of short latency vestibular responses in the chicken

    NASA Technical Reports Server (NTRS)

    Nazareth, A. M.; Jones, T. A.

    1998-01-01

    Far-field recordings of short latency vestibular responses to pulsed cranial translation are composed of a series of positive and negative peaks occurring within 10 ms following stimulus onset. In the bird, these vestibular evoked potentials (VsEPs) can be recorded noninvasively and have been shown in the chicken and quail to depend strictly upon the activation of the vestibular component of the eighth nerve. The utility of the VsEP in the study of vestibular systems is dependent upon a clear understanding of the neural sources of response components. The primary aim of the current research in the chicken was to critically test the hypotheses that 1) responses are generated by both peripheral and central neurons and 2) peaks P1 and N1 originate from first order vestibular neurons, whereas later waves primarily depend on activity in higher order neurons. The principal strategy used here was to surgically isolate the eighth nerve as it enters the brainstem. Interruption of primary afferents of the eighth nerve in the brainstem substantially reduced or eliminated peaks beyond P2, whereas P1 and N1 were generally spared. Surgical sections that spared vestibular pathways had little effect on responses. The degree of change in response components beyond N1 was correlated with the extent of damage to central vestibular relays. These findings support the conclusion that responses are produced by both peripheral and central elements of the vestibular system. Further, response peaks later than N1 appear to be dependent upon central relays, whereas P1 and N1 reflect activity of the peripheral nerve. These findings clarify the roles of peripheral and central neurons in the generation of vestibular evoked potentials and provide the basis for a more useful and detailed interpretation of data from vestibular response testing.

  9. Epidemiological aspects of self-reported sleep onset latency in Japanese junior high school children.

    PubMed

    Alexandru, Gaina; Michikazu, Sekine; Shimako, Hamanishi; Xiaoli, Chen; Hitomi, Kanayama; Takashi, Yamagami; Robert, Williams W; Sadanobu, Kagamimori

    2006-09-01

    The purpose of this study was to investigate the relationships between sleep onset latency (SOL) and other sleep-wake patterns and media use habits in Japanese schoolchildren. A total of 9,718 junior high school children responded (12.8 years) and 9199 questionnaires were used in the present analyses. The questionnaire assessed sleep-wake patterns, TV viewing and videogame habits. Overall, 72.1% of the subjects reported short SOL (20 min) were strongly associated with disturbed sleep manifested especially by increased risk of night awakenings, decreased sleep depth, and bad sleep in general (overall sleep quality). Prolonged SOL was also associated with daytime sleepiness, difficulties in falling asleep, bad morning feeling and sleep insufficiency. We found a U-shaped relationship between sleep period and SOL. Increase in bedtime was accompanied by increased risk of prolonged SOL. The impact of ultra-short and ultra-long SOL (or=40 min) was also analysed. Long durations of watching television and playing videogame were significantly associated with prolonged SOL. After adjustment for sex, girls presented significantly higher risk of prolonged SOL. Body mass index adjustment did not reveal any significant results. SOL presents a significant component of sleep-wake habits; poor sleep hygiene and insufficient sleep time significantly increase SOL. Parents, healthcare practitioners and children themselves should be aware of the potentially negative influence of prolonged SOL. Additionally, the optimal coherent sleep-wake schedule must be promoted in parallel with the limitation on the viewing TV and game practices. PMID:16911029

  10. Capturing the electromagnetic counterparts of binary neutron star mergers through low-latency gravitational wave triggers

    NASA Astrophysics Data System (ADS)

    Chu, Q.; Howell, E. J.; Rowlinson, A.; Gao, H.; Zhang, B.; Tingay, S. J.; Boër, M.; Wen, L.

    2016-06-01

    We i