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Sample records for latency requires pim-1

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Cell and gene therapy for severe heart failure patients: The time and place for Pim-1 Kinase

    PubMed Central

    Siddiqi, Sailay; Sussman, Mark A

    2014-01-01

    Regenerative therapy in severe heart failure patients presents a challenging set of circumstances including a damaged myocardial environment that accelerates senescence in myocytes and cardiac progenitor cells. Failing myocardium suffers from deterioration of contractile function coupled with impaired regenerative potential that drives the heart toward decompensation. Efficacious regenerative cell therapy for severe heart failure requires disruption of this vicious circle that can be accomplished by alteration of the compromised myocyte phenotype and rejuvenation of progenitor cells. This review focuses upon potential for Pim-1 kinase to mitigate chronic heart failure by improving myocyte quality through preservation of mitochondrial integrity, prevention of hypertrophy and inhibition of apoptosis. In addition, cardiac progenitors engineered with Pim-1 possess enhanced regenerative potential, making Pim-1 an important player in future treatment of severe heart failure. PMID:23984924

  9. 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

  10. IL-6 stimulates STAT3 and Pim-1 kinase in pancreatic cancer cell lines

    PubMed Central

    Block, Katherine M.; Hanke, Neale T.; Maine, Erin A.; Baker, Amanda F.

    2011-01-01

    Objectives We investigated the signaling pathways activated in response to Interleukin (IL-6) in pancreatic cell lines, with a focus on signal transducer and activator of transcription 3 (STAT3) and proto-oncogene serine/threonine-protein (Pim-1) kinase. Methods IL-6 receptor (IL-6R) expression and IL-6 induced cell signaling was measured by Western blotting in human pancreatic cell lines. Cucurbitacin I was used as a pharmacological tool to investigate the role of STAT3 in Pim-1 activation. Stably over-expressing Pim-1 kinase cell lines were characterized for their response to IL-6 in vitro, and for their growth rate as flank tumors in scid mice. Results IL-6R was expressed across multiple cancer cell lines. In Panc-1 cells, IL-6 treatment increased expression of P-STAT3 and Pim-1 kinase. Cucurbitacin I treatment alone increased pErk1/2 expression in wild-type and Pim-1 over-expressing cell lines and resulted in exaggerated Pim-1 kinase protein levels in control and IL-6 stimulated cells, suggesting upregulation of Pim-1 may be partially STAT3 independent. Pim-1 over-expression did not significantly impact growth rate in vitro or in vivo in Panc-1 or MiaPaCa2 cell lines. Conclusions IL-6 activates STAT3 and stimulates Pim-1 kinase in pancreatic cell line models. The regulation and consequence of Pim-1 expression appears to be highly context dependent. PMID:22273698

  11. 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

  12. 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

  13. 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.

  14. Pim1 serine/threonine kinase regulates the number and functions of murine hematopoietic stem cells.

    PubMed

    An, Ningfei; Lin, Ying-Wei; Mahajan, Sandeep; Kellner, Joshua N; Wang, Yong; Li, Zihai; Kraft, Andrew S; Kang, Yubin

    2013-06-01

    The genes and pathways that govern the functions and expansion of hematopoietic stem cells (HSC) are not completely understood. In this study, we investigated the roles of serine/threonine Pim kinases in hematopoiesis in mice. We generated PIM1 transgenic mice (Pim1-Tx) overexpressing human PIM1 driven by vav hematopoietic promoter/regulatory elements. Compared to wild-type littermates, Pim1-Tx mice showed enhanced hematopoiesis as demonstrated by increased numbers of Lin(-) Sca-1 (+) c-Kit (+) (LSK) hematopoietic stem/progenitor cells and cobblestone area forming cells, higher BrdU incorporation in long-term HSC population, and a better ability to reconstitute lethally irradiated mice. We then extended our study using Pim1(-/-), Pim2(-/-), Pim3(-/-) single knockout (KO) mice. HSCs from Pim1(-/-) KO mice showed impaired long-term hematopoietic repopulating capacity in secondary and competitive transplantations. Interestingly, these defects were not observed in HSCs from Pim2(-/-) or Pim3(-/-) KO mice. Limiting dilution competitive transplantation assay estimated that the frequency of LSKCD34(-) HSCs was reduced by approximately 28-fold in Pim1(-/-) KO mice compared to wild-type littermates. Mechanistic studies demonstrated an important role of Pim1 kinase in regulating HSC cell proliferation and survival. Finally, our polymerase chain reaction (PCR) array and confirmatory real-time PCR (RT-PCR) studies identified several genes including Lef-1, Pax5, and Gata1 in HSCs that were affected by Pim1 deletion. Our data provide the first direct evidence for the important role of Pim1 kinase in the regulation of HSCs. Our study also dissects out the relative role of individual Pim kinase in HSC functions and regulation. PMID:23495171

  15. Phosphorylation of the androgen receptor by PIM1 in hormone refractory prostate cancer.

    PubMed

    Ha, S; Iqbal, N J; Mita, P; Ruoff, R; Gerald, W L; Lepor, H; Taneja, S S; Lee, P; Melamed, J; Garabedian, M J; Logan, S K

    2013-08-22

    Integration of cellular signaling pathways with androgen receptor (AR) signaling can be achieved through phosphorylation of AR by cellular kinases. However, the kinases responsible for phosphorylating the AR at numerous sites and the functional consequences of AR phosphorylation are only partially understood. Bioinformatic analysis revealed AR serine 213 (S213) as a putative substrate for PIM1, a kinase overexpressed in prostate cancer. Therefore, phosphorylation of AR serine 213 by PIM1 was examined using a phosphorylation site-specific antibody. Wild-type PIM1, but not catalytically inactive PIM1, specifically phosphorylated AR but not an AR serine-to-alanine mutant (S213A). In vitro kinase assays confirmed that PIM1 can phosphorylate AR S213 in a ligand-independent manner and cell type-specific phosphorylation was observed in prostate cancer cell lines. Upon PIM1 overexpression, AR phosphorylation was observed in the absence of hormone and was further increased in the presence of hormone in LNCaP, LNCaP-abl and VCaP cells. Moreover, phosphorylation of AR was reduced in the presence of PIM kinase inhibitors. An examination of AR-mediated transcription showed that reporter gene activity was reduced in the presence of PIM1 and wild-type AR, but not S213A mutant AR. Androgen-mediated transcription of endogenous PSA, Nkx3.1 and IGFBP5 was also decreased in the presence of PIM1, whereas IL6, cyclin A1 and caveolin 2 were increased. Immunohistochemical analysis of prostate cancer tissue microarrays showed significant P-AR S213 expression that was associated with hormone refractory prostate cancers, likely identifying cells with catalytically active PIM1. In addition, prostate cancers expressing a high level of P-AR S213 were twice as likely to be from biochemically recurrent cancers. Thus, AR phosphorylation by PIM1 at S213 impacts gene transcription and is highly prevalent in aggressive prostate cancer.

  16. The proto-oncogene Pim-1 is a target of miR-33a.

    PubMed

    Thomas, M; Lange-Grünweller, K; Weirauch, U; Gutsch, D; Aigner, A; Grünweller, A; Hartmann, R K

    2012-02-16

    The constitutively active serine/threonine kinase Pim-1 is upregulated in different cancer types, mainly based on the action of several interleukines and growth factors at the transcriptional level. So far, a regulation of oncogenic Pim-1 by microRNAs (miRNAs) has not been reported. Here, we newly establish miR-33a as a miRNA with potential tumor suppressor activity, acting through inhibition of Pim-1. A screen for miRNA expression in K562 lymphoma, LS174T colon carcinoma and several other cell lines revealed generally low endogenous miR-33a levels relative to other miRNAs. Transfection of K562 and LS174T cells with a miR-33a mimic reduced Pim-1 levels substantially. In contrast, the cell-cycle regulator cyclin-dependent kinase 6 predicted to be a conserved miR-33a target, was not downregulated by the miR-33a mimic. Seed mutagenesis of the Pim-1 3'-untranslated region in a luciferase reporter construct and in a Pim-1 cDNA expressed in Pim-1-deficient Skov-3 cells demonstrated specific and direct downregulation of Pim-1 by the miR-33a mimic. The persistence of this effect was comparable to that of a small interfering RNA-mediated knockdown of Pim-1, resulting in decelerated cell proliferation. In conclusion, we demonstrate the potential of miR-33a to act as a tumor suppressor miRNA, which suggests miR-33a replacement therapy through delivery of miR mimics as a novel therapeutic strategy.

  17. A combination strategy to inhibit Pim-1: synergism between noncompetitive and ATP-competitive inhibitors.

    PubMed

    Mori, Mattia; Tintori, Cristina; Christopher, Robert Selwyne Arul; Radi, Marco; Schenone, Silvia; Musumeci, Francesca; Brullo, Chiara; Sanità, Patrizia; Delle Monache, Simona; Angelucci, Adriano; Kissova, Miroslava; Crespan, Emmanuele; Maga, Giovanni; Botta, Maurizio

    2013-03-01

    Pim-1 is a serine/threonine kinase critically involved in the initiation and progression of various types of cancer, especially leukemia, lymphomas and solid tumors such as prostate, pancreas and colon, and is considered a potential drug target against these malignancies. In an effort to discover new potent Pim-1 inhibitors, a previously identified ATP-competitive indolyl-pyrrolone scaffold was expanded to derive structure-activity relationship data. A virtual screening campaign was also performed, which led to the discovery of additional ATP-competitive inhibitors as well as a series of 2-aminothiazole derivatives, which are noncompetitive with respect to both ATP and peptide substrate. This mechanism of action, which resembles allosteric inhibition, has not previously been characterized for Pim-1. Notably, further evaluation of the 2-aminothiazoles indicated a synergistic inhibitory effect in enzymatic assays when tested in combination with ATP-competitive inhibitors. A synergistic effect in the inhibition of cell proliferation by ATP-competitive and ATP-noncompetitive compounds was also observed in prostate cancer cell lines (PC3), where all Pim-1 inhibitors tested in showed synergism with the known anticancer agent, paclitaxel. These results further establish Pim-1 as a target in cancer therapy, and highlight the potential of these agents for use as adjuvant agents in the treatment of cancer diseases in which Pim-1 is associated with chemotherapeutic resistance.

  18. 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.

  19. The putative oncogene Pim-1 in the mouse: its linkage and variation among t haplotypes.

    PubMed

    Nadeau, J H; Phillips, S J

    1987-11-01

    Pim-1, a putative oncogene involved in T-cell lymphomagenesis, was mapped between the pseudo-alpha globin gene Hba-4ps and the alpha-crystallin gene Crya-1 on mouse chromosome 17 and therefore within the t complex. Pim-1 restriction fragment variants were identified among t haplotypes. Analysis of restriction fragment sizes obtained with 12 endonucleases demonstrated that the Pim-1 genes in some t haplotypes were indistinguishable from the sizes for the Pim-1b allele in BALB/c inbred mice. There are now three genes, Pim-1, Crya-1 and H-2 I-E, that vary among independently derived t haplotypes and that have indistinguishable alleles in t haplotypes and inbred strains. These genes are closely linked within the distal inversion of the t complex. Because it is unlikely that these variants arose independently in t haplotypes and their wild-type homologues, we propose that an exchange of chromosomal segments, probably through double crossingover, was responsible for indistinguishable Pim-1 genes shared by certain t haplotypes and their wild-type homologues. There was, however, no apparent association between variant alleles of these three genes among t haplotypes as would be expected if a single exchange introduced these alleles into t haplotypes. If these variant alleles can be shown to be identical to the wild-type allele, then lack of association suggests that multiple exchanges have occurred during the evolution of the t complex.

  20. EBNA3C Augments Pim-1 Mediated Phosphorylation and Degradation of p21 to Promote B-Cell Proliferation

    PubMed Central

    Banerjee, Shuvomoy; Lu, Jie; Cai, Qiliang; Sun, Zhiguo; Jha, Hem Chandra; Robertson, Erle S.

    2014-01-01

    Epstein–Barr virus (EBV), a ubiquitous human herpesvirus, can latently infect the human population. EBV is associated with several types of malignancies originating from lymphoid and epithelial cell types. EBV latent antigen 3C (EBNA3C) is essential for EBV-induced immortalization of B-cells. The Moloney murine leukemia provirus integration site (PIM-1), which encodes an oncogenic serine/threonine kinase, is linked to several cellular functions involving cell survival, proliferation, differentiation, and apoptosis. Notably, enhanced expression of Pim-1 kinase is associated with numerous hematological and non-hematological malignancies. A higher expression level of Pim-1 kinase is associated with EBV infection, suggesting a crucial role for Pim-1 in EBV-induced tumorigenesis. We now demonstrate a molecular mechanism which reveals a direct role for EBNA3C in enhancing Pim-1 expression in EBV-infected primary B-cells. We also showed that EBNA3C is physically associated with Pim-1 through its amino-terminal domain, and also forms a molecular complex in B-cells. EBNA3C can stabilize Pim-1 through abrogation of the proteasome/Ubiquitin pathway. Our results demonstrate that EBNA3C enhances Pim-1 mediated phosphorylation of p21 at the Thr145 residue. EBNA3C also facilitated the nuclear localization of Pim-1, and promoted EBV transformed cell proliferation by altering Pim-1 mediated regulation of the activity of the cell-cycle inhibitor p21/WAF1. Our study demonstrated that EBNA3C significantly induces Pim-1 mediated proteosomal degradation of p21. A significant reduction in cell proliferation of EBV-transformed LCLs was observed upon stable knockdown of Pim-1. This study describes a critical role for the oncoprotein Pim-1 in EBV-mediated oncogenesis, as well as provides novel insights into oncogenic kinase-targeted therapeutic intervention of EBV-associated cancers. PMID:25121590

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

    PubMed Central

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

    2016-01-01

    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

  2. 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

  3. Pim1 kinase protects airway epithelial cells from cigarette smoke-induced damage and airway inflammation.

    PubMed

    de Vries, M; Heijink, I H; Gras, R; den Boef, L E; Reinders-Luinge, M; Pouwels, S D; Hylkema, M N; van der Toorn, M; Brouwer, U; van Oosterhout, A J M; Nawijn, M C

    2014-08-01

    Exposure to cigarette smoke (CS) is the main risk factor for developing chronic obstructive pulmonary disease and can induce airway epithelial cell damage, innate immune responses, and airway inflammation. We hypothesized that cell survival factors might decrease the sensitivity of airway epithelial cells to CS-induced damage, thereby protecting the airways against inflammation upon CS exposure. Here, we tested whether Pim survival kinases could protect from CS-induced inflammation. We determined expression of Pim kinases in lung tissue, airway inflammation, and levels of keratinocyte-derived cytokine (KC) and several damage-associated molecular patterns in bronchoalveolar lavage in mice exposed to CS or air. Human bronchial epithelial BEAS-2B cells were treated with CS extract (CSE) in the presence or absence of Pim1 inhibitor and assessed for loss of mitochondrial membrane potential, induction of cell death, and release of heat shock protein 70 (HSP70). We observed increased expression of Pim1, but not of Pim2 and Pim3, in lung tissue after exposure to CS. Pim1-deficient mice displayed a strongly enhanced neutrophilic airway inflammation upon CS exposure compared with wild-type controls. Inhibition of Pim1 activity in BEAS-2B cells increased the loss of mitochondrial membrane potential and reduced cell viability upon CSE treatment, whereas release of HSP70 was enhanced. Interestingly, we observed release of S100A8 but not of double-strand DNA or HSP70 in Pim1-deficient mice compared with wild-type controls upon CS exposure. In conclusion, we show that expression of Pim1 protects against CS-induced cell death in vitro and neutrophilic airway inflammation in vivo. Our data suggest that the underlying mechanism involves CS-induced release of S100A8 and KC. PMID:24816488

  4. 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

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

    NASA Astrophysics Data System (ADS)

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

    2004-08-01

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

  6. 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.

  7. 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

  8. Evaluation of the Emu-pim-1 transgenic mouse model for short-term carcinogenicity testing.

    PubMed

    van Kreijl, C F; van der Houven van Oordt, C W; Kroese, E D; Sørensen, I K; Breuer, M L; Storer, R D

    1998-01-01

    The value of the chronic rodent carcinogenicity assay in adequately predicting cancer risk in humans has become a matter of debate over the past few years. Therefore, more rapid and accurate alternative tests are urgently needed. Transgenic mouse models, those harboring genetic changes that are relevant to the multistage cancer process, may provide such alternative tests. Transgenic Emu-pim-1 mice, developed by Berns and coworkers in 1989, contain the pimn-1 oncogene, which is expressed at elevated levels in their lymphoid compartments. As a result, these mice are predisposed to the development of T-cell lymphomas. Because of the low incidence of spontaneous tumors and the increased sensitivity to N-ethyl-N-nitrosourea-induced carcinogenesis, Emu-pim-1 mice were suggested to be one of the first potential and attractive candidates to be used in short-term carcinogenicity testing. In the present article, the results from 2 recent short-term assays (with mitomycin C and x-rays) are briefly presented, together with a review of all 11 performed bioassays and their corresponding histopathologic and molecular data. The overall results allow the first evaluation of the Emu-pim-1 mouse model with regard to its usefulness in short-term carcinogenicity testing. It has been shown that the model is primarily suitable as a sensitive short-term assay for genotoxic carcinogens that not only induce (at least) gene mutations and/or large deletions and rearrangements but that also sufficiently target the lymphoid system. However, the Emu-pim-1 mice lack sufficient sensitivity to justify their routine use in short-term carcinogenicity testing in general.

  9. 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.

  10. Thalidomide alters c-MYB and PIM-1 signaling in K-562 cells.

    PubMed

    Thadani, Natasha A; McNamee, James P; Winn, Louise M

    2006-08-01

    Despite causing birth defects thalidomide is being used therapeutically to treat a number of diseases. While thalidomide's mechanism of action still remains unknown, exposure to thalidomide leads to increased reactive oxygen species (ROS), which can interfere with cell signaling. We hypothesize that thalidomide acts by interfering with the c-Myb signaling pathway. To investigate this hypothesis, human K-562 cells were transfected with plasmids expressing a Myb-responsive luciferase reporter and c-Myb. Cells were then exposed to thalidomide (0 or 40 microg/ml) for 1h and luciferase activities were measured. Cells exposed to thalidomide (40 microg/ml) had significantly decreased c-Myb activity. Pre-incubation of cells with the anti-oxidative enzyme catalase (1600 units/ml), prevented thalidomide-induced decreased c-Myb activity, suggesting a role for ROS in the c-Myb signaling pathway. This result was further substantiated by the dichlorofluorescein assay. Western blot analysis on thalidomide exposed cells showed a decrease in both Pim-1 protein expression and phosphorylated c-Myb protein expression, suggesting that the decrease in Pim-1 and the amount of phosphorylated c-Myb protein may be responsible for the observed decreases in c-Myb activity. Together these results demonstrate that thalidomide affects c-Myb signaling, in part, through increased ROS production.

  11. 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

  12. 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.

  13. Mitochondrial integrity: preservation through Akt/Pim-1 kinase signaling in the cardiomyocyte

    PubMed Central

    Sussman, Mark A

    2014-01-01

    The central role of mitochondria as mediators of cell survival is indisputable and gathering increasing attention as a focal point for interventional strategies to mitigate apoptotic cell death in the wake of cardiomyopathic injury. A legacy of signal transduction studies has proven that mitochondrial integrity can be enhanced by kinases involved in cell survival. Among the many survival signaling cascades under investigation, the wide-ranging impact of Akt upon mitochondrial biology is well known. However, despite years of investigation, emerging research continues to reveal new mechanisms governing the protective effects of Akt signaling in the context of cardiomyocyte mitochondria. This review focuses on two emerging pathways that mediate preservation of mitochondrial function downstream of Akt: hexokinase and Pim-1 kinase. PMID:19673671

  14. A crystallographic fragment screen identifies cinnamic acid derivatives as starting points for potent Pim-1 inhibitors.

    PubMed

    Schulz, Michèle N; Fanghänel, Jörg; Schäfer, Martina; Badock, Volker; Briem, Hans; Boemer, Ulf; Nguyen, Duy; Husemann, Manfred; Hillig, Roman C

    2011-03-01

    A crystallographic fragment screen was carried out to identify starting points for the development of inhibitors of protein kinase Pim-1, a potential target for tumour therapy. All fragment hits identified via soaking in this study turned out to bind to the unusually hydrophobic pocket at the hinge region. The most potent fragments, two cinnamic acid derivatives (with a best IC(50) of 130 µM), additionally form a well defined hydrogen bond. The balance between hydrophobic and polar interactions makes these molecules good starting points for further optimization. Pim-2 inhibitors from a recently reported high-throughput screening campaign also feature a cinnamic acid moiety. Two of these Pim-2 inhibitors were synthesized, their potencies against Pim-1 were determined and their cocrystal structures were elucidated in order to determine to what degree the binding modes identified by fragment screening are conserved in optimized inhibitors. The structures show that the cinnamic acid moieties indeed adopt the same binding mode. Fragment screening thus correctly identified binding modes which are maintained when fragments are grown into larger and higher affinity inhibitors. The high-throughput screening-derived compound (E)-3-{3-[6-(4-aminocyclohexylamino)-pyrazin-2-yl]phenyl}acrylic acid (compound 1) is the most potent inhibitor of the cinnamic acid series for which the three-dimensional binding mode is known (IC(50) = 17 nM, K(d) = 28 nM). The structure reveals the molecular basis for the large gain in potency between the initial fragment hit and this optimized inhibitor.

  15. Design and synthesis of substituted pyrido[3,2-d]-1,2,3-triazines as potential Pim-1 inhibitors.

    PubMed

    Fan, Yin-Bo; Li, Kun; Huang, Min; Cao, Yu; Li, Ying; Jin, Shu-Yu; Liu, Wen-Bing; Wen, Jia-Chen; Liu, Dan; Zhao, Lin-Xiang

    2016-02-15

    A novel series of substituted pyrido[3,2-d]-1,2,3-triazines were designed and synthesized as Pim-1 inhibitors through scaffold hopping. Most of the derivatives showed potent in vitro Pim-1 inhibitory activities and anti-proliferative effects toward prostate cancer cells. Among them, 6b, 6h and 6m showed the best Pim-1 inhibitory activity with IC50 values of 0.69, 0.60 and 0.80 μM, respectively. Furthermore, compounds 6b, 6i, 6j and 6m showed strong inhibitory activity to human prostate cancer LNcap and PC-3 cell lines with IC50 values at low micromolar level. Structure-activity relationship analysis revealed that appropriate substitutions at C-6 positions contributed to the kinase inhibition and antiproliferative effects. Moreover, western blot assay suggested that 6j could decrease the levels of p-BAD and p-4E-BP1 in a dose-dependent manner in PC-3 cells. Docking studies showed that 3-N of the scaffold formed a hydrogen bond with Lys67, aromatic 4-aniline formed a key π-π stack with Phe49. Taken together, this study might provide the first sight for developing the pyrido[3,2-d]-1,2,3-triazine scaffold as novel Pim-1 inhibitors.

  16. 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

  17. 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

  18. 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

  19. Expression of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa co-determines the prognosis of colon cancer patients.

    PubMed

    Peng, Yong-hai; Li, Jian-jun; Xie, Fang-wei; Chen, Jian-fang; Yu, Ying-hao; Ouyang, Xue-nong; Liang, Hou-jie

    2013-01-01

    Provirus integration site for Moloney murine leukemia virus (pim-1) is a proto-oncogene that is linked to the development and progression of several cancers. In this study, we evaluated pim-1 expression in tumors, tumor stroma and tumor-adjacent mucosa together as an independent prognostic factor for colon cancer patients. The study included 343 colon cancer patients. Immunohistochemical staining was used to detect pim-1. Multivariate cox regression for disease-free survival (DFS) were used to identify independent prognostic factors. Analytic hierarchy process (AHP) was used to calculate the weight of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa in order to obtain a Pim-1 total score (PTS) for recurrence and survival. Kaplan-Meier DFS curves and OS curves for patients with different pim-1 expression levels were compared using the log-rank test. In this study, four independent prognostic factors were identified for colon cancer patients: pim-1 expression in tumors, tumor stroma, tumor-adjacent mucosa, as well as tumor stage. It has been established that clinical stage is an important prognostic factor for colon cancer patients. However, PTS can identify the patients who are likely to recur not only in the whole radical excision group but also within each stage of this group. Based on the results of this study we can conclude that the PTS combined with clinical staging system may be a better predictor of colon cancer patients' prognosis than using the clinical stage system alone. ClinicalTrials.gov Number: ChiCTR-PRCH-12002842.

  20. 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

  1. 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.

  2. New potent and selective inhibitor of Pim-1/3 protein kinases sensitizes human colon carcinoma cells to doxorubicin.

    PubMed

    Moreau, Pascale; Dezhenkova, Lyubov G; Anizon, Fabrice; Nauton, Lionel; Thery, Vincent; Liang, Shuguang; Kaluzhny, Dmitry N; Shtil, Alexander A

    2014-01-01

    The Pim protein kinases (provirus insertion site of Moloney murine leukemia virus) have been identified as important actors involved in tumor cell survival, proliferation, migration and invasion. Therefore, inhibition of Pim activity by low molecular weight compounds is under investigation as a part of anticancer therapeutic strategies. We have synthesized a series of pyrrolo[2,3-a]carbazole derivatives that significantly inhibited Pim protein kinases at submicromolar concentrations. Particularly, benzodiazocine derivative 1 potently inhibited Pim-1 and -3 isoforms in in vitro kinase assays (IC50 8 nM and 13 nM, respectively), whereas Pim-2 activity was less affected (IC50 350 nM). We show here that no inhibitory effect of 1 was detectable at 1 µM against other 22 serine/threonine and tyrosine kinases. In addition, 1, possessing a planar pyrrolocarbazole scaffold, demonstrated no significant binding to DNA, nor was it a potent topoisomerase I inhibitor, suggesting that 1 is likely to be highly selective for Pim-1 and -3. Importantly, whereas 1 exerted a negligible cytotoxicity for human colon carcinoma HCT116 cell line at concentrations >10 µM within 72 h of cell exposure, it synergized at nontoxic concentrations with the antitumor drug doxorubicin (Dox) in killing HCT116 cells: IC50 of Dox alone and Dox+1 were ~200 nM and ~25 nM, respectively. These data strongly suggest that 1 emerges as a prospective antitumor drug candidate due to its selectivity to individual Pim protein kinases and the ability to potentiate the efficacy of conventional chemotherapeutics. PMID:25175798

  3. 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

  4. HIV Latency

    PubMed Central

    Siliciano, Robert F.; Greene, Warner C.

    2011-01-01

    HIV-1 can establish a state of latent infection at the level of individual T cells. Latently infected cells are rare in vivo and appear to arise when activated CD4+ T cells, the major targets cells for HIV-1, become infected and survive long enough to revert back to a resting memory state, which is nonpermissive for viral gene expression. Because latent virus resides in memory T cells, it persists indefinitely even in patients on potent antiretroviral therapy. This latent reservoir is recognized as a major barrier to curing HIV-1 infection. The molecular mechanisms of latency are complex and include the absence in resting CD4+ T cells of nuclear forms of key host transcription factors (e.g., NFκB and NFAT), the absence of Tat and associated host factors that promote efficient transcriptional elongation, epigenetic changes inhibiting HIV-1 gene expression, and transcriptional interference. The presence of a latent reservoir for HIV-1 helps explain the presence of very low levels of viremia in patients on antiretroviral therapy. These viruses are released from latently infected cells that have become activated and perhaps from other stable reservoirs but are blocked from additional rounds of replication by the drugs. Several approaches are under exploration for reactivating latent virus with the hope that this will allow elimination of the latent reservoir. PMID:22229121

  5. PIM kinases are essential for chronic lymphocytic leukemia cell survival (PIM2/3) and CXCR4-mediated microenvironmental interactions (PIM1).

    PubMed

    Decker, Sarah; Finter, Johannes; Forde, Aaron James; Kissel, Sandra; Schwaller, Juerg; Mack, Thomas Sebastian; Kuhn, Anabel; Gray, Nathanael; Follo, Marie; Jumaa, Hassan; Burger, Meike; Zirlik, Katja; Pfeifer, Dietmar; Miduturu, Chandrasekhar V; Eibel, Hermann; Veelken, Hendrik; Dierks, Christine

    2014-05-01

    Overexpression of the CXCR4 receptor is a hallmark of chronic lymphocytic leukemia (CLL) and is important for CLL cell survival, migration, and interaction with their protective microenvironment. In acute myelogenous leukemia (AML), PIM1 was shown to regulate the surface expression of the CXCR4 receptor. Here, we show that PIM (proviral integration site for Moloney murine leukemia virus) kinases 1-3 are overexpressed and that the CXCR4 receptor is hyperphosphorylated on Ser339 in CLL compared with normal lymphocytes. Furthermore, CXCR4 phosphorylation correlates with PIM1 protein expression and PIM1 transcript levels in CLL. PIM kinase inhibition with three different PIM kinase inhibitors induced apoptosis in CLL cells independent of the presence of protective stromal cells. In addition, PIM inhibition caused dephosphorylation of the CXCR4 receptor on Ser339, resulting in enhanced ligand-dependent CXCR4 internalization and reduced re-externalization after withdrawal of CXCL12. Furthermore, PIM inhibition in CLL cells blocked CXCR4 functions, such as migration toward CXCL12- or CXCL12-induced extracellular signal-regulated kinase (ERK) phosphorylation. In concordance, pretreatment of CLL cells with PIM kinase inhibitors strongly reduced homing of CLL cells toward the bone marrow and the spleen of Rag2(-/-)γc(-/-) mice in vivo. Interestingly, the knockdown of PIM kinases in CLL cells demonstrated diverging functions, with PIM1 regulating CXCR4 surface expression and PIM2 and PIM3 as important for the survival of CLL cells. Our results show that PIM kinase inhibitors are an effective therapeutic option for CLL, not only by impairing PIM2/3-mediated CLL cell survival, but also by blocking the PIM1/CXCR4-mediated interaction of CLL cells with their protective microenvironment. PMID:24659821

  6. 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

  7. The Pim kinase inhibitor SGI-1776 decreases cell surface expression of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and drug transport by Pim-1-dependent and -independent mechanisms

    PubMed Central

    Natarajan, Karthika; Bhullar, Jasjeet; Shukla, Suneet; Burcu, Mehmet; Chen, Zhe-Sheng; Ambudkar, Suresh V.; Baer, Maria R.

    2013-01-01

    Overexpression of the ATP-binding cassette (ABC) drug efflux proteins P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on malignant cells is associated with inferior chemotherapy outcomes. Both, ABCB1 and ABCG2, are substrates of the serine/threonine kinase Pim-1; Pim-1 knockdown decreases their cell surface expression, but SGI-1776, the first clinically tested Pim inhibitor, was shown to reverse drug resistance by directly inhibiting ABCB1-mediated transport. We sought to characterize Pim-1-dependent and -independent effects of SGI-1776 on drug resistance. SGI-1776 at the Pim-1-inhibitory and non-cytotoxic concentration of 1 μM decreased the IC50s of the ABCG2 and ABCB1 substrate drugs in cytotoxicity assays in resistant cells, with no effect on the IC50 of non-substrate drug, nor in parental cells. SGI-1776 also increased apoptosis of cells overexpressing ABCG2 or ABCB1 exposed to substrate chemotherapy drugs and decreased their colony formation in the presence of substrate, but not non-substrate, drugs, with no effect on parental cells. SGI-1776 decreased ABCB1 and ABCG2 surface expression on K562/ABCB1 and K562/ABCG2 cells, respectively, with Pim-1 overexpression, but not HL60/VCR and 8226/MR20 cells, with lower-level Pim-1 expression. Finally, SGI-1776 inhibited uptake of ABCG2 and ABCB1 substrates in a concentration-dependent manner irrespective of Pim-1 expression, inhibited ABCB1 and ABCG2 photoaffinity labeling with the transport substrate [125I]iodoarylazidoprazosin ([125I]IAAP) and stimulated ABCB1 and ABCG2 ATPase activity. Thus SGI-1776 decreases cell surface expression of ABCB1 and ABCG2 and inhibits drug transport by Pim-1-dependent and -independent mechanisms, respectively. Decrease in ABCB1 and ABCG2 cell surface expression mediated by Pim-1 inhibition represents a novel mechanism of chemosensitization. PMID:23261525

  8. Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).

    PubMed

    Ark, B; Gummere, G; Bennett, D; Artzt, K

    1991-06-01

    Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Saccadic latency in amblyopia

    PubMed Central

    McKee, Suzanne P.; Levi, Dennis M.; Schor, Clifton M.; Movshon, J. Anthony

    2016-01-01

    We measured saccadic latencies in a large sample (total n = 459) of individuals with amblyopia or risk factors for amblyopia, e.g., strabismus or anisometropia, and normal control subjects. We presented an easily visible target randomly to the left or right, 3.5° from fixation. The interocular difference in saccadic latency is highly correlated with the interocular difference in LogMAR (Snellen) acuity—as the acuity difference increases, so does the latency difference. Strabismic and strabismic-anisometropic amblyopes have, on average, a larger difference between their eyes in LogMAR acuity than anisometropic amblyopes and thus their interocular latency difference is, on average, significantly larger than anisometropic amblyopes. Despite its relation to LogMAR acuity, the longer latency in strabismic amblyopes cannot be attributed either to poor resolution or to reduced contrast sensitivity, because their interocular differences in grating acuity and in contrast sensitivity are roughly the same as for anisometropic amblyopes. The correlation between LogMAR acuity and saccadic latency arises because of the confluence of two separable effects in the strabismic amblyopic eye—poor letter recognition impairs LogMAR acuity while an intrinsic sluggishness delays reaction time. We speculate that the frequent microsaccades and the accompanying attentional shifts, made while strabismic amblyopes struggle to maintain fixation with their amblyopic eyes, result in all types of reactions being irreducibly delayed. PMID:26943348

  10. 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

  11. 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

  12. 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

  13. Hypoxia-responsive miR-124 and miR-144 reduce hypoxia-induced autophagy and enhance radiosensitivity of prostate cancer cells via suppressing PIM1.

    PubMed

    Gu, Hao; Liu, Mingzhu; Ding, Changmao; Wang, Xin; Wang, Rui; Wu, Xinyu; Fan, Ruitai

    2016-06-01

    Cancer cells in hypoxia usually make adaptive changes in cellular metabolism, such as altered autophagy. This might be a cause of enhanced radioresistance in some types of cancer. In this study, we investigated hypoxia-responsive miRNAs in two prostate cancer cell lines (DU145 and PC3). This study firstly reported that hypoxia induces further downregulation of miR-124 and miR-144, which might be a result of impaired dicer expression. These two miRNAs can simultaneously target 3'UTR of PIM1. Functional study showed that miR-124 or miR-144 overexpression can inhibit hypoxia-induced autophagy and enhance radiosensitivity at least via downregulating PIM1. Therefore, hypoxia induced miR-124 and miR-144 downregulation may contribute to a prosurvival mechanism of prostate cancer cells to hypoxia and irradiation at least through attenuated suppressing of PIM1. This finding presents a potential therapeutic target for prostate cancer. PMID:26990493

  14. 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.

  15. Long-term exposure of E-mu-Pim1 transgenic mice to 898.4 MHz microwaves does not increase lymphoma incidence.

    PubMed

    Utteridge, Tammy D; Gebski, Val; Finnie, John W; Vernon-Roberts, Barrie; Kuchel, Tim R

    2002-09-01

    A total of 120 E mu-Pim1 heterozygous mice and 120 wild-type mice were exposed for 1 h/day 5 days/week at each of the four exposure levels in "Ferris-wheel" exposure systems for up to 104 weeks to GSM-modulated 898.4 MHz radiation at SARs of 0.25, 1.0, 2.0 and 4.0 W/kg. In addition, 120 heterozygous and 120 wild-type mice were sham-exposed; there was also an unrestrained negative control group. Four exposure levels were used to investigate whether a dose-response effect could be detected. Independent verification confirmed that the exposures in the current study were nonthermal. There was no significant difference in the incidence of lymphomas between exposed and sham-exposed groups at any of the exposure levels. A dose-response effect was not detected. The findings showed that long-term exposures of lymphoma-prone mice to 898.4 MHz GSM radiofrequency (RF) radiation at SARs of 0.25, 1.0, 2.0 and 4.0 W/kg had no significant effects when compared to sham-irradiated animals. A previous study (Repacholi et al., Radiat. Res. 147, 631-640, 1997) reported that long-term exposure of lymphoma-prone mice to one exposure level of 900 MHz RF radiation significantly increased the incidence of non-lymphoblastic lymphomas when compared to sham-irradiated animals. PMID:12175314

  16. 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.

  17. 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.

  18. A Readout Mechanism for Latency Codes

    PubMed Central

    Zohar, Oran; Shamir, Maoz

    2016-01-01

    Response latency has been suggested as a possible source of information in the central nervous system when fast decisions are required. The accuracy of latency codes was studied in the past using a simplified readout algorithm termed the temporal-winner-take-all (tWTA). The tWTA is a competitive readout algorithm in which populations of neurons with a similar decision preference compete, and the algorithm selects according to the preference of the population that reaches the decision threshold first. It has been shown that this algorithm can account for accurate decisions among a small number of alternatives during short biologically relevant time periods. However, one of the major points of criticism of latency codes has been that it is unclear how can such a readout be implemented by the central nervous system. Here we show that the solution to this long standing puzzle may be rather simple. We suggest a mechanism that is based on reciprocal inhibition architecture, similar to that of the conventional winner-take-all, and show that under a wide range of parameters this mechanism is sufficient to implement the tWTA algorithm. This is done by first analyzing a rate toy model, and demonstrating its ability to discriminate short latency differences between its inputs. We then study the sensitivity of this mechanism to fine-tuning of its initial conditions, and show that it is robust to wide range of noise levels in the initial conditions. These results are then generalized to a Hodgkin-Huxley type of neuron model, using numerical simulations. Latency codes have been criticized for requiring a reliable stimulus-onset detection mechanism as a reference for measuring latency. Here we show that this frequent assumption does not hold, and that, an additional onset estimator is not needed to trigger this simple tWTA mechanism. PMID:27812332

  19. 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.

  20. 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.

  1. Latency: the hidden HIV-1 challenge

    PubMed Central

    Marcello, Alessandro

    2006-01-01

    Eradication of HIV-1 from an infected individual cannot be achieved by current regimens. Viral reservoirs established early during the infection remain unaffected by anti-retroviral therapy for a long time and are able to replenish systemic infection upon interruption of the treatment. Therapeutic targeting of viral latency will require a better understanding of the basic mechanisms underlying the establishment and long-term maintenance of HIV-1 in resting memory CD4 T cells, the most prominent reservoir of transcriptionally silent provirus. Since the molecular mechanisms that permit long term transcriptional control of proviral gene expression in these cells are still obscure, this review aims at summarizing the various aspects of the problem that need to be considered. In particular, this review will focus the attention on the control of transcription imposed by chromatin through various epigenetic mechanisms. Exploring the molecular details of viral latency will provide new insights for eventual future therapeutics that aim at viral eradication. PMID:16412247

  2. Latency Minimizing Tasking for Information Processing Systems

    SciTech Connect

    Horey, James L; Lagesse, Brent J

    2011-01-01

    Real-time cyber-physical systems and information processing clusters require system designers to consider the total latency involved in collecting and aggregating data. For example, applications such as wild-fire monitoring require data to be presented to users in a timely manner. However, most models and algorithms for sensor networks have focused on alternative metrics such as energy efficiency. In this paper, we present a new model of sensor network aggregation that focuses on total latency. Our model is flexible and enables users to configure varying transmission and computation time on a node-by-node basis, and thus enables the simulation of complex computational phenomena. In addition, we present results from three tasking algorithms that trade-off local communication for overall latency performance. These algorithms are evaluated in simulated networks of up to 200 nodes. We've presented an aggregation-focused model of sensor networks that can be used to study the trade-offs between computational coverage and total latency. Our model explicitly takes into account transmission and computation times, and enables users to define different values for the basestation. In addition, we've presented three different tasking algorithms that operate over model to produce aggregation schedules of varying quality. In the future, we expect to continue exploring distributed tasking algorithms for information processing systems. We've shown that the gap between highly optimized schedules that use global information is quite large relative to our distributed algorithms. This gives us encouragement that future distributed tasking algorithms can still make large gains.

  3. Altered sleep latency and arousal regulation in mice lacking norepinephrine.

    PubMed

    Hunsley, Melissa S; Palmiter, Richard D

    2004-08-01

    Latency to sleep and the amount of sensory stimulation required to awaken an animal are measures of arousal threshold, which are ultimately modulated by an arousal regulation system involving many brain areas. Among these brain areas and network connections are wake-promoting nuclei of the brainstem and their corresponding neurotransmitters, including norepinephrine (NE). In this study, we used mice that are unable to produce NE to study its role in regulating sleep latency after a variety of interventions, and to study arousal from sleep after sleep deprivation (SD). Sleep latency was measured after gentle awakening or after injections of saline, caffeine or modafinil. Sleep latency was also measured before and after partial restoration of NE pharmacologically. Arousal threshold was measured by recording the number of decibels of white noise required to wake each mouse from NREM sleep after 0, 3 and 3 + 3 h SD (3 h SD followed by < 2 min sleep, followed by an additional 3 h SD). Results showed that when mice were awakened without being touched, there were no differences in sleep latency between the genotypes. However, after an injection of saline, the control mice increased their sleep latency, whereas the NE-deficient mice did not. There were no group differences in sleep latency after treatment with either stimulant. The sleep latency difference between the genotypes was ameliorated by partial restoration of NE. The arousal threshold experiments revealed that significantly more noise was required to wake the NE-deficient mice after 3 and 3 + 3 h of SD. These findings show that mice lacking NE fall asleep more rapidly only after a mild stressor, such as an intraperitoneal injection. NE-deficient mice are also more difficult to wake up using audio stimulation after SD. The results presented here suggest that NE promotes wakefulness during transitions between sleep and wake under conditions involving mild stress and SD, but not under baseline circumstances.

  4. 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

  5. Expression of the herpes simplex virus type 1 latency-associated transcripts does not influence latency establishment of virus mutants deficient for neuronal replication.

    PubMed

    Nicoll, M P; Efstathiou, S

    2013-11-01

    Herpes simplex virus type 1 establishes latency within neurons of the trigeminal ganglion. During latency, viral gene expression is largely restricted to the latency-associated transcripts (LATs), which, whilst not essential for any aspect of latency, function to suppress lytic gene expression and enhance the survival of virus-infected neurons. The latent cell population comprises primary-order neurons infected directly from peripheral tissues and cells infected following further virus spread within the ganglion. In order to assess the role of LAT expression on latency establishment within first-order neurons, we infected ROSA26R reporter mice with Cre recombinase-expressing recombinant viruses harbouring deletion of the thymidine kinase lytic gene and/or the core LAT promoter. We found that LAT expression did not impact on latency establishment in viruses unable to replicate in neurons, and under these conditions, it was not required for the survival of neurons between 3 and 31 days post-infection. PMID:23907392

  6. EOS Data Products Latency and Reprocessing Evaluation

    NASA Astrophysics Data System (ADS)

    Ramapriyan, H. K.; Wanchoo, L.

    2012-12-01

    NASA's Earth Observing System (EOS) Data and Information System (EOSDIS) program has been processing, archiving, and distributing EOS data since the launch of Terra platform in 1999. The EOSDIS Distributed Active Archive Centers (DAACs) and Science-Investigator-led Processing Systems (SIPSs) are generating over 5000 unique products with a daily average volume of 1.7 Petabytes. Initially EOSDIS had requirements to make process data products within 24 hours of receiving all inputs needed for generating them. Thus, generally, the latency would be slightly over 24 and 48 hours after satellite data acquisition, respectively, for Level 1 and Level 2 products. Due to budgetary constraints these requirements were relaxed, with the requirement being to avoid a growing backlog of unprocessed data. However, the data providers have been generating these products in as timely a manner as possible. The reduction in costs of computing hardware has helped considerably. It is of interest to analyze the actual latencies achieved over the past several years in processing and inserting the data products into the EOSDIS archives for the users to support various scientific studies such as land processes, oceanography, hydrology, atmospheric science, cryospheric science, etc. The instrument science teams have continuously evaluated the data products since the launches of EOS satellites and improved the science algorithms to provide high quality products. Data providers have periodically reprocessed the previously acquired data with these improved algorithms. The reprocessing campaigns run for an extended time period in parallel with forward processing, since all data starting from the beginning of the mission need to be reprocessed. Each reprocessing activity involves more data than the previous reprocessing. The historical record of the reprocessing times would be of interest to future missions, especially those involving large volumes of data and/or computational loads due to

  7. 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

  8. 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

  9. Chromatin, gene silencing and HIV latency

    PubMed Central

    Mok, Hoi-Ping; Lever, Andrew ML

    2007-01-01

    One of the cellular defenses against virus infection is the silencing of viral gene expression. There is evidence that at least two gene-silencing mechanisms are used against the human immuno-deficiency virus (HIV). Paradoxically, this cellular defense mechanism contributes to viral latency and persistence, and we review here the relationship of viral latency to gene-silencing mechanisms. PMID:18036274

  10. 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...

  11. An experimental study of memory fault latency

    NASA Technical Reports Server (NTRS)

    Chillarege, Ram; Iyer, Ravi K.

    1989-01-01

    The difficulty with the measurement of fault latency is due to the lack of observability of the fault occurrence and error generation instants in a production environment. The authors describe an experiment, using data from a VAX 11/780 under real workload, to study fault latency in the memory subsystem accurately. Fault latency distributions are generated for stuck-at-zero (s-a-0) and stuck-at-one (s-a-1) permanent fault models. The results show that the mean fault latency of an s-a-0 fault is nearly five times that of the s-a-1 fault. An analysis of variance is performed to quantify the relative influence of different workload measures on the evaluated latency.

  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. First spike latency code for interaural phase difference discrimination in the guinea pig inferior colliculus.

    PubMed

    Zohar, Oran; Shackleton, Trevor M; Nelken, Israel; Palmer, Alan R; Shamir, Maoz

    2011-06-22

    First spike latency has been suggested as a source of the information required for fast discrimination tasks. However, the accuracy of such a mechanism has not been analyzed rigorously. Here, we investigate the utility of first spike latency for encoding information about the location of a sound source, based on the responses of inferior colliculus (IC) neurons in the guinea pig to interaural phase differences (IPDs). First spike latencies of many cells in the guinea pig IC show unimodal tuning to stimulus IPD. We investigated the discrimination accuracy of a simple latency code that estimates stimulus IPD from the preferred IPD of the single cell that fired first. Surprisingly, despite being based on only a single spike, the accuracy of the latency code is comparable to that of a conventional rate code computed over the entire response. We show that spontaneous firing limits the capacity of the latency code to accumulate information from large neural populations. This detrimental effect can be overcome by generalizing the latency code to estimate the stimulus IPD from the preferred IPDs of the population of cells that fired the first n spikes. In addition, we show that a good estimate of the neural response time to the stimulus, which can be obtained from the responses of the cells whose response latency is invariant to stimulus identity, limits the detrimental effect of spontaneous firing. Thus, a latency code may provide great improvement in response speed at a small cost to the accuracy of the decision. PMID:21697370

  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. 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

  16. Regulation of HIV-1 Latency by T-cell Activation

    PubMed Central

    Williams, Samuel A.; Greene, Warner C.

    2007-01-01

    HIV infected patients harbor ~105–106 memory CD4 T-cells that contain fully integrated but transcriptionally silent HIV proviruses. While small in number, these latently infected cells form a drug-insensitive reservoir that importantly contributes to the life-long persistence of HIV despite highly effective antiviral therapy. In tissue culture, latent HIV proviruses can be activated when their cellular hosts are exposed to select proinflammatory cytokines or their T-cell receptors are ligated. However, due to a lack of potency and/or dose-limiting toxicity, attempts to purge virus from this latent reservoir in vivo with immune-activating agents including anti-CD3 antibodies and IL-2 have failed. A deeper understanding of the molecular underpinnings of HIV latency is clearly required, including determining whether viral latency is actively reinforced by transcriptional repressors, defining which inducible host transcription factors most effectively antagonize latency, and elucidating the role of chromatin in viral latency. Only through such an improved understanding will it be possible to identify combination therapies that might allow complete purging of the latent reservoir and realization of the difficult and elusive goal of complete eradication of HIV in infected patients. PMID:17643313

  17. Advanced LIGO low-latency searches

    NASA Astrophysics Data System (ADS)

    Kanner, Jonah; LIGO Scientific Collaboration, Virgo Collaboration

    2016-06-01

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

  18. Investigation of fullerenes for high speed low latency, photonic switching

    SciTech Connect

    Lee, H. W. H; Shelton, R.N.

    1997-02-13

    The components in high-speed, all-optical photonic systems must satisfy two essential requirements: (1) high switching speeds in the range of Tbit/s, and (2) low latency, where the latency is the amount of time that the optical signal remains in the device. An important problem precluding the practical implementation of high-speed, all- optical switching is the lack of a material with appropriate nonlinear optical properties needed to effect the switching. Numerous material systems have been studied in the past, but none have met all the necessary requirements. Development of such a material and its incorporation into photonic devices would advance the field tremendously. This Lab-wide LDRD project resolved this critical problem.

  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.

    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.

  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.

    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.

  1. 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

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

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

    Initial, science-directed human exploration of Mars will benefit from low-latency, high-bandwidth telerobotics operated by astronauts from Mars orbit. This paper describes the scientific framework and technological requirements to achieve this goal.

  3. 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.

  4. Error latency measurements in symbolic architectures

    NASA Technical Reports Server (NTRS)

    Young, L. T.; Iyer, R. K.

    1991-01-01

    Error latency, the time that elapses between the occurrence of an error and its detection, has a significant effect on reliability. In computer systems, failure rates can be elevated during a burst of system activity due to increased detection of latent errors. A hybrid monitoring environment is developed to measure the error latency distribution of errors occurring in main memory. The objective of this study is to develop a methodology for gauging the dependability of individual data categories within a real-time application. The hybrid monitoring technique is novel in that it selects and categorizes a specific subset of the available blocks of memory to monitor. The precise times of reads and writes are collected, so no actual faults need be injected. Unlike previous monitoring studies that rely on a periodic sampling approach or on statistical approximation, this new approach permits continuous monitoring of referencing activity and precise measurement of error latency.

  5. Low Latency Messages on Distributed Memory Multiprocessors

    DOE PAGES

    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

  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. The Impact of System Latency on Dynamic Performance In Virtual Acoustic Environments

    NASA Technical Reports Server (NTRS)

    Wenzel, Elizabeth M.; Ahumada, Albert (Technical Monitor)

    1998-01-01

    Engineering constraints that may be encountered when implementing interactive virtual acoustic displays are examined In particular, system parameters such as the update rate and total system latency are defined and the impact they may have on perception is discussed. For example, examination of the head motions that listeners used to aid localization in a previous study suggests that some head motions may be as fast as about 400 degrees/sec for short time periods. Analysis of latencies in virtual acoustic environments (VAEs) suggests that: (1) commonly-specified parameters such as the audio update rate determine only the "best-case" latency possible in a VAE, (2) total system latency and individual latencies of system components, including head-trackers, are frequently not measured by VAE developers, and (3) typical system latencies may result in under-sampling of relative listener-source motion of 400 degrees/sec as well as positional "jitter" in the simulated source. To clearly specify the dynamic performance of a particular VAE, users and developers need to make measurements of average system latency, update rate, and their variability using standardized rendering scenarios. a parameters such as the minimum audible movement angle can then be used as target guidelines to assess whether a given system meets perceptual requirements.

  8. 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.

  9. 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…

  10. Hypoxia: a window into Mycobacterium tuberculosis latency.

    PubMed

    Rustad, Tige R; Sherrid, Ashley M; Minch, Kyle J; Sherman, David R

    2009-08-01

    Tuberculosis is a massive public health problem on a global scale and the success of Mycobacterium tuberculosis is linked to its ability to persist within humans for long periods without causing any overt disease symptoms. Hypoxia is predicted to be a key host-induced stress limiting growth of the pathogen in vivo. However, multiple studies in vitro and in vivo indicate that M. tuberculosis adapts to oxygen limitation by entering into a metabolically altered state, while awaiting the opportunity to reactivate. Molecular signatures of bacteria adapted to hypoxia in vitro are accumulating, although correlations to human disease are only now being established. Similarly, defining the mechanisms that control this adaptation is an active area of research. In this review we discuss the historical precedents linking hypoxia and latency, and the gathering knowledge of M. tuberculosis hypoxic responses. We also examine the role of these responses in tuberculosis latency, and identify promising avenues for future studies.

  11. Arbitration in crossbar interconnect for low latency

    SciTech Connect

    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.

  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. Identification of N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies.

    PubMed

    Burger, Matthew T; Nishiguchi, Gisele; Han, Wooseok; Lan, Jiong; Simmons, Robert; Atallah, Gordana; Ding, Yu; Tamez, Victoriano; Zhang, Yanchen; Mathur, Michelle; Muller, Kristine; Bellamacina, Cornelia; Lindvall, Mika K; Zang, Richard; Huh, Kay; Feucht, Paul; Zavorotinskaya, Tatiana; Dai, Yumin; Basham, Steve; Chan, Julie; Ginn, Elaine; Aycinena, Alex; Holash, Jocelyn; Castillo, Joseph; Langowski, John L; Wang, Yingyun; Chen, Min Y; Lambert, Amy; Fritsch, Christine; Kauffmann, Audry; Pfister, Estelle; Vanasse, K Gary; Garcia, Pablo D

    2015-11-12

    Pan proviral insertion site of Moloney murine leukemia (PIM) 1, 2, and 3 kinase inhibitors have recently begun to be tested in humans to assess whether pan PIM kinase inhibition may provide benefit to cancer patients. Herein, the synthesis, in vitro activity, in vivo activity in an acute myeloid leukemia xenograft model, and preclinical profile of the potent and selective pan PIM kinase inhibitor compound 8 (PIM447) are described. Starting from the reported aminopiperidyl pan PIM kinase inhibitor compound 3, a strategy to improve the microsomal stability was pursued resulting in the identification of potent aminocyclohexyl pan PIM inhibitors with high metabolic stability. From this aminocyclohexyl series, compound 8 entered the clinic in 2012 in multiple myeloma patients and is currently in several phase 1 trials of cancer patients with hematological malignancies. PMID:26505898

  14. 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.

  15. Middle Latency Response in Children with Learning Disabilities: Preliminary Findings.

    ERIC Educational Resources Information Center

    Arehole, Shalini; And Others

    1995-01-01

    Simultaneous recordings of auditory brainstem and middle latency responses were obtained in both vertex-ipsilateral and vertex-contralateral derivations in 22 children, ages 8-12. For specific recording conditions, the latencies of middle latency responses differ significantly between children with and without learning disabilities, offering…

  16. 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

  17. Differentiation of hamstring short latency versus medium latency responses after tibia translation.

    PubMed

    Friemert, B; Bumann-Melnyk, M; Faist, M; Schwarz, W; Gerngross, H; Claes, L

    2005-01-01

    After injuries to the anterior cruciate ligament (ACL) a functional instability is frequently observed which has been attributed to a disturbed sensorimotor function. In light of the clinical importance of ACL injuries and the resulting functional instability, it is of enormous clinical interest to elucidate the role of sensorimotor pathways that involve the ACL. In animals and humans a direct reflex pathway between the ACL and the hamstrings has been shown. The onset latencies of responses reported after ventral tibia translation were around 40-50 ms (range 17.9-65) and were regarded as medium latency responses (MLR). However, ventral tibia translation should also induce a stretch of the hamstring muscles and evoke a short latency response (SLR). Before any muscle response after ventral tibia translation can be ascribed to anatomical structures, it is crucial to analyze the obtained muscle responses carefully. The aim of the present study was the development of an algorithm to differentiate SLR and MLR responses after ventral tibia translation. In ten healthy subjects reflex responses of the hamstrings after anterior tibia translation and after tendon taps on the biceps femoris tendon were evaluated. To investigate the influence of skin afferents, control experiments were performed after lidocain injection of the dorsal calf. The mean onset latency of the tendon jerk reflex was 21.9 +/- 3.1 ms (range 17.3 - 28.7 ms). Both SLR responses (mean onset latency: 20.3 +/- 3.5 ms; range 15.4 - 25.8) and MLR responses (mean onset latency: 38.9 +/- 4.2 ms; range 32.9 - 46.7) were obtained in all subjects. Skin afferents from the calf do not play a major role. The development of an evaluation algorithm is presented that allows a safe differentiation between these partly superimposed SLR and MLR components. It is demonstrated that by measuring the first part of the SLR from the onset to the first peak the end of the SLR can be predicted and that the onset latency of the MLR

  18. 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…

  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 Reduction during Telemetry Transmission in Brain-Machine Interfaces.

    PubMed

    Oweiss, Karim

    2005-01-01

    Advanced array processing techniques are becoming an indispensable requirement for integrating the rapid developments in wireless high-density electronic interfaces to the central nervous system with computational neuroscience. This work aims at describing a systems approach for latency reduction in telemetry-linked brain machine interfaces to enable real-time transmission of high volumes of neural data. We show that the tradeoff between transmission bit rate and processing complexity requires a smart processing mechanism to strip the redundancy and extract the useful information early in the data stream. The results presented demonstrate that space-time processing offers tremendous savings in communication costs compared to on-chip spike detection followed by off-chip classification. They also demonstrate that the performance asymptotically approaches that of on-chip spike detection and sorting. Detailed performance evaluation is described.

  1. 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

  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. 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

  4. 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

  5. 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.

  6. Low latency and persistent data storage

    SciTech Connect

    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.

  7. Low latency and persistent data storage

    SciTech Connect

    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.

  8. Method of data communications with reduced latency

    DOEpatents

    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.

  9. 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…

  10. 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…

  11. 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…

  12. 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.

  13. Characterization of a Novel Golgi Apparatus-Localized Latency Determinant Encoded by Human Cytomegalovirus▿

    PubMed Central

    Petrucelli, Alex; Rak, Michael; Grainger, Lora; Goodrum, Felicia

    2009-01-01

    Human cytomegalovirus (HCMV) exists indefinitely in infected individuals by a yet poorly characterized latent infection in hematopoietic cells. We previously demonstrated a requirement for the putative UL138 open reading frame (ORF) in promoting a latent infection in CD34+ hematopoietic progenitor cells (HPCs) infected in vitro. In our present study, we have identified two coterminal transcripts of 2.7 and 3.6 kb and a 21-kilodalton (kDa) protein (pUL138) that are derived from the UL138 locus with early-late gene kinetics during productive infection. The UL138 transcripts and protein are detected in both fibroblasts and HPCs. A recombinant virus, FIX-UL138STOP, that synthesizes the UL138 transcripts but not the protein exhibited a partial loss-of-latency phenotype in HPCs, similar to the phenotype observed for the UL138-null recombinant virus. This finding suggests that the UL138 protein is required for latency, but it does not exclude the possibility that the UL138 transcripts or other ORFs also contribute to latency. The mechanisms by which pUL138 contributes to latency remain unknown. While the 86- and 72-kDa immediate-early proteins were not detected in HPCs infected with HCMV in vitro, pUL138 did not function directly to suppress expression from the major immediate-early promoter in reporter assays. Interestingly, pUL138 localizes to the Golgi apparatus in infected cells but is not incorporated into virus particles. The localization of pUL138 to the Golgi apparatus suggests that pUL138 contributes to HCMV latency by a novel mechanism. pUL138 is the first HCMV protein demonstrated to promote an infection with the hallmarks of latency in CD34+ HPCs. PMID:19297488

  14. 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

  15. 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

  16. 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

  17. Giant fiber activation of flight muscles in Drosophila: asynchrony in latency of wing depressor fibers.

    PubMed

    Hummon, M R; Costello, W J

    1989-09-01

    In Drosophila, brain stimulation of the giant fiber pathway brings about highly stereotyped electrical responses in target muscles involved in the escape response. Both the order of muscle response and the latency of that response are predictable in wild-type flies. The neuronal circuit to the targets is well defined and has been used in the analysis of a number of mutant phenotypes, including induced anomalies in temperature-sensitive (ts) mutations such as shibire (shi). It has been assumed that the stereotyped response includes simultaneous activation of all six fibers of the wing depressor muscle, DLM, resulting in equal latencies for all fibers. We report here a small, but distinct, inherent difference in latency between two sets of DLM fibers in a proportion of two wild-type strains as well as in a strain carrying the ts mutation shi. This difference may occur on one or both sides of an individual, is stable over time, and persists when the motor axon is stimulated peripherally. These results, due to the circuit leading to the target, suggest that the difference in latency arises peripherally. In flies reared at the shi permissive temperature (22 degrees C), the difference is more common in shi than in wild-type flies; however, in shi flies reared at 18 degrees C, the prevalence resembles that of wild-type flies. This indicates a subtle expression of the shi defect even at the presumed permissive temperature of 22 degrees C. The difference in latency is similar to that induced in shi flies whose development is affected by pupal heat pulse. Thus, correct interpretation of differences in latency, e.g., in shi/wild-type mosaic flies or in flies with mutations affecting the GF pathway, requires recognition of the inherent asynchrony that can occur between DLM fibers.

  18. Modelling Transposition Latencies: Constraints for Theories of Serial Order Memory

    ERIC Educational Resources Information Center

    Farrell, Simon; Lewandowsky, Stephan

    2004-01-01

    Several competing theories of short-term memory can explain serial recall performance at a quantitative level. However, most theories to date have not been applied to the accompanying pattern of response latencies, thus ignoring a rich and highly diagnostic aspect of performance. This article explores and tests the error latency predictions of…

  19. 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,…

  20. Low-latency adaptive optics system processing electronics

    NASA Astrophysics Data System (ADS)

    Duncan, Terry S.; Voas, Joshua K.; Eager, Robert J.; Newey, Scott C.; Wynia, John L.

    2003-02-01

    Extensive system modeling and analysis clearly shows that system latency is a primary performance driver in closed loop adaptive optical systems. With careful attention to all sensing, processing, and controlling components, system latency can be significantly reduced. Upgrades to the Starfire Optical Range (SOR) 3.5-meter telescope facility adaptive optical system have resulted in a reduction in overall latency from 660 μsec to 297 μsec. Future efforts will reduce the system latency even more to the 170 msec range. The changes improve system bandwidth significantly by reducing the "age" of the correction that is applied to the deformable mirror. Latency reductions have been achieved by increasing the pixel readout pattern and rate on the wavefront sensor, utilizing a new high-speed field programmable gate array (FPGA) based wavefront processor, doubling the processing rate of the real-time reconstructor, and streamlining the operation of the deformable mirror drivers.

  1. 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

  2. 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

    2012-04-02

    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

  3. 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

  4. Rates of Vaccine Evolution Show Strong Effects of Latency: Implications for Varicella Zoster Virus Epidemiology

    PubMed Central

    Weinert, Lucy A.; Depledge, Daniel P.; Kundu, Samit; Gershon, Anne A.; Nichols, Richard A.; Balloux, Francois; Welch, John J.; Breuer, Judith

    2015-01-01

    Varicella-zoster virus (VZV) causes chickenpox and shingles, and is found in human populations worldwide. The lack of temporal signal in the diversity of VZV makes substitution rate estimates unreliable, which is a barrier to understanding the context of its global spread. Here, we estimate rates of evolution by studying live attenuated vaccines, which evolved in 22 vaccinated patients for known periods of time, sometimes, but not always undergoing latency. We show that the attenuated virus evolves rapidly (∼10−6 substitutions/site/day), but that rates decrease dramatically when the virus undergoes latency. These data are best explained by a model in which viral populations evolve for around 13 days before becoming latent, but then undergo no replication during latency. This implies that rates of viral evolution will depend strongly on transmission patterns. Nevertheless, we show that implausibly long latency periods are required to date the most recent common ancestor of extant VZV to an “out-of-Africa” migration with humans, as has been previously suggested. PMID:25568346

  5. Rates of vaccine evolution show strong effects of latency: implications for varicella zoster virus epidemiology.

    PubMed

    Weinert, Lucy A; Depledge, Daniel P; Kundu, Samit; Gershon, Anne A; Nichols, Richard A; Balloux, Francois; Welch, John J; Breuer, Judith

    2015-04-01

    Varicella-zoster virus (VZV) causes chickenpox and shingles, and is found in human populations worldwide. The lack of temporal signal in the diversity of VZV makes substitution rate estimates unreliable, which is a barrier to understanding the context of its global spread. Here, we estimate rates of evolution by studying live attenuated vaccines, which evolved in 22 vaccinated patients for known periods of time, sometimes, but not always undergoing latency. We show that the attenuated virus evolves rapidly (∼ 10(-6) substitutions/site/day), but that rates decrease dramatically when the virus undergoes latency. These data are best explained by a model in which viral populations evolve for around 13 days before becoming latent, but then undergo no replication during latency. This implies that rates of viral evolution will depend strongly on transmission patterns. Nevertheless, we show that implausibly long latency periods are required to date the most recent common ancestor of extant VZV to an "out-of-Africa" migration with humans, as has been previously suggested.

  6. Waking up the sleepers: HIV latency and reactivation.

    PubMed

    Mok, Hoi Ping; Lever, Andrew

    2008-12-01

    In a patient infected with HIV-1, the presence of latently infected cells from which the virus can be reactivated and rekindle HIV infection in the patient necessitates lifelong administration of antiretroviral treatment. The biology of HIV latency and viral silencing is now becoming clearer at a molecular and cellular level. However, our understanding of HIV-1 latency in vivo is still inadequate. Attempts to therapeutically reactivate the virus in infected patients have yielded disappointing results. This article reviews the research and clinical findings and discusses current thinking on the subject of HIV latency and reactivation.

  7. System Latency in Linked Spot and Futures Markets

    NASA Astrophysics Data System (ADS)

    Wagener, Martin; Riordan, Ryan

    We examine the lead-lag effect between DAX index and DAX index futures under asymmetric latency in the exchange infrastructure. Using 1-min high frequency observations in 2006-2007, it is found that the market integration between stock index and stock index futures has significantly grown compared to prior research. While the degree of price discovery in the futures market decreased both markets react mostly contemporaneously towards new information. An event story of latency reduction on Xetra reveals that exchange latency is one important factor explaining this development. We find evidence that smaller asymmetric round-trip-times between Xetra and Eurex lead to a higher degree of market integration.

  8. Acceleration dependence and task-specific modulation of short- and medium-latency reflexes in the ankle extensors

    PubMed Central

    Finley, James M; Dhaher, Yasin Y; Perreault, Eric J

    2013-01-01

    Involuntary responses to muscle stretch are often composed of a short-latency reflex (SLR) and more variable responses at longer latencies such as the medium-latency (MLR) and long-latency stretch reflex (LLR). Although longer latency reflexes are enhanced in the upper limb during stabilization of external loads, it remains unknown if they have a similar role in the lower limb. This uncertainty results in part from the inconsistency with which longer latency reflexes have been observed in the lower limb. A review of the literature suggests that studies that only observe SLRs have used perturbations with large accelerations, possibly causing a synchronization of motoneuron refractory periods or an activation of force-dependent inhibition. We therefore hypothesized that the amplitude of longer latency reflexes would vary with perturbation acceleration. We further hypothesized that if longer latency reflexes were elicited, they would increase in amplitude during control of an unstable load, as has been observed in the upper limb. These hypotheses were tested at the ankle while subjects performed a torque or position control task. SLR and MLR reflex components were elicited by ankle flexion perturbations with a fixed peak velocity and variable acceleration. Both reflex components initially scaled with acceleration, however, while the SLR continued to increase at high accelerations, the MLR weakened. At accelerations that reliably elicited MLRs, both the SLR and MLR were reduced during control of the unstable load. These findings clarify the conditions required to elicit MLRs in the ankle extensors and provide additional evidence that rapid feedback pathways are downregulated when stability is compromised in the lower limb. PMID:24303134

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  10. 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

  11. Changes in middle latency auditory evoked potentials during meditation.

    PubMed

    Telles, Shirley; Naveen, K V

    2004-04-01

    In the present study of middle latency auditory evoked potentials during Brahmakumaris Raja Yoga meditation there was a decrease in the peak latency of the Na wave (a negative wave between 14 and 19 msec.) during meditation. Since the neural generator of this wave lies at the midbrain-thalamic level, from the results one can infer that the meditation reduces conduction time at this level.

  12. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

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

  14. Eye Movement Latencies to Direction Change for Different Classes of Motion

    NASA Technical Reports Server (NTRS)

    Mulligan, Jeffrey B.; Null, Cynthia H. (Technical Monitor)

    1997-01-01

    In the analysis of visual motion, local features such as orientation are analyzed early in the cortical processing stream (V1), while integration across orientation and space is thought to occur in higher cortical areas such as MT, MST, etc. If all areas provide inputs to eye movement control centers, we would expect that local properties would drive eye movements with relatively short latencies, while global properties would require longer latencies. When such latencies are observed, they can provide information about when (and where?) various stimulus properties are analyzed. To this end, a stimulus was employed in which local and global properties determining perceived direction-of-motion could be manipulated independently: an elliptical Gabor patch with a drifting carrier, with variable orientation of the carrier grating and the contrast window. We have previously demonstrated that the directional percepts evoked by this stimulus vary between the "grating direction" (the normal to the grating's orientation) and the "window direction" (ARVO 91, 94), and that similar effects can be observed in reflexive eye movements (ARVO 95). Subjects viewed such a stimulus while attempting to maintain steady fixation on the center of the pattern, and the small reflexive eye movements ("stare OKN") were recorded. In the middle of the trial, the orientation of either the grating or the window was rotated smoothly by 30 degrees. Responses to the shift of both grating orientation and window orientation are seen in the average OKN slow phase velocity. Grating rotations produce a rapid OKN rotation to the grating direction (100 ms latency, 300 ms time constant), followed by a slower rebound to the steady state perceived direction midway between the grating and window directions. Window rotations, on the other hand, evoke a slower response (200 ms latency, 500 ms time constant). The results demonstrate multiple cortical inputs to eye movement control: a taste early input driven by

  15. The spatial impact of visual distractors on saccade latency.

    PubMed

    McSorley, Eugene; McCloy, Rachel; Lyne, Clare

    2012-05-01

    Remote transient changes in the environment, such as the onset of visual distractors, impact on the execution of target directed saccadic eye movements. Studies that have examined the latency of the saccade response have shown conflicting results. When there was an element of target selection, saccade latency increased as the distance between distractor and target increased. In contrast, when target selection is minimized by restricting the target to appear on one axis position, latency has been found to be slowest when the distractor is shown at fixation and reduces as it moves away from this position, rather than from the target. Here we report four experiments examining saccade latency as target and distractor positions are varied. We find support for both a dependence of saccade latency on distractor distance from target and from fixation: saccade latency was longer when distractor is shown close to fixation and even longer still when shown in an opposite location (180°) to the target. We suggest that this is due to inhibitory interactions between the distractor, fixation and the target interfering with fixation disengagement and target selection.

  16. 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

  17. 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.

  18. Combining modalities with different latencies for optimal motor control

    PubMed Central

    Bissmarck, Fredrik; Nakahara, Hiroyuki; Doya, Kenji; Hikosaka, Okihide

    2010-01-01

    Feedback signals may be of different modality, latency and accuracy. To learn and control motor tasks the feedback available may be redundant, and it would not be necessary to rely on every accessible feedback loop. Which feedback loops should then be utilized? In this article, we propose that the latency is a critical factor to determine which signals will be influential at different learning stages. We use a computational framework to study the role of feedback modules with different latencies in optimal motor control. Instead of explicit gating between modules, the reinforcement learning algorithm learns to rely on the more useful module. We tested our paradigm for two different implementations, which confirmed our hypthesis. In the first, we examined how feedback latency affects the competitiveness of two identical modules. In the second, we examined an example of visuomotor sequence learning, where a plastic, faster somatosensory module interacts with a preacquired, slower visual module. We found that the overall performance depended on the latency of the faster module alone, while the relative latency determines the independence of the faster from the slower. In the second implementation, the somatosensory module with shorter latency overtook the slower visual module, and realized better overall performance. The visual module played different roles in early and late learning. First, it worked as a guide for the exploration of the somatosensory module. Then, when learning had converged, it contributed to robustness against system noise and external perturbations. Overall, these results demonstrate that our framework successfully learns to utilize the most useful available feedback for optimal control. PMID:18416676

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

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

    PubMed

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

    1999-01-01

    Cortical evoked potentials were evaluated in patients with cochlear implants. In a group of 8 adults of different ages, the lingual state before implantation and during rehabilitation were evaluated. Using cortical evoked potentials, the results of the P300 wave in response to two tones, one frequent (1,000 Hz) and the other infrequent (2,000 Hz), presented at 70 and 80 dB HL were studied. Results were analyzed and compared in relation to locutive state, rehabilitation stage, and intensity of stimulus. Absolute latencies did not differ significantly. However, latency values in relation to reaction time were significantly longer in prelingual than in postlingual patients (p < 0.05, Student test). The results confirmed the normality of central cognitive processes in patients with cochlear implants in objective assessment of P300 latency. The results suggest differences between prelingual and postlingual patients in relation to central signal processing.

  5. 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.

  6. 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.

  7. Presynaptic Spontaneous Activity Enhances the Accuracy of Latency Coding.

    PubMed

    Levakova, Marie; Tamborrino, Massimiliano; Kostal, Lubomir; Lansky, Petr

    2016-10-01

    The time to the first spike after stimulus onset typically varies with the stimulation intensity. Experimental evidence suggests that neural systems use such response latency to encode information about the stimulus. We investigate the decoding accuracy of the latency code in relation to the level of noise in the form of presynaptic spontaneous activity. Paradoxically, the optimal performance is achieved at a nonzero level of noise and suprathreshold stimulus intensities. We argue that this phenomenon results from the influence of the spontaneous activity on the stabilization of the membrane potential in the absence of stimulation. The reported decoding accuracy improvement represents a novel manifestation of the noise-aided signal enhancement. PMID:27557098

  8. The determinants of spoken and written picture naming latencies.

    PubMed

    Bonin, Patrick; Chalard, Marylène; Méot, Alain; Fayol, Michel

    2002-02-01

    The influence of nine variables on the latencies to write down or to speak aloud the names of pictures taken from Snodgrass and Vanderwart (1980) was investigated in French adults. The major determinants of both written and spoken picture naming latencies were image variability, image agreement and age of acquisition. To a lesser extent, name agreement was also found to have an impact in both production modes. The implications of the findings for theoretical views of both spoken and written picture naming are discussed. PMID:11839103

  9. Presynaptic Spontaneous Activity Enhances the Accuracy of Latency Coding.

    PubMed

    Levakova, Marie; Tamborrino, Massimiliano; Kostal, Lubomir; Lansky, Petr

    2016-10-01

    The time to the first spike after stimulus onset typically varies with the stimulation intensity. Experimental evidence suggests that neural systems use such response latency to encode information about the stimulus. We investigate the decoding accuracy of the latency code in relation to the level of noise in the form of presynaptic spontaneous activity. Paradoxically, the optimal performance is achieved at a nonzero level of noise and suprathreshold stimulus intensities. We argue that this phenomenon results from the influence of the spontaneous activity on the stabilization of the membrane potential in the absence of stimulation. The reported decoding accuracy improvement represents a novel manifestation of the noise-aided signal enhancement.

  10. An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones.

    PubMed

    Proença, João T; Coleman, Heather M; Nicoll, Michael P; Connor, Viv; Preston, Christopher M; Arthur, Jane; Efstathiou, Stacey

    2011-11-01

    Herpes simplex virus (HSV) type-1 establishes lifelong latency in sensory neurones and it is widely assumed that latency is the consequence of a failure to initiate virus immediate-early (IE) gene expression. However, using a Cre reporter mouse system in conjunction with Cre-expressing HSV-1 recombinants we have previously shown that activation of the IE ICP0 promoter can precede latency establishment in at least 30% of latently infected cells. During productive infection of non-neuronal cells, IE promoter activation is largely dependent on the transactivator VP16 a late structural component of the virion. Of significance, VP16 has recently been shown to exhibit altered regulation in neurones; where its de novo synthesis is necessary for IE gene expression during both lytic infection and reactivation from latency. In the current study, we utilized the Cre reporter mouse model system to characterize the full extent of viral promoter activity compatible with cell survival and latency establishment. In contrast to the high frequency activation of representative IE promoters prior to latency establishment, cell marking using a virus recombinant expressing Cre under VP16 promoter control was very inefficient. Furthermore, infection of neuronal cultures with VP16 mutants reveals a strong VP16 requirement for IE promoter activity in non-neuronal cells, but not sensory neurones. We conclude that only IE promoter activation can efficiently precede latency establishment and that this activation is likely to occur through a VP16-independent mechanism. PMID:21752961

  11. Apparent response incompatibility effects on P3 latency depend on the task.

    PubMed

    Pfefferbaum, A; Christensen, C; Ford, J M; Kopell, B S

    1986-11-01

    Ten young women were tested with an ERP paradigm that used the words 'left,' 'right,' 'LEFT,' 'RIGHT' as stimuli. The stimulus sequence was presented as several separate runs with varying response instructions. Subjects were instructed to respond according to the meaning of the stimulus in the (WORD task), to the case in which the stimulus was written (CASE task), or to both the case and meaning of the stimulus (CASE/WORD) task. In each task, half the trials called for a response that was incompatible with the stimulus. For the WORD task, compatible and incompatible trials were presented as separate blocks of trials. For all 3 tasks an additional stimulus sequence was presented in which the words were degraded with superimposed visual random noise. Reaction time (RT) in the CASE/WORD task was more than 100 msec later than in the other tasks. In the WORD and CASE/WORD tasks, RT was delayed more than 100 msec when the response was incompatible with the stimulus. Degrading the stimulus additionally delayed RT by about 100 msec. In the WORD and CASE tasks, error RTs were earlier than correct RTs. P3 latency was measured with a single-trial latency adjustment algorithm. P3 latency was delayed in the CASE/WORD task compared to the other 2 tasks. P3 was delayed by degrading the stimuli. Contrary to some previous reports, P3 was delayed by about 70 msec when incompatible responses were required, but only in the WORD task. Taken together with error and RT data, these P3 latency data are consistent with the notion that the task causes subjects to adopt different strategies and hence different types of processing (i.e., serial vs. parallel). Depending on the type of processing, P3 may appear to be affected by response incompatibility.

  12. 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.

  13. 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…

  14. 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…

  15. 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…

  16. 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

  17. 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

  18. Effects of Differential Reinforcement of Short Latencies on Response Latency, Task Completion, and Accuracy of an Adolescent with Autism

    ERIC Educational Resources Information Center

    Donohue, Melanie M.; Casey, Laura Baylot; Bicard, David F.; Bicard, Sara E.

    2012-01-01

    Children with Autism Spectrum Disorder (ASD) are faced with many challenging behaviors that could impede their learning. One commonly reported problem behavior is noncompliance, which is often defined as a delay in response (latency), decrease in rate of responding (fluency), or failure to complete a task. This failure to comply in an appropriate…

  19. 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.

  20. Genetic variants in RBFOX3 are associated with sleep latency.

    PubMed

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

    2016-10-01

    Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10(-08), 6.59 × 10(-)(08) and 9.17 × 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10(-)(02), 7.0 × 10(-)(03) and 2.5 × 10(-)(03); combined meta-analysis P-values=5.5 × 10(-07), 5.4 × 10(-07) and 1.0 × 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10(-316)) and the central nervous system (P-value=7.5 × 10(-)(321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 × 10(-11)) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency. PMID:27142678

  1. Genetic variants in RBFOX3 are associated with sleep latency.

    PubMed

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

    2016-10-01

    Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10(-08), 6.59 × 10(-)(08) and 9.17 × 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10(-)(02), 7.0 × 10(-)(03) and 2.5 × 10(-)(03); combined meta-analysis P-values=5.5 × 10(-07), 5.4 × 10(-07) and 1.0 × 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10(-316)) and the central nervous system (P-value=7.5 × 10(-)(321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 × 10(-11)) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency.

  2. 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.

  3. 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.

  4. 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.

  5. Rewards modulate saccade latency but not exogenous spatial attention

    PubMed Central

    Dunne, Stephen; Ellison, Amanda; Smith, Daniel T.

    2015-01-01

    The eye movement system is sensitive to reward. However, whilst the eye movement system is extremely flexible, the extent to which changes to oculomotor behavior induced by reward paradigms persist beyond the training period or transfer to other oculomotor tasks is unclear. To address these issues we examined the effects of presenting feedback that represented small monetary rewards to spatial locations on the latency of saccadic eye movements, the time-course of learning and extinction of the effects of rewarding saccades on exogenous spatial attention and oculomotor inhibition of return. Reward feedback produced a relative facilitation of saccadic latency in a stimulus driven saccade task which persisted for three blocks of extinction trials. However, this hemifield-specific effect failed to transfer to peripheral cueing tasks. We conclude that rewarding specific spatial locations is unlikely to induce long-term, systemic changes to the human oculomotor or attention systems. PMID:26284004

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. Impact of the Ku complex on HIV-1 expression and latency.

    PubMed

    Manic, Gwenola; Maurin-Marlin, Aurélie; Laurent, Fanny; Vitale, Ilio; Thierry, Sylvain; Delelis, Olivier; Dessen, Philippe; Vincendeau, Michelle; Leib-Mösch, Christine; Hazan, Uriel; Mouscadet, Jean-François; Bury-Moné, Stéphanie

    2013-01-01

    Ku, a cellular complex required for human cell survival and involved in double strand break DNA repair and multiple other cellular processes, may modulate retroviral multiplication, although the precise mechanism through which it acts is still controversial. Recently, Ku was identified as a possible anti-human immunodeficiency virus type 1 (HIV-1) target in human cells, in two global approaches. Here we investigated the role of Ku on the HIV-1 replication cycle by analyzing the expression level of a panel of non-replicative lentiviral vectors expressing the green fluorescent protein in human colorectal carcinoma HCT 116 cells, stably or transiently depleted of Ku. We found that in this cellular model the depletion of Ku did not affect the efficiency of (pre-)integrative steps but decreased the early HIV-1 expression by acting at the transcriptional level. This negative effect was specific of the HIV-1 promoter, required the obligatory step of viral DNA integration and was reversed by transient depletion of p53. We also provided evidence on a direct binding of Ku to HIV-1 LTR in transduced cells. Ku not only promotes the early transcription from the HIV-1 promoter, but also limits the constitution of viral latency. Moreover, in the presence of a normal level of Ku, HIV-1 expression was gradually lost over time, likely due to the counter-selection of HIV-1-expressing cells. On the contrary, the reactivation of transgene expression from HIV-1 by means of trichostatin A- or tumor necrosis factor α-administration was enhanced under condition of Ku haplodepletion, suggesting a phenomenon of provirus latency. These observations plead in favor of the hypothesis that Ku has an impact on HIV-1 expression and latency at early- and mid-time after integration.

  11. Latencies of extracted distortion-product otoacoustic source components

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  12. Eye closure affects flash VEP latency in dementia.

    PubMed

    Tartaglione, A; Bandini, F; Maculotti, M; Marogna, M; Spadavecchia, L; Favale, E

    1995-05-01

    In a group of 27 demented patients (21 with DAT and 6 with MID) with normal pattern VEP (PVEP), the latencies of the main flash VEP (FVEP) components (P1, N2, P2 and N3) were assessed both with open and closed eyes. At variance from controls, demented patients showed that both P2 and N3 components are significantly delayed with closed eyes while neither P1 nor N2 timings are affected. Control studies ruled out the possibility that such an outcome might depend on a defective pupillary responsiveness and/or an impaired sensitivity to luminance changes. On these grounds it is suggested that the effect of mode of stimulation on FVEP latency in demented patients is more likely to depend on "central" than on "peripheral" mechanisms. The dependence of latency changes on closure of the eyes seems to negate the direct effect of lesions upon visual structures and suggests an impairment of the modulatory action of non-visual afferents upon the activity of the visual cortex.

  13. Latency relationships between cerebral blood flow velocity and intracranial pressure.

    PubMed

    Asgari, Shadnaz; Vespa, Paul M; Bergsneider, Marvin; Hu, Xiao

    2012-01-01

    Pulsatile intracranial pressure (ICP) is a key to the understanding of several neurological disorders in which compliance is altered, e.g., hydrocephalus. A recently proposed model suggests that ICP pulse is a standing wave and not a transmitted wave. The present work, aimed at obtaining a better understanding of the pulsatility in the cranium, tries to test the following hypotheses: first, ICP pulse onset latency would be lower than that of cerebral blood flow velocity (CBFV) pulses measured at a distal vessel; second, CBFV pulse at different intracranial arteries will have different pulse onset latencies, and hence they are not generated as a standing wave. The dataset used in the present study consists of ICP and CBFV signals collected from 60 patients with different diagnoses. The results reveal that the ICP pulse leads CBFV for 90% of the patients regardless of the diagnosis and mean ICP value. In addition, we show that CBFV pulse onset latency is roughly determined by the distance of the measurement point to the heart. We conclude that the ICP signal is not generated as a standing wave and that ICP pulse onset may be related to the arteries proximal to the heart.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Real-time imaging with radial GRAPPA: Implementation on a heterogeneous architecture for low-latency reconstructions.

    PubMed

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

    2014-07-01

    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 reconstruction times are reported.

  19. 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.

  20. Herpes simplex virus type 1 latency-associated transcription unit promotes anatomical site-dependent establishment and reactivation from latency.

    PubMed Central

    Sawtell, N M; Thompson, R L

    1992-01-01

    Defined herpes simplex virus type 1 (HSV-1) mutants KOS/1 and KOS/62 (positive and negative, respectively, for latency-associated transcripts [LATs]) express the Escherichia coli beta-galactosidase (beta-Gal) gene during latency. These mutants were employed to assess the functions of the latency-associated transcription unit on establishment and maintenance of and reactivation from the latent state. It was found that in the trigeminal ganglia, the frequencies of hyperthermia-induced reactivation of KOS/62 and an additional LATs- mutant (KOS/29) were reduced by at least 80%. Quantification of latently infected neurons expressing the beta-Gal gene revealed that the LATs- mutant KOS/62 established approximately 80% fewer latent infections in the trigeminal ganglia than did KOS/1 (LATs+). This reduction in establishment which is evident in the trigeminal ganglia could account for the reduced frequency of reactivation from this site. In striking contrast, both LATs- mutants reactivated with wild-type frequencies from lumbosacral ganglia. Quantification of beta-Gal-positive neurons at this site revealed that KOS/62 established as many as or more latent infections than the LATs+ virus, KOS/1. Colocalization of HSV antigen and beta-Gal suggested that the decreased establishment by LATs- mutants in trigeminal ganglia was the result of inefficient viral shutoff. Thus, one function of the HSV-1 LATs transcription unit is to promote the establishment of latency in trigeminal but not lumbosacral ganglia. Such a function may be relevant to understanding the distinct clinical recurrent disease patterns of HSV-1 and HSV-2. Images PMID:1312626

  1. 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)

  2. 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.

  3. 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.

  4. 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

  5. A Procedure for Measuring Latencies in Brain-Computer Interfaces

    PubMed Central

    Wilson, J. Adam; Mellinger, Jürgen; Schalk, Gerwin; Williams, Justin

    2011-01-01

    Brain-computer interface (BCI) systems must process neural signals with consistent timing in order to support adequate system performance. Thus, it is important to have the capability to determine whether a particular BCI configuration (i.e., hardware, software) provides adequate timing performance for a particular experiment. This report presents a method of measuring and quantifying different aspects of system timing in several typical BCI experiments across a range of settings, and presents comprehensive measures of expected overall system latency for each experimental configuration. PMID:20403781

  6. Auditory middle latency responses under different task conditions.

    PubMed

    Nishihira, Y; Araki, H; Ishihara, A; Funase, K; Nagao, T; Kinjo, S

    1994-01-01

    We examined the relationship between the Na and Pa components of human MLRs and the performance of different tasks. We also investigated whether MLRs are reliable indices of activity in the central motor-sensory system. The click stimuli we used consistently evoked the Na and Pa components. At CZ, the Na and Pa components significantly decreased for all tasks other than pegging with right hand while at FZ, these components were significantly decreased for all tasks. The Na and Pa latencies were slightly increased during task performances. These results indicate that the Na and Pa components of human MLRs decreased when various tasks were performed, while subjects were concentrating. A general principle of evoked potentials is that latencies decrease as amplitudes increase in excitation due to neural activation. Thus, it would appear that, under the conditions of this study, the pathways from the reticular formation and the thalamus to the primary auditory cortex were inhibited. Since the thalamus is considered to be the relay region for poly-sensory inputs, it is thought that the attenuation of the MLRs and SEPs occurs at the level of cerebral cortex, including the reticular formation, the thalamus, and the primary auditory cortex. Accordingly, since it is inferred that central factors are responsible for the attenuation of the MLRs, Na and Pa components observed during the performance of tasks carried out in the present experiment, it may be concluded that MLRs are reliable indices of activity in the central-motor system.

  7. Latency and persistence of diet volatile biomarkers in lamb fats.

    PubMed

    Sivadier, Guilhem; Ratel, Jérémy; Engel, Erwan

    2009-01-28

    Several studies have shown that volatile compounds are particularly well-suited for the authentication lamb diet by gas chromatography-mass spectrometry (GC-MS) analysis of adipose tissue. The aim of the present work was to use dynamic headspace-GC-MS to study the variations in the amounts of volatile diet tracers in perirenal fat (PRF) and caudal subcutaneous fat (CSCF) in lambs (n = 24) that were fed with concentrate and then allowed to graze for 0, 17, 51, or 85 days. Twenty-six volatile compounds were found to distinguish between the four diets (p < 0.05) in both PRF and CSCF. Of these diet tracers, 16 were found to be related to the pasture diet and increased at different rates according to the time spent at pasture (latency), while 10 were found in higher amounts in tissues of lambs fed with exclusive concentrate and exhibited different rates of clearance (persistence). Twenty-four of these discriminant compounds, including alkanes, ketones, terpenes, and 2,3-octanedione, were previously stated as pasture diet tracers in several earlier studies, suggesting their potential universality. All degrees of latency or persistence were exhibited by the pasture and concentrate diet tracers, respectively. A principal component analysis performed on ratios of selected diet tracers from both adipose tissues evidenced successful differentiation of the four feeding situations. PMID:19154165

  8. Lost in Transcription: Molecular Mechanisms that Control HIV Latency

    PubMed Central

    Taube, Ran; Peterlin, Boris Matija

    2013-01-01

    Highly active antiretroviral therapy (HAART) has limited the replication and spread of the human immunodeficiency virus (HIV). However, despite treatment, HIV infection persists in latently infected reservoirs, and once therapy is interrupted, viral replication rebounds quickly. Extensive efforts are being directed at eliminating these cell reservoirs. This feat can be achieved by reactivating latent HIV while administering drugs that prevent new rounds of infection and allow the immune system to clear the virus. However, current approaches to HIV eradication have not been effective. Moreover, as HIV latency is multifactorial, the significance of each of its molecular mechanisms is still under debate. Among these, transcriptional repression as a result of reduced levels and activity of the positive transcription elongation factor b (P-TEFb: CDK9/cyclin T) plays a significant role. Therefore, increasing levels of P-TEFb expression and activity is an excellent strategy to stimulate viral gene expression. This review summarizes the multiple steps that cause HIV to enter into latency. It positions the interplay between transcriptionally active and inactive host transcriptional activators and their viral partner Tat as valid targets for the development of new strategies to reactivate latent viral gene expression and eradicate HIV. PMID:23518577

  9. The impact of motor activity on intracerebral ERPs: P3 latency variability in modified auditory odd-ball paradigms involving a motor task.

    PubMed

    Kanovský, Petr; Streitová, Hana; Klajblová, Hana; Bares, Martin; Daniel, Pavel; Rektor, Ivan

    2003-09-01

    The P3 wave of event-related potentials was recorded with intracranial electrodes in 24 epileptic patients during the pre-surgical evaluation of epilepsy surgery. Three different cognitive auditory paradigms were used: (1) odd-ball paradigm with no output required (PGI) where patients had simply to recognize target tones, (2) odd-ball with motor response (PGII), where patients had to press a button in response to target tones, and (3) odd-ball with both counting task and motor response (PGIII), where patients had to recognize target tones, press a button in response to them, and count their number. The occurrence of P3 potential, its latency and amplitude, and the dependence of P3 latency on the task complexity were calculated. Identifiable P3 potentials in all the three paradigms were recorded from locations in mesial cortex (18 locations mesial temporal, eight locations mesial frontal, two locations mesial parietal) and lateral sites (eight sites lateral temporal, five lateral frontal, and two lateral parietal). P3 latency values ranged from 257 to 320 ms in all explored cortical areas when PGI was used; they significantly increased or decreased during PGII and PGIII, depending on the task and structure explored. In the mesial temporal cortex, the changes of P3 latency between paradigms were minimal. In the mesial parietal cortex, there was significant P3 delay in both PGII and PGIII relative to PGI. In the mesial frontal cortex, there was a significant latency decrease in PGII, and practically identical mean latency in PGI and PGIII. In all lateral cortices (temporal, frontal and parietal), there was always a P3 latency increase in PGII and PGIII relative to PGI, the most significant results being observed in the parietal and frontal lateral areas. The results support the multi-generator theory of P3. Prolongation of the mean P3 latency in lateral frontal and parietal cortices when the paradigm involved the execution of a motor task might reflect specific gating

  10. 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.

  11. 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

  12. Perturbation Predictability Can Influence the Long-Latency Stretch Response

    PubMed Central

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

    2016-01-01

    Perturbations applied to the upper limbs elicit short (M1: 25–50 ms) and long-latency (M2: 50–100 ms) responses in the stretched muscle. M1 is produced by a spinal reflex loop, and M2 receives contribution from multiple spinal and supra-spinal pathways. While M1 is relatively immutable to voluntary intention, the remarkable feature of M2 is that its size can change based on intention or goal of the participant (e.g., increasing when resisting the perturbation and decreasing when asked to let-go or relax following the perturbation). While many studies have examined modulation of M2 between passive and various active conditions, through the use of constant foreperiods (interval between warning signal and a perturbation), it has also been shown that the magnitude of the M2 response in a passive condition can change based on factors such as habituation and anticipation of perturbation delivery. To prevent anticipation of a perturbation, most studies have used variable foreperiods; however, the range of possible foreperiod duration differs between experiments. The present study examined the influence of different variable foreperiods on modulation of the M2 response. Fifteen participants performed active and passive responses to a perturbation that stretched wrist flexors. Each block of trials had either a short (2.5–3.5 seconds; high predictability) or long (2.5–10.5 seconds; low predictability) variable foreperiod. As expected, no differences were found between any conditions for M1, while M2 was larger in the active rather than passive conditions. Interestingly, within the two passive conditions, the long variable foreperiods resulted in greater activity at the end of the M2 response than the trials with short foreperiods. These results suggest that perturbation predictability, even when using a variable foreperiod, can influence circuitry contributing to the long-latency stretch response. PMID:27727293

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

    PubMed Central

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

    2013-01-01

    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

  14. 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.

  15. 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.

  16. Auditory P3 latency and amplitude: relationships to earlier exogenous auditory events.

    PubMed

    Spongberg, T; Decker, T N

    1990-01-01

    The purpose of the present study was to determine the relationship for latency and amplitude between exogenous auditory potentials arising at the level of cranial nerve VIII and continuing through the level of the cortex and the auditory P3 endogenous potential. Thirty-four normal hearing adults participated in the study. Binaural ABR, MLR, LCR, and P3 recordings were obtained using 2 kHz tone bursts as the stimulus. Relationships between peak latencies and amplitudes from the early, middle, and late potentials were analyzed using Pearson Product-Moment correlation procedures and multiple regression analyses. Results indicated no significant positive relationships for latency or amplitude between early, middle, or late exogenous potentials and the endogenous P3 potential. Pa of the MLR and P3 demonstrated significant latency/amplitude trading functions. The present data support the hypothesis that P3 latency and amplitude are not related to the latencies and amplitudes of the exogenous responses.

  17. 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.

  18. 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.

  19. 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.

  20. The functional independence of response latency and accuracy: implications for the concept of conceptual tempo.

    PubMed

    Williams, M; Lahey, B B

    1977-12-01

    Kagan (1965a) developed the concepts of impulsive and reflective cognitive styles (conceptual tempo) to add a new dimension to the understanding and assessment of human intelligence. Although latency (the principal component of conceptual tempo) is negatively correlated with academic performance, it may not be necessary to modify latency in order to modify accuracy.. With 40 disadvantaged preschool children, it was found that reinforcing long latencies in choice tasks did not increase accuracy and vice versa, and that reinforcing both long latencies and accuracy was no more effective than reinforcing accuracy alone. These data were used to question the usefulness of the construct of conceptual tempo.

  1. Maturational differences in thalamocortical white matter microstructure and auditory evoked response latencies in autism spectrum disorders

    PubMed Central

    Roberts, Timothy P.L.; Lanza, Matthew R.; Dell, John; Qasmieh, Saba; Hines, Katherine; Blaskey, Lisa; Zarnow, Deborah M.; Levy, Susan E.; Edgar, J. Christopher; Berman, Jeffrey I.

    2014-01-01

    White matter diffusion anisotropy in the acoustic radiations was characterized as a function of development in autistic and typically developing children. Auditory-evoked neuromagnetic fields were also recorded from the same individuals and the latency of the left and right middle latency superior temporal gyrus auditory ~50ms response (M50)1 was measured. Group differences in structural and functional auditory measures were examined, as were group differences in associations between white matter pathways, M50 latency, and age. Acoustic radiation white matter fractional anisotropy did not differ between groups. Individuals with autism displayed a significant M50 latency delay. Only in typically developing controls, white matter fractional anisotropy increased with age and increased white matter anisotropy was associated with earlier M50 responses. M50 latency, however, decreased with age in both groups. Present findings thus indicate that although there is loss of a relationship between white matter structure and auditory cortex function in autism spectrum disorders, and although there are delayed auditory responses in individuals with autism than compared with age-matched controls, M50 latency nevertheless decreases as a function of age in autism, parallel to the observation in typically developing controls (although with an overall latency delay). To understand auditory latency delays in autism and changes in auditory responses as a function of age in controls and autism, studies examining white matter as well as other factors that influence auditory latency, such as synaptic transmission, are of interest. PMID:24055954

  2. Latency and initiation of the human vestibuloocular reflex to pulsed galvanic stimulation.

    PubMed

    Aw, Swee T; Todd, Michael J; Halmagyi, G Michael

    2006-08-01

    Cathodal galvanic currents activate primary vestibular afferents, whereas anodal currents inhibit them. Pulsed galvanic vestibular stimulation (GVS) was used to determine the latency and initiation of the human vestibuloocular reflex. Three-dimensional galvanic vestibuloocular reflex (g-VOR) was recorded with binocular dual-search coils in response to a bilateral bipolar 100-ms rectangular pulse of current at 0.9 (near-threshold), 2.5, 5.0, 7.5, and 10.0 mA in 11 normal subjects. The g-VOR consisted of three components: conjugate torsional eye rotation away from cathode toward anode; vertical divergence (skew deviation) with hypertropia of the eye on the cathodal and hypotropia of the eye on the anodal sides; and conjugate horizontal eye rotation away from cathode toward anode. The g-VOR was repeatable across all subjects, its magnitude a linear function of the current intensity, its latency about 9.0 ms with GVS of >or=2.5 mA, and was not suppressed by visual fixation. At 10-mA stimulation, the g-VOR [x, y, z] on the cathodal side was [0.77 +/- 0.10, -0.05 +/- 0.05, -0.18 +/- 0.06 degrees ] (mean +/- 95% confidence intervals) and on the anodal side was [0.79 +/- 0.10, 0.16 +/- 0.05, -0.19 +/- 0.06 degrees ], with a vertical divergence of 0.20 degrees . Although the horizontal g-VOR could have arisen from activation of the horizontal semicircular canal afferents, the vertical-torsional g-VOR resembled the vestibuloocular reflex in response to roll-plane head rotation about an Earth-horizontal axis and might be a result of both vertical semicircular canal and otolith afferent activations. Pulsed GVS is a promising technique to investigate latency and initiation of the human vestibuloocular reflex because it does not require a large mechanical apparatus nor does it pose problems of head inertia or slippage.

  3. 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

  4. 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

  5. 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

  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. RAMCloud: A Low-Latency Datacenter Storage System

    NASA Astrophysics Data System (ADS)

    Ousterhout, John

    2014-04-01

    RAMCloud is a new general-purpose storage system for large-scale applications running in a datacenter. RAMCloud stores all data in DRAM at all times in order to provide the lowest possible latency for access, and it aggregates the memories of thousands of commodity servers to provide total capacities of 1 Pbyte or more. When RAMCloud is combined with high-speed networking, any application running in the same datacenter can access any byte of data from a RAMCloud cluster in about 5 microseconds, which is 100-1000x faster than most existing storage systems. RAMCloud maintains backup copies of data on secondary storage (disk or flash) so that data stored in RAMCloud is durable and highly available (durable writes take about 15 microseconds). Our hope is that RAMCloud will enable a new class of applications that manipulate large datasets much more intensively than has been possible before. In this talk I will describe the RAMCloud system and discuss the general characteristics of applications that are well-suited for RAMCloud, with the hope of stimulating discussion about whether RAMCloud is suitable for applications in Radio Astronomy.

  8. 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.

  9. 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

    2014-12-23

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

  10. Mental chronometry using latency-resolved functional MRI

    PubMed Central

    Menon, Ravi S.; Luknowsky, David C.; Gati, Joseph S.

    1998-01-01

    Vascular responses to neural activity are exploited as the basis of a number of brain imaging techniques. The vascular response is thought to be too slow to resolve the temporal sequence of events involved in cognitive tasks, and hence, imaging studies of mental chronometry have relied on techniques such as the evoked potential. Using rapid functional MRI (fMRI) of single trials of two simple behavioral tasks, we demonstrate that while the microvascular response to the onset of neural activity is delayed consistently by several seconds, the relative timing between the onset of the fMRI responses in different brain areas appears preserved. We examined a number of parameters that characterize the fMRI response and determined that its onset time is best defined by the inflection point from the resting baseline. We have found that fMRI onset latencies determined in this manner correlate well with independently measurable parameters of the tasks such as reaction time or stimulus presentation time and can be used to determine the origin of processing delays during cognitive or perceptual tasks with a temporal accuracy of tens of milliseconds and spatial resolution of millimeters. PMID:9724802

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  12. 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…

  13. 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;…

  14. 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…

  15. Frequency specificity of simultaneously recorded early and middle latency auditory evoked potentials.

    PubMed

    Scherg, M; Volk, S A

    1983-11-01

    Early and middle latency auditory evoked potentials were recorded simultaneously with a 2-channel wide-band recording technique. Latency and amplitude distributions of components V, Na and Pa were determined in 20 normal hearing adults for 3 different stimuli (click, plop, 500 Hz tone burst) presented at 70, 30 and 20 dB HL. Normative latency data of the middle latency components are presented. The detectability and amplitude of the Na-Pa complex were considerably larger than those of wave V at 20 and 30 dB HL for the two low frequency stimuli. Ten ears exhibiting high frequency sensorineural hearing loss were examined. In these cases, only click-evoked Na and Pa, but not wave V, were observed down to 20 dB HL. Also, the click latency-intensity function of Na-Pa was found to be similar to the normal low frequency latency functions. The results consistently suggested that the low frequency contributions to wave V cancel in phase because of short duration, whereas the duration of the Na-Pa complex allows for a positive superimposition of all frequency bands. Since these differences in frequency specificity of the EAEP and the MAEP affect latency, care is advised for the interpretation of inter-peak latencies.

  16. Using differential reinforcement to decrease academic response latencies of an adolescent with acquired brain injury.

    PubMed

    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 differential reinforcement was used to decrease slow responding to academic tasks.

  17. 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

  18. Longer latency of sensory response to intravenous odor injection predicts olfactory neural disorder

    PubMed Central

    Kikuta, Shu; Matsumoto, Yu; Kuboki, Akihito; Nakayama, Tsuguhisa; Asaka, Daiya; Otori, Nobuyoshi; Kojima, Hiromi; Sakamoto, Takashi; Akinori, Kashio; Kanaya, Kaori; Ueha, Rumi; Kagoya, Ryoji; Nishijima, Hironobu; Toma-Hirano, Makiko; Kikkawa, Yayoi; Kondo, Kenji; Tsunoda, Koichi; Miyaji, Tempei; Yamaguchi, Takuhiro; Kataoka, Kazunori; Mori, Kensaku; Yamasoba, Tatsuya

    2016-01-01

    A near loss of smell may result from conductive and/or neural olfactory disorders. However, an olfactory test to selectively detect neural disorders has not been established. We investigated whether onset latency of sensory response to intravenous odor injection can detect neural disorders in humans and mice. We showed that longer preoperative onset latency of odor recognition to intravenous odor in patients with chronic rhinosinusitis predicted worse recovery of olfactory symptoms following sinus surgery. The onset latency of the olfactory sensory neuron (OSN) response to intravenous odor using synaptopHluorin signals from OSN axon terminals was delayed in mice with reduced numbers of OSNs (neural disorder) but not with increased mucus or blocked orthonasal pathways (conductive disorders). Moreover, the increase in onset latency correlated with the decrease in mature OSN numbers. Longer onset latency to intravenous odor injection is a useful biomarker for presence and severity of olfactory disorders with neural etiology. PMID:27734933

  19. 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.

  20. 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

  1. 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

  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. Short and long-latency responses in human masseter muscle evoked by chin taps.

    PubMed

    Hellsing, G; Klineberg, I

    1984-01-01

    Ten healthy subjects received downward, backward and upward chin taps with standardized force and direction. Taps in all three directions elicited short (M1) and long (M2 and M3)-latency excitatory EMG responses in the masseter muscle. M1 (mean latency 8.9 ms, amplitude 150 microV) occurred more frequently and with shorter latency during clenching than during relaxation or opening. Downward taps were more efficient in evoking jaw-jerks (25 per cent) than upward (14 per cent) and backward ones (16 per cent). M2 was a weak biphasic deflection occurring during the silent period (mean latency 42 ms, amplitude 87 microV) and M3 was an EMG burst following the silent period (mean latency 69.3 ms, amplitude 169 microV). No long-latency evoked responses were obtained from the relaxed masseter. Thus, muscle stretch increases M1 response frequency but is not a necessary prerequisite. The hypothesis that vibratory transmission plays an important role was confirmed. Voluntary activation of the stimulated muscle (clenching) increases M1-response frequency and shortens response latency.

  4. 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.

  5. Attention Influences Single Unit and Local Field Potential Response Latencies in Visual Cortical Area V4

    PubMed Central

    Sundberg, Kristy A.; Mitchell, Jude F.; Gawne, Timothy J.

    2012-01-01

    Many previous studies have demonstrated that changes in selective attention can alter the response magnitude of visual cortical neurons, but there has been little evidence for attention affecting response latency. Small latency differences, though hard to detect, can potentially be of functional importance, and may also give insight into the mechanisms of neuronal computation. We therefore reexamined the effect of attention on the response latency of both single units and the local field potential (LFP) in primate visual cortical area V4. We find that attention does produce small (1–2 ms) but significant reductions in the latency of both the spiking and LFP responses. Though attention, like contrast elevation, reduces response latencies, we find that the two have different effects on the magnitude of the LFP. Contrast elevations increase and attention decreases the magnitude of the initial deflection of the stimulus-evoked LFP. Both contrast elevation and attention increase the magnitude of the spiking response. We speculate that latencies may be reduced at higher contrast because stronger stimulus inputs drive neurons more rapidly to spiking threshold, while attention may reduce latencies by placing neurons in a more depolarized state closer to threshold before stimulus onset. PMID:23136440

  6. 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. PMID:27626083

  7. Analysis of power management and system latency in wireless sensor networks

    NASA Astrophysics Data System (ADS)

    Oswald, Matthew T.; Rohwer, Judd A.; Forman, Michael A.

    2004-08-01

    Successful power management in a wireless sensor network requires optimization of the protocols which affect energy-consumption on each node and the aggregate effects across the larger network. System optimization for a given deployment scenario requires an analysis and trade off of desired node and network features with their associated costs. The sleep protocol for an energy-efficient wireless sensor network for event detection, target classification, and target tracking developed at Sandia National Laboratories is presented. The dynamic source routing (DSR) algorithm is chosen to reduce network maintenance overhead, while providing a self-configuring and self-healing network architecture. A method for determining the optimal sleep time is developed and presented, providing reference data which spans several orders of magnitude. Message timing diagrams show, that a node in a five-node cluster, employing an optimal cyclic single-radio sleep protocol, consumes 3% more energy and incurs a 16-s increase latency than nodes employing the more complex dual-radio STEM protocol.

  8. 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.

  9. 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.

  10. Human cytomegalovirus latency-associated protein LUNA is expressed during HCMV infections in vivo.

    PubMed

    Bego, Mariana G; Keyes, Lisa R; Maciejewski, Jarek; St Jeor, Stephen C

    2011-10-01

    Human cytomegalovirus (HCMV) latency is poorly understood. We previously described a novel HCMV latency-associated transcript, UL81-82ast, coding for a protein designated LUNA (latency unique natural antigen). The aim of this study was to confirm the presence of LUNA in HCMV-seropositive donors. Standard co-immunoprecipitation and ELISA assays were used to detect antibodies against the LUNA protein in the sera of HCMV-seropositive donors. Specific antibodies against LUNA were detected in all HCMV-seropositive donors but in none of the seronegative donors. These data confirm that LUNA is expressed during in vivo infections and is capable of eliciting an immune response.

  11. Reversal of Latency as Part of a Cure for HIV-1.

    PubMed

    Rasmussen, Thomas Aagaard; Tolstrup, Martin; Søgaard, Ole Schmeltz

    2016-02-01

    Here, the use of pharmacological agents to reverse HIV-1 latency will be explored as a therapeutic strategy towards a cure. However, while clinical trials of latency-reversing agents LRAs) have demonstrated their ability to increase production of latent HIV-1, such interventions have not had an effect on the size of the latent HIV-1 reservoir. Plausible explanations for this include insufficient host immune responses against virus-expressing cells, the presence of escape mutations in archived virus, or an insufficient scale of latency reversal. Importantly, these early studies of LRAs were primarily designed to investigate their ability to perturb the state of HIV-1 latency; using the absence of an impact on the size of the HIV-1 reservoir to discard their potential inclusion in curative strategies would be erroneous and premature.

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

    PubMed

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

    2016-10-01

    IFN responses control acute HSV infection, but their role in regulating HSV latency is poorly understood. To address this we used mice lacking IFN signaling specifically in neural tissues. These mice supported a higher acute viral load in nervous tissue and delayed establishment of latency. While latent HSV-1 genome copies were equivalent, ganglia from neuronal IFN signaling-deficient mice unexpectedly supported reduced reactivation. IFNβ promoted survival of primary sensory neurons after infection with HSV-1, indicating a role for IFN signaling in sustaining neurons. We observed higher levels of latency associated transcripts (LATs) per HSV genome in mice lacking neuronal IFN signaling, consistent with a role for IFN in regulating LAT expression. These data show that neuronal IFN signaling modulates the expression of LAT and may conserve the pool of neurons available to harbor latent HSV-1 genome. The data also show that neuronal IFN signaling is dispensable for the establishment of latency. PMID:27518540

  13. 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.

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

    PubMed

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

    2016-10-01

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

  15. 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.

  16. HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days--Implications for HIV Remission.

    PubMed

    Pinkevych, Mykola; Cromer, Deborah; Tolstrup, Martin; Grimm, Andrew J; Cooper, David A; Lewin, Sharon R; Søgaard, Ole S; Rasmussen, Thomas A; Kent, Stephen J; Kelleher, Anthony D; Davenport, Miles P

    2015-07-01

    HIV infection can be effectively controlled by anti-retroviral therapy (ART) in most patients. However therapy must be continued for life, because interruption of ART leads to rapid recrudescence of infection from long-lived latently infected cells. A number of approaches are currently being developed to 'purge' the reservoir of latently infected cells in order to either eliminate infection completely, or significantly delay the time to viral recrudescence after therapy interruption. A fundamental question in HIV research is how frequently the virus reactivates from latency, and thus how much the reservoir might need to be reduced to produce a prolonged antiretroviral-free HIV remission. Here we provide the first direct estimates of the frequency of viral recrudescence after ART interruption, combining data from four independent cohorts of patients undergoing treatment interruption, comprising 100 patients in total. We estimate that viral replication is initiated on average once every ≈6 days (range 5.1- 7.6 days). This rate is around 24 times lower than previous thought, and is very similar across the cohorts. In addition, we analyse data on the ratios of different 'reactivation founder' viruses in a separate cohort of patients undergoing ART-interruption, and estimate the frequency of successful reactivation to be once every 3.6 days. This suggests that a reduction in the reservoir size of around 50-70-fold would be required to increase the average time-to-recrudescence to about one year, and thus achieve at least a short period of anti-retroviral free HIV remission. Our analyses suggests that time-to-recrudescence studies will need to be large in order to detect modest changes in the reservoir, and that macaque models of SIV latency may have much higher frequencies of viral recrudescence after ART interruption than seen in human HIV infection. Understanding the mean frequency of recrudescence from latency is an important first step in approaches to prolong

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

    PubMed

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

    2013-01-01

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

  18. Earlier Visual N1 Latencies in Expert Video-Game Players: A Temporal Basis of Enhanced Visuospatial Performance?

    PubMed Central

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

    2013-01-01

    Increasing behavioural evidence suggests that expert video game players (VGPs) show enhanced visual attention and visuospatial abilities, but what underlies these enhancements remains unclear. We administered the Poffenberger paradigm with concurrent electroencephalogram (EEG) recording to assess occipital N1 latencies and interhemispheric transfer time (IHTT) in expert VGPs. Participants comprised 15 right-handed male expert VGPs and 16 non-VGP controls matched for age, handedness, IQ and years of education. Expert VGPs began playing before age 10, had a minimum 8 years experience, and maintained playtime of at least 20 hours per week over the last 6 months. Non-VGPs had little-to-no game play experience (maximum 1.5 years). Participants responded to checkerboard stimuli presented to the left and right visual fields while 128-channel EEG was recorded. Expert VGPs responded significantly more quickly than non-VGPs. Expert VGPs also had significantly earlier occipital N1s in direct visual pathways (the hemisphere contralateral to the visual field in which the stimulus was presented). IHTT was calculated by comparing the latencies of occipital N1 components between hemispheres. No significant between-group differences in electrophysiological estimates of IHTT were found. Shorter N1 latencies may enable expert VGPs to discriminate attended visual stimuli significantly earlier than non-VGPs and contribute to faster responding in visual tasks. As successful video-game play requires precise, time pressured, bimanual motor movements in response to complex visual stimuli, which in this sample began during early childhood, these differences may reflect the experience and training involved during the development of video-game expertise, but training studies are needed to test this prediction. PMID:24058667

  19. 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

  20. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2010-04-01

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

  2. USING DIFFERENTIAL REINFORCEMENT TO DECREASE ACADEMIC RESPONSE LATENCIES OF AN ADOLESCENT WITH ACQUIRED BRAIN INJURY

    PubMed Central

    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 differential reinforcement was used to decrease slow responding to academic tasks. PMID:20514195

  3. 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.

  4. 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.

  5. Vestibular evoked potentials with short and middle latencies recorded in humans.

    PubMed

    Leibner, E; Elidan, J; Freeman, S; Sela, M; Nitzan, M; Sohmer, H

    1990-01-01

    Following success in recording short latency vestibular evoked potentials in experimental animals, we have succeeded in our attempts to record such potentials in human subjects. The stimuli were repetitive, short steps of high intensity angular acceleration (10,000 degrees/sec2) with short rise times which would synchronously activate many neurons of the vestibular pathway. Stringent control procedures ensured that the recorded activity was not an artefact. Short latency vestibular evoked potentials were recorded in 10 normal subjects with peak latencies of 3.5, 6.0 and 8.4 msec and amplitudes of 0.5 microV. Middle latency potentials were also recorded with latencies of 8.8, 18.8 and 26.8 msec and amplitudes of 15 microV. These responses were absent in a cadaver and in patients with bilateral dead labyrinths. In normal subjects, these vestibular evoked potentials were not affected by white noise. In conclusion, short and middle latency vestibular evoked potentials were recorded in normal human subjects. PMID:2289418

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

    PubMed

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

    2012-07-18

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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Input/output functions of different-latency components of transient-evoked and stimulus-frequency otoacoustic emissions.

    PubMed

    Sisto, Renata; Sanjust, Filippo; Moleti, Arturo

    2013-04-01

    The input/output functions of the different-latency components of human transient-evoked and stimulus-frequency otoacoustic emissions are analyzed, with the goal of relating them to the underlying nonlinear dynamical properties of the basilar membrane response. Several cochlear models predict a cubic nonlinearity that would yield a correspondent compressive response. The otoacoustic response comes from different generation mechanisms, each characterized by a particular relation between local basilar membrane displacement and otoacoustic level. For the same mechanism (e.g., reflection from cochlear roughness), different generation places would imply differently compressive regimes of the local basilar membrane dynamics. Therefore, this kind of study requires disentangling these contributions, using suitable data acquisition and time-frequency analysis techniques. Fortunately, different generation mechanisms/places also imply different phase-gradient delays, knowledge of which can be used to perform this task. In this study, the different-latency otoacoustic components systematically show differently compressive response, consistent with two simple hypotheses: (1) all emissions come from the reflection mechanism and (2) the basilar membrane response is strongly compressive in the resonance region and closer to linear in more basal regions. It is not clear if such a compressive behavior also extends to arbitrarily low stimulus levels.

  12. 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

  13. P300 component identification using source analysis techniques: reduced latency variability.

    PubMed

    Elting, J W; van Weerden, T W; van der Naalt, J; De Keyser, J H A; Maurits, N M

    2003-02-01

    P300 latency variability in normal subjects is a complicating factor in clinical event-related potential studies because it limits diagnostic applicability. The current study was conducted to determine whether identification of P300 (P3A and P3B) components using source analysis techniques can reduce variability in P300 parameters. Data were recorded with a 128-channel EEG system in 18 healthy subjects. The authors used a standard, auditory two-tone oddball paradigm with targets of 2000 Hz and standards of 1000 Hz. Two simple source analysis models with one or two rotating dipoles were applied to grand average data and individual data. Dipole time courses were combined with mapping results to extract P3A and P3B component latencies. Latencies obtained with conventional P300 analysis were compared with source analysis results. The source analysis method identified both P3A and P3B components in a substantially larger percentage of subjects (88% vs. 33%) than the conventional method. The source analysis method yielded a later mean P3B latency (357 msec vs. 323 msec, P < 0,001) with a smaller standard deviation (9 msec vs. 23 msec, P = 0,003) than the conventional P300 method. The relative contribution of the temporally separate P3A and P3B components to the P300 complex amplitude is highly variable. This explains the larger latency standard deviation in conventional P300 analysis. The source analysis method was able to identify P300 components in a large percentage of the cases. The result is a considerable reduction of P300 latency variability in normal subjects. This could have important consequences for clinical event-related potential research, because diagnostic sensitivity and specificity of P300 latency may improve with this method.

  14. 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

  15. 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.

  16. Adapting human postural reflexes following localized cerebrovascular lesion: analysis of bilateral long latency responses.

    PubMed

    Di Fabio, R P; Badke, M B; Duncan, P W

    1986-01-22

    The symmetry and adaptability of long latency stretch responses was studied in a group of 4 adult hemiplegics and 5 normals of similar age. Subjects stood on a moveable platform which directly rotated the ankles unexpectedly during a series of horizontal anterioposterior (AP) translations. When the platform was rotated toes-up, long latency discharge of gastrocnemius and hamstring muscles enhanced loss of balance by pulling the body backwards. Toes-down platform rotation elicited a reflex response from tibialis anterior and quadriceps which inappropriately pulled the body forward. Attenuation of these long latency responses was necessary to minimize functional destabilization. Normal and stroke subjects demonstrated appropriate suppression of long latency responses, but the magnitude of attenuation was not uniform in hemiplegics. Adaptation was decreased in the proximal synergists compared to normal. Latency of muscle activation in the paretic limb was prolonged, and a preference for initial non-paretic limb activation was evident. Both lower extremities in hemiplegics showed a disruption of timing between distal and proximal synergists. These results suggest that stroke victims retain or recover the ability to modulate stretch reflex activity for balance. Temporal and spatial response asymmetries surface as critical factors underlying disequilibrium associated with localized cerebrovascular lesion. PMID:3942897

  17. Recording of auditory middle latency evoked potentials during the practice of meditation with the syllable 'OM'.

    PubMed

    Telles, S; Desiraju, T

    1993-10-01

    Middle latency auditory evoked potentials were examined in 7 proficient subjects during the practice of meditation on the syllable 'OM', to determine whether these potentials would differ significantly from those recorded during the baseline state without practicing mediation. Similar records were also obtained in 7 'naive' subjects, matched for age, before and during a control period which involved sitting with eyes closed, and with no special instructions for focusing their thoughts. There was considerable inter-subject variability in the different components. However, during meditation there was a small but significant reduction in the peak latency of the Nb wave (the maximum negativity occurring between 35 and 65 msec). This reduction was observed consistently during the 3 repeat sessions of each subject, while the 'naive' subjects did not show this change. These results suggest that the inter-subject variability of middle latency auditory evoked potentials precludes using them as the method of choice for assessing the effects of meditation. The small but consistent decrease in the Nb wave peak latency, indicates that the middle latency auditory evoked potentials do change with meditation. However, the variability of the potentials may mask subtle changes.

  18. HIV latency and integration site placement in five cell-based models

    PubMed Central

    2013-01-01

    Background HIV infection can be treated effectively with antiretroviral agents, but the persistence of a latent reservoir of integrated proviruses prevents eradication of HIV from infected individuals. The chromosomal environment of integrated proviruses has been proposed to influence HIV latency, but the determinants of transcriptional repression have not been fully clarified, and it is unclear whether the same molecular mechanisms drive latency in different cell culture models. Results Here we compare data from five different in vitro models of latency based on primary human T cells or a T cell line. Cells were infected in vitro and separated into fractions containing proviruses that were either expressed or silent/inducible, and integration site populations sequenced from each. We compared the locations of 6,252 expressed proviruses to those of 6,184 silent/inducible proviruses with respect to 140 forms of genomic annotation, many analyzed over chromosomal intervals of multiple lengths. A regularized logistic regression model linking proviral expression status to genomic features revealed no predictors of latency that performed better than chance, though several genomic features were significantly associated with proviral expression in individual models. Proviruses in the same chromosomal region did tend to share the same expressed or silent/inducible status if they were from the same cell culture model, but not if they were from different models. Conclusions The silent/inducible phenotype appears to be associated with chromosomal position, but the molecular basis is not fully clarified and may differ among in vitro models of latency. PMID:23953889

  19. A Minor Subset of Super Elongation Complexes Plays a Predominant Role in Reversing HIV-1 Latency

    PubMed Central

    Li, Zichong; Lu, Huasong

    2016-01-01

    Promoter-proximal pausing by RNA polymerase II (Pol II) is a key rate-limiting step in HIV-1 transcription and latency reversal. The viral Tat protein recruits human super elongation complexes (SECs) to paused Pol II to overcome this restriction. Despite the recent progress in understanding the functions of different subsets of SECs in controlling cellular and Tat-activated HIV transcription, little is known about the SEC subtypes that help reverse viral latency in CD4+ T cells. Here, we used the CRISPR-Cas9 genome-editing tool to knock out the gene encoding the SEC subunit ELL2, AFF1, or AFF4 in Jurkat/2D10 cells, a well-characterized HIV-1 latency model. Depletion of these proteins drastically reduced spontaneous and drug-induced latency reversal by suppressing HIV-1 transcriptional elongation. Surprisingly, a low-abundance subset of SECs containing ELL2 and AFF1 was found to play a predominant role in cooperating with Tat to reverse latency. By increasing the cellular level/activity of these Tat-friendly SECs, we could potently activate latent HIV-1 without using any drugs. These results implicate the ELL2/AFF1-SECs as an important target in the future design of a combinatorial therapeutic approach to purge latent HIV-1. PMID:26830226

  20. 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

  1. Adaptation-dependent differences in electroretinographic latency patterns in uniform and variegated horseshoe crabs.

    PubMed

    Kim, B; Wasserman, G S

    1998-01-01

    The carapaces of horseshoe crabs (Limulus polyphemus) differ. Some individuals have uniform carapaces and clear eyes while others have variegated carapaces and dark eyes. These differences have been reported to be correlated with latency differences in the electroretinogram (ERG) of the lateral eye. Such a result might have had a neural basis in the mechanisms underlying visual transduction but it could also have reflected a visual screening pigment difference. A direct experiment was therefore designed to choose between these two hypotheses by varying the relative state of adaptation. The results were as follows. In uniform animals, dark adaptation had the kind of effect seen in single photoreceptor cells - latencies were longer in dark-adapted eyes and latencies were also longer for dim flashes. However, variegated animals showed a significant adaptation interaction: in light adaptation, dimmer flashes produced the usual effect, namely a longer ERG latency, while in dark adaptation, latencies were close to equilatent, being within experimental error of each other for both flash energies. These data make it unlikely that the photoreceptor transduction mechanism is the locus of the visual differences between the two types of animals. Instead, they are consistent with an interaction of screening pigment effects with photoreceptor transduction effects.

  2. 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

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

    PubMed Central

    2009-01-01

    The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway. PMID:19961595

  4. Repeater F waves: a comparison of sensitivity with sensory antidromic wrist-to-palm latency and distal motor latency in the diagnosis of carpal tunnel syndrome.

    PubMed

    Macleod, W N

    1987-05-01

    Thirty-five thousand six hundred supramaximal shocks were applied to 209 healthy and 147 entrapped median nerves (carpal tunnel syndrome--CTS) to characterize the backfiring behavior of the alpha motor neuron pool of abductor pollicis brevis in health and the modifying effect of a compressive neuropathy. A contraction of the normal subpopulation of active F-wave generators was found in CTS, while active neurons backfired at higher than normal frequencies (p less than 0.001). These modifications in spinal behavior are reflected in the % Repeater F-wave value, whose sensitivity in the detection of CTS approaches that of sensory wrist-to-palm latency estimation. This technique offers an alternative to latency measurement in the diagnosis of CTS. An economical strategy for the electrodiagnosis of CTS is proposed.

  5. 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.

  6. Double sliding-window technique: a new method to calculate the neuronal response onset latency.

    PubMed

    Berényi, Antal; Benedek, György; Nagy, Attila

    2007-10-31

    Neuronal response onset latency provides important data on the information processing within the central nervous system. In order to enhance the quality of the onset latency estimation, we have developed a 'double sliding-window' technique, which combines the advantages of mathematical methods with the reliability of standard statistical processes. This method is based on repetitive series of statistical probes between two virtual time windows. The layout of the significance curve reveals the starting points of changes in neuronal activity in the form of break-points between linear segments. A second-order difference function is applied to determine the position of maximum slope change, which corresponds to the onset of the response. In comparison with Poisson spike-train analysis, the cumulative sum technique and the method of Falzett et al., this 'double sliding-window, technique seems to be a more accurate automated procedure to calculate the response onset latency of a broad range of neuronal response characteristics.

  7. Low Latency MAC Protocol in Wireless Sensor Networks Using Timing Offset

    NASA Astrophysics Data System (ADS)

    Choi, Seung Sik

    This paper proposes a low latency MAC protocol that can be used in sensor networks. To extend the lifetime of sensor nodes, the conventional solution is to synchronize active/sleep periods of all sensor nodes. However, due to these synchronized sensor nodes, packets in the intermediate nodes must wait until the next node wakes up before it can forward a packet. This induces a large delay in sensor nodes. To solve this latency problem, a clustered sensor network which uses two types of sensor nodes and layered architecture is considered. Clustered heads in each cluster are synchronized with different timing offsets to reduce the sleep delay. Using this concept, the latency problem can be solved and more efficient power usage can be obtained.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. Latency of modality-specific reactivation of auditory and visual information during episodic memory retrieval.

    PubMed

    Ueno, Daisuke; Masumoto, Kouhei; Sutani, Kouichi; Iwaki, Sunao

    2015-04-15

    This study used magnetoencephalography (MEG) to examine the latency of modality-specific reactivation in the visual and auditory cortices during a recognition task to determine the effects of reactivation on episodic memory retrieval. Nine right-handed healthy young adults participated in the experiment. The experiment consisted of a word-encoding phase and two recognition phases. Three encoding conditions were included: encoding words alone (word-only) and encoding words presented with either related pictures (visual) or related sounds (auditory). The recognition task was conducted in the MEG scanner 15 min after the completion of the encoding phase. After the recognition test, a source-recognition task was given, in which participants were required to choose whether each recognition word was not presented or was presented with which information during the encoding phase. Word recognition in the auditory condition was higher than that in the word-only condition. Confidence-of-recognition scores (d') and the source-recognition test showed superior performance in both the visual and the auditory conditions compared with the word-only condition. An equivalent current dipoles analysis of MEG data indicated that higher equivalent current dipole amplitudes in the right fusiform gyrus occurred during the visual condition and in the superior temporal auditory cortices during the auditory condition, both 450-550 ms after onset of the recognition stimuli. Results suggest that reactivation of visual and auditory brain regions during recognition binds language with modality-specific information and that reactivation enhances confidence in one's recognition performance. PMID:25756907

  16. 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.

  17. 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.

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

    PubMed

    Bahill, A T; McDonald, J D

    1983-01-01

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

  19. 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.

  20. 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

  1. Relating plastic changes of short latency human soleus stretch reflex to changes in task performance induced by training.

    PubMed

    Kundert, Robinson; Yagi, Tohru

    2012-01-01

    Recent findings in the field of neurophysiology showed that operant conditioning on the human H-Reflex is possible. This leads to many possible clinical applications as well as possible sophisticated training methods for athletes. Although stretch reflexes have been subject to extensive literature, knowledge about the influence of short latency stretch reflexes on task performance is lacking. Within this study an ankle control task was designed where perturbations in the magnitude of functional relevance were applied. Results analyzing angle over time after perturbation confirm previous findings which used to analyze the EMG and force response to ankle perturbations. Further it was found that after training the response to perturbations shifted from initially containing latencies which indicate conscious support by transcortical pathways to latencies which could only origin from unconscious stretch reflex responses. The trend of the short latency response to shift towards the long latency response and to diminish, while pre-defined performance criteria improved, denote a functional relevance of the short latency stretch reflex to task performance. Whereas short latency reflexes have any importance at all or if improvements emerge only out of enhancements in the long latency response future work making use of operant conditioning on the short latency H-Reflex will have to unravel. PMID:23366715

  2. 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

  3. Long-latency reflexes of elbow and shoulder muscles suggest reciprocal excitation of flexors, reciprocal excitation of extensors, and reciprocal inhibition between flexors and extensors.

    PubMed

    Kurtzer, Isaac; Meriggi, Jenna; Parikh, Nidhi; Saad, Kenneth

    2016-04-01

    Postural corrections of the upper limb are required in tasks ranging from handling an umbrella in the changing wind to securing a wriggling baby. One complication in this process is the mechanical interaction between the different segments of the arm where torque applied at one joint induces motion at multiple joints. Previous studies have shown the long-latency reflexes of shoulder muscles (50-100 ms after a limb perturbation) account for these mechanical interactions by integrating information about motion of both the shoulder and elbow. It is less clear whether long-latency reflexes of elbow muscles exhibit a similar capability and what is the relation between the responses of shoulder and elbow muscles. The present study utilized joint-based loads tailored to the subjects' arm dynamics to induce well-controlled displacements of their shoulder and elbow. Our results demonstrate that the long-latency reflexes of shoulder and elbow muscles integrate motion from both joints: the shoulder and elbow flexors respond to extension at both joints, whereas the shoulder and elbow extensors respond to flexion at both joints. This general pattern accounts for the inherent flexion-extension coupling of the two joints arising from the arm's intersegmental dynamics and is consistent with spindle-based reciprocal excitation of shoulder and elbow flexors, reciprocal excitation of shoulder and elbow extensors, and across-joint inhibition between the flexors and extensors.

  4. 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

  5. HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission

    PubMed Central

    Pinkevych, Mykola; Cromer, Deborah; Tolstrup, Martin; Grimm, Andrew J.; Cooper, David A.; Lewin, Sharon R.; Søgaard, Ole S.; Rasmussen, Thomas A.; Kent, Stephen J.; Kelleher, Anthony D.; Davenport, Miles P.

    2015-01-01

    HIV infection can be effectively controlled by anti-retroviral therapy (ART) in most patients. However therapy must be continued for life, because interruption of ART leads to rapid recrudescence of infection from long-lived latently infected cells. A number of approaches are currently being developed to ‘purge’ the reservoir of latently infected cells in order to either eliminate infection completely, or significantly delay the time to viral recrudescence after therapy interruption. A fundamental question in HIV research is how frequently the virus reactivates from latency, and thus how much the reservoir might need to be reduced to produce a prolonged antiretroviral-free HIV remission. Here we provide the first direct estimates of the frequency of viral recrudescence after ART interruption, combining data from four independent cohorts of patients undergoing treatment interruption, comprising 100 patients in total. We estimate that viral replication is initiated on average once every ≈6 days (range 5.1- 7.6 days). This rate is around 24 times lower than previous thought, and is very similar across the cohorts. In addition, we analyse data on the ratios of different ‘reactivation founder’ viruses in a separate cohort of patients undergoing ART-interruption, and estimate the frequency of successful reactivation to be once every 3.6 days. This suggests that a reduction in the reservoir size of around 50-70-fold would be required to increase the average time-to-recrudescence to about one year, and thus achieve at least a short period of anti-retroviral free HIV remission. Our analyses suggests that time-to-recrudescence studies will need to be large in order to detect modest changes in the reservoir, and that macaque models of SIV latency may have much higher frequencies of viral recrudescence after ART interruption than seen in human HIV infection. Understanding the mean frequency of recrudescence from latency is an important first step in approaches to

  6. 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…

  7. 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.…

  8. 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.

  9. 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

  10. A Training Program to Reduce "Visitation Stress" in Single Parents and Their Latency Age Children.

    ERIC Educational Resources Information Center

    Clark, Ron

    This practicum was designed to decrease single parent and latency age child stress associated with child and noncustodial parent visitations, and to improve children's school behaviors. A 9-session, 12-week education and training program for single mothers (N=6) and their elementary school age children (N=15), designed to reduce stress by…

  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. 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)…

  13. 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…

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

    PubMed

    Dağ, Franziska; Dölken, Lars; Holzki, Julia; Drabig, Anja; Weingärtner, Adrien; Schwerk, Johannes; Lienenklaus, Stefan; Conte, Ianina; Geffers, Robert; Davenport, Colin; Rand, Ulfert; Köster, Mario; Weiß, Siegfried; Adler, Barbara; Wirth, Dagmar; Messerle, Martin; Hauser, Hansjörg; Cičin-Šain, Luka

    2014-02-01

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

  15. 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…

  16. Written Spelling to Dictation: Sound-To-Spelling Regularity Affects Both Writing Latencies and Durations

    ERIC Educational Resources Information Center

    Delattre, Marie; Bonin, Patrick; Barry, Christopher

    2006-01-01

    The authors examined the effect of sound-to-spelling regularity on written spelling latencies and writing durations in a dictation task in which participants had to write each target word 3 times in succession. The authors found that irregular words (i.e., those containing low-probability phoneme-to-grapheme mappings) were slower both to…

  17. 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

  18. 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.

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

    PubMed

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

    2013-01-01

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

  20. 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. Why Are Written Picture Naming Latencies (Not) Longer than Spoken Naming?

    ERIC Educational Resources Information Center

    Perret, Cyril; Laganaro, Marina

    2013-01-01

    The comparison between spoken and handwritten production in picture naming tasks represents an important source of information for building models of cognitive processes involved in writing. Studies using this methodology systematically reported longer latencies for handwritten than for spoken production. To uncover the origin of this difference…

  2. Response Latency as an Index of Response Strength during Functional Analyses of Problem Behavior

    ERIC Educational Resources Information Center

    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…

  3. Effects of Tokens on Response Latency of Students with Hearing Impairments in a Resource Room.

    ERIC Educational Resources Information Center

    Buisson, Gerald J.; And Others

    1995-01-01

    Two elementary boys in a deaf education resource room who did not complete a writing assignment within the allotted time were subsequently given tokens contingent upon their starting promptly. The use of tokens was effective in reducing response latency. (Author/PB)

  4. 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.

  5. 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

  6. 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

  7. Development of the Plate Boundary Observatory GPS Low Latency Salton Trough Radio Network

    NASA Astrophysics Data System (ADS)

    Walls, C.; Miller, S.; Wilson, B.; Lawrence, S.; Arnitz, E.

    2008-05-01

    UNAVCO is developing a 20 GPS station low latency radio network that spans the San Andreas and San Jacinto faults in the region of highest strain in southern California and the narrowest part of the North America-Pacific plate boundary. The Salton Trough Radio Network (STRN) is instrumented with Ethernet bridge Intuicom EB6+ (900 MHz) radios to transmit a high rate low latency data stream from each permanent GPS site for the purpose of the following: 1) telemeter 15 second data (1 MB/day/station) to the Plate Boundary Observatory archive, 2) accommodate the timely download of 1 and 5 sample per second data following large earthquakes (4 MB/hour/station), and 3) test the UStream of 1Hz BINEX and RTCM data. Three of four phases have been completed. Office radio testing yielded transfer rates of 30-50 KB/s with subsecond latency while streaming 1 Hz data. Latency climbed to ~1.8 seconds while simultaneously streaming 1 Hz and downloading hourly 1 and 5 sample per second data files. Field testing demonstrated rates on the order of 30 KB/s. At present the radios are installed and have transfer rates of 10-40 KB/s between sites that span 10-32 km. The final phase will be the installation of the main telemetry relay where master radios will be connected to a high speed ISP near the town of Brawley. The high-rate low latency UStream data will be available to researchers who are developing prototype earthquake early warning systems in Southern California. A goal of the STRN is to make the data available rapidly enough for GPS-derived coseismic and dynamic displacements to be integrated into early warning system earthquake models. The improved earthquake models will better assist emergency response. UStream data will also aid surveyors who wish to use PBO GPS stations as permanent, high-quality base stations in real-time kinematic surveys.

  8. 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

  9. Frequency and Latency of Social Interaction in an Inclusive Kindergarten Setting: A Comparison between Typical Children and Children with Autism

    ERIC Educational Resources Information Center

    Jahr, Erik; Eikeseth, Svein; Eldevik, Sigmund; Aase, Heidi

    2007-01-01

    This study investigated the frequency and latency of naturally occurring social interaction with typically developing children and those with autism in inclusive kindergarten settings. The children with autism were also subdivided into two groups according to intellectual functioning in order to analyze frequency and latency of social interaction…

  10. Latency of tone-burst-evoked auditory brain stem responses and otoacoustic emissions: Level, frequency, and rise-time effects

    PubMed Central

    Rasetshwane, Daniel M.; Argenyi, Michael; Neely, Stephen T.; Kopun, Judy G.; Gorga, Michael P.

    2013-01-01

    Simultaneous measurement of auditory brain stem response (ABR) and otoacoustic emission (OAE) delays may provide insights into effects of level, frequency, and stimulus rise-time on cochlear delay. Tone-burst-evoked ABRs and OAEs (TBOAEs) were measured simultaneously in normal-hearing human subjects. Stimuli included a wide range of frequencies (0.5–8 kHz), levels (20–90 dB SPL), and tone-burst rise times. ABR latencies have orderly dependence on these three parameters, similar to previously reported data by Gorga et al. [J. Speech Hear. Res. 31, 87–97 (1988)]. Level dependence of ABR and TBOAE latencies was similar across a wide range of stimulus conditions. At mid-frequencies, frequency dependence of ABR and TBOAE latencies were similar. The dependence of ABR latency on both rise time and level was significant; however, the interaction was not significant, suggesting independent effects. Comparison between ABR and TBOAE latencies reveals that the ratio of TBOAE latency to ABR forward latency (the level-dependent component of ABR total latency) is close to one below 1.5 kHz, but greater than two above 1.5 kHz. Despite the fact that the current experiment was designed to test compatibility with models of reverse-wave propagation, existing models do not completely explain the current data. PMID:23654387

  11. 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…

  12. PIM-1 mixed matrix membranes for gas separations using cost-effective hypercrosslinked nanoparticle fillers.

    PubMed

    Mitra, Tamoghna; Bhavsar, Rupesh S; Adams, Dave J; Budd, Peter M; Cooper, Andrew I

    2016-04-25

    High-free-volume glassy polymers, such as polymers of intrinsic microporosity (PIMs) and poly(trimethylsilylpropyne), have attracted attention as membrane materials due to their high permeability. However, loss of free volume over time, or aging, limits their applicability. Introduction of a secondary filler phase can reduce this aging but either cost or instability rules out scale up for many fillers. Here, we report a cheap, acid-tolerant, nanoparticulate hypercrosslinked polymer 'sponge' as an alternative filler. On adding the filler, permeability is enhanced and aging is strongly retarded. This is accompanied by a CO2/N2 selectivity that increases over time, surpassing the Robeson upper bound.

  13. A Carbonaceous Membrane based on a Polymer of Intrinsic Microporosity (PIM-1) for Water Treatment

    PubMed Central

    Kim, Hee Joong; Kim, Dong-Gyun; Lee, Kyuchul; Baek, Youngbin; Yoo, Youngjae; Kim, Yong Seok; Kim, Byoung Gak; Lee, Jong-Chan

    2016-01-01

    As insufficient access to clean water is expected to become worse in the near future, water purification is becoming increasingly important. Membrane filtration is the most promising technologies to produce clean water from contaminated water. Although there have been many studies to prepare highly water-permeable carbon-based membranes by utilizing frictionless water flow inside the carbonaceous pores, the carbon-based membranes still suffer from several issues, such as high cost and complicated fabrication as well as relatively low salt rejection. Here, we report for the first time the use of microporous carbonaceous membranes via controlled carbonization of polymer membranes with uniform microporosity for high-flux nanofiltration. Further enhancement of membrane performance is observed by O2 plasma treatment. The optimized membrane exhibits high water flux (13.30 LMH Bar−1) and good MgSO4 rejection (77.38%) as well as antifouling properties. This study provides insight into the design of microporous carbonaceous membranes for water purification. PMID:27782212

  14. Thyroid carcinoma after radioiodide therapy for hyperthyroidism. Analysis based on age, latency, and administered dose of I-/sup 131/

    SciTech Connect

    Spencer, R.P.; Chapman, C.N.; Rao, H.

    1983-05-01

    Twenty-five reports in the medical literature of thyroid carcinomas which were detected after radioiodide therapy for hyperthyroidism were reviewed. These cases did not show a usual characteristic of radiation-associated tumors, namely a long latency period. That is, in 8/25 the latency period was under five years, and the mean latency was only 7.3 years. Further, there was no relationship between latency and age at treatment, or between latency and the dose of radioiodide employed. In 15/25 of the cases, there were known thyroid nodules. Three of the patients had thyroiditis (which itself has a correlation with thyroid carcinoma), and one individual had prior head and neck external radiation. There was no substantiating evidence that radioiodide treatment for hyperthyroidism was the cause of these thyroid carcinomas.

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. [Decrease of latency of auditory evoked potentials in humans practicing transcendental meditation (author's transl].

    PubMed

    Wandhöfer, A; Kobal, G; Plattig, K H

    1976-06-01

    Slow cortical auditory responses were recorded from humans practicing transcendental meditation. The potentials were computated according to Fig. 1, and the latencies of the positive peaks P1 and P2 and of the negative peaks N1 and N2 were measured as well as the areas of the on-effect FON, of the off-effect FOFF and of the DC-shift FDC during the stimulus duration. Latencies for most of the initial peaks during TM as well as during normal consciousness were significantly shorter than in a control group in a dozing state or during normal consciousness (Table 1 and Fig. 2). Certain differences were also found in regard to other parameters such as amplitudes and areas of the auditory evoked response.

  1. 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

  2. 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

  3. Zinc supplementation prolongs the latency of hyperthermia-induced febrile seizures in rats.

    PubMed

    Aydın, L; Erdem, S R; Yazıcı, C

    2016-03-01

    Some studies have shown a relationship between febrile seizures and zinc levels. The lowest dose zinc supplementation in pentylenetetrazole seizure model has a protective effect. But, zinc pretreatment has no effect in maximal electroshock model. However, it is unclear how zinc supplementation affects hyperthermia-induced febrile seizures. The aim of the present study was to investigate the effects of zinc supplementation on febrile seizures in male Sprague-Dawley rats. The rats were randomly assigned to four groups. Zinc supplementation was commenced 5 days prior to febrile seizure induction by placing the animals in a water bath at 45°C. We measured the rectal temperature and determined the febrile seizure latency, duration, and stage. In the zinc-supplemented group, both the seizure latency and the rectal temperature triggering seizure initiation were significantly higher than in the other groups. We suggest that zinc supplementation can positively modulate febrile seizure pathogenesis in rats.

  4. 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.

  5. 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

  6. Reducing latency overhead caused by using LDPC codes in NAND flash memory

    NASA Astrophysics Data System (ADS)

    Zhao, Wenzhe; Dong, Guiqiang; Sun, Hongbin; Zheng, Nanning; Zhang, Tong

    2012-12-01

    Semiconductor technology scaling makes NAND flash memory subject to continuous raw storage reliability degradation, leading to the demand for more and more powerful error correction codes. This inevitable trend makes conventional BCH code increasingly inadequate, and iterative coding solutions such as low-density parity-check (LDPC) codes become very natural alternative options. However, fine-grained soft-decision memory sensing must be used in order to fully leverage the strong error correction capability of LDPC codes, which results in significant data access latency overhead. This article presents a simple design technique that can reduce such latency overhead. The key is to cohesively exploit the NAND flash memory wear-out dynamics and impact of LDPC code structure on decoding performance. Based upon detailed memory device modeling and ASIC design, we carried out simulations to demonstrate the potential effectiveness of this design method and evaluate the involved trade-offs.

  7. 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

  8. Short latency vestibular potentials evoked by electrical round window stimulation in the guinea pig.

    PubMed

    Bordure, P; Desmadryl, G; Uziel, A; Sans, A

    1989-11-01

    Short-latency potentials evoked by round window electrical stimulation were recorded in guinea pig by means of vertex-pinna skin electrodes using averaging techniques. Constant current shocks of 20 microseconds or 50 microseconds (25-300 microA) were used to evoke both auditory and vestibular brain-stem potentials. Pure auditory potentials, comparable to those evoked by acoustic clicks, were obtained by 20 microseconds electrical stimuli and disappeared during an auditory masking procedure made with a continuous white noise (110 dB SPL). Short latency potentials labeled V1, V2 and V3 were obtained by 50 microseconds electrical stimuli during an auditory masking procedure. This response disappeared after specific vestibular neurectomy, whereas the auditory response evoked by acoustic clicks or by electrical stimulation remained unchanged, suggesting that these latter potentials had a vestibular origin.

  9. A study of application sensitivity to variation in message passing latency and bandwidth

    SciTech Connect

    Worley, P.H.; Mackay, D.R.; Robinson, A.C.; Barragy, E.J.

    1996-06-01

    This study measures the effects of changes in message latency and bandwidth for production-level codes on a current generation tightly coupled MPP, the Intel Paragon. Messages are sent multiple times to study the application sensitivity to variations in band - width and latency. This method preserves the effects of contention on the interconnection network. Two applications are studied, PCTH, a shock physics code developed at Sandia National Laboratories, and PSTSWM, a spectral shallow water code developed at Oak Ridge National Laboratory and Argonne National Laboratory. These codes are significant in that PCTH is a {open_quote}full physics{close_quotes} application code in production use, while PSTSWM serves as a parallel algorithm test bed and benchmark for production codes used in atmospheric modeling. They are also significant in that the message-passing behavior differs significantly between the two codes, each representing an important class of scientific message-passing applications.

  10. Data Latency Characteristics Observed Through Diverse Communication Links by the EarthScope USArray Transportable Array

    NASA Astrophysics Data System (ADS)

    Vernon, F. L.; Eakins, J. A.; Busby, R.

    2008-12-01

    The USArray Transportable Array has deployed over 600 stations in aggregate over the past four years. All stations communicate in near-real time using ip protocols over a variety of communication links including satellite, cell phone, and DSL. Several different communication providers have been used for each type of communication links. In addition, data are being acquired from several regional networks either directly from a data server or after passing through the IRIS DMC BUD system. We will present results about the latency of data arriving at the UCSD Array Network Facility where the real time data are acquired. Under normal operating conditions the median data latency is several seconds. We will also examine the data return rates through the near-real time systems. In addition we will examine the statistics of over 36,000 events which have automatic event locations and associations. We evaluate the timeliness of these results in the context of seismic early warning systems.

  11. 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.

  12. Short latency vestibular potentials evoked by electrical round window stimulation in the guinea pig.

    PubMed

    Bordure, P; Desmadryl, G; Uziel, A; Sans, A

    1989-11-01

    Short-latency potentials evoked by round window electrical stimulation were recorded in guinea pig by means of vertex-pinna skin electrodes using averaging techniques. Constant current shocks of 20 microseconds or 50 microseconds (25-300 microA) were used to evoke both auditory and vestibular brain-stem potentials. Pure auditory potentials, comparable to those evoked by acoustic clicks, were obtained by 20 microseconds electrical stimuli and disappeared during an auditory masking procedure made with a continuous white noise (110 dB SPL). Short latency potentials labeled V1, V2 and V3 were obtained by 50 microseconds electrical stimuli during an auditory masking procedure. This response disappeared after specific vestibular neurectomy, whereas the auditory response evoked by acoustic clicks or by electrical stimulation remained unchanged, suggesting that these latter potentials had a vestibular origin. PMID:2479525

  13. Ongoing Clinical Trials of Human Immunodeficiency Virus Latency-Reversing and Immunomodulatory Agents

    PubMed Central

    Delagrèverie, Héloïse M.; Delaugerre, Constance; Lewin, Sharon R.; Deeks, Steven G.; Li, Jonathan Z.

    2016-01-01

    In chronic human immunodeficiency virus (HIV)-1 infection, long-lived latently infected cells are the major barrier to virus eradication and functional cure. Several therapeutic strategies to perturb, eliminate, and/or control this reservoir are now being pursued in the clinic. These strategies include latency reversal agents (LRAs) designed to reactivate HIV-1 ribonucleic acid transcription and virus production and a variety of immune-modifying drugs designed to reverse latency, block homeostatic proliferation, and replenish the viral reservoir, eliminate virus-producing cells, and/or control HIV replication after cessation of antiretroviral therapy. This review provides a summary of ongoing clinical trials of HIV LRAs and immunomodulatory molecules, and it highlights challenges in the comparison and interpretation of the expected trial results. PMID:27757411

  14. 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

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

    PubMed

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

    2015-09-01

    Responsible for 9 million new cases of active disease and nearly 2 million deaths each year, tuberculosis (TB) remains a global health threat of overwhelming dimensions. Mycobacterium bovis BCG, the only licensed vaccine available, fails to confer lifelong protection and to prevent reactivation of latent infection. Although 15 new vaccine candidates are now in clinical trials, an effective vaccine against TB remains elusive, and new strategies for vaccination are vital. BCG vaccination fails to induce immunity against Mycobacterium tuberculosis latency antigens. Synthetic long peptides (SLPs) combined with adjuvants have been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved to induce efficient antitumor immunity. This study investigated an SLP derived from Rv1733c, a major M. tuberculosis latency antigen which is highly expressed by "dormant" M. tuberculosis and well recognized by T cells from latently M. tuberculosis-infected individuals. In order to assess its in vivo immunogenicity and protective capacity, Rv1733c SLP in CpG was administered to HLA-DR3 transgenic mice. Immunization with Rv1733c SLP elicited gamma interferon-positive/tumor necrosis factor-positive (IFN-γ(+)/TNF(+)) and IFN-γ(+) CD4(+) T cells and Rv1733c-specific antibodies and led to a significant reduction in the bacterial load in the lungs of M. tuberculosis-challenged mice. This was observed both in a pre- and in a post-M. tuberculosis challenge setting. Moreover, Rv1733c SLP immunization significantly boosted the protective efficacy of BCG, demonstrating the potential of M. tuberculosis latency antigens to improve BCG efficacy. These data suggest a promising role for M. tuberculosis latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a prophylactic and in a postinfection setting.

  16. Auditory Brainstem Response Latency in Noise as a Marker of Cochlear Synaptopathy

    PubMed Central

    Hickox, Ann E.; Bharadwaj, Hari M.; Goldberg, Hannah; Verhulst, Sarah; Liberman, M. Charles; Shinn-Cunningham, Barbara G.

    2016-01-01

    Evidence from animal and human studies suggests that moderate acoustic exposure, causing only transient threshold elevation, can nonetheless cause “hidden hearing loss” that interferes with coding of suprathreshold sound. Such noise exposure destroys synaptic connections between cochlear hair cells and auditory nerve fibers; however, there is no clinical test of this synaptopathy in humans. In animals, synaptopathy reduces the amplitude of auditory brainstem response (ABR) wave-I. Unfortunately, ABR wave-I is difficult to measure in humans, limiting its clinical use. Here, using analogous measurements in humans and mice, we show that the effect of masking noise on the latency of the more robust ABR wave-V mirrors changes in ABR wave-I amplitude. Furthermore, in our human cohort, the effect of noise on wave-V latency predicts perceptual temporal sensitivity. Our results suggest that measures of the effects of noise on ABR wave-V latency can be used to diagnose cochlear synaptopathy in humans. SIGNIFICANCE STATEMENT Although there are suspicions that cochlear synaptopathy affects humans with normal hearing thresholds, no one has yet reported a clinical measure that is a reliable marker of such loss. By combining human and animal data, we demonstrate that the latency of auditory brainstem response wave-V in noise reflects auditory nerve loss. This is the first study of human listeners with normal hearing thresholds that links individual differences observed in behavior and auditory brainstem response timing to cochlear synaptopathy. These results can guide development of a clinical test to reveal this previously unknown form of noise-induced hearing loss in humans. PMID:27030760

  17. 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

  18. 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…

  19. Latency-Efficient Communication in Wireless Mesh Networks under Consideration of Large Interference Range

    NASA Astrophysics Data System (ADS)

    Xin, Qin; Yao, Xiaolan; Engelstad, Paal E.

    2010-09-01

    Wireless Mesh Networking is an emerging communication paradigm to enable resilient, cost-efficient and reliable services for the future-generation wireless networks. We study here the minimum-latency communication primitive of gossiping (all-to-all communication) in multi-hop ad-hoc Wireless Mesh Networks (WMNs). Each mesh node in the WMN is initially given a message and the objective is to design a minimum-latency schedule such that each mesh node distributes its message to all other mesh nodes. Minimum-latency gossiping problem is well known to be NP-hard even for the scenario in which the topology of the WMN is known to all mesh nodes in advance. In this paper, we propose a new latency-efficient approximation scheme that can accomplish gossiping task in polynomial time units in any ad-hoc WMN under consideration of Large Interference Range (LIR), e.g., the interference range is much larger than the transmission range. To the best of our knowledge, it is first time to investigate such a scenario in ad-hoc WMNs under LIR, our algorithm allows the labels (e.g., identifiers) of the mesh nodes to be polynomially large in terms of the size of the WMN, which is the first time that the scenario of large labels has been considered in ad-hoc WMNs under LIR. Furthermore, our gossiping scheme can be considered as a framework which can be easily implied to the scenario under consideration of mobility-related issues since we assume that the mesh nodes have no knowledge on the network topology even for its neighboring mesh nodes.

  20. Analysis of the Role of Update Rate and System Latency in Interactive Virtual Acoustic Environments

    NASA Technical Reports Server (NTRS)

    Wenzel, Elizabeth M.; Ahumada, Albert (Technical Monitor); Schlickenmaier, Herbert (Technical Monitor); Johnson, Gerald (Technical Monitor); Frey, Mary Anne (Technical Monitor); Schneider, Victor S. (Technical Monitor)

    1997-01-01

    The ultimate goal of virtual acoustics is to simulate the complex acoustic field experienced by a listener freely moving around within an environment. This paper discusses some of the engineering constraints that may be faced during implementation and the perceptual consequences of these constraints. In particular, the perceptual impact of parameters like the update rate and overall system latency of interactive spatial audio systems is addressed.

  1. 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

  2. Analysis of variance of communication latencies in anesthesia: comparing means of multiple log-normal distributions.

    PubMed

    Ledolter, Johannes; Dexter, Franklin; Epstein, Richard H

    2011-10-01

    Anesthesiologists rely on communication over periods of minutes. The analysis of latencies between when messages are sent and responses obtained is an essential component of practical and regulatory assessment of clinical and managerial decision-support systems. Latency data including times for anesthesia providers to respond to messages have moderate (> n = 20) sample sizes, large coefficients of variation (e.g., 0.60 to 2.50), and heterogeneous coefficients of variation among groups. Highly inaccurate results are obtained both by performing analysis of variance (ANOVA) in the time scale or by performing it in the log scale and then taking the exponential of the result. To overcome these difficulties, one can perform calculation of P values and confidence intervals for mean latencies based on log-normal distributions using generalized pivotal methods. In addition, fixed-effects 2-way ANOVAs can be extended to the comparison of means of log-normal distributions. Pivotal inference does not assume that the coefficients of variation of the studied log-normal distributions are the same, and can be used to assess the proportional effects of 2 factors and their interaction. Latency data can also include a human behavioral component (e.g., complete other activity first), resulting in a bimodal distribution in the log-domain (i.e., a mixture of distributions). An ANOVA can be performed on a homogeneous segment of the data, followed by a single group analysis applied to all or portions of the data using a robust method, insensitive to the probability distribution.

  3. 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.

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

    PubMed

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

    1997-06-01

    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. PMID:9190045

  5. Blockade of in vitro ictogenesis by low-frequency stimulation coincides with increased epileptiform response latency.

    PubMed

    Kano, Toshiyuki; Inaba, Yuji; D'Antuono, Margherita; Biagini, Giuseppe; Levésque, Maxime; Avoli, Massimo

    2015-07-01

    Low-frequency stimulation, delivered through transcranial magnetic or deep-brain electrical procedures, reduces seizures in patients with pharmacoresistant epilepsy. A similar control of ictallike discharges is exerted by low-frequency electrical stimulation in rodent brain slices maintained in vitro during convulsant treatment. By employing field and "sharp" intracellular recordings, we analyzed here the effects of stimuli delivered at 0.1 or 1 Hz in the lateral nucleus of the amygdala on ictallike epileptiform discharges induced by the K(+) channel blocker 4-aminopyridine in the perirhinal cortex, in a rat brain slice preparation. We found that 1) ictal events were nominally abolished when the stimulus rate was brought from 0.1 to 1 Hz; 2) this effect was associated with an increased latency of the epileptiform responses recorded in perirhinal cortex following each stimulus; and 3) both changes recovered to control values following arrest of the 1-Hz stimulation protocol. The control of ictal activity by 1-Hz stimulation and the concomitant latency increase were significantly reduced by GABAB receptor antagonism. We propose that this frequency-dependent increase in latency represents a short-lasting, GABAB receptor-dependent adaptive mechanism that contributes to decrease epileptiform synchronization, thus blocking seizures in epileptic patients and animal models. PMID:25925325

  6. An Investigation on the Role of Spike Latency in an Artificial Olfactory System

    PubMed Central

    Martinelli, Eugenio; Polese, Davide; Dini, Francesca; Paolesse, Roberto; Filippini, Daniel; Lundström, Ingemar; Di Natale, Corrado

    2011-01-01

    Experimental studies have shown that the reactions to external stimuli may appear only few hundreds of milliseconds after the physical interaction of the stimulus with the proper receptor. This behavior suggests that neurons transmit the largest meaningful part of their signal in the first spikes, and than that the spike latency is a good descriptor of the information content in biological neural networks. In this paper this property has been investigated in an artificial sensorial system where a single layer of spiking neurons is trained with the data generated by an artificial olfactory platform based on a large array of chemical sensors. The capability to discriminate between distinct chemicals and mixtures of them was studied with spiking neural networks endowed with and without lateral inhibitions and considering as output feature of the network both the spikes latency and the average firing rate. Results show that the average firing rate of the output spikes sequences shows the best separation among the experienced vapors, however the latency code is able in a shorter time to correctly discriminate all the tested volatile compounds. This behavior is qualitatively similar to those recently found in natural olfaction, and noteworthy it provides practical suggestions to tail the measurement conditions of artificial olfactory systems defining for each specific case a proper measurement time. PMID:22194721

  7. Shorter REM latency associated with more sleep cycles of a shorter duration in healthy humans.

    PubMed

    Le Bon, O; Staner, L; Hoffmann, G; Kentos, M; Pelc, I; Linkowski, P

    2001-10-10

    A significant association between rapid eye movement (REM) sleep latency and the number of non-REM/REM sleep cycles was found 15 years ago in a large retrospective study. The present prospective study further explored this intra-sleep relationship and analyzed the links between these two variables and the mean cycle duration. It was based on a carefully selected group of healthy control subjects whose sleep was polysomnographically recorded at home for 4 sequential nights. The latency of REM sleep was inversely correlated with the number of cycles and positively correlated with the mean cycle duration, both in individual nights and on means of 4 nights. The present study demonstrated that variations in the number of cycles or the mean cycle duration between the nights are far less important than the substantial differences observed between subjects. Present outcomes support the study of sleep cycle periods and frequencies in those psychiatric disorders where REM sleep latencies have been found to be shorter, and they suggest that these variables be included in sleep studies in which cycles are compared with each other.

  8. 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.

  9. 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.

  10. Zebra Alphaherpesviruses (EHV-1 and EHV-9): Genetic Diversity, Latency and Co-Infections

    PubMed Central

    Abdelgawad, Azza; Damiani, Armando; Ho, Simon Y. W.; Strauss, Günter; Szentiks, Claudia A.; East, Marion L.; Osterrieder, Nikolaus; Greenwood, Alex D.

    2016-01-01

    Alphaherpesviruses are highly prevalent in equine populations and co-infections with more than one of these viruses’ strains frequently diagnosed. Lytic replication and latency with subsequent reactivation, along with new episodes of disease, can be influenced by genetic diversity generated by spontaneous mutation and recombination. Latency enhances virus survival by providing an epidemiological strategy for long-term maintenance of divergent strains in animal populations. The alphaherpesviruses equine herpesvirus 1 (EHV-1) and 9 (EHV-9) have recently been shown to cross species barriers, including a recombinant EHV-1 observed in fatal infections of a polar bear and Asian rhinoceros. Little is known about the latency and genetic diversity of EHV-1 and EHV-9, especially among zoo and wild equids. Here, we report evidence of limited genetic diversity in EHV-9 in zebras, whereas there is substantial genetic variability in EHV-1. We demonstrate that zebras can be lytically and latently infected with both viruses concurrently. Such a co-occurrence of infection in zebras suggests that even relatively slow-evolving viruses such as equine herpesviruses have the potential to diversify rapidly by recombination. This has potential consequences for the diagnosis of these viruses and their management in wild and captive equid populations. PMID:27657113

  11. 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.

  12. 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

  13. 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

  14. 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

  15. The Role of Sports in the Development of the Superego of the Male Latency Child.

    PubMed

    Shopper, Moisy

    2014-01-01

    Psychoanalytic literature has often overlooked the child's participation in organized sports, which often can facilitate or impede not only expression of aggression and narcissism, but enhance or skew the growth of the child's superego and ego ideal. Specific outcomes are largely determined by the experience and knowledge of the parents, the coaches, and sports organizations for latency-aged youth. Sports participation facilitates a major step forward in psychic development, that is, an agreed-upon adherence to a set of rules and regulations, monitored by an official embodying the final word regarding rules and their infractions. This paper is an attempt to delineate the role of sports in the life of the latency child, the parents who become involved, the coaches who teach and supervise, and the social and individual milieu within which sports take place. All these contribute to common goals: the engendering of good sportsmanship and the encouragement of psychic growth, particularly regarding how aggression and narcissism contribute to the development of superego and ego ideals. The fate of aggression and narcissism in superego and ego ideal development is influenced to a large degree by the nature, orientation, and motivations of all involved in sports for the latency-aged.

  16. Latencies in action potential stimulation in a two-dimensional bidomain: A numerical simulation

    NASA Astrophysics Data System (ADS)

    Barach, John Paul

    1991-05-01

    A numerical simulation is performed in which a uniform planar slab of idealized cardiac tissue is stimulated at the center. The cardiac slab is modeled as an anisotropic bidomain; within each domain current flow is determined by a forced diffusion equation in which the transmembrane current connecting the domains provides the forcing term. An action potential (AP) propagates outward after a time latency dependent upon the stimulus size and the physiological variables. Its isochrones are elliptical with an asymmetry that is a small fraction of the imposed asymmetry in resistivity. External voltages resemble the first derivative of those in the internal domain and tests with continuing stimuli exhibit a relaxation time of about 3 ms and space constants that agree with other work. The AP latency increases very strongly near threshold stimulus and decreases as the log (stimulus) for large stimuli in the ``virtual cathode'' range. Latencies in the longitudinal, transverse, and diagonal directions are found to be the same over a wide range of stimulus size and type.

  17. Short-latency compensatory eye movements associated with a brief period of free fall.

    PubMed

    Bush, G A; Miles, F A

    1996-03-01

    The vertical eye movements induced by a brief period of free fall were recorded from three monkeys (Macaca mulatta) using the electromagnetic search coil technique. Free fall was initiated in total darkness immediately following binocular fixation of one of six target lights located at viewing distances ranging from 20 to 107 cm. Responses consisted of an initial transient downward eye movement (anticompensatory direction) with a latency of a few milliseconds at most followed by a sustained upward (compensatory) eye movement. The early transient was independent of viewing distance and attributed to an artifact, whereas the later component was a linear function of the inverse of the prior viewing distance and attributed to the translational vestibulo-ocular reflex (TVOR). Response latencies for the four nearer viewing distances were determined from the individual eye velocity traces using a computerized algorithm: after removing the initial transient by subtracting the mean response obtained with the most distant viewing, a regression line was fitted to the initial rising phase of the residual response and then extrapolated back to the baseline to determine the onset. When so determined, median latencies for the nearest viewing ranged from 16.4 to 18.5 ms, values appreciably shorter than any in the literature.

  18. 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.

  19. 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

  20. Reduced input from foot sole skin through cooling differentially modulates the short latency and medium latency vestibular reflex responses to galvanic vestibular stimulation.

    PubMed

    Muise, Stephanie B; Lam, Chris K; Bent, Leah R

    2012-04-01

    Sensory afferent information from the skin of the foot sole and information from the vestibular system converge within the central nervous system; however, their mode of interaction remains unknown. The purpose of this study was to investigate the effect of reduced cutaneous foot sole information on the ability of the vestibular system to evoke short latency (SL) and medium latency (ML) lower limb muscle reflex responses. Galvanic vestibular stimulation (GVS; bipolar; binaural; 25 ms; 2 mA square-wave pulse) was applied to standing human subjects (four women, eight men, average age 21.1 ± 3.0 years) both before and after cooling the foot soles in 1°C ice water (15 min initially, followed by 5 min between blocks of 200 GVS pulses). Changes in soleus reflex amplitude were examined. Following ice water immersion, there was a 35.16% increase in the size of the ML response in the soleus muscle when expressed as a percentage of pre-stimulus electromyographic (EMG) activity (control 26.48 ± 4.91%; ice 36.16 ± 6.52%) with no change in size of the SL response (control 7.42 ± 1.12%; ice 8.72 ± 1.10%). These results support the previously proposed dissociation of the SL and ML responses with respect to their circuitry and functions. The results also suggest a greater role for cutaneous-vestibular interaction in the modulation of the ML than the SL response and at a location prior to the motoneuron pool.

  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. 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

  3. 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

  4. 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.

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

    ScienceCinema

    Jordan, Scott [Physik Instrumente

    2016-07-12

    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.

  6. 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.

  7. Time Slot Assignment Algorithms to Upstream Links for Decreasing Transmission Latency in IEEE 802.16j Networks

    NASA Astrophysics Data System (ADS)

    Hasegawa, Go; Tanaka, Shinpei; Taniguchi, Yoshiaki; Nakano, Hirotaka

    In this paper, the authors focus on upstream transmission in TDMA-based IEEE 802.16j and propose two time slot assignment algorithms to decrease end-to-end transmission latency. One of the proposed algorithms assigns time slots considering the hop count from a gateway node, and the other takes the path from the relay node to the gateway node into account. In addition, a restriction in assigning time slots is introduced to reduce the delay at each relay node. The algorithms with the restriction assign later time slots considering the time slot order of links connecting a relay node. The performance of the proposed algorithms is evaluated through simulation experiments from the viewpoints of frame size and end-to-end transmission latency, and it is confirmed that the proposed algorithms achieve small transmission latency regardless of packet generation rate in the network, and decrease the transmission latency by up to 70% compared with the existing algorithm.

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

    PubMed

    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

    2013-10-01

    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.

  9. 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

  10. 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

  11. 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).

  12. 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

  13. A computational feedforward model predicts categorization of masked emotional body language for longer, but not for shorter, latencies.

    PubMed

    Stienen, Bernard M C; Schindler, Konrad; de Gelder, Beatrice

    2012-07-01

    Given the presence of massive feedback loops in brain networks, it is difficult to disentangle the contribution of feedforward and feedback processing to the recognition of visual stimuli, in this case, of emotional body expressions. The aim of the work presented in this letter is to shed light on how well feedforward processing explains rapid categorization of this important class of stimuli. By means of parametric masking, it may be possible to control the contribution of feedback activity in human participants. A close comparison is presented between human recognition performance and the performance of a computational neural model that exclusively modeled feedforward processing and was engineered to fulfill the computational requirements of recognition. Results show that the longer the stimulus onset asynchrony (SOA), the closer the performance of the human participants was to the values predicted by the model, with an optimum at an SOA of 100 ms. At short SOA latencies, human performance deteriorated, but the categorization of the emotional expressions was still above baseline. The data suggest that, although theoretically, feedback arising from inferotemporal cortex is likely to be blocked when the SOA is 100 ms, human participants still seem to rely on more local visual feedback processing to equal the model's performance.

  14. 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.

  15. 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

  16. Brainstem auditory evoked potentials and middle latency auditory evoked potentials in young children.

    PubMed

    Luo, Jin Jun; Khurana, Divya S; Kothare, Sanjeev V

    2013-03-01

    Measurements of brainstem auditory evoked potentials (BAEP) and middle latency auditory evoked potentials (MLAEP) are readily available neurophysiologic assessments. The generators for BAEP are believed to involve the structures of cochlear nerve, cochlear nucleus, superior olive complex, dorsal and rostral pons, and lateral lemniscus. The generators for MLAEP are assumed to be located in the subcortical area and auditory cortex. BAEP are commonly used in evaluating children with autistic and hearing disorders. However, measurement of MLAEP is rarely performed in young children. To explore the feasibility of this procedure in young children, we retrospectively reviewed our neurophysiology databank and charts for a 3-year period to identify subjects who had both BAEP and MLAEP performed. Subjects with known or identifiable central nervous system abnormalities from the history, neurologic examination and neuroimaging studies were excluded. This cohort of 93 children up to 3 years of age was divided into 10 groups based on the age at testing (upper limits of: 1 week; 1, 2, 4, 6, 8, 10 and 12 months; 2 years; and 3 years of age). Evolution of peak latency, interpeak latency and amplitude of waveforms in BAEP and MLAEP were demonstrated. We concluded that measurement of BAEP and MLAEP is feasible in children, as early as the first few months of life. The combination of both MLAEP and BAEP may increase the diagnostic sensitivity of neurophysiologic assessment of the integrity or functional status of both the peripheral (acoustic nerve) and the central (brainstem, subcortical and cortical) auditory conduction systems in young children with developmental speech and language disorders.

  17. 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

  18. 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

  19. Short latency activation of pyramidal tract cells by Group I afferent volleys in the cat

    PubMed Central

    Swett, John E.; Bourassa, Charles M.

    1967-01-01

    1. The contralateral bulbar pyramids were explored with low impedance micro-electrodes in cats anaesthetized with chloralose to reveal the effect of Group I afferent volleys (deep radial nerve of the forelimb) on pyramidal tract (Pt) cells. 2. Low rate (0·5/sec) stimulation of Group I afferents produced small responses (5-30 μV) in the bulbar pyramid which could be detected only with response averaging methods. The responses appeared with an initial latency of 7·0-11·2 msec and reached peak amplitude in 15·7 msec (mean latency). The pyramidal tract origin of the potential was demonstrated by its depression at stimulus rates above 1-2 sec and its disappearance at rates above 4/sec. 3. Recordings of neurones in the Group I cortical projection zone of the posterior sigmoid gyrus revealed that several types of cells, including Pt cells, were activated by Group I afferent volleys. 4. Pt cells responding to Group I afferent volleys frequently received convergent actions from low threshold cutaneous nerve volleys. 5. Averaged response recordings from electrodes positioned in the medial portions of the lateral funiculus of the spinal cord at the level of C2, revealed a response to Group I afferent volleys as early as 7·4 msec which possessed the same characteristics as the relayed response to Group I in the bulbar pyramids. Some Pt cells, activated by Group I volleys orthodromically, could also be antidromically activated by stimulation of the recording site in C2. 6. It was concluded that group I afferent volleys can influence, after short latencies, Pt and non-Pt cells and that some of these Pt cells gave rise to axons incorporated in the corticospinal tract. PMID:16992239

  20. Low luminance/eyes closed and monochromatic stimulations reduce variability of flash visual evoked potential latency

    PubMed Central

    Subramanian, Senthil Kumar; Gaur, Giriwar Singh; Narayan, Sunil K.

    2013-01-01

    Context: Visual evoked potentials are useful in investigating the physiology and pathophysiology of the human visual system. Flash visual evoked potential (FVEP), though technically easier, has less clinical utility because it shows great variations in both latency and amplitude for normal subjects. Aim: To study the effect of eye closure, low luminance, and monochromatic stimulation on the variability of FVEPs. Subjects and Methods: Subjects in self-reported good health in the age group of 18-30 years were divided into three groups. All participants underwent FVEP recording with eyes open and with white light at 0.6 J luminance (standard technique). Next recording was done in group 1 with closed eyes, group 2 with 1.2 and 20 J luminance, and group 3 with red and blue lights, while keeping all the other parameters constant. Two trials were given for each eye, for each technique. The same procedure was repeated at the same clock time on the following day. Statistical Analysis: Variation in FVEP latencies between the individuals (interindividual variability) and the variations within the same individual for four trials (intraindividual variability) were assessed using coefficient of variance (COV). The technique with lower COV was considered the better method. Results: Recording done with closed eyes, 0.6 J luminance, and monochromatic light (blue > red) showed lower interindividual and intraindividual variability in P2 and N2 as compared to standard techniques. Conclusions: Low luminance flash stimulations and monochromatic light will reduce FVEP latency variability and may be clinically useful modifications of FVEP recording technique. PMID:24339591

  1. 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

  2. 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.

  3. The development of an improved murine iontophoresis reactivation model for the study of HSV-1 latency.

    PubMed

    Gordon, Y J; Araullo-Cruz, T P; Romanowski, E; Ruziczka, L; Balouris, C; Oren, J; Cheng, K P; Kim, S

    1986-08-01

    The present study reviews the development of an effective murine iontophoresis reactivation model for the study of HSV-1 latency. In a series of experiments, Balb C mice latently infected with HSV-1 McKrae strain were iontophoresed with epinephrine X 3 days (EPI X 3/ION) or 6-hydroxydopamine X 1 day followed by topical epinephrine (6-HD ION/EPI). Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, titration, and neutralization. Additional studies determined the effect of topical ocular steroids on viral recovery rate. The results demonstrated no recovery of McKrae strain in Balb C (0%) with EPI X 3/ION, and no enhancement with topical steroids. 6-HD ION/EPI demonstrated a low recovery rate in mice (8%). However, the recovery rate was significantly increased to 50% by the addition of topical steroids to form the 6-HD ION/EPI/STEROID model, a useful experimental tool. The substitution of a clinical isolate, W strain, for McKrae strain further improved the model. The results demonstrated that, following the acute infection in mice, W strain was associated with a significantly higher (P = .001) survival rate than McKrae strain (81% vs. 52%). There was no statistically significant difference between the two strains, W vs McKrae, in Balb C mice comparing keratitis, establishment of latency (by co-cultivation), spontaneous shedding rate, or induced ocular shedding following iontophoresis. The development of an effective murine iontophoresis model offers an economical method which is uniquely suited for immunological and genetic studies of HSV-1 latency.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Intended rather than actual movement velocity determines the latency of anticipatory postural adjustments.

    PubMed

    Esposti, Roberto; Bruttini, Carlo; Bolzoni, Francesco; Cavallari, Paolo

    2015-02-01

    The literature reports that anticipatory postural adjustments (APAs) are programmed according to movement velocity. However, the linkage between APAs and velocity has been highlighted within single subjects who were asked to voluntarily change movement velocity; therefore, till now, it has been impossible to discern whether the key factor determining APA latency was the intended movement velocity or the actual one. Aim of this study was to distinguish between these two factors. We analyzed the APA chain that stabilizes the arm during a brisk index finger flexion in two groups of subjects: (1) 29 who composed our database from previous experiments and were asked to "go-as-fast-as-possible" (go-fast), but actually performed the movement with different speeds (238-1, 180°/s), and (2) ten new subjects who performed the go-fast movement at more than 500°/s and were then asked to go-slow at about 50% of their initial velocity, thus moving at 300-800°/s. No correlation between APA latency and actual movement speed was observed when all subjects had to go-fast (p > 0.50), while delayed APAs were found in the ten new subjects when they had to go-slow (p < 0.001). Moreover, in the speed range between 300 and 800°/s, the APA latency depended only on movement instruction: subjects going fast showed earlier APAs than those going slow (p < 0.001). These data suggest a stronger role of the intended movement velocity versus the actual one in modifying the timing of postural muscles recruitment with respect to the prime mover. These results also strengthen the idea of a shared postural and voluntary command within the same motor act.

  9. 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.

  10. 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.

  11. Visual evoked potential latency and contrast sensitivity in patients with posterior chamber intraocular lens implants.

    PubMed Central

    Howe, J. W.; Mitchell, K. W.; Mahabaleswara, M.; Abdel-Khalek, M. N.

    1986-01-01

    An electrophysiological investigation of visual evoked potential (VEP) latency and contrast sensitivity was performed in a group of 13 patients who had undergone extracapsular cataract surgery with posterior chamber lens implantation. In spite of good postoperative visual acuity, abnormalities were detected in nine of the group (69%). This study suggests that, even with successfully implanted lenses, there may be a reduction in visual function which could be the result of altered transmission through the plastic lenticulus or fibrosis of the posterior lens capsule, and/or subtle changes in retinal architecture, not observed ophthalmoscopically. PMID:3801366

  12. The swept rule for breaking the latency barrier in time advancing PDEs

    NASA Astrophysics Data System (ADS)

    Alhubail, Maitham; Wang, Qiqi

    2016-02-01

    This article investigates the swept rule of space-time domain decomposition, an idea to break the latency barrier via communicating less often when explicitly solving time-dependent PDEs. The swept rule decomposes space and time among computing nodes in ways that exploit the domains of influence and the domain of dependency, making it possible to communicate once per many timesteps without redundant computation. The article presents simple theoretical analysis to the performance of the swept rule which then was shown to be accurate by conducting numerical experiments.

  13. Normative multitrial recall performance, metacognitive judgments, and retrieval latencies for Lithuanian-English paired associates.

    PubMed

    Grimaldi, Phillip J; Pyc, Mary A; Rawson, Katherine A

    2010-08-01

    Memory researchers using paired associates have benefited greatly from the Swahili-English norms reported by Nelson and Dunlosky (1994). Given recent increases in the amount and kinds of research using paired associates, however, researchers would now benefit from an expanded set of normative measures for foreign language vocabulary words. We report data for 120 Lithuanian-English word pairs collected from 236 undergraduates. Participants completed three study-test trials and were asked to make metacognitive judgments for each item. We report normative recall performance, recall latencies, and error types for each item across trials, as well as the perceived difficulty of each item on the basis of metacognitive judgments.

  14. 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.

  15. Herpes simplex virus type-1: replication, latency, reactivation and its antiviral targets.

    PubMed

    Pires de Mello, Camilly P; Bloom, David C; Paixão, Izabel Cnp

    2016-01-01

    Infection by herpes simplex virus type-1 (HSV-1) causes several diseases, ranging from cutaneous, oral and genital infections to fatal encephalitis. Despite the availability of antiviral therapies on the market, their efficacies are incomplete, and new cases of resistant strains arise, mainly in the immunocompromised, but also recently documented in immunocompetent patients. Over the last decades a lot has been discovered about the molecular basis of infection which has been of great benefit to the investigation of new anti-HSV-1 molecules. In this review we summarize replication, latency and reactivation highlighting potential antiviral targets and new molecules described in the past several years in the literature.

  16. Increased anti-saccade latency is an isolated lingering abnormality in Sydenham chorea.

    PubMed

    Cairney, Sheree; Maruff, Paul; Currie, Jon; Currie, Bart J

    2009-06-01

    Sydenham chorea (SC) is an autoimmune response to group A beta-hemolytic streptococcal infection whose clinical and imaging manifestations usually resolve within 6 months. We used ocular motor analysis and neuropsychologic assessment to investigate residual striatal dysfunction in two individuals with histories of childhood SC whose most recent episodes of chorea had occurred 5 and 17 years before testing. Compared with the performance of 33 age-matched control subjects, both SC subjects showed significantly increased anti-saccade latencies. These findings support recent theories that acute episodes of SC may cause long-term corticostriatal changes in some individuals.

  17. Processing Direct Broadcast Data to Reduce Latency of Aqua AMSR-E Products

    NASA Astrophysics Data System (ADS)

    Regner, K.; Conover, H.; Beaumont, B.; Teague, M.; Graves, S. J.; Hardin, D. M.

    2011-12-01

    Standard data products from NASA's Advanced Microwave Scanning Radiometer for Earth Observing Systems (AMSR-E) have served the climate research community well since the launch of the Aqua satellite in 2002. But the time from observation until swath products are made available to end users (approximately 12-15 hours after observation) diminishes their usefulness to such disciplines as weather prediction and nowcasting, natural hazards monitoring, disaster relief, and agricultural monitoring. To address the needs of these communities, NASA's Earth Science Division built the Land Atmosphere Near-real-time Capability for EOS (Earth Observing Systems), or LANCE, which generates products from several instruments, including AMSR-E, flying aboard the Aqua, Aura and Terra satellites. As for the standard products, the raw satellite data is transmitted from satellite to the EOS Data and Operations System (EDOS), via ground stations in Alaska and Norway, for distribution to the processing elements. The LANCE AMSR-E system generates a variety of Level-2 swath products using essentially the same science algorithms as are used for the standard science products, but with predictive rather than definitive ephemeris. The average latency for these LANCE AMSR-E swath products is approximately three hours from observation; most of this latency is due to the wait time for the on-board recorder to transmit data to the ground. One of the recommendations arising from the first meeting of the LANCE User Working Group was for the data centers to investigate the feasibility of processing direct broadcast data. Since direct broadcast data is transmitted directly from the satellite to the ground and attainable by anyone with ground receiving equipment and in direct line of sight to the satellite, the wait time associated with ground station contacts is eliminated, thereby significantly reducing latency for these datasets. However, direct broadcast data provide limited geographic coverage, in

  18. 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

  19. NEDDylation is essential for Kaposi's sarcoma-associated herpesvirus latency and lytic reactivation and represents a novel anti-KSHV target.

    PubMed

    Hughes, David J; Wood, Jennifer J; Jackson, Brian R; Baquero-Pérez, Belinda; Whitehouse, Adrian

    2015-03-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), which are aggressive malignancies associated with immunocompromised patients. For many non-viral malignancies, therapeutically targeting the ubiquitin proteasome system (UPS) has been successful. Likewise, laboratory studies have demonstrated that inhibition of the UPS might provide a promising avenue for the treatment of KSHV-associated diseases. The largest class of E3 ubiquitin ligases are the cullin-RING ligases (CRLs) that are activated by an additional ubiquitin-like protein, NEDD8. We show that pharmacological inhibition of NEDDylation (using the small molecule inhibitor MLN4924) is cytotoxic to PEL cells by inhibiting NF-κB. We also show that CRL4B is a novel regulator of latency as its inhibition reactivated lytic gene expression. Furthermore, we uncovered a requirement for NEDDylation during the reactivation of the KSHV lytic cycle. Intriguingly, inhibition prevented viral DNA replication but not lytic cycle-associated gene expression, highlighting a novel mechanism that uncouples these two features of KSHV biology. Mechanistically, we show that MLN4924 treatment precluded the recruitment of the viral pre-replication complex to the origin of lytic DNA replication (OriLyt). These new findings have revealed novel mechanisms that regulate KSHV latency and reactivation. Moreover, they demonstrate that inhibition of NEDDylation represents a novel approach for the treatment of KSHV-associated malignancies.

  20. The Tat Inhibitor Didehydro-Cortistatin A Prevents HIV-1 Reactivation from Latency

    PubMed Central

    Mousseau, Guillaume; Kessing, Cari F.; Fromentin, Rémi; Trautmann, Lydie; Chomont, Nicolas

    2015-01-01

    ABSTRACT Antiretroviral therapy (ART) inhibits HIV-1 replication, but the virus persists in latently infected resting memory CD4+ T cells susceptible to viral reactivation. The virus-encoded early gene product Tat activates transcription of the viral genome and promotes exponential viral production. Here we show that the Tat inhibitor didehydro-cortistatin A (dCA), unlike other antiretrovirals, reduces residual levels of viral transcription in several models of HIV latency, breaks the Tat-mediated transcriptional feedback loop, and establishes a nearly permanent state of latency, which greatly diminishes the capacity for virus reactivation. Importantly, treatment with dCA induces inactivation of viral transcription even after its removal, suggesting that the HIV promoter is epigenetically repressed. Critically, dCA inhibits viral reactivation upon CD3/CD28 or prostratin stimulation of latently infected CD4+ T cells from HIV-infected subjects receiving suppressive ART. Our results suggest that inclusion of a Tat inhibitor in current ART regimens may contribute to a functional HIV-1 cure by reducing low-level viremia and preventing viral reactivation from latent reservoirs. PMID:26152583

  1. Alterations in auditory middle latency evoked potentials during meditation on a meaningful symbol--"Om".

    PubMed

    Telles, S; Nagarathna, R; Nagendra, H R; Desiraju, T

    1994-05-01

    Middle latency auditory evoked potentials were recorded in 18 male volunteers with ages between 25 and 45 years, 9 of whom had more than 10 years of experience in "Om" meditation (senior subjects), whereas the other 9 had no meditation experience (naive subjects). Both groups were studied in two types of sessions. (1) Before, during, and after 20 minutes of mentally repeating "one" (control session), and (2) a similar session, though with 20 minutes of mentally chanting "Om" (meditation session). The senior subjects showed a statistically significant (paired t-test) increase in the peak amplitude of Na wave (the maximum negative peak between 14 and 18 ms) during meditation, while the same subjects showed a statistically significant reduction in the Na wave peak amplitude during control sessions. In contrast, the naive subjects had a significant decrease in the Na wave peak amplitude during meditation sessions and a nonsignificant trend of reduction during control sessions, as well. This difference between senior and naive subjects was significant (two-way ANOVA). There were no significant changes in short latency wave V or Pa wave (the positive peak between the Na wave and 35 ms). The changes in the Na wave suggest that both mediation on a meaningful symbol, and mental repetition of a neutral word cause neural changes at the same level (possibly diencephalic). However, the change could be in opposite directions, and this difference could be correlated with differences in the duration of experience in meditation between senior and naive subjects.

  2. 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

  3. Theoretical bases of short-latency spike volleys in the peripheral vestibular system.

    PubMed

    Lewis, E R; Parnas, B R

    1994-01-01

    If a spike trigger zone exhibits the same sort of accommodation that has been found universally in peripheral axons and is an emergent property of the Hodgkin-Huxley model and other synthetic models of axonal membrane (1,2), then spike production will be favored by steep positive slopes of the waveform of the current into the trigger zone. Thus, large positive steps of axial current flowing nearly simultaneously into the trigger zones of many vestibular axons should produce a short-latency spike volley over those axons. Reasoning in terms of the small-signal (linear) transfer relationship for the cascade of components preceding the trigger zone, one can show that the ability to translate a stepwise change in head acceleration into a rapid increase in axial current into the trigger zone is more strongly dependent on the number of zeros at infinity from poles with long time constants (longer than those of the spike initiator) than it is on the values of the time constants themselves. Larger numbers of zeros at infinity make such translation increasingly difficult. Evidence from the work of Fernandez and Goldberg and others suggests (3-7) that the number is low. It may be lowest in jerk-sensitive units (8-9), in which case one would expect such units to make the greatest contributions to short-latency spike volleys.

  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. Psycholinguistic norms for action photographs in French and their relationships with spoken and written latencies.

    PubMed

    Bonin, Patrick; Boyer, Bruno; Méot, Alain; Fayol, Michel; Droit, Sylvie

    2004-02-01

    A set of 142 photographs of actions (taken from Fiez & Tranel, 1997) was standardized in French on name agreement, image agreement, conceptual familiarity, visual complexity, imageability, age of acquisition, and duration of the depicted actions. Objective word frequency measures were provided for the infinitive modal forms of the verbs and for the cumulative frequency of the verbal forms associated with the photographs. Statistics on the variables collected for action items were provided and compared with the statistics on the same variables collected for object items. The relationships between these variables were analyzed, and certain comparisons between the current database and other similar published databases of pictures of actions are reported. Spoken and written naming latencies were also collected for the photographs of actions, and multiple regression analyses revealed that name agreement, image agreement, and age of acquisition are the major determinants of action naming speed. Finally, certain analyses were performed to compare object and action naming times. The norms and the spoken and written naming latencies corresponding to the pictures are available on the Internet (http://www.psy.univ-bpclermont.fr/~pbonin/pbonin-eng.html) and should be of great use to researchers interested in the processing of actions. PMID:15190708

  6. SMAC: A soft MAC to reduce control overhead and latency in CDMA-based AMI networks

    DOE PAGES

    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

  7. Short-latency Disparity-Vergence Eye Movements in Humans: Sensitivity to Simulated Orthogonal Tropias

    PubMed Central

    Yang, D. -S.; FitzGibbon, E. J.; Miles, F. A.

    2008-01-01

    Small disparity stimuli applied to large random-dot patterns elicit machine-like vergence eye movements at short latency. We have examined the sensitivity of these eye movements to simulated orthogonal tropias in three normal subjects by recording 1) the effects of vertical disparities on the initial horizontal vergence responses elicited by 2° crossed and uncrossed (horizontal) disparity stimuli, and 2) the effects of horizontal disparities on the initial vertical vergence responses elicited by 1.2° left-hyper and 0.8° right-hyper (vertical) disparity stimuli. Initial vergence responses were strongest when the orthogonal disparity was close to zero, and decreased to zero as the orthogonal disparity increased to 3–5°, i.e., there was only a limited tolerance for orthogonal disparity. Tuning curves describing the dependence of the initial change in the vergence angle on the orthogonal disparity were well fit by a Gaussian function. An additional subject, who had an esotropia of ~10° in our experimental setup, showed almost no horizontal vergence responses but did show vertical vergence responses to vertical disparity stimuli at short latency (albeit slightly longer than normal) despite the fact that her esotropia resulted in uncrossed disparities that would have totally disabled the vertical vergence mechanism of a normal subject, cf., anomalous retinal correspondence. PMID:12536000

  8. 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.

  9. 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.

  10. FM signals produce robust paradoxical latency shifts in the bat's inferior colliculus.

    PubMed

    Wang, Xinming; Galazyuk, Alexander V; Feng, Albert S

    2007-01-01

    Previous studies in echolocating bats, Myotis lucifugus, showed that paradoxical latency shift (PLS) is essential for neural computation of target range and that a number of neurons in the inferior colliculus (IC) exhibit unit-specific PLS (characterized by longer first-spike latency at higher sound levels) in response to tone pulses at the unit's best frequency. The present study investigated whether or not frequency-modulated (FM) pulses that mimic the bat's echolocation sonar signals were equally effective in eliciting PLS. For two-thirds of PLS neurons in the IC, both FM and tone pulses could elicit PLS, but only FM pulses consistently produced unit-specific PLS. For the remainder of PLS neurons, only FM pulses effectively elicited PLS; these cells showed either no PLS or no response, to tone pulses. PLS neurons generally showed more pronounced PLS in response to narrow-band FM (each sweeping 20 kHz in 2 ms) pulse that contained the unit's best frequency. In addition, almost all PLS neurons showed duration-independent PLS to FM pulses, but the same units exhibited duration-dependent PLS to tone pulses. Taken together, when compared to tone pulses, FM stimuli can provide more reliable estimates of target range.

  11. Effects of complex tonal stimuli on latency and amplitude of a late auditory evoked potential.

    PubMed

    Marx, Charles G; Goshorn, Edward L

    2016-05-01

    An optimum stimulus for evoking late auditory potentials is not well established. A typical stimulus for clinical purposes is either a brief speech signal or a brief single-frequency tone. Based on previous research, it is reasonable to assume that a complex stimulus may enhance waveform morphology relative to a single-frequency stimulus. The current project investigated the effects on P1 latency and P1/N1 amplitude of a two-frequency complex stimulus with the second frequency having either a dissonant or harmonic relationship to a single-frequency reference stimulus. An 80 ms 1000 Hz tone with 10 ms rise/fall times served as the reference stimulus. The two-frequency complex stimuli consisted of the reference (1000 Hz) frequency mixed with a second frequency of equal duration and amplitude at 1100, 1250, 1500, 2000, or 4000 Hz, resulting in three dissonant and two harmonic stimuli. One dissonant stimulus (1000 + 1100 Hz) was designed to fall within the critical band of the reference stimulus. Stimuli were presented in a counterbalanced order to 20 normal hearing adult subjects. Two replicate runs were obtained for each stimulus condition. Results showed that the complex stimuli had no significant effect on P1 latency relative to the reference stimulus, but produced a significant increase in P1/N1 amplitude for the harmonic stimuli. PMID:27250127

  12. A Conserved Gammaherpesvirus Cyclin Specifically Bypasses Host p18INK4c To Promote Reactivation from Latency

    PubMed Central

    Williams, Lisa M.; Niemeyer, Brian F.; Franklin, David S.; Clambey, Eric T.

    2015-01-01

    ABSTRACT Gammaherpesviruses (GHVs) carry homologs of cellular genes, including those encoding a viral cyclin that promotes reactivation from latent infection. The viral cyclin has reduced sensitivity to host cyclin-dependent kinase inhibitors in vitro; however, the in vivo significance of this is unclear. Here, we tested the genetic requirement for the viral cyclin in mice that lack the host inhibitors p27Kip1 and p18INK4c, two cyclin-dependent kinase inhibitors known to be important in regulating B cell proliferation and differentiation. While the viral cyclin was essential for reactivation in wild-type mice, strikingly, it was dispensable for reactivation in mice lacking p27Kip1 and p18INK4c. Further analysis revealed that genetic ablation of only p18INK4c alleviated the requirement for the viral cyclin for reactivation from latency. p18INK4c regulated reactivation in a dose-dependent manner so that the viral cyclin was dispensable in p18INK4c heterozygous mice. Finally, treatment of wild-type cells with the cytokine BAFF, a known attenuator of p18INK4c function in B lymphocytes, was also able to bypass the requirement for the viral cyclin in reactivation. These data show that the gammaherpesvirus viral cyclin functions specifically to bypass the cyclin-dependent kinase inhibitor p18INK4c, revealing an unanticipated specificity between a GHV cyclin and a single cyclin-dependent kinase inhibitor. IMPORTANCE The gammaherpesviruses (GHVs) cause lifelong infection and can cause chronic inflammatory diseases and cancer, especially in immunosuppressed individuals. Many GHVs encode a conserved viral cyclin that is required for infection and disease. While a common property of the viral cyclins is that they resist inhibition by normal cellular mechanisms, it remains unclear how important it is that the GHVs resist this inhibition. We used a mouse GHV that either contained or lacked a viral cyclin to test whether the viral cyclin lost importance when these inhibitory

  13. Preterm prelabour rupture of membranes: effect of latency on neonatal and maternal outcomes.

    PubMed

    Frenette, Priscilla; Dodds, Linda; Armson, B Anthony; Jangaard, Krista

    2013-08-01

    Objectifs : Comparer les risques d’infection et les issues associées à la prématurité en fonction des périodes de latence chez les femmes qui présentent une rupture prématurée des membranes préterme (RPMP). Méthodes : Les femmes qui ont présenté une RPMP se manifestant entre 24+0 et 36+6 semaines de gestation ont été identifiées au sein d’une base de données périnatale en population générale provinciale, en Nouvelle-Écosse. Parmi les critères d’évaluation primaires, on trouvait des variables composites représentant la morbidité infectieuse maternelle et néonatale grave, et la morbidité néonatale liée à la prématurité. Une régression logistique a été utilisée pour quantifier la relation entre la période de latence (< 24 heures, de 24 heures à < 48 heures, de 48 heures à < 7 jours et ≥ 7 jours) et les issues maternelles et néonatales. Des analyses distinctes ont été menées pour ce qui est des groupes d’âge gestationnel allant de 24+0 à 33+6 semaines et de 34+0 à 36+6 semaines. Résultats : La cohorte comptait 4 329 femmes. Les variables composites représentant la morbidité infectieuse maternelle ou néonatale grave n’ont pas été associées de façon significative à la latence dans l’un ou l’autre des groupes d’âge gestationnel. Pour ce qui est de la RPMP se manifestant aux âges gestationnels situés entre 24+0 et 33+6 semaines de gestation, la probabilité d’une morbidité néonatale liée à la prématurité était considérablement amoindrie en présence de périodes de latence de 48 heures ou plus, par comparaison avec la latence < 24 heures. Pour ce qui est de la RPMP se manifestant aux âges gestationnels situés entre 34+0 et 36+6 semaines de gestation, la probabilité d’une morbidité liée à la prématurité en présence d’une période de latence se situant entre 48 heures et < 7 jours était amoindrie, par comparaison avec les latences < 24 heures (RC, 0

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

    PubMed

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

    2015-12-01

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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Assessing the effects of multiple infections and long latency in the dynamics of tuberculosis

    PubMed Central

    2010-01-01

    In order to achieve a better understanding of multiple infections and long latency in the dynamics of Mycobacterium tuberculosis infection, we analyze a simple model. Since backward bifurcation is well documented in the literature with respect to the model we are considering, our aim is to illustrate this behavior in terms of the range of variations of the model's parameters. We show that backward bifurcation disappears (and forward bifurcation occurs) if: (a) the latent period is shortened below a critical value; and (b) the rates of super-infection and re-infection are decreased. This result shows that among immunosuppressed individuals, super-infection and/or changes in the latent period could act to facilitate the onset of tuberculosis. When we decrease the incubation period below the critical value, we obtain the curve of the incidence of tuberculosis following forward bifurcation; however, this curve envelops that obtained from the backward bifurcation diagram. PMID:21059256

  20. 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.

  1. [Effect of the contraction of other muscle groups on muscle strength, latency period and endurance].

    PubMed

    Zimkin, N V; Hernandez, K A; Panov, V G

    1979-08-01

    The following investigation was undertaken in connection with Sechenov's idea on mutual influence of muscles performing different work. It deals with the influence on test muscle (TM) efficiency of other simultaneously working muscles (SWM). It was shown that tension of SWM or maintenance of complex postures exert a negative influence on the force and latency of the visual-motor reaction and the static effort endurance. The mechanism involved is external inhibition. After its extinction as a result of repeated combinations of both activities the degree of lowering of TM activity grows less and finally its improvement is observed as compared to data obtained in the absence of SWM contractions. It is suggested that when external inhibition is extinguished impulses arising in SWM reinforce and improve according to the law of dominant the functions of nervous centers regulating activities of the TM.

  2. Differences in perceptual latency estimated from judgments of temporal order, simultaneity and duration are inconsistent

    PubMed Central

    Linares, Daniel; Holcombe, Alex O.

    2014-01-01

    Differences in perceptual latency (ΔL) for two stimuli, such as an auditory and a visual stimulus, can be estimated from temporal order judgments (TOJ) and simultaneity judgments (SJ), but previous research has found evidence that ΔL estimated from these tasks do not coincide. Here, using an auditory and a visual stimulus we confirmed this and further show that ΔL as estimated from duration judgments also does not coincide with ΔL estimated from TOJ or SJ. These inconsistencies suggest that each judgment is subject to different processes that bias ΔL in different ways: TOJ might be affected by sensory interactions, a bias associated with the method of single stimuli and an order difficulty bias; SJ by sensory interactions and an asymmetrical criterion bias; duration judgments by an order duration bias. PMID:26034565

  3. All-optical hash code generation and verification for low latency communications.

    PubMed

    Paquot, Yvan; Schröder, Jochen; Pelusi, Mark D; Eggleton, Benjamin J

    2013-10-01

    We introduce an all-optical, format transparent hash code generator and a hash comparator for data packets verification with low latency at high baudrate. The device is reconfigurable and able to generate hash codes based on arbitrary functions and perform the comparison directly in the optical domain. Hash codes are calculated with custom interferometric circuits implemented with a Fourier domain optical processor. A novel nonlinear scheme featuring multiple four-wave mixing processes in a single waveguide is implemented for simultaneous phase and amplitude comparison of the hash codes before and after transmission. We demonstrate the technique with single polarisation BPSK and QPSK signals up to a data rate of 80 Gb/s.

  4. 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

  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. 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.

  7. 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.

  8. Reinstatement of short-latency responses after asymptotic Pavlovian conditioning training by the presentation of an extraneous stimulus.

    PubMed

    Vogel, Edgar H

    2012-01-01

    The purpose of this study was to examine whether the progressive disappearance of short-latency conditioned responses, or inhibition of delay, observed in Pavlovian conditioning with long inter-stimulus intervals, could be reverted by the presentation of a novel stimulus. In one experiment, two groups of rabbits received extensive training with a short (250 ms) or a long (1500 ms) tone that overlapped and terminated with a periorbital shock unconditioned stimulus. After training, the presentation of an extraneous stimulus prior to tone onset produced a reinstatement of short latency CRs in the group trained with the long CS, but did not affect CR latency in the group trained with the short CS. This finding is consistent with Pavlov's (1927) view that conditioning with long conditioned stimuli involves the acquisition of response tendencies in the early portion of the stimulus that are subsequently suppressed by the development of an inhibitory process.

  9. Persistence of viral DNA in the epithelial basal layer suggests a model for papillomavirus latency following immune regression

    PubMed Central

    Maglennon, Gareth Adam; McIntosh, Pauline; Doorbar, John

    2011-01-01

    Rabbit oral papillomavirus (ROPV) causes benign and spontaneously regressing oral lesions in rabbits, and is a useful model of disease associated with low-risk human papillomavirus types. Here we have adapted the ROPV system to study papillomavirus latency. Following lesion regression, ROPV DNA persists at the majority of regressed sites at levels substantially lower than those found in productive papillomas. Spliced viral transcripts were also detected. ROPV persistence in the absence of disease could be demonstrated for a year following infection and lesion-regression. This was not associated with completion of the virus life-cycle or new virion production, indicating that ROPV persists in a latent state. Using novel laser capture microdissection techniques, we could show that the site of latency is a subset of basal epithelial cells at sites of previous experimental infection. We hypothesize that these cells are epithelial stem cells and that reactivation of latency may be a source of recurrent disease. PMID:21492895

  10. Effect of Number of Graphic Symbols, Levels, and Listening Conditions on Symbol Identification and Latency in Persons with Aphasia.

    PubMed

    Petroi, Diana; Koul, Rajinder K; Corwin, Melinda

    2014-02-27

    This study investigated the ability of persons with aphasia to complete a series of experimental tasks involving single symbol and subject-verb-object sentence identification on a speech-generating device (SGD) in the presence/absence of competing stimuli. In all, 10 persons with Broca's aphasia and 10 persons in the control group were compared on accuracy and response latency of symbol identification across three listening conditions. Persons with aphasia identified fewer symbols accurately and had longer response latencies than persons in the control group. Number of symbols on the screen and location level had a significant effect on accuracy and latency for both groups. Persons with aphasia perceived tasks to be more difficult than persons in the control group. Results indicate that effective use of SGDs by persons with aphasia may depend on several message organization factors including location and number of symbols per screen. PMID:24575783

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. The latency information theory revolution, part III: knowledge-unaided power-centroid adaptive radar

    NASA Astrophysics Data System (ADS)

    Feria, Erlan H.

    2010-04-01

    Knowledge unaided power centroid (KUPC) adaptive radar and its latency information theory (LIT) roots are reviewed in this third paper of a three paper series. 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. While the first and third quadrants are concerned with the life time of physical signal movers and the life space of physical signal retainers, respectively, the second and fourth quadrants are about the intelligence space of mathematical signal sources and the processing time of mathematical signal processors, respectively. The four quadrants of LIT are assumed to be physically independent with their system design methodologies guided by dualities and performance bounds. Moreover, all the LIT quadrants are bridged by statistical physics, inclusive of a recently discovered time dual for thermodynamics that has been named lingerdynamics. The theoretical and practical relevance of LIT has already been demonstrated using real-world control, physics, biochemistry and the KUPC adaptive radar application that is reviewed in this paper. KUPC adaptive radar is a technique that falls within the fourth quadrant of LIT, and is thus a mathematical signal processing technique whose goal is the efficient detection of moving targets in real-world taxing environments. As is highlighted in this review KUPC adaptive radar is found to come relatively close to the signal to

  16. Long-latency TMS-evoked potentials during motor execution and inhibition.

    PubMed

    Yamanaka, Kentaro; Kadota, Hiroshi; Nozaki, Daichi

    2013-01-01

    Transcranial magnetic stimulation (TMS) has often been used in conjunction with electroencephalography (EEG), which is effective for the direct demonstration of cortical reactivity and corticocortical connectivity during cognitive tasks through the spatio-temporal pattern of long-latency TMS-evoked potentials (TEPs). However, it remains unclear what pattern is associated with the inhibition of a planned motor response. Therefore, we performed TMS-EEG recording during a go/stop task, in which participants were instructed to click a computer mouse with a right index finger when an indicator that was moving with a constant velocity reached a target (go trial) or to avoid the click when the indicator randomly stopped just before it reached the target (stop trial). Single-pulse TMS to the left (contralateral) or right (ipsilateral) motor cortex was applied 500 ms before or just at the target time. TEPs related to motor execution and inhibition were obtained by subtractions between averaged EEG waveforms with and without TMS. As a result, in TEPs induced by both contralateral and ipsilateral TMS, small oscillations were followed by a prominent negative deflection around the TMS site peaking at approximately 100 ms post-TMS (N100), and a less pronounced later positive component (LPC) over the broad areas that was centered at the midline-central site in both go and stop trials. However, compared to the pattern in go and stop trials with TMS at 500 ms before the target time, N100 and LPC were differently modulated in the go and stop trials with TMS just at the target time. The amplitudes of both N100 and LPC decreased in go trials, while the amplitude of LPC decreased and the latency of LPC was delayed in both go and stop trials. These results suggested that TMS-induced neuronal reactions in the motor cortex and subsequent their propagation to surrounding cortical areas might change functionally according to task demand when executing and inhibiting a motor response.

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

    PubMed

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

    2010-08-01

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

  18. Ovine herpesvirus-2-encoded microRNAs target virus genes involved in virus latency.

    PubMed

    Riaz, Aayesha; Dry, Inga; Levy, Claire S; Hopkins, John; Grey, Finn; Shaw, Darren J; Dalziel, Robert G

    2014-02-01

    Herpesviruses encode microRNAs (miRNAs) that target both virus and host genes; however, their role in herpesvirus biology is understood poorly. We identified previously eight miRNAs encoded by ovine herpesvirus-2 (OvHV-2), the causative agent of malignant catarrhal fever (MCF), and have now investigated the role of these miRNAs in regulating expression of OvHV-2 genes that play important roles in virus biology. ORF20 (cell cycle inhibition), ORF50 (reactivation) and ORF73 (latency maintenance) each contain predicted targets for several OvHV-2 miRNAs. Co-transfection of miRNA mimics with luciferase reporter constructs containing the predicted targets showed the 5' UTRs of ORF20 and ORF73 contain functional targets for ovhv-miR-2 and ovhv2-miR-8, respectively, and the 3' UTR of ORF50 contains a functional target for ovhv2-miR-5. Transfection of BJ1035 cells (an OvHV-2-infected bovine T-cell line) with the relevant miRNA mimic resulted in a significant decrease in ORF50 and a smaller but non-significant decrease in ORF20. However, we were unable to demonstrate a decrease in ORF73. MCF is a disease of dysregulated lymphocyte proliferation; miRNA inhibition of ORF20 expression may play a role in this aberrant lymphocyte proliferation. The proteins encoded by ORF50 and ORF73 play opposing roles in latency. It has been hypothesized that miRNA-induced inhibition of virus genes acts to ensure that fluctuations in virus mRNA levels do not result in reactivation under conditions that are unfavourable for viral replication and our data supported this hypothesis. PMID:24172907

  19. 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

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

    PubMed

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

    2015-11-01

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

  1. 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.

  2. 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.

  3. Latency-information theory and applications: Part II. On real-world knowledge aided radar

    NASA Astrophysics Data System (ADS)

    Feria, Erlan H.

    2008-04-01

    In this second of a multi-paper series latency-information theory (LIT), the integration of information theory with its time dual, i.e., latency theory, is successfully applied to DARPA's knowledge aided sensor signal processing expert reasoning (KASSPER) program. LIT encapsulates the concept of the time dual of a lossy source coder, i.e., a lossy processor coder. A lossy processor coder is a replacement for a signal-processor. This lossy processor coder is faster, simpler to implement, and yields a better performance than the original signal-processor when the processor input appears in a highly compressed-decompressed lossy fashion. In particular, a lossy clutter covariance processor (CCP) architecture is investigated that has successfully replaced KASSPER's originally advanced lossless CCP and enabled its SAR imagery prior knowledge to be highly compressed-decompressed. This result is illustrated with a typical SAR image which is compresseddecompressed by a factor 8,172. Using this image and under severely taxing environmental disturbances outstanding detections are achieved with the lossy CCP. Furthermore, this result is derived with a lossy CCP that is at least five orders of magnitude faster and significantly simpler to implement than the corresponding lossless CCP whose SINR detection performance is nevertheless unsatisfactory. As a final comment it is also observed that LIT illuminates biological system studies since it provides a lossy mechanism that explains how outstanding detections may be arrived at by biological systems that use highly lossy compressed prior knowledge, e.g., when a human expertly detects a face seen only once before even though that face cannot be accurately described prior to such new viewing.

  4. Short latency vestibular evoked potentials (VsEPs) to linear acceleration impulses in rats.

    PubMed

    Plotnik, M; Elidan, J; Mager, M; Sohmer, H

    1997-11-01

    In this study, short latency (t < 12.7 ms) vestibular evoked potentials (VsEPs) in response to linear acceleration impulses were recorded in 37 rats. A new technique (based on a solenoid) was used for generating linear force impulses that were delivered to the animal's head. The impulse had a maximal peak acceleration of 12 g. During the impulse, the displacement was 50 microns (at 4 g) and the rise time was 1.0 ms. A stimulation rate of 2/s was usually used. The VsEPs (averaged responses to 128 stimulations, digital filter: 300-1500 Hz) were recorded with electrodes on pinna and vertex, and were composed of 4-6 clear waves with mean amplitudes (for a 4 g stimulus) of 1-5 microV. The VsEPs were resistant to white noise masking, and were significantly suppressed (P < 0.05) following bilateral application of a saturated KCl solution to the inner ear, showing that contributions of the auditory and somatosensory systems are negligible. The latency of the response decreased as a power law function of stimulus magnitude, and the amplitude of the first wave increased as a sigmoid function of stimulus magnitude. VsEP responses were still present at the lowest intensities attainable (0.06-0.4 g) and reached saturation at 9 g. The amplitude of the later components was reduced when stimulus rate was elevated to 20/s. These results suggest that VsEPs in response to linear accelerations are similar in their nature to VsEPs in response to angular acceleration impulses that were previously recorded. These VsEPs to linear accelerations are most likely initiated in the otolith organs. PMID:9402894

  5. Objective markers for sleep propensity: comparison between the Multiple Sleep Latency Test and the Vigilance Algorithm Leipzig.

    PubMed

    Olbrich, Sebastian; Fischer, Marie M; Sander, Christian; Hegerl, Ulrich; Wirtz, Hubert; Bosse-Henck, Andrea

    2015-08-01

    The regulation of wakefulness is important for high-order organisms. Its dysregulation is involved in the pathomechanism of several psychiatric disorders. Thus, a tool for its objective but little time-consuming assessment would be of importance. The Vigilance Algorithm Leipzig allows the objective measurement of sleep propensity, based on a single resting state electroencephalogram. To compare the Vigilance Algorithm Leipzig with the standard for objective assessment of excessive daytime sleepiness, a four-trial Multiple Sleep Latency Test in 25 healthy subjects was conducted. Between the first two trials, a 15-min, 25-channel resting electroencephalogram was recorded, and Vigilance Algorithm Leipzig was used to classify the sleep propensity (i.e., type of vigilance regulation) of each subject. The results of both methods showed significant correlations with the Epworth Sleepiness Scale (ρ = -0.70; ρ = 0.45, respectively) and correlated with each other (ρ = -0.54). Subjects with a stable electroencephalogram-vigilance regulation yielded significant increased sleep latencies compared with an unstable regulation (multiple sleep latency 898.5 s versus 549.9 s; P = 0.03). Further, Vigilance Algorithm Leipzig classifications allowed the identification of subjects with average sleep latencies <6 min with a sensitivity of 100% and a specificity of 77%. Thus, Vigilance Algorithm Leipzig provides similar information on wakefulness regulation in comparison to the much more cost- and time-consuming Multiple Sleep Latency Test. Due to its high sensitivity and specificity for large sleep propensity, Vigilance Algorithm Leipzig could be an effective and reliable alternative to the Multiple Sleep Latency Test, for example for screening purposes in large cohorts, where objective information about wakefulness regulation is needed.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. A low-latency, low-overhead encoder for data transmission in the ATLAS Liquid Argon Calorimeter trigger upgrade

    NASA Astrophysics Data System (ADS)

    Xiao, Le; Li, Xiaoting; Gong, Datao; Chen, Jinghong; Deng, Binwei; Fan, Qingjun; Feng, Yulang; Guo, Di; He, Huiqin; Hou, Suen; Huang, Guangming; Liu, Chonghan; Liu, Tiankuan; Sun, Xiangming; Tang, Yuxuan; Teng, Ping-Kun; Vosooghi, Bozorgmehr; Xiang, Annie C.; Ye, Jingbo; You, Yang; Zuo, Zhiheng

    2016-09-01

    In this paper, we present the design and test results of an encoder integrated circuit for the ATLAS Liquid Argon Calorimeter trigger upgrade. The encoder implements a low-latency and low-overhead line code called LOCic. The encoder operates at 320 MHz with a latency of no greater than 21 ns. The overhead of the encoder is 14.3%. The encoder is an important block of the transmitter ASIC LOCx2, which is prototyped with a commercial 0.25 μm Silicon-on-Sapphire CMOS technology and packaged in a 100-pin QFN package.

  11. [Investigation of maximal motor nerve conductivity and distal latency before and after galvanic cell bath (author's transl)].

    PubMed

    Trnavsky, G

    1982-04-30

    Measurements about maximal motor nerve conductivity of ulnaris and medianus were carried out before and after constant galvanisation from neck to hand. Significant results of conductivity, distal latency and amplitude of summation potential could not be registered neither by plus nor by minus pole at the hand.

  12. 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

  13. Anticipation of direction and time of perturbation modulates the onset latency of trunk muscle responses during sitting perturbations.

    PubMed

    Milosevic, Matija; Shinya, Masahiro; Masani, Kei; Patel, Kramay; McConville, Kristiina M V; Nakazawa, Kimitaka; Popovic, Milos R

    2016-02-01

    Trunk muscles are responsible for maintaining trunk stability during sitting. However, the effects of anticipation of perturbation on trunk muscle responses are not well understood. The objectives of this study were to identify the responses of trunk muscles to sudden support surface translations and quantify the effects of anticipation of direction and time of perturbation on the trunk neuromuscular responses. Twelve able-bodied individuals participated in the study. Participants were seated on a kneeling chair and support surface translations were applied in the forward and backward directions with and without direction and time of perturbation cues. The trunk started moving on average approximately 40ms after the perturbation. During unanticipated perturbations, average latencies of the trunk muscle contractions were in the range between 103.4 and 117.4ms. When participants anticipated the perturbations, trunk muscle latencies were reduced by 16.8±10.0ms and the time it took the trunk to reach maximum velocity was also reduced, suggesting a biomechanical advantage caused by faster muscle responses. These results suggested that trunk muscles have medium latency responses and use reflexive mechanisms. Moreover, anticipation of perturbation decreased trunk muscles latencies, suggesting that the central nervous system modulated readiness of the trunk based on anticipatory information. PMID:26746011

  14. 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.

  15. 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…

  16. In vitro system using human neurons demonstrates that varicella-zoster vaccine virus is impaired for reactivation, but not latency

    PubMed Central

    Sadaoka, Tomohiko; Depledge, Daniel P.; Rajbhandari, Labchan; Venkatesan, Arun; Breuer, Judith; Cohen, Jeffrey I.

    2016-01-01

    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

  17. 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.

  18. Auditory brainstem responses to a chirp stimulus designed from derived-band latencies in normal-hearing subjects

    PubMed Central

    Elberling, Claus; Don, Manuel

    2008-01-01

    In an attempt to compensate for the temporal dispersion in the human cochlea, a chirp has previously been designed from estimates of the cochlear delay based on derived-band auditory brain-stem response (ABR) latencies [Elberling et al. (2007). “Auditory steady-state responses to chirp stimuli based on cochlear traveling wave delay,” J. Acoust. Soc. Am. 122, 2772–2785]. To evaluate intersubject variability and level effects of such delay estimates, a large dataset is analyzed from 81 normal-hearing adults (fixed click level) and from a subset thereof (different click levels). At a fixed click level, the latency difference between 5700 and 710 Hz ranges from about 2.0 to 5.0 ms, but over a range of 60 dB, the mean relative delay is almost constant. Modeling experiments demonstrate that the derived-band latencies depend on the cochlear filter buildup time and on the unit response waveform. Because these quantities are partly unknown, the relationship between the derived-band latencies and the basilar membrane group delay cannot be specified. A chirp based on the above delay estimates is used to record ABRs in ten normal-hearing adults (20 ears). For levels below 60 dB nHL, the gain in amplitude of chirp-ABRs to click-ABRs approaches 2, and the effectiveness of chirp-ABRs compares favorably to Stacked-ABRs obtained under similar conditions. PMID:19045789

  19. Habituation behavior of the medium-latency reflex over the anterior tibial muscle after electrical stimulation of the sural nerve.

    PubMed

    Alaid, S; Hanke, D; Kornhuber, M

    2014-11-01

    Over human leg muscles, three motor responses (MR) can commonly be elicited, namely short-latency reflex (SLR), medium-latency reflex (MLR), and long-latency reflex (LLR). The MLR is less well understood than SLR and LLR. As the response to subsequent stimuli may be used to characterize central influences of an MR, we were interested, whether the MLR differs from SLR and LLR with respect to its habituation and facilitation behavior. MR were examined over the anterior tibial (TA) muscle at different contraction levels after electrical single or train stimuli (time intervals of 3 ms) over the ipsilateral sural nerve. Furthermore, MR were selectively averaged after each of four subsequent stimuli (1Hz, 0.4 Hz, trains-of-3). After single stimuli, the peak latency values were 46.2±2.3 ms, 88.0±5.8 ms (MLR), and 131.7±22.2 ms (LLR). All three MR gained similarly strong and significantly in amplitude when up to 10 kg of weight was loaded compared with no weight load. After train stimuli, the LLR but not SLR and MLR gained significantly in amplitude as compared with single stimuli. Different to SLR and LLR, the MLR showed significant habituation behavior at a stimulus repetition rate of 1Hz but not of 0.4 Hz. Thus, inhibitory interneurons seem to be involved in the MLR pathway.

  20. Temporal dynamics of choice behavior in rats and humans: an examination of pre- and post-choice latencies.

    PubMed

    Fam, Justine; Westbrook, Fred; Arabzadeh, Ehsan

    2016-02-10

    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.

  1. 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

  2. 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

  3. 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…

  4. 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…

  5. Slower Visuomotor Corrections with Unchanged Latency are Consistent with Optimal Adaptation to Increased Endogenous Noise in the Elderly

    PubMed Central

    Sherback, Michael; Valero-Cuevas, Francisco J.; D'Andrea, Raffaello

    2010-01-01

    We analyzed age-related changes in motor response in a visuomotor compensatory tracking task. Subjects used a manipulandum to attempt to keep a displayed cursor at the center of a screen despite random perturbations to its location. Cross-correlation analysis of the perturbation and the subject response showed no age-related increase in latency until the onset of response to the perturbation, but substantial slowing of the response itself. Results are consistent with age-related deterioration in the ratio of signal to noise in visuomotor response. The task is such that it is tractable to use Bayesian and quadratic optimality assumptions to construct a model for behavior. This model assumes that behavior resembles an optimal controller subject to noise, and parametrizes response in terms of latency, willingness to expend effort, noise intensity, and noise bandwidth. The model is consistent with the data for all young (n = 12, age 20–30) and most elderly (n = 12, age 65–92) subjects. The model reproduces the latency result from the cross-correlation method. When presented with increased noise, the computational model reproduces the experimentally observed age-related slowing and the observed lack of increased latency. The model provides a precise way to quantitatively formulate the long-standing hypothesis that age-related slowing is an adaptation to increased noise. PMID:20300648

  6. Anticipation of direction and time of perturbation modulates the onset latency of trunk muscle responses during sitting perturbations.

    PubMed

    Milosevic, Matija; Shinya, Masahiro; Masani, Kei; Patel, Kramay; McConville, Kristiina M V; Nakazawa, Kimitaka; Popovic, Milos R

    2016-02-01

    Trunk muscles are responsible for maintaining trunk stability during sitting. However, the effects of anticipation of perturbation on trunk muscle responses are not well understood. The objectives of this study were to identify the responses of trunk muscles to sudden support surface translations and quantify the effects of anticipation of direction and time of perturbation on the trunk neuromuscular responses. Twelve able-bodied individuals participated in the study. Participants were seated on a kneeling chair and support surface translations were applied in the forward and backward directions with and without direction and time of perturbation cues. The trunk started moving on average approximately 40ms after the perturbation. During unanticipated perturbations, average latencies of the trunk muscle contractions were in the range between 103.4 and 117.4ms. When participants anticipated the perturbations, trunk muscle latencies were reduced by 16.8±10.0ms and the time it took the trunk to reach maximum velocity was also reduced, suggesting a biomechanical advantage caused by faster muscle responses. These results suggested that trunk muscles have medium latency responses and use reflexive mechanisms. Moreover, anticipation of perturbation decreased trunk muscles latencies, suggesting that the central nervous system modulated readiness of the trunk based on anticipatory information.

  7. HIV Integration Site Analysis of Cellular Models of HIV Latency with a Probe-Enriched Next-Generation Sequencing Assay

    PubMed Central

    Sunshine, Sara; Kirchner, Rory; Amr, Sami S.; Mansur, Leandra; Shakhbatyan, Rimma; Kim, Michelle; Bosque, Alberto; Siliciano, Robert F.; Planelles, Vicente; Hofmann, Oliver; Ho Sui, Shannan

    2016-01-01

    ABSTRACT Antiretroviral therapy (ART) is successful in the suppression of HIV but cannot target and eradicate the latent proviral reservoir. The location of retroviral integration into the human genome is thought to play a role in the clonal expansion of infected cells and HIV persistence. We developed a high-throughput targeted sequence capture assay that uses a pool of HIV-specific probes to enrich Illumina libraries prior to deep sequencing. Using an expanded clonal population of ACH-2 cells, we demonstrate that this sequence capture assay has an extremely low false-positive rate. This assay assessed four cellular models commonly used to study HIV latency and latency-reversing agents: ACH-2 cells, J-Lat cells, the Bcl-2-transduced primary CD4+ model, and the cultured TCM (central memory) CD4+ model. HIV integration site characteristics and genes were compared between these cellular models and to previously reported patient data sets. Across these cellular models, there were significant differences in integration site characteristics, including orientation relative to that of the host gene, the proportion of clonally expanded sites, and the proportion located within genic regions and exons. Despite a greater diversity of minority integration sites than expected in ACH-2 cells, their integration site characteristics consistently differed from those of the other models and from the patient samples. Gene ontology analysis of highly represented genes from the patient samples found little overlap with HIV-containing genes from the cell lines. These findings show that integration site differences exist among the commonly used cellular models of HIV latency and in comparison to integration sites found in patient samples. IMPORTANCE Despite the success of ART, currently there is no successful therapy to eradicate integrated proviruses. Cellular models of HIV latency are used to test the efficacy of latency-reversing agents, but it is unclear how well these models reflect

  8. P300 component identification in auditory oddball and novel paradigms using source analysis techniques: reduced latency variability in the elderly.

    PubMed

    Maurits, Natasha M; Elting, Jan Willem; Jager, Dick K R B; van der Hoeven, Johannes H; Brouwer, Wiebo H

    2005-06-01

    P300 latency variability in normal subjects limits its diagnostic applicability as a test for cognitive function. One of the causes of variation is the overlap in P300 (P3A and P3B) components resulting in inaccurate latency determination. Recently, we have shown that identification of P3A and P3B components using source analysis techniques significantly reduces P300 latency variability in healthy younger subjects. Here, we included a novel paradigm to enhance sensitivity and investigated the efficiency of the source analysis technique in reducing the P300 latency variability in healthy older subjects. Data were recorded with a 128-channel EEG system in 28 healthy subjects (aged 53-82 years, 12 males). We used a standard two-tone and a novel three-tone auditory oddball paradigm and an established source analysis technique, and compared the latencies to those obtained with conventional P300 analysis. The source analysis method identified both P3A and P3B components in a substantially larger percentage of subjects (93% versus 32%) than the conventional method. Both for the standard and novel paradigm, the source analysis method yielded a later mean P3B latency (361.4 versus 344.2 milliseconds, P = 0.017, and 374.4 milliseconds versus 354.3 milliseconds, P = 0.014, respectively) with a smaller standard deviation (15.8 versus 26.2 milliseconds, P = 0.013, and 18.9 versus 30.0 milliseconds, P = 0.052, borderline significant, respectively) than the conventional P300 method, for subjects aged 50 to 70 years. When applying the source analysis technique, as in young healthy subjects, a considerable reduction of P300 latency variability was thus found in healthy older subjects aged 50 to 70 years for both paradigms. This may have important consequences for applications of clinical event-related potential research in the early diagnosis of dementia, because the first signs of this disease are mostly observed in this age category.

  9. 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

  10. 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

  11. 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

  12. Solvation-Dependent Latency of Photoacid Dissociation and Transient IR Signatures of Protonation Dynamics.

    PubMed

    Bekçioğlu, Gül; Hoffmann, Felix; Sebastiani, Daniel

    2015-09-01

    We elucidate the characteristic proton pathways and the transient infrared signatures of intermediate complexes during the first picoseconds of photoinduced protonation dynamics of a photoacid (N-methyl-6-hydroxyquinolinium) in aqueous solution from first-principles molecular dynamics simulations. Our results indicate that the typical latency time between photoexcitation and proton dissociation ranges from 1 ps to longer time time scales (∼100 ps). The rate-limiting step for the actual dissociation of the proton into the solvent is the solvation structure of the first accepting water molecule. The nature of the proton pathway in water (stepwise or concerted) is not unique but determined by the coordination number of the accepting water molecules along the hydrogen bond chain. We find a characteristic uncommon infrared mode at ∼1300 cm(-1) of the transient photobase-Eigen cation complex immediately after photodissociation that we predict to be observable experimentally in time-resolved IR spectroscopy. A broad continuous absorption band from 1500 to 2000 cm(-1) arises from the acidic proton imminently before dissociation.

  13. 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

  14. Analysis of koi herpesvirus latency in wild common carp and ornamental koi in Oregon, USA.

    PubMed

    Xu, Jia-Rong; Bently, Jennifer; Beck, Linda; Reed, Aimee; Miller-Morgan, Tim; Heidel, Jerry R; Kent, Michael L; Rockey, Daniel D; Jin, Ling

    2013-02-01

    Koi herpesvirus (KHV) infection is associated with high mortalities in both common carp (Cyprinus carpio carpio) and koi carp (Cyprinus carpio koi) worldwide. Although acute infection has been reported in both domestic and wild common carp, the status of KHV latent infection is largely unknown in wild common carp. To investigate whether KHV latency is present in wild common carp, the distribution of KHV latent infection was investigated in two geographically distinct populations of wild common carp in Oregon, as well as in koi from an Oregon-based commercial supplier. Latent KHV infection was demonstrated in white blood cells from each of these populations. Although KHV isolated from acute infections has two distinct genetic groups, Asian and European, KHV detected in wild carp has not been genetically characterized. DNA sequences from ORF 25 to 26 that are unique between Asian and European were investigated in this study. KHV from captive koi and some wild common carp were found to have ORF-25-26 sequences similar to KHV-J (Asian), while the majority of KHV DNA detected in wild common carp has similarity to KHV-U/-I (European). In addition, DNA sequences from IL-10, and TNFR were sequenced and compared with no differences found, which suggests immune suppressor genes of KHV are conserved between KHV in wild common carp and koi, and is consistent with KHV-U, -I, -J.

  15. 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.

  16. Solvation-Dependent Latency of Photoacid Dissociation and Transient IR Signatures of Protonation Dynamics.

    PubMed

    Bekçioğlu, Gül; Hoffmann, Felix; Sebastiani, Daniel

    2015-09-01

    We elucidate the characteristic proton pathways and the transient infrared signatures of intermediate complexes during the first picoseconds of photoinduced protonation dynamics of a photoacid (N-methyl-6-hydroxyquinolinium) in aqueous solution from first-principles molecular dynamics simulations. Our results indicate that the typical latency time between photoexcitation and proton dissociation ranges from 1 ps to longer time time scales (∼100 ps). The rate-limiting step for the actual dissociation of the proton into the solvent is the solvation structure of the first accepting water molecule. The nature of the proton pathway in water (stepwise or concerted) is not unique but determined by the coordination number of the accepting water molecules along the hydrogen bond chain. We find a characteristic uncommon infrared mode at ∼1300 cm(-1) of the transient photobase-Eigen cation complex immediately after photodissociation that we predict to be observable experimentally in time-resolved IR spectroscopy. A broad continuous absorption band from 1500 to 2000 cm(-1) arises from the acidic proton imminently before dissociation. PMID:26280280

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. HIV Latency-Reversing Agents Have Diverse Effects on Natural Killer Cell Function

    PubMed Central

    Garrido, Carolina; Spivak, Adam M.; Soriano-Sarabia, Natalia; Checkley, Mary Ann; Barker, Edward; Karn, Jonathan; Planelles, Vicente; Margolis, David M.

    2016-01-01

    In an effort to clear persistent HIV infection and achieve a durable therapy-free remission of HIV disease, extensive pre-clinical studies and early pilot clinical trials are underway to develop and test agents that can reverse latent HIV infection and present viral antigen to the immune system for clearance. It is, therefore, critical to understand the impact of latency-reversing agents (LRAs) on the function of immune effectors needed to clear infected cells. We assessed the impact of LRAs on the function of natural killer (NK) cells, the main effector cells of the innate immune system. We studied the effects of three histone deacetylase inhibitors [SAHA or vorinostat (VOR), romidepsin, and panobinostat (PNB)] and two protein kinase C agonists [prostratin (PROST) and ingenol] on the antiviral activity, cytotoxicity, cytokine secretion, phenotype, and viability of primary NK cells. We found that ex vivo exposure to VOR had minimal impact on all parameters assessed, while PNB caused a decrease in NK cell viability, antiviral activity, and cytotoxicity. PROST caused non-specific NK cell activation and, interestingly, improved antiviral activity. Overall, we found that LRAs can alter the function and fate of NK cells, and these effects must be carefully considered as strategies are developed to clear persistent HIV infection. PMID:27708642

  2. Lyme arthritis in a 12-year-old patient after a latency period of 5 years.

    PubMed

    Albert, S; Schulze, J; Riegel, H; Brade, V

    1999-01-01

    Lyme arthritis (LA) may be confused with other rheumatic diseases, particularly in the absence of a history of erythema migrans (EM). We report the case of a 12-year-old patient who developed a large effusion of the right knee joint. The titer for antinuclear antibodies was 1:80 and the test for rheumatoid factor was negative. Investigations for antibody response to Borrelia burgdorferi demonstrated remarkable elevation of IgG antibody and no specific IgM response. These results were confirmed by immunoblotting reactivity with the bands p83/100, p58, p43, p41, p39, OspA, p30, OspC, p21, and p17. We subsequently learned that the child had suffered a tick bite followed by an EM 5 years earlier and had been treated with trimethoprim/sulfamethoxazole at that time. The patient now was given intravenous ceftriaxone, 2 g daily for 14 days. In the absence of clinical improvement 3 weeks later a knee joint aspiration was performed which resulted in a positive polymerase chain reaction (PCR) test for B. burgdorferi DNA (OspA) in the synovial fluid. The patient fully recovered 2 months later without further treatment. The case indicates that the latency period between EM and onset of LA may last up to 5 years. In addition to serologic test methods, analysis of synovial fluid using PCR may be decisive for making the final diagnosis of LA.

  3. Short-latency afferent inhibition determined by the sensory afferent volley.

    PubMed

    Bailey, Aaron Z; Asmussen, Michael J; Nelson, Aimee J

    2016-08-01

    Short-latency afferent inhibition (SAI) is characterized by the suppression of the transcranial magnetic stimulation motor evoked potential (MEP) by the cortical arrival of a somatosensory afferent volley. It remains unknown whether the magnitude of SAI reflects changes in the sensory afferent volley, similar to that observed for somatosensory evoked potentials (SEPs). The present study investigated stimulus-response relationships between sensory nerve action potentials (SNAPs), SAI, and SEPs and their interrelatedness. Experiment 1 (n = 23, age 23 ± 1.5 yr) investigated the stimulus-response profile for SEPs and SAI in the flexor carpi radialis muscle after stimulation of the mixed median nerve at the wrist using ∼25%, 50%, 75%, and 100% of the maximum SNAP and at 1.2× and 2.4× motor threshold (the latter equated to 100% of the maximum SNAP). Experiment 2 (n = 20, age 23.1 ± 2 yr) probed SEPs and SAI stimulus-response relationships after stimulation of the cutaneous digital nerve at ∼25%, 50%, 75%, and 100% of the maximum SNAP recorded at the elbow. Results indicate that, for both nerve types, SAI magnitude is dependent on the volume of the sensory afferent volley and ceases to increase once all afferent fibers within the nerve are recruited. Furthermore, for both nerve types, the magnitudes of SAI and SEPs are related such that an increase in excitation within somatosensory cortex is associated with an increase in the magnitude of afferent-induced MEP inhibition. PMID:27226451

  4. 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

  5. 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.

  6. Analysis of the transcriptional promoter which regulates the latency-related transcript of bovine herpesvirus 1.

    PubMed

    Jones, C; Delhon, G; Bratanich, A; Kutish, G; Rock, D

    1990-03-01

    As a transcriptional promoter in primary cultures of sensory ganglionic neurons, DNA sequences near the 5' terminus of the latency-related (LR) gene of bovine herpesvirus 1 were at least 10 times more efficient than the simian virus 40 early promoter-enhancer. In contrast, as a promoter in bovine, rodent, or monkey cells, the LR promoter was approximately six times less efficient than the simian virus 40 early promoter-enhancer. The LR promoter had strict orientation preferences in neurons and all other mammalian cell lines tested. Removal of a 146-base-pair XhoI fragment from the LR promoter resulted in stimulation of LR promoter activity in bovine cells but not rabbit neurons, monkey fibroblasts, or rodent cells. LR promoter activity in bovine cells is stimulated by bovine herpesvirus 1 lytic infection, suggesting that viral gene products or virus-induced factors positively regulate the expression of the LR gene. A synthetic glucocorticoid, dexamethasone, repressed LR promoter activity in bovine cells. These results imply that a variety of factors can influence the expression of the LR gene during latent infections of neurons as well as during the lytic infection cycle.

  7. 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

  8. The cellular steady-state of H2O2: latency concepts and gradients.

    PubMed

    Marinho, H Susana; Cyrne, Luísa; Cadenas, Enrique; Antunes, Fernando

    2013-01-01

    Hydrogen peroxide (H2O2) is able to diffuse across biomembranes but, when cells are exposed to external H2O2, the fast consumption of H2O2 inside the cells due to H2O2-removing enzymes provides the driving force for setting up a H2O2 gradient across the plasma membrane. Knowing this gradient is fundamental to standardize studies with H2O2 as for the same extracellular H2O2 concentration cells with different H2O2 gradients may be exposed to different intracellular H2O2 concentrations. Here, we present the kinetic background behind the establishment of the H2O2 gradient and show how the gradient can be determined experimentally using the principle of enzyme latency. Furthermore, we discuss some of the caveats that may arise when determining the H2O2 gradient. Finally, we describe detailed protocols for the experimental determination of the H2O2 gradient across the plasma membrane in Saccharomyces cerevisiae cells and in mammalian cell lines. PMID:23830623

  9. 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.

  10. 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

  11. 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.

  12. Environmental enrichment improves response strength, threshold, selectivity, and latency of auditory cortex neurons.

    PubMed

    Engineer, Navzer D; Percaccio, Cherie R; Pandya, Pritesh K; Moucha, Raluca; Rathbun, Daniel L; Kilgard, Michael P

    2004-07-01

    Over the last 50 yr, environmental enrichment has been shown to generate more than a dozen changes in brain anatomy. The consequences of these physical changes on information processing have not been well studied. In this study, rats were housed in enriched or standard conditions either prior to or after reaching sexual maturity. Evoked potentials from awake rats and extracellular recordings from anesthetized rats were used to document responses of auditory cortex neurons. This report details several significant, new findings about the influence of housing conditions on the responses of rat auditory cortex neurons. First, enrichment dramatically increases the strength of auditory cortex responses. Tone-evoked potentials of enriched rats, for example, were more than twice the amplitude of rats raised in standard laboratory conditions. Second, cortical responses of both young and adult animals benefit from exposure to an enriched environment and are degraded by exposure to an impoverished environment. Third, housing condition resulted in rapid remodeling of cortical responses in <2 wk. Fourth, recordings made under anesthesia indicate that enrichment increases the number of neurons activated by any sound. This finding shows that the evoked potential plasticity documented in awake rats was not due to differences in behavioral state. Finally, enrichment made primary auditory cortex (A1) neurons more sensitive to quiet sounds, more selective for tone frequency, and altered their response latencies. These experiments provide the first evidence of physiologic changes in auditory cortex processing resulting from generalized environmental enrichment.

  13. 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

  14. Updating and validating a new framework for restoring and analyzing latency-variable ERP components from single trials with residue iteration decomposition (RIDE).

    PubMed

    Ouyang, Guang; Sommer, Werner; Zhou, Changsong

    2015-06-01

    Trial-to-trial latency variability pervades cognitive EEG responses and may mix and smear ERP components but is usually ignored in conventional ERP averaging. Existing attempts to decompose temporally overlapping and latency-variable ERP components show major limitations. Here, we propose a theoretical framework and model of ERPs consisting of temporally overlapping components locked to different external events or varying in latency from trial to trial. Based on this model, a new ERP decomposition and reconstruction method was developed: residue iteration decomposition (RIDE). Here, we describe an update of the method and compare it to other decomposition methods in simulated and real datasets. The updated RIDE method solves the divergence problem inherent to previous latency-based decomposition methods. By implementing the model of ERPs as consisting of time-variable and invariable single-trial component clusters, RIDE obtains latency-corrected ERP waveforms and topographies of the components, and yields dynamic information about single trials.

  15. 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

  16. 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

  17. Fetal MEG evoked response latency from beamformer with random field theory

    PubMed Central

    McCubbin, J.; Vrba, J.; Murphy, P.; Temple, J.; Eswaran, H.; Lowery, C.L.; Preissl, H.

    2009-01-01

    Analysis of fetal magnetoencephalographic brain recordings is restricted by low signal to noise ratio (SNR) and non-stationarity of the sources. Beamformer techniques have been applied to improve SNR of fetal evoked responses. However, until now the effect of non-stationarity was not taken into account in detail, because the detection of evoked responses is in most cases determined by averaging a large number of trials. We applied a windowing technique to improve the stationarity of the data by using short time segments recorded during a flash evoked study. In addition, we implemented a random field theory approach for more stringent control of false positives in the statistical parametric map of the search volume for the beamformer. The search volume was based on detailed individual fetal/maternal biometrics from ultrasound scans and fetal heart localization. Average power over a sliding window within the averaged evoked response against a randomized average background power was used as the test z – statistic. The significance threshold was set at 10% over all members of a contiguous cluster of voxels. There was at least one significant response for 62% of fetal and 95% of newborn recordings with gestational age (GA) between 28 and 45 weeks from 29 subjects. We found that the latency was either substantially unchanged or decreased with increasing GA for most subjects, with a nominal rate of about −11 ms/week. These findings support the anticipated neurophysiological development, provide validation for the beamformer model search as a methodology, and may lead to a clinical test for fetal cognitive development. PMID:19686855

  18. Differential effects of theta/beta and SMR neurofeedback in ADHD on sleep onset latency.

    PubMed

    Arns, Martijn; Feddema, Ilse; Kenemans, J Leon

    2014-01-01

    Recent studies suggest a role for sleep and sleep problems in the etiology of attention deficit hyperactivity disorder (ADHD) and a recent model about the working mechanism of sensori-motor rhythm (SMR) neurofeedback, proposed that this intervention normalizes sleep and thus improves ADHD symptoms such as inattention and hyperactivity/impulsivity. In this study we compared adult ADHD patients (N = 19) to a control group (N = 28) and investigated if differences existed in sleep parameters such as Sleep Onset Latency (SOL), Sleep Duration (DUR) and overall reported sleep problems (PSQI) and if there is an association between sleep-parameters and ADHD symptoms. Secondly, in 37 ADHD patients we investigated the effects of SMR and Theta/Beta (TBR) neurofeedback on ADHD symptoms and sleep parameters and if these sleep parameters may mediate treatment outcome to SMR and TBR neurofeedback. In this study we found a clear continuous relationship between self-reported sleep problems (PSQI) and inattention in adults with- and without-ADHD. TBR neurofeedback resulted in a small reduction of SOL, this change in SOL did not correlate with the change in ADHD symptoms and the reduction in SOL only happened in the last half of treatment, suggesting this is an effect of symptom improvement not specifically related to TBR neurofeedback. SMR neurofeedback specifically reduced the SOL and PSQI score, and the change in SOL and change in PSQI correlated strongly with the change in inattention, and the reduction in SOL was achieved in the first half of treatment, suggesting the reduction in SOL mediated treatment response to SMR neurofeedback. Clinically, TBR and SMR neurofeedback had similar effects on symptom reduction in ADHD (inattention and hyperactivity/impulsivity). These results suggest differential effects and different working mechanisms for TBR and SMR neurofeedback in the treatment of ADHD. PMID:25566034

  19. In vitro model for lytic replication, latency, and transformation of an oncogenic alphaherpesvirus.

    PubMed

    Schermuly, Julia; Greco, Annachiara; Härtle, Sonja; Osterrieder, Nikolaus; Kaufer, Benedikt B; Kaspers, Bernd

    2015-06-01

    Marek's disease virus (MDV) is an alphaherpesvirus that causes deadly T-cell lymphomas in chickens and serves as a natural small animal model for virus-induced tumor formation. In vivo, MDV lytically replicates in B cells that transfer the virus to T cells in which the virus establishes latency. MDV also malignantly transforms CD4+ T cells with a T(r