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Sample records for latency requires pim-1

  1. In vivo analysis of Pim-1 deficiency.

    PubMed Central

    Laird, P W; van der Lugt, N M; Clarke, A; Domen, J; Linders, K; McWhir, J; Berns, A; Hooper, M

    1993-01-01

    The Pim-1 proto-oncogene encodes a highly conserved serine/threonine phosphokinase which is predominantly expressed in hematopoietic organs and gonads in mammals. Overexpression of Pim-1 predisposes to lymphomagenesis in mice. To develop a further understanding of Pim-1 in molecular terms, as well as in terms of its potential role in hematopoietic development, we have generated mice deficient in Pim-1 function. Pim-1-deficient mice are ostensibly normal, healthy and fertile. Detailed comparative analyses of the hematopoietic systems of the mutant mice and their wild-type littermates showed that they are indistinguishable for most of the parameters studied. Our analyses revealed one unexpected phenotype that correlated with the level of Pim-1 expression: Pim-1 deficiency correlated with a erythrocyte microcytosis, whereas overexpression of Pim-1 in E mu-Pim-1-transgenic mice resulted in erythrocyte macrocytosis. In order to confirm that the observed decrease in erythrocyte Mean Cell Volume (MCV) was attributable to the Pim-1 deficiency, we developed mice transgenic for a Pim-1 gene construct with its own promoter and showed that this transgene could restore the low erythrocyte Mean Cell Volume observed in the Pim-1-deficient mice to near wild-type levels. These results might be relevant to the observed involvement of the Pim-1 gene in mouse erythroleukemogenesis. The surprising lack of a readily observed phenotype in the lymphoid compartment of the Pim-1-deficient mice, suggests a heretofore unrecognized degree of in vivo functional redundancy of this highly conserved proto-oncogene. Images PMID:8233823

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

    SciTech Connect

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

    2006-07-20

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

  4. Expression of a Pim-1 transgene accelerates lymphoproliferation and inhibits apoptosis in lpr/lpr mice.

    PubMed Central

    Möröy, T; Grzeschiczek, A; Petzold, S; Hartmann, K U

    1993-01-01

    Transgenic mice expressing the Pim-1 kinase are predisposed to develop T-cell lymphomas with a long latency period of about 7-9 months. However, the exact functional basis of the oncogenic activity of Pim-1 remains obscure. C57BL/6 mice homozygous for the lpr mutation develop a well-described lymphoproliferative syndrome at about 26-30 weeks of age. This syndrome is characterized mainly by the accumulation of abnormal T cells in lymph nodes because of the lack of Fas receptor-induced apoptosis. We find that backcross of E mu-Pim-1 transgenics (mice with a transgene that carries the mouse Pim-1 gene under the transcriptional control of the immunoglobulin heavy chain gene enhancer E mu) into lpr/lpr mice results in strong acceleration of lymphoproliferation and dramatic enlargement of lymph nodes. In addition, we show here that cultured lymph node cells from E mu-Pim-1 lpr/lpr mice are rescued from rapid apoptosis that normally occurs in nontransgenic lpr cells in vitro. We also present evidence that CD4+/CD8+ double-positive thymocytes from lpr/lpr mice are sensitive to dexamethasone-induced apoptosis, although lpr/lpr mice lack the Fas receptor. In contrast, E mu-Pim-1 lpr/lpr animals show considerable protection from dexamethasone-induced apoptosis. These results show that Pim-1 can strongly accelerate lymphoproliferation through inhibition of apoptosis and thereby provide first insight into the functional basis for the oncogenic activity of Pim-1. Images Fig. 1 Fig. 3 PMID:7504280

  5. 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.

  6. 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

  7. PIM1-minicircle as a therapeutic treatment for myocardial infarction

    PubMed Central

    Wang, Bingyan J.; Broughton, Kathleen M.; Alvarez, Roberto; Siddiqi, Sailay; Loaiza, Rebeca; Nguyen, Nicky; Quijada, Pearl; Gude, Natalie; Sussman, Mark A.

    2017-01-01

    PIM1, a pro-survival gene encoding a serine/ threonine kinase, influences cell proliferation and survival. Modification of cardiac progenitor cells (CPCs) or cardiomyocytes with PIM1 using a lentivirus-based delivery method showed long-term improved cardiac function after myocardial infarction (MI). However, lentivirus based delivery methods have stringent FDA regulation with respect to clinical trials. To provide an alternative and low risk PIM1 delivery method, this study examined the use of a non-viral modified plasmid-minicircle (MC) as a vehicle to deliver PIM1 into mouse CPCs (mCPCs) in vitro and the myocardium in vivo. MC containing a turbo gfp reporter gene (gfp-MC) was used as a transfection and injection control. PIM1 was subcloned into gfp-MC (PIM1-MC) and then transfected into mCPCs at an efficiency of 29.4±3.7%. PIM1-MC engineered mCPCs (PIM1-mCPCs) exhibit significantly (P<0.05) better survival rate under oxidative treatment. PIM1-mCPCs also exhibit 1.9±0.1 and 2.2±0.2 fold higher cell proliferation at 3 and 5 days post plating, respectively, as compared to gfp-MC transfected mCPCs control. PIM1-MC was injected directly into ten-week old adult FVB female mice hearts in the border zone immediately after MI. Delivery of PIM1 into myocardium was confirmed by GFP+ cardiomyocytes. Mice with PIM1-MC injection showed increased protection compared to gfp-MC injection groups measured by ejection fraction at 3 and 7 days post injury (P = 0.0379 and P = 0.0262 by t-test, respectively). Success of PIM1 delivery and integration into mCPCs in vitro and cardiomyocytes in vivo by MC highlights the possibility of a non-cell based therapeutic approach for treatment of ischemic heart disease and MI. PMID:28323876

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

    PubMed Central

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

    2012-01-01

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

  9. 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.

  10. NFκB-Pim-1-Eomesodermin axis is critical for maintaining CD8 T-cell memory quality.

    PubMed

    Knudson, Karin M; Pritzl, Curtis J; Saxena, Vikas; Altman, Amnon; Daniels, Mark A; Teixeiro, Emma

    2017-02-28

    T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory. Strikingly, we found that antigen receptor [T-cell receptor (TCR)] signaling regulates this process through expression of the NFκB-dependent kinase proviral integration site for Moloney murine leukemia virus-1 (PIM-1), which in turn regulates NFκB and Eomes. T cells defective in TCR-dependent NFκB signaling were impaired in late expression of Pim-1, Eomes, and CD8 memory. These defects were rescued when TCR-dependent NFκB signaling was restored. We also found that NFκB-Pim-1 signals were required at memory to maintain memory CD8 T-cell longevity, effector function, and Eomes expression. Hence, an NFκB-Pim-1-Eomes axis regulates Eomes levels to maintain memory fitness.

  11. Pim1 kinase synergizes with c-MYC to induce advanced prostate carcinoma

    PubMed Central

    Wang, Jie; Kim, Jongchan; Roh, Meejeon; Franco, Omar E.; Hayward, Simon W.; Wills, Marcia L.; Abdulkadir, Sarki A.

    2010-01-01

    The oncogenic PIM1 kinase has been implicated as a cofactor for c-MYC in prostate carcinogenesis. Here we show that in human prostate tumors, coexpression of c-MYC and PIM1 is associated with higher Gleason grades. Using a tissue recombination model coupled with lentiviral-mediated gene transfer we find that Pim1 is weakly oncogenic in naïve adult mouse prostatic epithelium. However, it cooperates dramatically with c-MYC to induce prostate cancer within 6-weeks. Importantly, c-MYC/Pim1 synergy is critically dependent on Pim1 kinase activity. c-MYC/Pim1 tumors showed increased levels of the active serine-62 (S62) phosphorylated form of c-MYC. Grafts expressing a phosphomimetic c-MYCS62D mutant had higher rates of proliferation than grafts expressing wild type c-MYC but did not form tumors like c-MYC/Pim1 grafts, indicating that Pim1 cooperativity with c-MYC in vivo involves additional mechanisms other than enhancement of c-MYC activity by S62 phosphorylation. c-MYC/Pim1-induced prostate carcinomas demonstrate evidence of neuroendocrine (NE) differentiation. Additional studies, including the identification of tumor cells coexpressing androgen receptor and NE cell markers synaptophysin and Ascl1 suggested that NE tumors arose from adenocarcinoma cells through transdifferentiation. These results directly demonstrate functional cooperativity between c-MYC and PIM1 in prostate tumorigenesis in vivo and support efforts for targeting PIM1 in prostate cancer. PMID:20140016

  12. Pim1 promotes human prostate cancer cell tumorigenicity and c-MYC transcriptional activity

    PubMed Central

    2010-01-01

    Background The serine/threonine kinase PIM1 has been implicated as an oncogene in various human cancers including lymphomas, gastric, colorectal and prostate carcinomas. In mouse models, Pim1 is known to cooperate with c-Myc to promote tumorigenicity. However, there has been limited analysis of the tumorigenic potential of Pim1 overexpression in benign and malignant human prostate cancer cells in vivo. Methods We overexpressed Pim1 in three human prostate cell lines representing different disease stages including benign (RWPE1), androgen-dependent cancer (LNCaP) and androgen-independent cancer (DU145). We then analyzed in vitro and in vivo tumorigenicity as well as the effect of Pim1 overexpression on c-MYC transcriptional activity by reporter assays and gene expression profiling using an inducible MYC-ER system. To validate that Pim1 induces tumorigenicity and target gene expression by modulating c-MYC transcriptional activity, we inhibited c-MYC using a small molecule inhibitor (10058-F4) or RNA interference. Results Overexpression of Pim1 alone was not sufficient to convert the benign RWPE1 cell to malignancy although it enhanced their proliferation rates when grown as xenografts in vivo. However, Pim1 expression enhanced the in vitro and in vivo tumorigenic potentials of the human prostate cancer cell lines LNCaP and DU145. Reporter assays revealed increased c-MYC transcriptional activity in Pim1-expressing cells and mRNA expression profiling demonstrated that a large fraction of c-MYC target genes were also regulated by Pim1 expression. The c-MYC inhibitor 10058-F4 suppressed the tumorigenicity of Pim1-expressing prostate cancer cells. Interestingly, 10058-F4 treatment also led to a reduction of Pim1 protein but not mRNA. Knocking-down c-MYC using short hairpin RNA reversed the effects of Pim1 on Pim1/MYC target genes. Conclusion Our results suggest an in vivo role of Pim1 in promoting prostate tumorigenesis although it displayed distinct oncogenic activities

  13. 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

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

    PubMed

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

    2012-12-07

    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(-/-) 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, suggesting that nuclear localization of PIM1 is important for resistance of MAEC to rapamycin-mediated inhibition of proliferation.

  15. Pim1 kinase promotes angiogenesis through phosphorylation of endothelial nitric oxide synthase at Ser-633

    PubMed Central

    Chen, Ming; Yi, Bing; Zhu, Ni; Wei, Xin; Zhang, Guan-Xin; Huang, Shengdong; Sun, Jianxin

    2016-01-01

    Aims Posttranslational modification, such as phosphorylation, plays an essential role in regulating activation of endothelial NO synthase (eNOS). In the present study, we aim to determine whether eNOS could be phosphorylated and regulated by a novel serine/threonine–protein kinase Pim1 in vascular endothelial cells (ECs). Methods and results Using immunoprecipitation and protein kinase assays, we demonstrated that Pim1 specifically interacts with eNOS, which leads to a marked phosphorylation of eNOS at Ser-633 and increased production of nitric oxide (NO). Intriguingly, in response to VEGF stimulation, eNOS phosphorylation at Ser-633 exhibits two distinct phases: transient phosphorylation occurring between 0 and 60 min and sustained phosphorylation occurring between 2 and 24 h, which are mediated by the protein kinase A (PKA) and Pim1, respectively. Inhibiting Pim1 by either pharmacological inhibitor SMI-4a or the dominant-negative form of Pim1 markedly attenuates VEGF-induced tube formation, while Pim1 overexpression significantly increases EC tube formation and migration in an NO-dependent manner. Importantly, Pim1 expression and eNOS phosphorylation at Ser-633 were substantially decreased in high glucose-treated ECs and in the aorta of db/db diabetic mice. Increased Pim1 expression ameliorates impaired vascular angiogenesis in diabetic mice, as determined by an ex vivo aortic ring assay. Conclusion Our findings demonstrate Pim1 as a novel kinase that is responsible for the phosphorylation of eNOS at Ser-633 and enhances EC sprouting of aortic rings from diabetic mice, suggesting that Pim1 could potentially serve as a novel therapeutic target for revascularization strategies. PMID:26598507

  16. ERG deregulation induces PIM1 over-expression and aneuploidy in prostate epithelial cells.

    PubMed

    Magistroni, Vera; Mologni, Luca; Sanselicio, Stefano; Reid, James Frances; Redaelli, Sara; Piazza, Rocco; Viltadi, Michela; Bovo, Giorgio; Strada, Guido; Grasso, Marco; Gariboldi, Manuela; Gambacorti-Passerini, Carlo

    2011-01-01

    The ERG gene belongs to the ETS family of transcription factors and has been found to be involved in atypical chromosomal rearrangements in several cancers. To gain insight into the oncogenic activity of ERG, we compared the gene expression profile of NIH-3T3 cells stably expressing the coding regions of the three main ERG oncogenic fusions: TMPRSS2/ERG (tERG), EWS/ERG and FUS/ERG. We found that all three ERG fusions significantly up-regulate PIM1 expression in the NIH-3T3 cell line. PIM1 is a serine/threonine kinase frequently over-expressed in cancers of haematological and epithelial origin. We show here that tERG expression induces PIM1 in the non-malignant prostate cell line RWPE-1, strengthening the relation between tERG and PIM1 up-regulation in the initial stages of prostate carcinogenesis. Silencing of tERG reversed PIM1 induction. A significant association between ERG and PIM1 expression in clinical prostate carcinoma specimens was found, suggesting that such a mechanism may be relevant in vivo. Chromatin Immunoprecipitation experiments showed that tERG directly binds to PIM1 promoter in the RWPE-1 prostate cell line, suggesting that tERG could be a direct regulator of PIM1 expression. The up-regulation of PIM1 induced by tERG over-expression significantly modified Cyclin B1 levels and increased the percentage of aneuploid cells in the RWPE-1 cell line after taxane-based treatment. Here we provide the first evidence for an ERG-mediated PIM1 up-regulation in prostate cells in vitro and in vivo, suggesting a direct effect of ERG transcriptional activity in the alteration of genetic stability.

  17. Pim-1 levels determine the size of early B lymphoid compartments in bone marrow

    PubMed Central

    1993-01-01

    The mouse proto-oncogene Pim-1, which encodes two cytoplasmic serine- threonine-specific protein kinases, is frequently activated by proviral insertion in murine leukemia virus-induced hematopoietic tumors. Transgenic mice overexpressing Pim-1 show a low incidence of spontaneous T cell lymphomas, whereas null mutant mice lack an obvious phenotype. We have analyzed the early B lymphoid compartment from both null mutant and E mu-Pim-1 transgenic mice. The level of Pim-1 expression appears to be a determining factor in the ability of these cells to respond to the growth factors interleukin 7 (IL-7) and SF (steel factor). The impaired response in null mutant mice could be rescued by introduction of a functional Pim-1 transgene. Moreover, overexpression of Pim-1 facilitates the derivation of primitive lymphoid cell lines that are dependent on combined stimulation with IL- 7 and SF or insulin-like growth factor 1. These results for the first time identify the involvement of Pim-1 in a normal cellular function, as an important regulator of early B lymphopoiesis in mice. PMID:8228813

  18. Structural basis of constitutive activity and a unique nucleotide binding mode of human Pim-1 kinase.

    PubMed

    Qian, Kevin C; Wang, Lian; Hickey, Eugene R; Studts, Joey; Barringer, Kevin; Peng, Charline; Kronkaitis, Anthony; Li, Jun; White, Andre; Mische, Sheenah; Farmer, Bennett

    2005-02-18

    Pim-1 kinase is a member of a distinct class of serine/threonine kinases consisting of Pim-1, Pim-2, and Pim-3. Pim kinases are highly homologous to one another and share a unique consensus hinge region sequence, ER-PXPX, with its two proline residues separated by a non-conserved residue, but they (Pim kinases) have <30% sequence identity with other kinases. Pim-1 has been implicated in both cytokine-induced signal transduction and the development of lymphoid malignancies. We have determined the crystal structures of apo Pim-1 kinase and its AMP-PNP (5'-adenylyl-beta,gamma-imidodiphosphate) complex to 2.1-angstroms resolutions. The structures reveal the following. 1) The kinase adopts a constitutively active conformation, and extensive hydrophobic and hydrogen bond interactions between the activation loop and the catalytic loop might be the structural basis for maintaining such a conformation. 2) The hinge region has a novel architecture and hydrogen-bonding pattern, which not only expand the ATP pocket but also serve to establish unambiguously the alignment of the Pim-1 hinge region with that of other kinases. 3) The binding mode of AMP-PNP to Pim-1 kinase is unique and does not involve a critical hinge region hydrogen bond interaction. Analysis of the reported Pim-1 kinase-domain structures leads to a hypothesis as to how Pim kinase activity might be regulated in vivo.

  19. The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors.

    PubMed

    Xiang, Yibin; Hirth, Bradford; Asmussen, Gary; Biemann, Hans-Peter; Bishop, Kimberly A; Good, Andrew; Fitzgerald, Maria; Gladysheva, Tatiana; Jain, Annuradha; Jancsics, Katherine; Liu, Jinyu; Metz, Markus; Papoulis, Andrew; Skerlj, Renato; Stepp, J David; Wei, Ronnie R

    2011-05-15

    Novel benzofuran-2-carboxylic acids, exemplified by 29, 38 and 39, have been discovered as potent Pim-1 inhibitors using fragment based screening followed by X-ray structure guided medicinal chemistry optimization. The compounds demonstrate potent inhibition against Pim-1 and Pim-2 in enzyme assays. Compound 29 has been tested in the Ambit 442 kinase panel and demonstrates good selectivity for the Pim kinase family. X-ray structures of the inhibitor/Pim-1 binding complex reveal important salt-bridge and hydrogen bond interactions mediated by the compound's carboxylic acid and amino groups.

  20. Pim-1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

    DTIC Science & Technology

    2006-10-01

    phosphorylation site for PIM1 on the p105/NFKB1 precursor protein • Identication of quercetagetin as a moderately potent and specific, cell-permeable PIM1...an orthotopic murine model. J Urology 173, 604-609 (2005). 48. Kim K-T, Baird K, Ahn J-Y, Meltzer P, Lilly M, Small D: Pim-1 is upregulated... Donald C, Lilly MB, Kraft AS. Pim family kinases enhance tumor growth of prostate cancer cells. Mol Cancer Res. 2005 Aug;3(8):443-51. 50

  1. Pim-1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

    DTIC Science & Technology

    2007-10-01

    7 • Identication of quercetagetin as a moderately potent and specific, cell-permeable PIM1 kinase inhibitor • Demonstration...Baird K, Ahn J-Y, Meltzer P, Lilly M, Small D: Pim-1 is upregulated in constitutively activating FLT3 mutants and plays a role in FLT3-mediated cell...survival. Blood 105(4), 1759-1767 (2005). 49. Chen WW, Chan DC, Donald C, Lilly MB, Kraft AS. Pim family kinases enhance tumor growth of

  2. Synthesis and Transport Properties of Novel MOF/PIM-1/MOF Sandwich Membranes for Gas Separation.

    PubMed

    Fuoco, Alessio; Khdhayyer, Muhanned R; Attfield, Martin P; Esposito, Elisa; Jansen, Johannes C; Budd, Peter M

    2017-02-11

    Metal-organic frameworks (MOFs) were supported on polymer membrane substrates for the fabrication of composite polymer membranes based on unmodified and modified polymer of intrinsic microporosity (PIM-1). Layers of two different MOFs, zeolitic imidazolate framework-8 (ZIF-8) and Copper benzene tricarboxylate ((HKUST-1), were grown onto neat PIM-1, amide surface-modified PIM-1 and hexamethylenediamine (HMDA) -modified PIM-1. The surface-grown crystalline MOFs were characterized by a combination of several techniques, including powder X-ray diffraction, infrared spectroscopy and scanning electron microscopy to investigate the film morphology on the neat and modified PIM-1 membranes. The pure gas permeabilities of He, H₂, O₂, N₂, CH₄, CO₂ were studied to understand the effect of the surface modification on the basic transport properties and evaluate the potential use of these membranes for industrially relevant gas separations. The pure gas transport was discussed in terms of permeability and selectivity, highlighting the effect of the MOF growth on the diffusion coefficients of the gas in the new composite polymer membranes. The results confirm that the growth of MOFs on polymer membranes can enhance the selectivity of the appropriately functionalized PIM-1, without a dramatic decrease of the permeability.

  3. Synthesis and Transport Properties of Novel MOF/PIM-1/MOF Sandwich Membranes for Gas Separation

    PubMed Central

    Fuoco, Alessio; Khdhayyer, Muhanned R.; Attfield, Martin P.; Esposito, Elisa; Jansen, Johannes C.; Budd, Peter M.

    2017-01-01

    Metal-organic frameworks (MOFs) were supported on polymer membrane substrates for the fabrication of composite polymer membranes based on unmodified and modified polymer of intrinsic microporosity (PIM-1). Layers of two different MOFs, zeolitic imidazolate framework-8 (ZIF-8) and Copper benzene tricarboxylate ((HKUST-1), were grown onto neat PIM-1, amide surface-modified PIM-1 and hexamethylenediamine (HMDA) -modified PIM-1. The surface-grown crystalline MOFs were characterized by a combination of several techniques, including powder X-ray diffraction, infrared spectroscopy and scanning electron microscopy to investigate the film morphology on the neat and modified PIM-1 membranes. The pure gas permeabilities of He, H2, O2, N2, CH4, CO2 were studied to understand the effect of the surface modification on the basic transport properties and evaluate the potential use of these membranes for industrially relevant gas separations. The pure gas transport was discussed in terms of permeability and selectivity, highlighting the effect of the MOF growth on the diffusion coefficients of the gas in the new composite polymer membranes. The results confirm that the growth of MOFs on polymer membranes can enhance the selectivity of the appropriately functionalized PIM-1, without a dramatic decrease of the permeability. PMID:28208658

  4. 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.

  5. Pim-1 Kinase Regulating Dynamics Related Protein 1 Mediates Sevoflurane Postconditioning-induced Cardioprotection

    PubMed Central

    Liu, Jin-Dong; Chen, Hui-Juan; Wang, Da-Liang; Wang, Hui; Deng, Qian

    2017-01-01

    Background: It is well documented that sevoflurane postconditioning (SP) has a significant myocardial protection effect. However, the mechanisms underlying SP are still unclear. In the present study, we investigated the hypothesis that the Pim-1 kinase played a key role in SP-induced cardioprotection by regulating dynamics-related protein 1 (Drp1). Methods: A Langendorff model was used in this study. Seventy-two rats were randomly assigned into six groups as follows: CON group, ischemia reperfusion (I/R) group, SP group, SP+proto-oncogene serine/threonine-protein kinase 1 (Pim-1) inhibitor II group, SP+dimethylsufoxide group, and Pim-1 inhibitor II group (n = 12, each). Hemodynamic parameters and infarct size were measured to reflect the extent of myocardial I/R injury. The expressions of Pim-1, B-cell leukemia/lymphoma 2 (Bcl-2) and cytochrome C (Cyt C) in cytoplasm and mitochondria, the Drp1 in mitochondria, and the total Drp1 and p-Drp1ser637 were measured by Western blotting. In addition, transmission electron microscope was used to observe mitochondrial morphology. The experiment began in October 2014 and continued until July 2016. Results: SP improved myocardial I/R injury-induced hemodynamic parametric changes, cardiac function, and preserved mitochondrial phenotype and decreased myocardial infarct size (24.49 ± 1.72% in Sev group compared with 41.98 ± 4.37% in I/R group; P < 0.05). However, Pim-1 inhibitor II significantly (P < 0.05) abolished the protective effect of SP. Western blotting analysis demonstrated that, compared with I/R group, the expression of Pim-1 and Bcl-2 in cytoplasm and mitochondria as well as the total p-Drp1ser637 in Sev group (P < 0.05) were upregulated. Meanwhile, SP inhibited Drp1 compartmentalization to the mitochondria followed by a reduction in the release of Cyt C. Pretreatment with Pim-1 inhibitor II significantly (P < 0.05) abolished SP-induced Pim-1/p-Drp1ser637 signaling activation. Conclusions: These findings suggested

  6. Crystal Structures of Proto-oncogene Kinase Pim1: A Target of Aberrant Somatic Hypermutations in Diffuse Large Cell Lymphoma

    SciTech Connect

    Kumar, Abhinav; Mandiyan, Valsan; Suzuki, Yoshihisa; Zhang, Chao; Rice, Julie; Tsai, James; Artis, Dean R.; Ibrahim, Prabha; Bremer, Ryan

    2010-07-19

    Pim1, a serine/threonine kinase, is involved in several biological functions including cell survival, proliferation, and differentiation. While pim1 has been shown to be involved in several hematopoietic cancers, it was also recently identified as a target of aberrant somatic hypermutation in diffuse large cell lymphoma (DLCL), the most common form of non-Hodgkin's lymphoma. The crystal structures of Pim1 in apo form and bound with AMPPNP have been solved and several unique features of Pim1 were identified, including the presence of an extra {beta}-hairpin in the N-terminal lobe and an unusual conformation of the hinge connecting the two lobes of the enzyme. While the apo Pim1 structure is nearly identical with that reported recently, the structure of AMPPNP bound to Pim1 is significantly different. Pim1 is unique among protein kinases due to the presence of a proline residue at position 123 that precludes the formation of the canonical second hydrogen bond between the hinge backbone and the adenine moiety of ATP. One crystal structure reported here shows that changing P123 to methionine, a common residue that offers the backbone hydrogen bond to ATP, does not restore the ATP binding pocket of Pim1 to that of a typical kinase. These unique structural features in Pim1 result in novel binding modes of AMP and a known kinase inhibitor scaffold, as shown by co-crystallography. In addition, the kinase activities of five Pim1 mutants identified in DLCL patients have been determined. In each case, the observed effects on kinase activity are consistent with the predicted consequences of the mutation on the Pim1 structure. Finally, 70 co-crystal structures of low molecular mass, low-affinity compounds with Pim1 have been solved in order to identify novel chemical classes as potential Pim1 inhibitors. Based on the structural information, opportunities for optimization of one specific example are discussed.

  7. A novel Pim-1 kinase inhibitor targeting residues that bind the substrate peptide.

    PubMed

    Tsuganezawa, Keiko; Watanabe, Hisami; Parker, Lorien; Yuki, Hitomi; Taruya, Shigenao; Nakagawa, Yukari; Kamei, Daisuke; Mori, Masumi; Ogawa, Naoko; Tomabechi, Yuri; Handa, Noriko; Honma, Teruki; Yokoyama, Shigeyuki; Kojima, Hirotatsu; Okabe, Takayoshi; Nagano, Tetsuo; Tanaka, Akiko

    2012-03-30

    A new screening method using fluorescent correlation spectroscopy was developed to select kinase inhibitors that competitively inhibit the binding of a fluorescently labeled substrate peptide. Using the method, among approximately 700 candidate compounds selected by virtual screening, we identified a novel Pim-1 kinase inhibitor targeting its peptide binding residues. X-ray crystal analysis of the complex structure of Pim-1 with the inhibitor indicated that the inhibitor actually binds to the ATP-binding site and also forms direct interactions with residues (Asp128 and Glu171) that bind the substrate peptide. These interactions, which cause small side-chain movements, seem to affect the binding ability of the fluorescently labeled substrate. The compound inhibited Pim-1 kinase in vitro, with an IC(50) value of 150 nM. Treatment of cultured leukemia cells with the compound reduced the amount of p21 and increased the amount of p27, due to Pim-1 inhibition, and then triggered apoptosis after cell-cycle arrest at the G(1)/S phase. This screening method may be widely applicable for the identification of various new Pim-1 kinase inhibitors targeting the residues that bind the substrate peptide.

  8. Pim-1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

    DTIC Science & Technology

    2005-10-01

    the p105/NFKB1 precursor protein • Identication of quercetagetin as a moderately potent and specific, cell-permeable PIM1 kinase inhibitor...173, 604-609 (2005). 48. Kim K-T, Baird K, Ahn J-Y, Meltzer P, Lilly M, Small D: Pim-1 is upregulated in constitutively activating FLT3 mutants...and plays a role in FLT3-mediated cell survival. Blood 105(4), 1759-1767 (2005). 49. Chen WW, Chan DC, Donald C, Lilly MB, Kraft AS. Pim family

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

    PubMed

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

    2013-04-09

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

  10. The role of PIM1/PIM2 kinases in tumors of the male reproductive system

    PubMed Central

    Jiménez-García, Manuel Pedro; Lucena-Cacace, Antonio; Robles-Frías, María José; Narlik-Grassow, Maja; Blanco-Aparicio, Carmen; Carnero, Amancio

    2016-01-01

    The PIM family of serine/threonine kinases has three highly conserved isoforms (PIM1, PIM2 and PIM3). PIM proteins are regulated through transcription and stability by JAK/STAT pathways and are overexpressed in hematological malignancies and solid tumors. The PIM kinases possess weak oncogenic abilities, but enhance other genes or chemical carcinogens to induce tumors. We generated conditional transgenic mice that overexpress PIM1 or PIM2 in male reproductive organs and analyzed their contribution to tumorigenesis. We found an increase in alterations of sexual organs and hyperplasia in the transgenic mice correlating with inflammation. We also found that PIM1/2 are overexpressed in a subset of human male germ cells and prostate tumors correlating with inflammatory features and stem cell markers. Our data suggest that PIM1/2 kinase overexpression is a common feature of male reproductive organs tumors, which provoke tissue alterations and a large inflammatory response that may act synergistically during the process of tumorigenesis. There is also a correlation with markers of cancer stem cells, which may contribute to the therapy resistance found in tumors overexpressing PIM kinases. PMID:27901106

  11. The role of PIM1/PIM2 kinases in tumors of the male reproductive system.

    PubMed

    Jiménez-García, Manuel Pedro; Lucena-Cacace, Antonio; Robles-Frías, María José; Narlik-Grassow, Maja; Blanco-Aparicio, Carmen; Carnero, Amancio

    2016-11-30

    The PIM family of serine/threonine kinases has three highly conserved isoforms (PIM1, PIM2 and PIM3). PIM proteins are regulated through transcription and stability by JAK/STAT pathways and are overexpressed in hematological malignancies and solid tumors. The PIM kinases possess weak oncogenic abilities, but enhance other genes or chemical carcinogens to induce tumors. We generated conditional transgenic mice that overexpress PIM1 or PIM2 in male reproductive organs and analyzed their contribution to tumorigenesis. We found an increase in alterations of sexual organs and hyperplasia in the transgenic mice correlating with inflammation. We also found that PIM1/2 are overexpressed in a subset of human male germ cells and prostate tumors correlating with inflammatory features and stem cell markers. Our data suggest that PIM1/2 kinase overexpression is a common feature of male reproductive organs tumors, which provoke tissue alterations and a large inflammatory response that may act synergistically during the process of tumorigenesis. There is also a correlation with markers of cancer stem cells, which may contribute to the therapy resistance found in tumors overexpressing PIM kinases.

  12. Multiple Histone Lysine Methyltransferases Are Required for the Establishment and Maintenance of HIV-1 Latency

    PubMed Central

    Nguyen, Kien; Das, Biswajit; Dobrowolski, Curtis

    2017-01-01

    ABSTRACT We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5′ long terminal repeat (LTR) and rapidly displaced upon proviral reactivation. Clustered regularly interspaced short palindromic repeat(s) (CRISPR)-mediated knockout of EZH2 caused depletion of both EZH2 and EHMT2, but CRISPR-mediated knockout of EHMT2 was selective for EHMT2, consistent with the failure of EHMT2 knockouts to induce latent proviruses in this system. Either (i) knockout of methyltransferase by short hairpin RNA in Jurkat T cells prior to HIV-1 infection or (ii) inhibition of the enzymes with drugs significantly reduced the levels of the resulting silenced viruses, demonstrating that both enzymes are required to establish latency. To our surprise, inhibition of EZH2 (by GSK-343 or EPZ-6438) or inhibition of EHMT2 (by UNC-0638) in the Th17 primary cell model of HIV latency or resting memory T cells isolated from HIV-1-infected patients receiving highly active antiretroviral therapy, was sufficient to induce the reactivation of latent proviruses. The methyltransferase inhibitors showed synergy with interleukin-15 and suberanilohydroxamic acid. We conclude that both PRC2 and EHMT2 are required for the establishment and maintenance of HIV-1 proviral silencing in primary cells. Furthermore, EZH2 inhibitors such as GSK-343 and EPZ-6438 and the EHMT2 inhibitor UNC-0638 are strong candidates for use as latency-reversing agents in clinical studies. PMID:28246360

  13. 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.

  14. Multiple Histone Lysine Methyltransferases Are Required for the Establishment and Maintenance of HIV-1 Latency.

    PubMed

    Nguyen, Kien; Das, Biswajit; Dobrowolski, Curtis; Karn, Jonathan

    2017-02-28

    We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation. Clustered regularly interspaced short palindromic repeat(s) (CRISPR)-mediated knockout of EZH2 caused depletion of both EZH2 and EHMT2, but CRISPR-mediated knockout of EHMT2 was selective for EHMT2, consistent with the failure of EHMT2 knockouts to induce latent proviruses in this system. Either (i) knockout of methyltransferase by short hairpin RNA in Jurkat T cells prior to HIV-1 infection or (ii) inhibition of the enzymes with drugs significantly reduced the levels of the resulting silenced viruses, demonstrating that both enzymes are required to establish latency. To our surprise, inhibition of EZH2 (by GSK-343 or EPZ-6438) or inhibition of EHMT2 (by UNC-0638) in the Th17 primary cell model of HIV latency or resting memory T cells isolated from HIV-1-infected patients receiving highly active antiretroviral therapy, was sufficient to induce the reactivation of latent proviruses. The methyltransferase inhibitors showed synergy with interleukin-15 and suberanilohydroxamic acid. We conclude that both PRC2 and EHMT2 are required for the establishment and maintenance of HIV-1 proviral silencing in primary cells. Furthermore, EZH2 inhibitors such as GSK-343 and EPZ-6438 and the EHMT2 inhibitor UNC-0638 are strong candidates for use as latency-reversing agents in clinical studies.IMPORTANCE Highly active antiretroviral therapy (HAART) reduces the circulating virus to undetectable levels. Although patients adhering to the HAART regimen have minimal viremia, HIV

  15. 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.

  16. Pim-1 ligand-bound structures reveal the mechanism of serine/threonine kinase inhibition by LY294002.

    PubMed

    Jacobs, Marc D; Black, James; Futer, Olga; Swenson, Lora; Hare, Brian; Fleming, Mark; Saxena, Kumkum

    2005-04-08

    Pim-1 is an oncogene-encoded serine/threonine kinase primarily expressed in hematopoietic and germ cell lines. Pim-1 kinase was originally identified in Maloney murine leukemia virus-induced T-cell lymphomas and is associated with multiple cellular functions such as proliferation, survival, differentiation, apoptosis, and tumorigenesis (Wang, Z., Bhattacharya, N., Weaver, M., Petersen, K., Meyer, M., Gapter, L., and Magnuson, N. S. (2001) J. Vet. Sci. 2, 167-179). The crystal structures of Pim-1 complexed with staurosporine and adenosine were determined. Although a typical two-domain serine/threonine protein kinase fold is observed, the inter-domain hinge region is unusual in both sequence and conformation; a two-residue insertion causes the hinge to bulge away from the ATP-binding pocket, and a proline residue in the hinge removes a conserved main chain hydrogen bond donor. Without this hydrogen bond, van der Waals interactions with the hinge serve to position the ligand. The hinge region of Pim-1 resembles that of phosphatidylinositol 3-kinase more closely than it does other protein kinases. Although the phosphatidylinositol 3-kinase inhibitor LY294002 also inhibits Pim-1, the structure of the LY294002.Pim-1 complex reveals a new binding mode that may be general for Ser/Thr kinases.

  17. The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition

    PubMed Central

    Mologni, Luca; Magistroni, Vera; Casuscelli, Francesco; Montemartini, Marisa; Gambacorti-Passerini, Carlo

    2017-01-01

    PIM1 is over-expressed in multiple tumors, including prostate cancer (PCa). PIM1 upregulation is mediated by direct binding of the ERG transcription factor to its promoter. About 50% of PCa cases are characterized by the presence of the TMPRSS2/ERG fusion, leading to ERG over-expression and thus to PIM1 transcriptional activation. PIM kinases are considered as weak oncogenes, but when combined with additional genetic alterations can induce strong transforming effects. Here we show anti-proliferative activity of the newly described PIM1 inhibitor NMS-P645 in combination with the PI3K inhibitor GDC-0941 in TMPRSS2/ERG positive and negative PCa cells. Treatment with NMS-P645 alone can reverse PIM1-mediated pro-survival signals in prostate cells, such as activation of STAT3 through Tyr705 phosphorylation and resistance to taxane-based treatments, but does not exert a strong anti-tumoral effect. However, the simultaneous treatment with NMS-P645 and GDC-0941 induces a significant anti-proliferative response in PCa cells. These results support the use of combination strategies with PIM and PI3K inhibitors as effective treatment for PCa cases. PMID:28123608

  18. Discovery of imidazopyridazines as potent Pim-1/2 kinase inhibitors.

    PubMed

    Wurz, Ryan P; Sastri, Christine; D'Amico, Derin C; Herberich, Brad; Jackson, Claire L M; Pettus, Liping H; Tasker, Andrew S; Wu, Bin; Guerrero, Nadia; Lipford, J Russell; Winston, Jeffrey T; Yang, Yajing; Wang, Paul; Nguyen, Yen; Andrews, Kristin L; Huang, Xin; Lee, Matthew R; Mohr, Christopher; Zhang, J D; Reid, Darren L; Xu, Yang; Zhou, Yihong; Wang, Hui-Ling

    2016-11-15

    High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers, suggesting that inhibition of Pim signaling could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal using a screening hit (rac-1) as a starting point. Modification of the indazole ring resulted in the discovery of a series of imidazopyridazine-based Pim inhibitors exemplified by compound 22m, which was found to be a subnanomolar inhibitor of the Pim-1 and Pim-2 isoforms (IC50 values of 0.024nM and 0.095nM, respectively) and to potently inhibit the phosphorylation of BAD in a cell line that expresses high levels of all Pim isoforms, KMS-12-BM (IC50=28nM). Profiling of Pim-1 and Pim-2 expression levels in a panel of multiple myeloma cell lines and correlation of these data with the potency of compound 22m in a proliferation assay suggests that Pim-2 inhibition would be advantageous for this indication.

  19. Cytoplasmic Irradiation Induces Metabolic Shift in Human Small Airway Epithelial Cells via Activation of Pim-1 Kinase.

    PubMed

    Wu, Jinhua; Zhang, Qin; Wuu, Yen-Ruh; Zou, Sirui; Hei, Tom K

    2017-02-07

    The unique cellular and molecular consequences of cytoplasmic damage caused by ionizing radiation were studied using a precision microbeam irradiator. Our results indicated that targeted cytoplasmic irradiation induced metabolic shift from an oxidative to glycolytic phenotype in human small airway epithelial cells (SAE). At 24 h postirradiation, there was an increase in the mRNA expression level of key glycolytic enzymes as well as lactate secretion in SAE cells. Using RNA-sequencing analysis to compare genes that were responsive to cytoplasmic versus nuclear irradiation, we found a glycolysis related gene, Pim-1, was significantly upregulated only in cytoplasmic irradiated SAE cells. Inhibition of Pim-1 activity using the selective pharmaceutic inhibitor Smi-4a significantly reduced the level of lactate production and glucose uptake after cytoplasmic irradiation. In addition, Pim-1 also inhibited AMPK activity, which is a well-characterized negative regulator of glycolysis. Distinct from the glycolysis induced by cytoplasmic irradiation, targeted nuclear irradiation also induced a transient and minimal increase in glycolysis that correlated with increased expression of Hif-1α. In an effort to explore the underline mechanism, we found that inhibition of mitochondria fission using the cell-permeable inhibitor mdivi-1 suppressed the induction of Pim-1, thus confirming Pim-1 upregulation as a downstream effect of mitochondrial dysfunction. Our data show and, for the first time, that cytoplasmic irradiation mediate expression level of Pim-1, which lead to glycolytic shift in SAE cells. Additionally, since glycolysis is frequently linked to cancer cell metabolism, our findings further suggest a role of cytoplasmic damage in promoting neoplastic changes.

  20. Implications of promiscuous Pim-1 kinase fragment inhibitor hydrophobic interactions for fragment-based drug design.

    PubMed

    Good, Andrew C; Liu, Jinyu; Hirth, Bradford; Asmussen, Gary; Xiang, Yibin; Biemann, Hans-Peter; Bishop, Kimberly A; Fremgen, Trisha; Fitzgerald, Maria; Gladysheva, Tatiana; Jain, Annuradha; Jancsics, Katherine; Metz, Markus; Papoulis, Andrew; Skerlj, Renato; Stepp, J David; Wei, Ronnie R

    2012-03-22

    We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallographic and docking data analyses have been undertaken using inhibitor complexes derived from an in-house surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallographically observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone.

  1. Time of flight in MUSE at PIM1 at Paul Scherrer Institute

    NASA Astrophysics Data System (ADS)

    Lin, Wan; Gilman, Ronald; MUSE Collaboration

    2016-09-01

    The MUSE experiment at PIM1 at Paul Scherrer Institute in Villigen, Switzerland, measures elastic scattering of electrons and muons from a liquid hydrogen target. The intent of the experiment is to deduce whether the radius of the proton is the same when determined from the two different particle types. Precision timing is an important aspect of the experiment, used to determine particle types, reaction types, and beam momentum. Here we present results for a test setup measuring time of flight between prototypes of two detector systems to be used in the experiment, compared to Geant4 simulations. The results demonstrate time of flight resolution better than 100 ps, and beam momentum determination at the level of a few tenths of a percent. Douglass Project for Rutgers Women in Math, Science & Engineering, National Science Foundation Grant 1306126 to Rutgers University.

  2. Carcinogenicity study of 217 Hz pulsed 900 MHz electromagnetic fields in Pim1 transgenic mice.

    PubMed

    Oberto, Germano; Rolfo, Katia; Yu, Ping; Carbonatto, Michela; Peano, Sergio; Kuster, Niels; Ebert, Sven; Tofani, Santi

    2007-09-01

    In an 18-month carcinogenicity study, Pim1 transgenic mice were exposed to pulsed 900 MHz (pulse width: 0.577 ms; pulse repetition rate: 217 Hz) radiofrequency (RF) radiation at a whole-body specific absorption rate (SAR) of 0.5, 1.4 or 4.0 W/kg [uncertainty (k = 2): 2.6 dB; lifetime variation (k = 1): 1.2 dB]. A total of 500 mice, 50 per sex per group, were exposed, sham-exposed or used as cage controls. The experiment was an extension of a previously published study in female Pim1 transgenic mice conducted by Repacholi et al. (Radiat. Res. 147, 631-640, 1997) that reported a significant increase in lymphomas after exposure to the same 900 MHz RF signal. Animals were exposed for 1 h/day, 7 days/week in plastic tubes similar to those used in inhalation studies to obtain well-defined uniform exposure. The study was conducted blind. The highest exposure level (4 W/kg) used in this study resulted in organ-averaged SARs that are above the peak spatial SAR limits allowed by the ICNIRP (International Commission on Non-ionizing Radiation Protection) standard for environmental exposures. The whole-body average was about three times greater than the highest average SAR reported in the earlier study by Repacholi et al. The results of this study do not suggest any effect of 217 Hz-pulsed RF-radiation exposure (pulse width: 0.577 ms) on the incidence of tumors at any site, and thus the findings of Repacholi et al. were not confirmed. Overall, the study shows no effect of RF radiation under the conditions used on the incidence of any neoplastic or non-neoplastic lesion, and thus the study does not provide evidence that RF radiation possesses carcinogenic potential.

  3. Myc is required for the maintenance of Kaposi's sarcoma-associated herpesvirus latency.

    PubMed

    Li, Xudong; Chen, Shijia; Feng, Jun; Deng, Hongyu; Sun, Ren

    2010-09-01

    Myc is deregulated by Kaposi's sarcoma-associated herpesvirus (KSHV) latent proteins, but its role in KSHV latency is not clear. We found that Myc knockdown with RNA interference (RNAi) induced KSHV reactivation and increased the protein and mRNA levels of RTA, a key viral regulator of KSHV reactivation. Myc knockdown increased, whereas Myc overexpression inhibited, RTA promoter activity. KSHV reactivation and the activation of the RTA promoter induced by Myc depletion were inhibited by c-Jun N-terminal kinase (JNK) and p38 inhibitors but not by a MEK1 inhibitor. Myc knockdown inhibited primary effusion lymphoma (PEL) cell proliferation through inducing apoptosis and G(1) cell cycle arrest. Thus, Myc may be a key cellular node coupling cellular transformation and KSHV latency.

  4. Pim-1 kinase-dependent phosphorylation of p21Cip1/WAF1 regulates its stability and cellular localization in H1299 cells.

    PubMed

    Zhang, Yandong; Wang, Zeping; Magnuson, Nancy S

    2007-09-01

    Previous studies from our laboratory showed that p21Cip1/WAF1 can be phosphorylated by Pim-1 kinase in vitro, implying that part of the function of Pim-1 might involve influencing the cell cycle. In the present study, site-directed mutagenesis and phosphorylated-specific antibodies were used as tools to identify the sites phosphorylated by Pim-1 and the consequences of this phosphorylation. What we found was that Pim-1 can efficiently phosphorylate p21 on Thr145 in vitro using recombinant protein and in vivo in intact cells. Unexpectedly, we found that Ser146 is a second site that is phosphorylated in vivo, but this phosphorylation event seems to be an indirect result of Pim-1 expression. More importantly, the consequences of phosphorylation of either Thr145 or Ser146 are distinct. When p21 is phosphorylated on Thr145, it localizes to the nucleus and results in the disruption of the association between proliferating cell nuclear antigen and p21. Furthermore, phosphorylation of Thr145 promotes stabilization of p21. On the other hand, when p21 is phosphorylated on Ser146, it localizes primarily in the cytoplasm and the effect of phosphorylation on stability is minimal. Cotransfection of wild-type Pim-1 with p21 increases the rate of proliferation compared with cotransfection of p21 with kinase-dead Pim-1. Knocking down Pim-1 expression greatly decreases the rate of proliferation of H1299 cells and their ability to grow in soft agar. These data suggest that Pim-1 overexpression may contribute to tumorigenesis in part by influencing the cellular localization and stability of p21 and by promoting cell proliferation.

  5. Alpinumisoflavone induces apoptosis in esophageal squamous cell carcinoma by modulating miR-370/PIM1 signaling

    PubMed Central

    Han, Yantao; Yang, Xiuwei; Zhao, Ning; Peng, Jianjun; Gao, Hui; Qiu, Xia

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is the most prevalent type of esophageal cancer and accumulating evidence has confirmed the role of miRNAs in ESCC. One such miRNA, miR-370, was found to be aberrantly downregulated in various human malignancies. This study showed that the expression of miR-370 was significantly lower in ESCC tissues and cell lines, and miR-370 functioned as a tumor suppressor in ESCC. Moreover, this is the first report that showed miR-370 suppresses cell proliferation and tumor growth by directly targeting Pim family kinases 1 (PIM1). Furthermore, alpinumisoflavone, a naturally occurring flavonoid, could inhibit tumor growth of ESCC by targeting miR-370/PIM1 signaling. PMID:28042498

  6. The human Pim-1 gene is selectively transcribed in different hemato-lymphoid cell lines in spite of a G + C-rich housekeeping promoter.

    PubMed Central

    Meeker, T C; Loeb, J; Ayres, M; Sellers, W

    1990-01-01

    The expression of the Pim-1 proto-oncogene was studied by using the K562, Daudi, and Jurkat cell lines. In K562, Pim-1 mRNA levels were more than 20-fold higher than in Daudi and 50-fold higher than in Jurkat. Nuclear run-on assay data correlated directly with the steady-state mRNA levels, suggesting that the rate of transcription was responsible for the selective expression of this gene. Furthermore, the half-life of Pim-1 mRNA was shown to be 47 min in K562, 71 min in Daudi, and 35 min in Jurkat. This indicated that selective Pim-1 mRNA expression did not depend on posttranscriptional regulation. Therefore, 1.7 kilobases of the Pim-1 promoter was sequenced and studied in detail. The sequence showed that the region from nucleotide -1 to -873 was G + C rich (71%). Study of promoter deletions defined two major functional regions, a proximal element (nucleotide -104 to -1) and a distal element (nucleotide -427 to -336). DNase I protection assays identified binding sites for the Sp1 and AP2 proteins in these elements. A possible new transcription factor binds at position -348 in the distal element. In our study of the 1.7-kilobase Pim-1 promoter, we found no differences between K562 and Jurkat that could explain large differences in transcription. Therefore, the Pim-1 promoter appears to function constitutively, and we conclude that distant elements must regulate the tissue-selective expression of this gene. Although the Pim-1 gene has a G + C-rich housekeeping promoter, expression is carefully regulated at the level of transcription. Images PMID:2181282

  7. Identification of novel inhibitors for Pim-1 kinase using pharmacophore modeling based on a novel method for selecting pharmacophore generation subsets

    NASA Astrophysics Data System (ADS)

    Shahin, Rand; Swellmeen, Lubna; Shaheen, Omar; Aboalhaija, Nour; Habash, Maha

    2016-01-01

    Targeting Proviral integration-site of murine Moloney leukemia virus 1 kinase, hereafter called Pim-1 kinase, is a promising strategy for treating different kinds of human cancer. Headed for this a total list of 328 formerly reported Pim-1 kinase inhibitors has been explored and divided based on the pharmacophoric features of the most active molecules into 10 subsets projected to represent potential active binding manners accessible to ligands within the binding pocket of Pim-1 kinase. Discovery Studio 4.1 (DS 4.1) was employed to detect potential pharmacophoric active binding manners anticipated by Pim-1 Kinase inhibitors. The pharmacophoric models were then allowed to compete within Quantitative Structure Activity Relationship (QSAR) framework with other 2D descriptors. Accordingly Genetic algorithm and multiple linear regression investigation were engaged to find the finest QSAR equation that has the best predictive power r 262 2 = 0.70, F = 119.14, r LOO 2 = 0.693, r PRESS 2 against 66 external test inhibitors = 0.71 q2 = 0.55. Three different pharmacophores appeared in the successful QSAR equation this represents three different binding modes for inhibitors within the Pim-1 kinase binding pocket. Pharmacophoric models were later used to screen compounds within the National Cancer Institute database. Several low micromolar Pim-1 Kinase inhibitors were captured. The most potent hits show IC50 values of 0.77 and 1.03 µM. Also, upon analyzing the successful QSAR Equation we found that some polycyclic aromatic electron-rich structures namely 6-Chloro-2-methoxy-acridine can be considered as putative hits for Pim-1 kinase inhibition.

  8. 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.

  9. Flexibility of the P-loop of Pim-1 kinase: observation of a novel conformation induced by interaction with an inhibitor.

    PubMed

    Parker, Lorien J; Watanabe, Hisami; Tsuganezawa, Keiko; Tomabechi, Yuri; Handa, Noriko; Shirouzu, Mikako; Yuki, Hitomi; Honma, Teruki; Ogawa, Naoko; Nagano, Tetsuo; Yokoyama, Shigeyuki; Tanaka, Akiko

    2012-08-01

    The serine/threonine kinase Pim-1 is emerging as a promising target for cancer therapeutics. Much attention has recently been focused on identifying potential Pim-1 inhibitor candidates for the treatment of haematopoietic malignancies. The outcome of a rational drug-design project has recently been reported [Nakano et al. (2012), J. Med. Chem. 55, 5151-5156]. The report described the process of optimization of the structure-activity relationship and detailed from a medicinal chemistry perspective the development of a low-potency and nonselective compound initially identified from in silico screening into a potent, selective and metabolically stable Pim-1 inhibitor. Here, the structures of the initial in silico hits are reported and the noteworthy features of the Pim-1 complex structures are described. A particular focus was placed on the rearrangement of the glycine-rich P-loop region that was observed for one of the initial compounds, (Z)-7-(azepan-1-ylmethyl)-2-[(1H-indol-3-yl)methylidene]-6-hydroxy-1-benzofuran-3(2H)-one (compound 1), and was also found in all further derivatives. This novel P-loop conformation, which appears to be stabilized by an additional interaction with the β3 strand located above the binding site, is not usually observed in Pim-1 structures.

  10. Flexibility of the P-loop of Pim-1 kinase: observation of a novel conformation induced by interaction with an inhibitor

    PubMed Central

    Parker, Lorien J.; Watanabe, Hisami; Tsuganezawa, Keiko; Tomabechi, Yuri; Handa, Noriko; Shirouzu, Mikako; Yuki, Hitomi; Honma, Teruki; Ogawa, Naoko; Nagano, Tetsuo; Yokoyama, Shigeyuki; Tanaka, Akiko

    2012-01-01

    The serine/threonine kinase Pim-1 is emerging as a promising target for cancer therapeutics. Much attention has recently been focused on identifying potential Pim-1 inhibitor candidates for the treatment of haematopoietic malignancies. The outcome of a rational drug-design project has recently been reported [Nakano et al. (2012 ▶), J. Med. Chem. 55, 5151–5156]. The report described the process of optimization of the structure–activity relationship and detailed from a medicinal chemistry perspective the development of a low-potency and nonselective compound initially identified from in silico screening into a potent, selective and metabolically stable Pim-1 inhibitor. Here, the structures of the initial in silico hits are reported and the noteworthy features of the Pim-1 complex structures are described. A particular focus was placed on the rearrangement of the glycine-rich P-loop region that was observed for one of the initial compounds, (Z)-7-(azepan-1-ylmethyl)-2-[(1H-indol-3-­yl)methylidene]-6-hydroxy-1-benzofuran-3(2H)-one (compound 1), and was also found in all further derivatives. This novel P-loop conformation, which appears to be stabilized by an additional interaction with the β3 strand located above the binding site, is not usually observed in Pim-1 structures. PMID:22869110

  11. 3D-QSAR and virtual screening studies of thiazolidine-2,4-dione analogs: Validation of experimental inhibitory potencies towards PIM-1 kinase

    NASA Astrophysics Data System (ADS)

    Asati, Vivek; Bharti, Sanjay Kumar; Budhwani, Ashok Kumar

    2017-04-01

    The proviral insertion site in moloney murine leukemia virus (PIM) is a family of serine/threonine kinase of Ca2+-calmodulin-dependent protein kinase (CAMK) group which is responsible for the activation and regulation of cellular transcription and translation. The three isoforms of PIM kinase (PIM-1, PIM-2 and PIM-3) share high homology and functional idleness are widely expressed and involved in a variety of biological processes including cell survival, proliferation, differentiation and apoptosis. Altered expression of PIM-1 kinase correlated with hematologic malignancies and solid tumors. In the present study, atom-based 3D-QSAR, docking and virtual screening studies have been performed on a series of thiazolidine-2,4-dione derivatives as PIM-1 kinase inhibitors. 3D-QSAR and docking approach has shortlisted the most active thiazolidine-2,4-dione derivatives such as 28, 31, 33 and 35 with the incorporation of more than one structural feature in a single molecule. External validations by various parameters and molecular docking studies at the active site of PIM-1 kinase have proved the reliability of the developed 3D-QSAR model. The generated pharmacophore (AADHR.33) from 3D-QSAR study was used for screening of drug like compounds from ZINC database, where ZINC15056464 and ZINC83292944 showed potential binding affinities at the active site amino acid residues (LYS67, GLU171, ASP128 and ASP186) of PIM-1 kinase (PDB ID: "pdb:4DTK").

  12. 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.

  13. 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

  14. 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

  15. Measuring latency in virtual environments.

    PubMed

    Friston, Sebastian; Steed, Anthony

    2014-04-01

    Latency of interactive computer systems is a product of the processing, transport and synchronisation delays inherent to the components that create them. In a virtual environment (VE) system, latency is known to be detrimental to a user's sense of immersion, physical performance and comfort level. Accurately measuring the latency of a VE system for study or optimisation, is not straightforward. A number of authors have developed techniques for characterising latency, which have become progressively more accessible and easier to use. In this paper, we characterise these techniques. We describe a simple mechanical simulator designed to simulate a VE with various amounts of latency that can be finely controlled (to within 3ms). We develop a new latency measurement technique called Automated Frame Counting to assist in assessing latency using high speed video (to within 1ms). We use the mechanical simulator to measure the accuracy of Steed's and Di Luca's measurement techniques, proposing improvements where they may be made. We use the methods to measure latency of a number of interactive systems that may be of interest to the VE engineer, with a significant level of confidence. All techniques were found to be highly capable however Steed's Method is both accurate and easy to use without requiring specialised hardware.

  16. Human Cytomegalovirus Requires Epidermal Growth Factor Receptor Signaling To Enter and Initiate the Early Steps in the Establishment of Latency in CD34(+) Human Progenitor Cells.

    PubMed

    Kim, Jung Heon; Collins-McMillen, Donna; Buehler, Jason C; Goodrum, Felicia D; Yurochko, Andrew D

    2017-03-01

    The establishment of human cytomegalovirus (HCMV) latency and persistence relies on the successful infection of hematopoietic cells, which serve as sites of viral persistence and contribute to viral spread. Here, using blocking antibodies and pharmacological inhibitors, we document that HCMV activation of the epidermal growth factor receptor (EGFR) and downstream phosphatidylinositol 3-kinase (PI3K) mediates viral entry into CD34(+) human progenitor cells (HPCs), resulting in distinct cellular trafficking and nuclear translocation of the virus compared to that in other immune cells, such as we have documented in monocytes. We argue that the EGFR allows HCMV to regulate the cellular functions of these replication-restricted cells via its signaling activity following viral binding. In addition to regulating HCMV entry/trafficking, EGFR signaling may also shape the early steps required for the successful establishment of viral latency in CD34(+) cells, as pharmacological inhibition of EGFR increases the transcription of lytic IE1/IE2 mRNA while curbing the expression of latency-associated UL138 mRNA. EGFR signaling following infection of CD34(+) HPCs may also contribute to changes in hematopoietic potential, as treatment with the EGFR kinase (EGFRK) inhibitor AG1478 alters the expression of the cellular hematopoietic cytokine interleukin 12 (IL-12) in HCMV-infected cells but not in mock-infected cells. These findings, along with our previous work with monocytes, suggest that EGFR likely serves as an important determinant of HCMV tropism for select subsets of hematopoietic cells. Moreover, our new data suggest that EGFR is a key receptor for efficient viral entry and that the ensuing signaling regulates important early events required for successful infection of CD34(+) HPCs by HCMV.IMPORTANCE HCMV establishes lifelong persistence within the majority of the human population without causing overt pathogenesis in healthy individuals. Despite this, reactivation of HCMV

  17. Characterization of pal-1, a common proviral insertion site in murine leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice.

    PubMed Central

    Scheijen, B; Jonkers, J; Acton, D; Berns, A

    1997-01-01

    Insertional mutagenesis with Moloney murine leukemia virus (MoMLV) in c-myc and Pim-1 transgenic mice permits the identification of oncogenes that collaborate with the transgenes in lymphomagenesis. The recently identified common insertion site pal-1, in MoMLV-induced lymphomas, is located in a region in which several independent integration clusters are found: eis-1, gfi-1, and evi-5. Proviral insertions of MoMLV in the different integration clusters upregulate the transcriptional activity of the Gfi-1 gene, which is located within the pal-1 locus. The eis-1/pal-1/gfi-1/evi-5 locus serves as a target for MoMLV proviral insertions in pre-B-cell lymphomas of Emu-myc transgenic mice (20%) and in T-cell lymphomas of H-2K-myc (75%) and Emu-pim-1 (93%) transgenic mice. Many tumors overexpress both Gfi-1 as well as Myc and Pim gene family members, indicating that Gfi-1 collaborates with Myc and Pim in lymphomagenesis. Proviral integrations in the previously identified insertion site bmi-1 are, however, mutually exclusive with integrations in the eis-1/pal-1/gfi-1/evi-5 locus. This finding suggests that Bmi-1 and Gfi-1 belong to the same complementation group in lymphoid transformation. PMID:8985317

  18. MiR-328 targeting PIM-1 inhibits proliferation and migration of pulmonary arterial smooth muscle cells in PDGFBB signaling pathway

    PubMed Central

    Qian, Zhengjiang; Zhang, Limin; Chen, Jidong; Li, Yanjiao; Kang, Kang; Qu, Junle; Wang, Zhiwei; Zhai, Yujia; Li, Li; Gou, Deming

    2016-01-01

    MicroRNAs (miRNAs) have been recognized to mediate PDGF-induced cell dysregulation, but their exact functions remain to be elucidated. By using a sensitive S-Poly(T) Plus qRT-PCR method, the expression profiling of 1,078 miRNAs were investigated in pulmonary artery smooth muscle cells (PASMCs) with or without PDGFBB stimulation. MiR-328 was found as a prominent down-regulated miRNA, displaying a specific dose- and time-dependent downregulation upon PDGFBB exposure. Functional analyses revealed that miR-328 could inhibit PASMCs proliferation and migration both with and without PDGFBB treatment. The Ser/Thr-protein kinase-1 (PIM-1) was identified as a direct target of miR-328, and functionally confirmed by a rescue experiment. In addition, the decrease of miR-328 by PDGFBB might be due to the increased expression of DNA methylation transferase 1 (DNMT1) and DNA methylation. Finally, serum miR-328 level was downregulated in PAH patients associated with congenital heart disease (CHD- PAH). Overall, this study provides critical insight into fundamental regulatory mechanism of miR-328 in PDGFBB-activited PASMCs via targeting PIM- 1, and implies the potential of serum miR-328 level as a circulating biomarker for CHD- PAH diagnosis. PMID:27448984

  19. 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)

  20. Double mutant P53 (N340Q/L344R) promotes hepatocarcinogenesis through upregulation of Pim1 mediated by PKM2 and LncRNA CUDR

    PubMed Central

    Wu, Mengying; An, Jiahui; Zheng, Qidi; Xin, Xiaoru; Lin, Zhuojia; Li, Xiaonan; Li, Haiyan; Lu, Dongdong

    2016-01-01

    P53 is frequently mutated in human tumors as a novel gain-of-function to promote tumor development. Although dimeric (M340Q/L344R) influences on tetramerisation on site-specific post-translational modifications of p53, it is not clear how dimeric (M340Q/L344R) plays a role during hepatocarcinogenesis. Herein, we reveal that P53 (N340Q/L344R) promotes hepatocarcinogenesis through upregulation of PKM2. Mechanistically, P53 (N340Q/L344R) forms complex with CUDR and the complex binds to the promoter regions of PKM2 which enhances the expression, phosphorylation of PKM2 and its polymer formation. Thereby, the polymer PKM2 (tetramer) binds to the eleventh threonine on histone H3 that increases the phosphorylation of the eleventh threonine on histone H3 (pH3T11). Furthermore, pH3T11 blocks HDAC3 binding to H3K9Ac that prevents H3K9Ac from deacetylation and stabilizes the H3K9Ac modification. On the other hand, it also decreased tri-methylation of histone H3 on the ninth lysine (H3K9me3) and increases one methylation of histone H3 on the ninth lysine (H3K9me1). Moreover, the combination of H3K9me1 and HP1 α forms more H3K9me3-HP1α complex which binds to the promoter region of Pim1, enhancing the expression of Pim1 that enhances the expression of TERT, oncogenic lncRNA HOTAIR and reduces the TERRA expression. Ultimately, P53 (N340Q/L344R) accerlerates the growth of liver cancer cells Hep3B by activating telomerase and prolonging telomere through the cascade of P53 (N340Q/L344R)-CUDR-PKM2-pH3T11- (H3K9me1-HP1α)-Pim1- (TERT-HOTAIR-TERRA). Understanding the novel functions of P53 (N340Q/L344R) will help in the development of new liver cancer therapeutic approaches that may be useful in a broad range of cancer types. PMID:27167190

  1. Feline immunodeficiency virus latency

    PubMed Central

    2013-01-01

    Despite highly effective anti-retroviral therapy, HIV is thought to persist in patients within long-lived cellular reservoirs in the form of a transcriptionally inactive (latent) integrated provirus. Lentiviral latency has therefore come to the forefront of the discussion on the possibility of a cure for HIV infection in humans. Animal models of lentiviral latency provide an essential tool to study mechanisms of latency and therapeutic manipulation. Of the three animal models that have been described, the feline immunodeficiency virus (FIV)-infected cat is the most recent and least characterized. However, several aspects of this model make it attractive for latency research, and it may be complementary to other model systems. This article reviews what is known about FIV latency and chronic FIV infection and how it compares with that of other lentiviruses. It thereby offers a framework for the usefulness of this model in future research aimed at lentiviral eradication. PMID:23829177

  2. Ego Functioning During Latency

    PubMed Central

    Adams, Milton S.

    1979-01-01

    The latency period is an extremely important transition between the preschool years and adolescence. Normal ego functioning is described, especially cognition, socialization, motor development, and defensive functions. PMID:529320

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. A Readout Mechanism for Latency Codes.

    PubMed

    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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Vibration Feedback Latency Affects Material Perception during Rod Tapping Interactions.

    PubMed

    Hachisu, Taku; Kajimoto, Hiroyuki

    2016-11-15

    We investigated the effect of vibration feedback latency on material perception during a tapping interaction using a rod device. When a user taps a surface, the perception of the material can be modulated by providing a decaying sinusoidal vibration at the moment of contact. To achieve this haptic material augmentation on a touchscreen, a system that can measure the approach velocity and provide vibration with low latency is required. To this end, we developed a touchscreen system that is capable of measuring the approach velocity and providing vibration feedback via a rod device with latency of 0.1 ms. Using this system, we experimentally measured the human detection threshold of the vibration feedback latency adopting a psychophysical approach. We further investigated the effect of latency on the perception of the material using a subjective questionnaire. Results show that the threshold was around 5.5 ms and the latency made the user feel that the surface is soft. In addition, users reported bouncing and denting sensations induced by the latency.

  14. 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

  15. The saccadic size-latency phenomenon explored: Proximal target size is a determining factor in the saccade latency.

    PubMed

    De Vries, J P; Azadi, R; Harwood, M R

    2016-12-01

    Saccade latencies are known to increase for targets presented close to fixation. Recently, it was shown that not only target eccentricity, but the size of a proximal saccade target also plays a crucial role: latencies increase rapidly with increasing target size. Interestingly, these latency increases are greater than those typically found for other supra-threshold manipulations of target properties. Here we evaluate to what extent this phenomenon is distinct from known delays in saccade initiation and whether the phenomenon is truly related to the size of a proximal target. In Experiment 1 we focus on the importance of the required amplitude. Employing a saccade adaptation paradigm we find that the required amplitude is not a determining factor. Focusing on the role of size, in Experiment 2, we find that while latency increases are strongest for targets elongated in the direction of the fovea, elongations perpendicular to this direction also lead to an increase in latencies. Finally, in Experiment 3 we verify that the latency increases are driven by the properties of the saccade target rather than visual input in general. Together these experiments provide converging evidence that the current phenomenon is both novel and a consequence of the relation between proximal target size and its eccentricity.

  16. Pursuit Latency for Chromatic Targets

    NASA Technical Reports Server (NTRS)

    Mulligan, Jeffrey B.; Ellis, Stephen R. (Technical Monitor)

    1998-01-01

    The temporal dynamics of eye movement response to a change in direction of stimulus motion has been used to compare the processing speeds of different types of stimuli (Mulligan, ARVO '97). In this study, the pursuit response to colored targets was measured to test the hypothesis that the slow response of the chromatic system (as measured using traditional temporal sensitivity measures such as contrast sensitivity) results in increased eye movement latencies. Subjects viewed a small (0.4 deg) Gaussian spot which moved downward at a speed of 6.6 deg/sec. At a variable time during the trajectory, the dot's direction of motion changed by 30 degrees, either to the right or left. Subjects were instructed to pursue the spot. Eye movements were measured using a video ophthalmoscope with an angular resolution of approximately 1 arc min and a temporal sampling rate of 60 Hz. Stimuli were modulated in chrominance for a variety of hue directions, combined with a range of small luminance increments and decrements, to insure that some of the stimuli fell in the subjects' equiluminance planes. The smooth portions of the resulting eye movement traces were fit by convolving the stimulus velocity with an exponential having variable onset latency, time constant and amplitude. Smooth eye movements with few saccades were observed for all stimuli. Pursuit responses to stimuli having a significant luminance component are well-fit by exponentials having latencies and time constants on the order of 100 msec. Increases in pursuit response latency on the order of 100-200 msec are observed in response to certain stimuli, which occur in pairs of complementary hues, corresponding to the intersection of the stimulus section with the subjects' equiluminant plane. Smooth eye movements can be made in response to purely chromatic stimuli, but are slower than responses to stimuli with a luminance component.

  17. Mechanisms and benefits of granule cell latency coding in the mouse olfactory bulb

    PubMed Central

    Giridhar, Sonya; Urban, Nathaniel N.

    2012-01-01

    Inhibitory circuits are critical for shaping odor representations in the olfactory bulb. There, individual granule cells can respond to brief stimulation with extremely long (up to 1000 ms), input-specific latencies that are highly reliable. However, the mechanism and function of this long timescale activity remain unknown. We sought to elucidate the mechanism responsible for long-latency activity, and to understand the impact of widely distributed interneuron latencies on olfactory coding. We used a combination of electrophysiological, optical, and pharmacological techniques to show that long-latency inhibition is driven by late onset synaptic excitation to granule cells. This late excitation originates from tufted cells, which have intrinsic properties that favor longer latency spiking than mitral cells. Using computational modeling, we show that widely distributed interneuron latency increases the discriminability of similar stimuli. Thus, long-latency inhibition in the olfactory bulb requires a combination of circuit- and cellular-level mechanisms that function to improve stimulus representations. PMID:22754503

  18. 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

  19. Effects of stimulus intensity on latency and conduction time of short-latency somatosensory evoked potentials.

    PubMed

    Shiga, Y; Yamada, T; Ofuji, A; Fujita, Y; Kawamura, T; Inoue, K; Hada, Y; Yamazaki, H; Cheng, M H; Yeh, M H

    2001-04-01

    We studied the effect of stimulus intensity on latencies of short-latency somatosensory evoked potentials (SSEP) by measuring both onset and peak latencies individually. The latencies of N9, N13, N20 and N9-N13 peripheral conduction time (PCT) of median nerve (MN) SSEP, and N8, N23, P37 and N8-N23 PCT of tibial nerve (TN) and sural nerve (SN) SSEP significantly shortened with increasing stimulus intensity by onset latency measurement. However, those latencies by peak latency measurement were less significantly shortened or had only a trend of latency shortening without statistical significance. In contrast to PCT, N13-N20 central conduction time (CCT) of MN-SSEP and N23-P37 CCT of TN- or SN-SSEP showed no latency changes with the increased stimulus intensity by both onset and peak latencies measurement. As peak latencies had greater interindividual variability than onset latencies shown by larger standard deviation, shortening of onset latencies were more consistent than that of peak latencies. We think shortening of onset latencies indicates the recruitment of faster conduction fiber along with increased stimulus intensity. As the degree of latency shortening was less if stimulus intensity was above 2.5 times sensory threshold, the stimulus intensity greater than 2.5 times the sensory threshold should be used for clinical application.

  20. Monitoring data transfer latency in CMS computing operations

    SciTech Connect

    Bonacorsi, Daniele; Diotalevi, Tommaso; Magini, Nicolo; Sartirana, A.; Taze, Meric; Wildish, Tony

    2015-12-23

    During the first LHC run, the CMS experiment collected tens of Petabytes of collision and simulated data, which need to be distributed among dozens of computing centres with low latency in order to make efficient use of the resources. While the desired level of throughput has been successfully achieved, it is still common to observe transfer workflows that cannot reach full completion in a timely manner due to a small fraction of stuck files which require operator intervention.For this reason, in 2012 the CMS transfer management system, PhEDEx, was instrumented with a monitoring system to measure file transfer latencies, and to predict the completion time for the transfer of a data set. The operators can detect abnormal patterns in transfer latencies while the transfer is still in progress, and monitor the long-term performance of the transfer infrastructure to plan the data placement strategy.Based on the data collected for one year with the latency monitoring system, we present a study on the different factors that contribute to transfer completion time. As case studies, we analyze several typical CMS transfer workflows, such as distribution of collision event data from CERN or upload of simulated event data from the Tier-2 centres to the archival Tier-1 centres. For each workflow, we present the typical patterns of transfer latencies that have been identified with the latency monitor.We identify the areas in PhEDEx where a development effort can reduce the latency, and we show how we are able to detect stuck transfers which need operator intervention. Lastly, we propose a set of metrics to alert about stuck subscriptions and prompt for manual intervention, with the aim of improving transfer completion times.

  1. Monitoring data transfer latency in CMS computing operations

    DOE PAGES

    Bonacorsi, Daniele; Diotalevi, Tommaso; Magini, Nicolo; ...

    2015-12-23

    During the first LHC run, the CMS experiment collected tens of Petabytes of collision and simulated data, which need to be distributed among dozens of computing centres with low latency in order to make efficient use of the resources. While the desired level of throughput has been successfully achieved, it is still common to observe transfer workflows that cannot reach full completion in a timely manner due to a small fraction of stuck files which require operator intervention.For this reason, in 2012 the CMS transfer management system, PhEDEx, was instrumented with a monitoring system to measure file transfer latencies, andmore » to predict the completion time for the transfer of a data set. The operators can detect abnormal patterns in transfer latencies while the transfer is still in progress, and monitor the long-term performance of the transfer infrastructure to plan the data placement strategy.Based on the data collected for one year with the latency monitoring system, we present a study on the different factors that contribute to transfer completion time. As case studies, we analyze several typical CMS transfer workflows, such as distribution of collision event data from CERN or upload of simulated event data from the Tier-2 centres to the archival Tier-1 centres. For each workflow, we present the typical patterns of transfer latencies that have been identified with the latency monitor.We identify the areas in PhEDEx where a development effort can reduce the latency, and we show how we are able to detect stuck transfers which need operator intervention. Lastly, we propose a set of metrics to alert about stuck subscriptions and prompt for manual intervention, with the aim of improving transfer completion times.« less

  2. Measurement and application of fault latency

    NASA Technical Reports Server (NTRS)

    Shin, K. G.; Lee, Y.-H.

    1986-01-01

    The time interval between the occurrence of a fault and the detection of the error caused by the fault is divided by the generation of that error into two parts: fault latency and error latency. Since the moment of error generation is not directly observable, all related works in the literature have dealt with only the sum of fault and error latencies, thereby making the analysis of their separate effects impossible. To remedy this deficiency, (1) a new methodology for indirectly measuring fault latency is presented; the distribution of fault latency is derived from the methodology; and (3) the knowledge of fault latency is applied to the analysis of two important examples. The proposed methodology has been implemented for measuring fault latency in the Fault-Tolerant Multiprocessor (FTMP) at the NASA Airlab. The experimental results show wide variations in the mean fault latencies of different function circuits within FTMP. Also, the measured distributions of fault latency are shown to have monotone hazard rates. Consequently, Gamma and Weibull distributions are selected for the least-squares fit as the distribution of fault latency.

  3. Identification of noisy response latency

    NASA Astrophysics Data System (ADS)

    Tamborrino, Massimiliano; Ditlevsen, Susanne; Lansky, Petr

    2012-08-01

    In many physical systems there is a time delay before an applied input (stimulation) has an impact on the output (response), and the quantification of this delay is of paramount interest. If the response can only be observed on top of an indistinguishable background signal, the estimation can be highly unreliable, unless the background signal is accounted for in the analysis. In fact, if the background signal is ignored, however small it is compared to the response and however large the delay is, the estimate of the time delay will go to zero for any reasonable estimator when increasing the number of observations. Here we propose a unified concept of response latency identification in event data corrupted by a background signal. It is done in the context of information transfer within a neural system, more specifically on spike trains from single neurons. The estimators are compared on simulated data and the most suitable for specific situations are recommended.

  4. Avoiding and tolerating latency in large-scale next-generation shared-memory multiprocessors

    NASA Technical Reports Server (NTRS)

    Probst, David K.

    1993-01-01

    A scalable solution to the memory-latency problem is necessary to prevent the large latencies of synchronization and memory operations inherent in large-scale shared-memory multiprocessors from reducing high performance. We distinguish latency avoidance and latency tolerance. Latency is avoided when data is brought to nearby locales for future reference. Latency is tolerated when references are overlapped with other computation. Latency-avoiding locales include: processor registers, data caches used temporally, and nearby memory modules. Tolerating communication latency requires parallelism, allowing the overlap of communication and computation. Latency-tolerating techniques include: vector pipelining, data caches used spatially, prefetching in various forms, and multithreading in various forms. Relaxing the consistency model permits increased use of avoidance and tolerance techniques. Each model is a mapping from the program text to sets of partial orders on program operations; it is a convention about which temporal precedences among program operations are necessary. Information about temporal locality and parallelism constrains the use of avoidance and tolerance techniques. Suitable architectural primitives and compiler technology are required to exploit the increased freedom to reorder and overlap operations in relaxed models.

  5. 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...

  6. 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.

  7. 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.

  8. 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

  9. Head Tracking Latency in Virtual Environments Revisited: Do Users with Multiple Sclerosis Notice Latency Less?

    PubMed

    Samaraweera, Gayani; Guo, Rongkai; Quarles, John

    2016-05-01

    Latency (i.e., time delay) in a virtual environment is known to disrupt user performance, presence and induce simulator sickness. Thus, with emerging use of virtual rehabilitation, the target populations' latency perception thresholds need to be considered to fully understand and possibly control the implications of latency in a Virtual Rehabilitation environment. We present a study that quantifies the latency discrimination thresholds of a yet untested population-a specific subset of mobility impaired participants where participants suffer from Multiple Sclerosis-and compare the results to a control group of healthy participants. The study was modeled after previous latency discrimination research and shows significant differences in latency perception between the two populations with MS participants showing lower sensitivity to latency than healthy participants.

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  11. Evidence and Impact of Human Papillomavirus Latency

    PubMed Central

    Gravitt, Patti E

    2012-01-01

    At present, there is no consensus in the scientific community regarding the ability for human papillomavirus (HPV) infections to establish latency. Based on animal studies, a model of papillomavirus latency has been proposed in which papillomaviruses can be retained in the basal epithelial stem cell pool as latent infections and periodically induced to reactivate when the stem cell divides and one daughter cell is committed to terminal differentiation and induction of the viral life cycle. Tissue resident memory T-cells are hypothesized to control these periodic reactivation episodes and thus limit their duration. In this paper, evidence from human studies consistent with this model of papillomavirus latency is reviewed. Given the strong circumstantial evidence supporting a natural history of HPV infection which includes a immunologically controlled latent state, the longer term implications of HPV latency on a highly infected and aging population may warrant a more serious evaluation. PMID:23341855

  12. HIV-1 latency in actively dividing human T cell lines

    PubMed Central

    Jeeninga, Rienk E; Westerhout, Ellen M; van Gerven, Marja L; Berkhout, Ben

    2008-01-01

    Background Eradication of HIV-1 from an infected individual cannot be achieved by current drug regimens. Viral reservoirs established early during the infection remain unaffected by anti-retroviral therapy 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 transcriptional silent provirus. However, the molecular mechanisms that permit long-term transcriptional control of proviral gene expression in these cells are still not well understood. Exploring the molecular details of viral latency will provide new insights for eventual future therapeutics that aim at viral eradication. Results We set out to develop a new in vitro HIV-1 latency model system using the doxycycline (dox)-inducible HIV-rtTA variant. Stable cell clones were generated with a silent HIV-1 provirus, which can subsequently be activated by dox-addition. Surprisingly, only a minority of the cells was able to induce viral gene expression and a spreading infection, eventhough these experiments were performed with the actively dividing SupT1 T cell line. These latent proviruses are responsive to TNFα treatment and alteration of the DNA methylation status with 5-Azacytidine or genistein, but not responsive to the regular T cell activators PMA and IL2. Follow-up experiments in several T cell lines and with wild-type HIV-1 support these findings. Conclusion We describe the development of a new in vitro model for HIV-1 latency and discuss the advantages of this system. The data suggest that HIV-1 proviral latency is not restricted to resting T cells, but rather an intrinsic property of the virus. PMID:18439275

  13. 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.

  14. 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.

  15. 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

  16. CTCF Regulates Kaposi's Sarcoma-Associated Herpesvirus Latency Transcription by Nucleosome Displacement and RNA Polymerase Programming

    PubMed Central

    Cho, Hyosun; Sung, Gi-Ho

    2013-01-01

    CCCTC-binding factor (CTCF) has been implicated in various aspects of viral and host chromatin organization and transcriptional control. We showed previously that CTCF binds to a cluster of three sites in the first intron of the Kaposi's sarcoma-associated herpesvirus (KSHV) multicistronic latency-associated transcript that encodes latency-associated nuclear antigen (LANA), viral cyclin (vCyclin), vFLIP, viral microRNAs, and kaposin. We show here that these CTCF binding sites regulate mRNA production, RNA polymerase II (RNAPII) programming, and nucleosome organization of the KSHV latency transcript control region. We also show that KSHV bacmids lacking these CTCF binding sites have elevated and altered ratios of spliced latency transcripts. CTCF binding site mutations altered RNAPII and RNAPII-accessory factor interactions with the latency control region. CTCF binding sites were required for the in vitro recruitment of RNAPII to the latency control region, suggesting that direct interactions between CTCF and RNAPII contribute to transcription regulation. Histone modifications in the latency control region were also altered by mutations in the CTCF binding sites. Finally, we show that CTCF binding alters the regular phasing of nucleosomes in the latency gene transcript and intron, suggesting that nucleosome positioning can be an underlying biochemical mechanism of CTCF function. We propose that RNAPII interactions and nucleosome displacement serve as a biochemical basis for programming RNAPII in the KSHV transcriptional control region. PMID:23192870

  17. 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.

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

    PubMed

    Ohl, Stephan; Willert, Malte; Staadt, Oliver

    2015-12-01

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

  19. 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

  20. 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

  1. 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.

  2. P300 latency indexes nitrogen narcosis.

    PubMed

    Fowler, B; Pogue, J; Porlier, G

    1990-03-01

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

  3. 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.

  4. 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…

  5. 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.

  6. Therapeutics for HIV-1 reactivation from latency.

    PubMed

    Sgarbanti, Marco; Battistini, Angela

    2013-08-01

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

  7. New results in fault latency modelling

    NASA Technical Reports Server (NTRS)

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

    1983-01-01

    Studies carried out by McGough and Swern (1981, 1983) are summarized. In these studies, an avionics processor was simulated and a series of fault injection experiments was carried out to determine the degree of fault latency in a redundant flight control system that employed comparison monitoring as the exclusive means of failure detection. A determination was also made of the fault coverage of a typical self-test program. The summary presented stresses that a self-test program should be designed to capitalize on the hardware mechanization of the processor. If this is not done, subtests tend to repeatedly exercise the same hardware components while neglecting to exercise a substantial proportion of the remainder. It is also pointed out that fault latency is relatively independent of both the length and instruction mix of a program. A significant difference is found in fault coverage assessed using pin-level and gate-level fault models.

  8. Arbitration in crossbar interconnect for low latency

    DOEpatents

    Ohmacht, Martin; Sugavanam, Krishnan

    2013-02-05

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

  9. Error latency estimation using functional fault modeling

    NASA Technical Reports Server (NTRS)

    Manthani, S. R.; Saxena, N. R.; Robinson, J. P.

    1983-01-01

    A complete modeling of faults at gate level for a fault tolerant computer is both infeasible and uneconomical. Functional fault modeling is an approach where units are characterized at an intermediate level and then combined to determine fault behavior. The applicability of functional fault modeling to the FTMP is studied. Using this model a forecast of error latency is made for some functional blocks. This approach is useful in representing larger sections of the hardware and aids in uncovering system level deficiencies.

  10. Detecting Intermediary Hosts by TCP Latency Measurements

    NASA Astrophysics Data System (ADS)

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

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

  11. 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.

  12. Glomerular Latency Coding in Artificial Olfaction

    PubMed Central

    Yamani, Jaber Al; Boussaid, Farid; Bermak, Amine; Martinez, Dominique

    2011-01-01

    Sensory perception results from the way sensory information is subsequently transformed in the brain. Olfaction is a typical example in which odor representations undergo considerable changes as they pass from olfactory receptor neurons (ORNs) to second-order neurons. First, many ORNs expressing the same receptor protein yet presenting heterogeneous dose–response properties converge onto individually identifiable glomeruli. Second, onset latency of glomerular activation is believed to play a role in encoding odor quality and quantity in the context of fast information processing. Taking inspiration from the olfactory pathway, we designed a simple yet robust glomerular latency coding scheme for processing gas sensor data. The proposed bio-inspired approach was evaluated using an in-house SnO2 sensor array. Glomerular convergence was achieved by noting the possible analogy between receptor protein expressed in ORNs and metal catalyst used across the fabricated gas sensor array. Ion implantation was another technique used to account both for sensor heterogeneity and enhanced sensitivity. The response of the gas sensor array was mapped into glomerular latency patterns, whose rank order is concentration-invariant. Gas recognition was achieved by simply looking for a “match” within a library of spatio-temporal spike fingerprints. Because of its simplicity, this approach enables the integration of sensing and processing onto a single-chip. PMID:22319491

  13. Effect of data latency upon missile accuracy

    NASA Astrophysics Data System (ADS)

    Monroe, L. J.

    1983-12-01

    This study examined the effect of data latency upon air-to-air guided missile accuracy. This research was done by modeling a digital guided missile, inserting the model into a computer simulation and generating miss distance statistics. The digital guided missile was modeled after the DIS microcomputer architecture. The DIS (Digital Integrating Subsystem) approach involves a number of loosely coupled microprocessors which communicate over a serial multiplex bus. It was developed at the Air Force Armament Lab., Eglin AFB, FL. The missile simulation, Tactics IV, involves three degrees of freedom and is written in FORTRAN IV. It was developed by Science Applications, Inc. in conjunction with AFWAL/FIMB, Wright Patterson AFB, OH. The results of this study indicate that typical data latency values generate only small increases in miss distance. The maximum delays tested were .01 seconds and the average increase in miss distance was 2.12 feet. Additionally, it was discovered that the transmission rate of the DIS microcomputers greatly affected miss distance. Microcomputers transmitting at 10 HZ generated large miss distances, even without data latency present. The identical missile engagements using transmission rates of 100 HZ resulted in much smaller miss distances.

  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. Estimating the distribution of fault latency in a digital processor

    NASA Technical Reports Server (NTRS)

    Ellis, Erik L.; Butler, Ricky W.

    1987-01-01

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

  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. Latency causes and reduction in optical metro networks

    NASA Astrophysics Data System (ADS)

    Bobrovs, Vjaceslavs; Spolitis, Sandis; Ivanovs, Girts

    2013-12-01

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

  18. Rapid eye movement latency in children and adolescents.

    PubMed

    Mason, Thornton B A; Teoh, Laurel; Calabro, Kristen; Traylor, Joel; Karamessinis, Laurie; Schultz, Brian; Samuel, John; Gallagher, Paul R; Marcus, Carole L

    2008-09-01

    Rapid eye movement sleep distribution changes during development, but little is known about rapid eye movement latency variation in childhood by age, sex, or pathologic sleep states. We hypothesized that: (1) rapid eye movement latency would differ in normal children by age, with a younger cohort (1-10 years) demonstrating shorter rapid eye movement latency than an older group (>10-18 years); (2) rapid eye movement latency in children would differ from typical adult rapid eye movement latency; and (3) intrinsic sleep disorders (narcolepsy, pediatric obstructive sleep apnea syndrome) would disrupt normal developmental patterns of rapid eye movement latency. A retrospective chart review included data from clinic visits and of rapid eye movement latency and other parameters measured by overnight polysomnography. Participants included 98 control children, 90 children with obstructive sleep apnea syndrome, and 13 children with narcolepsy. There were no statistically significant main effects of age category or sex on rapid eye movement latency. Rapid eye movement latency, however, exhibited a significant inverse correlation with age within the older control children. Healthy children exhibited rapid eye movement latencies significantly longer than adults. Normal control patients demonstrated significantly longer rapid eye movement latency than obstructive sleep apnea syndrome and narcolepsy patients.

  19. 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.

  20. 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

  1. Context-dependent inhibition of unloaded muscles during the long-latency epoch.

    PubMed

    Nashed, Joseph Y; Kurtzer, Isaac L; Scott, Stephen H

    2015-01-01

    A number of studies have highlighted the sophistication of corrective responses in lengthened muscles during the long-latency epoch. However, in various contexts, unloading can occur, which requires corrective actions from a shortened muscle. Here, we investigate the sophistication of inhibitory responses in shortened muscles due to unloading. Our first experiment quantified the inhibitory responses following an unloading torque that displaced the hand either into or away from a peripheral target. We observed larger long-latency inhibitory responses when perturbed into the peripheral target compared with away from the target. In our second experiment, we characterized the degree of inhibition following unloading with respect to different levels of preperturbation muscle activity. We initially observed that the inhibitory activity during the short-latency epoch scaled with increased levels of preperturbation muscle activity. However, this scaling peaked early in the R2 epoch (∼ 50 ms) but then quickly diminished through the rest of the long-latency epoch. Finally, in experiment 3, we investigated whether inhibitory perturbation responses consider intersegmental dynamics of the limb. We quantified unloading responses for either pure shoulder or pure elbow torques that evoked similar motion at the shoulder but different elbow motion. The long-latency inhibitory response in the shoulder, unlike the short-latency, was greater for the shoulder torque compared with the response following an elbow torque, as previously observed for a loading response. Taken together, these results illustrate that the long-latency unloading response is capable of a similar level of complexity as observed when loads are applied to the limb.

  2. The Effects of Low Latency on Pointing and Steering Tasks.

    PubMed

    Friston, Sebastian; Karlström, Per; Steed, Anthony

    2016-05-01

    Latency is detrimental to interactive systems, especially pseudo-physical systems that emulate real-world behaviour. It prevents users from making quick corrections to their movement, and causes their experience to deviate from their expectations. Latency is a result of the processing and transport delays inherent in current computer systems. As such, while a number of studies have hypothesized that any latency will have a degrading effect, few have been able to test this for latencies less than ∼ 50 ms. In this study we investigate the effects of latency on pointing and steering tasks. We design an apparatus with a latency lower than typical interactive systems, using it to perform interaction tasks based on Fitts's law and the Steering law. We find evidence that latency begins to affect performance at ∼ 16 ms, and that the effect is non-linear. Further, we find latency does not affect the various components of an aiming motion equally. We propose a three stage characterisation of pointing movements with each stage affected independently by latency. We suggest that understanding how users execute movement is essential for studying latency at low levels, as high level metrics such as total movement time may be misleading.

  3. 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.

  4. Low latency and persistent data storage

    DOEpatents

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

    2014-11-04

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

  5. Low latency and persistent data storage

    DOEpatents

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

    2014-02-18

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

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

    PubMed

    Wang, Wan-rong; Xie, Sheng

    2016-02-01

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

  7. 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…

  8. 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…

  9. 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…

  10. Short latency cerebellar modulation of the basal ganglia

    PubMed Central

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

    2014-01-01

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

  11. Short latency cerebellar modulation of the basal ganglia.

    PubMed

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

    2014-12-01

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

  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. 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

  14. Treating excessively slow responding of a young man with Asperger syndrome using differential reinforcement of short response latencies.

    PubMed

    Tiger, Jeffrey H; Bouxsein, Kelly J; Fisher, Wayne W

    2007-01-01

    Fjellstedt and Sulzer-Azaroff (1973) used differential reinforcement of short latencies to decrease a child's latency to comply with instructions. We replicated this contingency with a young man diagnosed with Asperger syndrome across two tasks (question answering and math problem solving). We added a differential reinforcement contingency to teach the participant to discriminate between math problems that could be answered rapidly and those that required more time for accurate performance.

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

    PubMed

    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.

  16. Response Latency as a Function of Training Method, Information Level, Acquisition, and Overlearning. Learning Research and Development Center Reprint Number 52.

    ERIC Educational Resources Information Center

    Judd, Wilson A.; Glaser, Robert.

    Response latency was studied as a measure of associative strength or degree of learning and possible basis for instructional decision making in computer-assisted instruction. Latency was investigated in a paired-associate task as a function of training procedure and information transmission requirements during acquisition and overlearning. The…

  17. Novel technology for reducing wavefront image processing latency

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  18. Transient evoked otoacoustic emission with unexpectedly short latency.

    PubMed

    Kruglov, A V; Artamasov, S V; Frolenkov, G I; Tavartkiladze, G A

    1997-03-01

    Two alternative approaches for studying short-latency click-evoked otoacoustic emission (OAE) in normal-hearing subjects were employed. Growth of a click-evoked "ear canal response" with stimulus increase became progressively more non-linear and saturated when the latency of the analyzed segment of response increased. This relation between latency and shape of the response input/output function was observed even after linear component cancellation, indicating that it could be an intrinsic property of OAE. Hence, the existence of an essentially linear short-latency OAE component which is probably eliminated by commonly used artifact cancellation technique is suggested. Taking into account the fact that transient evoked otoacoustic emission (TEOAE) may be completely suppressed by simultaneously presented noise, a "true" artifact cancellation was performed by subtracting the ear canal response in the presence of a masker from the conventional click-evoked OAE recording. An additional TEOAE component with a latency of 2.5-5 ms was found. Its growth with stimulus intensity was indeed more linear than that of later components. However, latency and frequency of this TEOAE component, being specific for each subject, can hardly be explained by both a commonly assumed latency-frequency relationship of TEOAE and a generally used estimation of TEOAE latency as the sum of the forward and backward traveling wave propagation times.

  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. Quantitative evaluation and optimization of co-drugging to improve anti-HIV latency therapy

    PubMed Central

    Wong, Victor C.; Fong, Linda E.; Adams, Nicholas M.; Xue, Qiong; Dey, Siddharth S.; Miller-Jensen, Kathryn

    2014-01-01

    Human immunodeficiency virus 1 (HIV) latency remains a significant obstacle to curing infected patients. One promising therapeutic strategy is to purge the latent cellular reservoir by activating latent HIV with latency-reversing agents (LRAs). In some cases, co-drugging with multiple LRAs is necessary to activate latent infections, but few studies have established quantitative criteria for determining when co-drugging is required. Here we systematically quantified drug interactions between histone deacetylase inhibitors and transcriptional activators of HIV and found that the need for co-drugging is determined by the proximity of latent infections to the chromatin-regulated viral gene activation threshold at the viral promoter. Our results suggest two classes of latent viral integrations: those far from the activation threshold that benefit from co-drugging, and those close to the threshold that are efficiently activated by a single drug. Using a primary T cell model of latency, we further demonstrated that the requirement for co-drugging was donor dependent, suggesting that the host may set the level of repression of latent infections. Finally, we showed that single drug or co-drugging doses could be optimized, via repeat stimulations, to minimize unwanted side effects while maintaining robust viral activation. Our results motivate further study of patient-specific latency-reversing strategies. PMID:26191086

  1. The molecular basis of herpes simplex virus latency.

    PubMed

    Nicoll, Michael P; Proença, João T; Efstathiou, Stacey

    2012-05-01

    Herpes simplex virus type 1 is a neurotropic herpesvirus that establishes latency within sensory neurones. Following primary infection, the virus replicates productively within mucosal epithelial cells and enters sensory neurones via nerve termini. The virus is then transported to neuronal cell bodies where latency can be established. Periodically, the virus can reactivate to resume its normal lytic cycle gene expression programme and result in the generation of new virus progeny that are transported axonally back to the periphery. The ability to establish lifelong latency within the host and to periodically reactivate to facilitate dissemination is central to the survival strategy of this virus. Although incompletely understood, this review will focus on the mechanisms involved in the regulation of latency that centre on the functions of the virus-encoded latency-associated transcripts (LATs), epigenetic regulation of the latent virus genome and the molecular events that precipitate reactivation.

  2. 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

  3. Neural latencies do not explain the auditory and audio-visual flash-lag effect.

    PubMed

    Arrighi, Roberto; Alais, David; Burr, David

    2005-11-01

    A brief flash presented physically aligned with a moving stimulus is perceived to lag behind, a well studied phenomenon termed the Flash-Lag Effect (FLE). It has been recently shown that the FLE also occurs in audition, as well as cross-modally between vision and audition. The present study has two goals: to investigate the acoustic and cross-modal FLE using a random motion technique; and to investigate whether neural latencies may account for the FLE in general. The random motion technique revealed a strong cross-modal FLE for visual motion stimuli and auditory probes, but not for the other conditions. Visual and auditory latencies for stimulus appearance and for motion were measured with three techniques: integration, temporal alignment and reaction times. All three techniques showed that a brief static acoustic stimulus is perceived more rapidly than a brief static visual stimulus, while a sound source in motion is perceived more slowly than a comparable visual stimulus. While the results of these three techniques agreed closely with each other, they were exactly opposite that required to account for the FLE by neural latencies. We conclude that neural latencies do not, in general, explain the flash-lag effect. Rather, our data suggest that neural integration times are more important.

  4. 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.

  5. 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

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

    PubMed

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

    2013-08-01

    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.

  7. 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

  8. 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

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

    NASA Astrophysics Data System (ADS)

    Zabołotny, Wojciech M.

    2016-09-01

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

  10. 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)

  11. Role of microRNAs in herpesvirus latency and persistence.

    PubMed

    Grey, Finn

    2015-04-01

    The identification of virally encoded microRNAs (miRNAs) has had a major impact on the field of herpes virology. Given their ability to target cellular and viral transcripts, and the lack of immune response to small RNAs, miRNAs represent an ideal mechanism of gene regulation during viral latency and persistence. In this review, we discuss the role of miRNAs in virus latency and persistence, specifically focusing on herpesviruses. We cover the current knowledge on miRNAs in establishing and maintaining virus latency and promoting survival of infected cells through targeting of both viral and cellular transcripts, highlighting key publications in the field. We also discuss potential areas of future research and how novel technologies may aid in determining how miRNAs shape virus latency in the context of herpesvirus infections.

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

    PubMed

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

    2016-04-06

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

  13. Optimizing System Call Latency of ARM Virtual Machines

    NASA Astrophysics Data System (ADS)

    Sok, Song-Woo; Jung, Young-Woo; Lee, Cheol-Hun

    2017-01-01

    This paper introduces ViMo-S, a type 1 hypervisor for ARMv7 and ARMv8-based ARM server systems. It supports full virtualization to run existing operating systems and applications unmodified. It uses ARM hardware virtualization extensions to optimize the performance of virtual machines, especially system call latency. Therefore, its virtual machines’ system call latency is near physical machine’s, while other hypervisors like Xen and KVM show relatively slower and unstable performances in benchmark tests.

  14. 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.

  15. Identification of Human Herpesvirus 6 Latency-Associated Transcripts

    PubMed Central

    Kondo, Kazuhiro; Shimada, Kazuya; Sashihara, Junji; Tanaka-Taya, Keiko; Yamanishi, Koichi

    2002-01-01

    Four kinds of latency-associated transcripts of human herpesvirus 6 were identified which were detected only in latently infected cells. Although they were oriented in the same direction as the immediate-early 1 and 2 (IE1/IE2) genes and shared their protein-coding region with IE1/IE2, their transcription start sites and exon(s) were latency associated. PMID:11907257

  16. 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

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

    PubMed

    Webb, Paul W

    2004-02-01

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

  18. 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.

  19. The mTOR Complex Controls HIV Latency.

    PubMed

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

    2016-12-14

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

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

    PubMed

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

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

  1. Combining modalities with different latencies for optimal motor control.

    PubMed

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

    2008-11-01

    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 hypothesis. 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, whereas 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.

  2. 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.

  3. An improved approximation ratio for the minimum latency problem

    SciTech Connect

    Goemans, M.; Kleinberg, J.

    1996-12-31

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

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

    PubMed

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

    2015-02-26

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

  5. 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.

  6. Compact binary coalescence searches with low latency: why and how

    NASA Astrophysics Data System (ADS)

    Fotopoulos, Nickolas; Cannon, Kipp; Frei, Melissa; Hanna, Chad; Keppel, Drew; Privitera, Stephen; Singer, Leo

    2011-04-01

    Low-latency gravitational-wave (GW) detection of a compact binary coalescence (CBC) will allow electromagnetic (EM) followups to observe earlier parts of the corresponding lightcurves, which are brighter, convey more information about the progenitor system, and allow a more confident association of GW and EM transients. Conventional matched filter banks, common in CBC searches, are computationally efficient, but incur a latency of many minutes. Searches with latencies of seconds and significantly increased throughput are achievable with techniques such as principal component analysis, to reduce the number of filtered templates, hierarchical detection with singular value decomposition by-products, and exploitation of the quasi-monochromatic structure of chirps to filter time-slices at different sample rates. We present an implementation of these ideas called LLOID, based on the LSC Algorithm Library and the GStreamer multimedia framework.

  7. Characterising latency for AO optical sensors: an implementation

    NASA Astrophysics Data System (ADS)

    Dixon, Thomas; Bennet, Francis; Price, Ian; Rigaut, Francois

    2016-07-01

    The latency of electro-optical components is of high importance in the design of Adaptive Optics systems, as it limits the performance of the control loop. There exists a need for a latency measurement method that can be constructed with simple components found in most Adaptive Optics labs that still provides a measurement accurate to sub-microseconds. Through a combination of research and experimentation, potential methodologies were investigated with the aim of producing reliable latency measurements. This document will discuss one such method, involving coupling a LED pulse output and detected pulse input signals to the same clock for easy comparison. For this method, a proof-of-concept was developed using MATLAB and small analogue electronics, and the performance characterised. This characterisation showed that although there is some merit to the method, improvements are necessary to increase the precision of the measurement to a level usable in Adaptive Optics systems.

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

    NASA Technical Reports Server (NTRS)

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

    2017-01-01

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

  9. 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.

  10. 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.

  11. Low-latency data analysis for the spherical detector Mario Schenberg

    NASA Astrophysics Data System (ADS)

    Filipe Da Silva Costa, Carlos; Costa, César Augusto; Denys Aguiar, Odylio

    2014-04-01

    The confrontation of gravitational waves (GWs) with their electromagnetic (EM) counterparts will be rich with information about astrophysical events. Initially, this confrontation will corroborate GW detections; afterwards, when GW detections become more recurrent, it will allow astrophysics to combine information from different channels (GW, EM and also neutrinos). A low-latency data analysis which provides the direction of an incoming GW candidate is required to confront it with fast follow-up EM observations. Until now, no low-latency data analysis has been developed for spherical detectors. One spherical detector alone is capable of determining both the GW direction and polarization. By using this capability, we have developed a low-latency data analysis pipeline for the Mario Schenberg detector. This pipeline is able to retrieve the direction of GW triggers with an average angular resolution from δs ˜ 8° at SNR ˜ 12 to δs ˜ 1° at SNR ˜ 80, in a timespan of a 4 s for 32 s of data being analyzed. We apply a veto which reduces fake events up to 90% when maintaining the GW efficiency above 90% for high SNRs. We provide here a description of the method and its efficiency: resolution on the direction, false alarm rate and computational time.

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. Reconstructing ERP amplitude effects after compensating for trial-to-trial latency jitter: A solution based on a novel application of residue iteration decomposition.

    PubMed

    Ouyang, Guang; Sommer, Werner; Zhou, Changsong

    2016-11-01

    Stimulus-locked averaged event-related potentials (ERPs) are among the most frequently used signals in Cognitive Neuroscience. However, the late, cognitive or endogenous ERP components are often variable in latency from trial to trial in a component-specific way, compromising the stability assumption underlying the averaging scheme. Here we show that trial-to-trial latency variability of ERP components not only blurs the average ERP waveforms, but may also attenuate existing or artificially induce condition effects in amplitude. Hitherto this problem has not been well investigated. To tackle this problem, a method to measure and compensate component-specific trial-to-trial latency variability is required. Here we first systematically analyze the problem of single trial latency variability for condition effects based on simulation. Then, we introduce a solution by applying residue iteration decomposition (RIDE) to experimental data. RIDE separates different clusters of ERP components according to their time-locking to stimulus onsets, response times, or neither, based on an algorithm of iterative subtraction. We suggest to reconstruct ERPs by re-aligning the component clusters to their most probable single trial latencies. We demonstrate that RIDE-reconstructed ERPs may recover amplitude effects that are diminished or exaggerated in conventional averages by trial-to-trial latency jitter. Hence, RIDE-corrected ERPs may be a valuable tool in conditions where ERP effects may be compromised by latency variability.

  15. 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.

  16. Using Transparent Informed Prefetching (TIP) to reduce file read latency

    NASA Technical Reports Server (NTRS)

    Patterson, R. H.; Gibson, G. A.; Satyanarayanan, M.

    1993-01-01

    As processor performance gains continue to outstrip Input/Output gains, I/O performance is becoming critical to overall system performance. File read latency is the most significant bottleneck for high performance I/O. Other aspects of I/O performance benefit from recent advances in disk bandwidth and throughput resulting from disk arrays, and in write performance derived from buffered write behind and the Log-structured File System. The access gap problem limiting improvements in read latency is exacerbated by distributed file systems operating over networks with diverse bandwidth. Focus is on extending the power of caching and prefetching to reduce file read latencies by exploiting hints from high-levels of a system. Such Transparent Informed Prefetching, TIP, and its benefits are described. It is argued that hints that disclose high level knowledge are a means for transferring optimization information across, without violating, module boundaries. How TIP can be used to convert the high throughput of new technologies such as disk arrays and log-structured file systems into low latency for applications is discussed. Our preliminary experiments show reductions in wall - clock execution time of 13 percent and 20 percent for a multiple module compilation tool (make) accessing data on a local disk and remote Coda file server, respectively, and a reduction of 30 percent for a text search (grep) remotely accessing many small files.

  17. Assessing Personality Traits through Response Latencies Using Item Response Theory

    ERIC Educational Resources Information Center

    Ranger, Jochen; Ortner, Tuulia M.

    2011-01-01

    Recent studies have revealed a relation between the given response and the response latency for personality questionnaire items in the form of an inverted-U effect, which has been interpreted in light of schema-driven behavior. In general, more probable responses are given faster. In the present study, the relationship between the probability of…

  18. Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice

    PubMed Central

    Freeman, Michael L.; Burkum, Claire E.; Lanzer, Kathleen G.; Roberts, Alan D.; Pinkevych, Mykola; Itakura, Asako; Kummer, Lawrence W.; Szaba, Frank M.; Davenport, Miles P.; McCarty, Owen J.T.; Woodland, David L.; Smiley, Stephen T.; Blackman, Marcia A.

    2012-01-01

    Human herpesviruses establish lifelong latency. Viral recrudescence can lead to the development of cancers, immunoproliferative disorders, transplantation complications, and thrombocytopenia. Although platelet-specific autoantibodies have been reported in patients infected with the Epstein-Barr virus (EBV), the mechanisms by which thrombocytopenia is induced remain unclear, as do the relative contributions of lytic viral replication and latent viral gene expression. The human gammaherpesviruses are tightly restricted in their ability to infect other mammals, so they are difficult to study in live animal models. Here we show that infection of mice with murine gammaherpesvirus-68 (γHV68), a rodent-specific pathogen closely related to EBV, induces the production of platelet-binding antibodies and causes thrombocytopenia. Infection of antibody-deficient mice does not lead to thrombocytopenia, indicating the platelet decrease is mediated by antibody. Additionally, infection with a latency-null recombinant γHV68 does not induce thrombocytopenia, suggesting factors associated with viral latency drive the infection-induced antibody-mediated thrombocytopenia. These studies describe an important animal model of gammaherpesvirus-induced autoimmune thrombocytopenia and demonstrate that this pathology is mediated by antibody and dependent on viral latency. This model will allow studies of the underlying mechanisms of disease progression and the testing of therapeutic strategies for the alleviation of virus-induced thrombocytopenia. PMID:23245703

  19. Saccade latency indexes exogenous and endogenous object-based attention.

    PubMed

    Şentürk, Gözde; Greenberg, Adam S; Liu, Taosheng

    2016-10-01

    Classic studies of object-based attention have utilized keypress responses as the main dependent measure. However, people typically make saccades to fixate important objects. Recent work has shown that attention may act differently when it is deployed covertly versus in advance of a saccade. We further investigated the link between saccades and attention by examining whether object-based effects can be observed for saccades. We adapted the classical double-rectangle cueing paradigm of Egly, Driver, and Rafal (1994), and measured both the first saccade latency and the keypress reaction time (RT) to a target that appeared at the end of one of the two rectangles. Our results showed that saccade latencies exhibited higher sensitivity than did RTs for detecting effects of attention. We also assessed the generality of the attention effects by testing three types of cues: hybrid (predictive and peripheral), exogenous (nonpredictive and peripheral), and endogenous (predictive and central). We found that both RTs and saccade latencies exhibited effects of both space-based and object-based attentional selection. However, saccade latencies showed a more robust attentional modulation than RTs. For the exogenous cues, we observed a spatial inhibition of return along with an object-based effect, implying that object-based attention is independent of space-based attention. Overall, our results revealed an oculomotor correlate of object-based attention, suggesting that, in addition to spatial priority, object-level priority also affects saccade planning.

  20. 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…

  1. 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…

  2. 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…

  3. 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

  4. 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…

  5. 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.

  6. 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.

  7. Kaposi's Sarcoma-Associated Herpesvirus Latency Locus Compensates for Interleukin-6 in Initial B Cell Activation.

    PubMed

    Sin, Sang-Hoon; Kang, Sun Ah; Kim, Yongbaek; Eason, Anthony; Tan, Kelly; An, Hyowon; Dittmer, Dirk P

    2015-12-09

    Interleukin 6 (IL-6) is considered a proliferation and survival factor for B cells. To assess the role of IL-6 in Kaposi sarcoma-associated herpesvirus (KSHV) latency, KSHV latency locus-transgenic mice (referred to as latency mice) lacking IL-6 were evaluated. IL-6(-/-) latency mice had the same phenotypes as the latency mice, i.e., increased frequency of marginal zone B cells, hyperplasia, and hyperglobulinemia, indicating that the KSHV latency locus, which includes all viral microRNAs (miRNAs), can compensate for lack of IL-6 in premalignant B cell activation.

  8. Analysis of a ``phase transition'' from tumor growth to latency

    NASA Astrophysics Data System (ADS)

    Delsanto, P. P.; Romano, A.; Scalerandi, M.; Pescarmona, G. P.

    2000-08-01

    A mathematical model, based on the local interaction simulation approach, is developed in order to allow simulations of the spatiotemporal evolution of neoplasies. The model consists of a set of rules, which govern the interaction of cancerous cells among themselves and in competition with other cell populations for the acquisition of essential nutrients. As a result of small variations in the basic parameters, it leads to four different outcomes: indefinite growth, metastasis, latency, and complete regression. In the present contribution a detailed analysis of the dormant phase is carried on and the critical parameters for the transition to other phases are computed. Interesting chaotic behaviors can also be observed, with different attractors in the parameters space. Interest in the latency phase has been aroused by therapeutical strategies aiming to reduce a growing tumor to dormancy. The effect of such strategies may be simulated with our approach.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

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

    DTIC Science & Technology

    2014-01-01

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

  14. 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

  15. 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.

  16. Improved UT1 Predictions through Low-Latency VLBI Observations

    DTIC Science & Technology

    2010-03-14

    predictions of Earth orientation parameters (EOPs) in general, and of Universal Time (UT1) in particular, depends strongly on the time delay between the...reduced latency of the obser- vations has improved the accuracy of the combined Interna- tional Earth Rotation and Reference Systems Service (IERS... Earth orientation parameters (EOPs) in general, and of Universal Time (UT1) in particular, depends strongly on the time delay between the last

  17. Deploying Low-Latency Anonymity: Design Challenges and Social Factors

    DTIC Science & Technology

    2007-10-01

    Page 1 of 807-1226-2439.txt Printed: 12/16/08 Dec 16 4:39:54 PM Printed For: Kate Green Deploying Low-Latency Anonymity : Design Challenges and Social...Security & Privacy, September/October 2007 (Vol. 5, No. 5), pp. 83-87 Anonymous communication systems hide conversations against unwanted observations...Deploying an anonymous communications infrastructure presents surprises unlike those found in other types of systems. For example, given that

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

    PubMed

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

    2017-04-01

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

  19. Structure and Function of Latency-Associated Nuclear Antigen

    PubMed Central

    Verma, S. C.; Lan, K.

    2011-01-01

    Latency-associated nuclear antigen (LANA) encoded by open reading frame 73 (ORF73) is the major latent protein expressed in all forms of KSHV-associated malignancies. LANA is a large (222–234 kDa) nuclear protein that interacts with various cellular as well as viral proteins. LANA has been classified as an oncogenic protein as it dysregulates various cellular pathways including tumor suppressor pathways associated with pRb and p53 and can transform primary rat embryo fibroblasts in cooperation with the cellular oncogene Hras. It associates with GSK-3β, an important modulator of Wnt signaling pathway leading to the accumulation of cytoplasmic β-catenin, which upregulates Tcf/Lef regulated genes after entering into the nucleus. LANA also blocks the expression of RTA, the reactivation transcriptional activator, which is critical for the latency to lytic switch, and thus helps in maintaining viral latency. LANA tethers the viral episomal DNA to the host chromosomes by directly binding to its cognate binding sequence within the TR region of the genome through its C terminus and to the nucleosomes through the N terminus of the molecule. Tethering to the host chromosomes helps in efficient partitioning of the viral episomes in the dividing cells. Disruptions of LANA expression led to reduction in the episomal copies of the viral DNA, supporting its role in persistence of the viral DNA. The functions known so far suggest that LANA is a key player in KSHV-mediated pathogenesis. PMID:17089795

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

    PubMed Central

    2017-01-01

    Like all herpesviruses, herpes simplex virus 1 (HSV1) is able to produce lytic or latent infections depending on the host cell type. Lytic infections occur in a broad range of cells while latency is highly specific for neurons. Although latency suggests itself as an attractive target for novel anti-HSV1 therapies, progress in their development has been slowed due in part to a lack of agreement about the basic biochemical mechanisms involved. Among the possibilities being considered is a pathway in which DNA repair mechanisms play a central role. Repair is suggested to be involved in both HSV1 entry into latency and reactivation from it. Here I describe the basic features of the DNA repair-centered pathway and discuss some of the experimental evidence supporting it. The pathway is particularly attractive because it is able to account for important features of the latent response, including the specificity for neurons, the specificity for neurons of the peripheral compared to the central nervous system, the high rate of genetic recombination in HSV1-infected cells, and the genetic identity of infecting and reactivated virus. PMID:28255301

  1. 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.

  2. 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.

  3. [Answers and latencies dichotic digit test normoacoustic majoring in hearing].

    PubMed

    Serra, Silvana Valeria; Diaz Nocera, Aden; Brizuela, Mónica; Baydas, Lorena; Fotinós, Jerónimo; Soria, Elio Andres; Lucini, Maria Bernarda; Serra, Mariel Amanda

    2017-01-01

    Neurocognitive assessment by dichotic digit test provides selective stimulation of auditory pathway with contralateral suppression of the ipsilateral showing interhemispheric differences in concurrent tasks. In order to recognize the pattern of responses, recovery order of digits and latencies heard the original test was modified with the addition of a record of an audio track of the responses. The sample includes subjects with a history in hearing specialization linked to the music and listen to comprehensive second language, normoacoustic without otologic diseases or neurological. Sets 20 pairs of dichotic digits with a digital recording for recording the subject's responses was used. The results reveal: right ear advantage in the pattern of correct answers and the order in which the information provided is retrieved. As for the pattern of intrasets latencies an increase to the fourth repeated / digit recovered and more blunder is observed. Declining intratest latencies in the second part of the test suggest positive training. These modifications allow new prospects and existing applications with behavioral tests.

  4. 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

  5. Prolonged intracortical delay of long-latency reflexes: electrophysiological evidence for a cortical dysfunction in multiple sclerosis.

    PubMed

    Bonfiglio, Luca; Rossi, Bruno; Sartucci, Ferdinando

    2006-05-31

    Convincing evidence suggests that long-latency reflexes (LLRs) are capable of testing the transcortical sensorimotor reflex arch. By subtracting the sum of the latencies of N20 (afferent branch) and transcranially elicited motor evoked potentials (MEP; efferent branch) from the LLR II latency, the cortical relay time (CRT) can also be obtained, which is alleged to represent the time required for the cortical sensorimotor integration. The aim of the present study was to investigate if a cortical dysfunction occurs in multiple sclerosis (MS). Median nerve somatosensory evoked potentials (SEPs), MEPs and LLRs were recorded from the upper limbs of 23, not severely disabled MS patients in acute phases of the disease. Eighteen age and sex matched healthy volunteers served as controls. N20, MEP, LLR II latencies were measured, and the CRT was calculated for each limb. The statistical comparison between patients and controls was only weakly significant by taking into account conduction times along either the afferent (N20) or the efferent (MEP) pathways. On the contrary, it turned out to be considerably significant if both branches of the transcortical sensorimotor reflex arch, together with the intracortical pathway, were simultaneously tested by means of the LLRs. Moreover, the patients showed a significantly higher CRT compared with that found in the control subjects. These findings are consistent with a prolonged intracortical delay of LLRs in the MS group and suggest the occurrence of conduction velocity slowing and/or synaptic transmission impairment along the sensorimotor intracortical pathway in MS.

  6. A neuron-specific host microRNA targets herpes simplex virus-1 ICP0 expression and promotes latency.

    PubMed

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

    2014-04-09

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

  7. 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.

  8. 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

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

    PubMed

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

    2006-01-01

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

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

    PubMed

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

    2015-11-11

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

  11. 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.

  12. 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)

  13. Quantitative aspects of gain and latency in the cat retina

    PubMed Central

    Cleland, B. G.; Enroth-Cugell, Christina

    1970-01-01

    1. The gain of the central response mechanism and the latency of the pure central response of on-centre ganglion cells were studied by recording from single optic tract fibres the responses evoked by slow square-wave stimuli applied against some steady background. 2. The concept of effective flux was introduced and defined: if any portion of a stimulus extends beyond Ricco's area of complete summation, then that stimulus has an actual flux, equal to the product of its area and luminance, but it also has an effective flux which is that fraction of its actual flux which equals the actual flux of another stimulus which, when it falls entirely within Ricco's area, evokes an isobolic pure central response or has the same adaptive effect upon the central response mechanism as the first stimulus. 3. The most significant finding was that when the cell responded with a pure central response to the incremental flux (the square wave) applied against a steady effective background flux, then the gain and the latency were functions exclusively of the sum of the two fluxes (the total flux), not of the incremental or background flux as such. This shows that the level of field adaptation of the central mechanism is reset within the latent period of the response to an incremental flux. 4. Increment sensitivity curves based on isobolic suprathreshold responses all had the same slope of 0·9, when the log of the incremental flux was plotted against the log of the total flux. A plot of log latency against log total effective flux had a slope of -0·1. 5. The stimulus—response relation derived from (3) and (4) was [Formula: see text] and [Formula: see text], where R is the response amplitude, Fet the total flux, ΔFe the incremental flux and K1 and K2 are constants. PMID:5498461

  14. 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

  15. 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.

  16. Reducing the PAPR in FBMC-OQAM systems with low-latency trellis-based SLM technique

    NASA Astrophysics Data System (ADS)

    Bulusu, S. S. Krishna Chaitanya; Shaiek, Hmaied; Roviras, Daniel

    2016-12-01

    Filter-bank multi-carrier (FBMC) modulations, and more specifically FBMC-offset quadrature amplitude modulation (OQAM), are seen as an interesting alternative to orthogonal frequency division multiplexing (OFDM) for the 5th generation radio access technology. In this paper, we investigate the problem of peak-to-average power ratio (PAPR) reduction for FBMC-OQAM signals. Recently, it has been shown that FBMC-OQAM with trellis-based selected mapping (TSLM) scheme not only is superior to any scheme based on symbol-by-symbol approach but also outperforms that of the OFDM with classical SLM scheme. This paper is an extension of that work, where we analyze the TSLM in terms of computational complexity, required hardware memory, and latency issues. We have proposed an improvement to the TSLM, which requires very less hardware memory, compared to the originally proposed TSLM, and also have low latency. Additionally, the impact of the time duration of partial PAPR on the performance of TSLM is studied, and its lower bound has been identified by proposing a suitable time duration. Also, a thorough and fair comparison of performance has been done with an existing trellis-based scheme proposed in literature. The simulation results show that the proposed low-latency TSLM yields better PAPR reduction performance with relatively less hardware memory requirements.

  17. Towards an understanding of the herpes simplex virus type 1 latency-reactivation cycle.

    PubMed

    Perng, Guey-Chuen; Jones, Clinton

    2010-01-01

    Infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system. Recurrent ocular shedding can lead to corneal scarring and vision loss making HSV-1 a leading cause of corneal blindness due to an infectious agent. The primary site of HSV-1 latency is sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease. During latency, the latency-associated transcript (LAT) is abundantly expressed. LAT expression is important for the latency-reactivation cycle in animal models, in part, because it inhibits apoptosis, viral gene expression, and productive infection. A novel transcript within LAT coding sequences (AL3) and small nonprotein coding RNAs are also expressed in trigeminal ganglia of latently infected mice. In this review, an update of viral factors that are expressed during latency and their potential roles in regulating the latency-reactivation cycle is discussed.

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

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-05-01

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

  20. Thoracoscopic long myotomy in the prone position to treat rapid esophageal contractions with normal latency.

    PubMed

    Nomura, Tsutomu; Iwakiri, Katsuhiko; Matsutani, Takeshi; Hagiwara, Nobutoshi; Fujita, Itsuro; Nakamura, Yoshiharu; Kawami, Noriyuki; Miyashita, Masao; Uchida, Eiji

    2015-04-01

    A 56-year-old woman with an 8-year history of dysphagia and chest pain received a diagnosis of diffuse esophageal spasm by esophageal high-resolution manometry (HRM). Approximately 2 years of medical therapy was ineffective, and the patient's symptoms were worsening. Therefore, surgery was considered to be the most optimal treatment for this patient. The right thoracoscopic approach was selected because a long myotomy from the distal to proximal level of the esophagus was needed based on the HRM findings. The operation was performed in the prone position with establishment of pneumothorax. The total length of the myotomy was 16 cm, and the operation was finished within 2 hours. After the operation, the symptoms were considerably improved and no contractions were detected by HRM. The HRM findings before the operation were classified as rapid contractions with normal latency based on the 2012 Chicago classification of esophageal motility. Treatment for patients with rapid esophageal contractions with normal latency has not been previously described; however, treatment for diffuse esophageal spasm was considered to be pertinent to this patient. In conclusion, right thoracoscopic esophageal long myotomy in the prone position with establishment of pneumothorax may be useful when a proximal-level esophagomyotomy is required based on preoperative mapping by HRM.

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

    NASA Technical Reports Server (NTRS)

    Snyder, E.; Hillyard, S. A.

    1976-01-01

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

  2. Evaluative decision latencies mediated by induced affective states.

    PubMed

    Hermans, D; De Houwer, J; Eelen, P

    1996-01-01

    Recent priming studies (e.g. Hermans, De Houwer & Eelen, 1994, Cognition and Emotion, 8, 515-533) have demonstrated that response latencies to target stimuli are mediated by the affective relation between prime and target. The time needed to evaluate or pronounce targets is facilitated if preceded by similarly valenced primes, but is inhibited for trials on which prime and target have an opposite affective valence. These data suggest that information stored in memory is associatively linked with similarly evaluated information, through association with some general representation of goodness or badness. To investigate whether affective priming is merely one type of conventional semantic priming, or whether it is mediated by affective responses, the affective context provided by the primes was replaced in this study by the induction of an emotional state using a Musical Mood Induction procedure (Depression/Elation). Subjects had to evaluate target pictures as quickly as possible. The data revealed a significant Mood Change (More Depressed/Less Depressed/No Change) x Target Valence (Positive/Negative) interaction, indicating that emotional states can mediate evaluate response latencies to affectively valenced target stimuli. The results are interpreted in the context of a biphasic emotion theory, and are related to previous research on mood congruency effects on perceptual responses.

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

    PubMed

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

    2006-01-01

    While cryotherapy has direct physiological effects on contractile tissues, the extent to which joint cooling affects the neuromuscular system is not well understood. The purpose of the study was to detect changes in ankle dynamic restraint (peroneal short latency response and muscle activity amplitude) during inversion perturbation following ankle joint cryotherapy. A 2x3 factorial design was used to compare reaction time and EMG amplitude data of treatment conditions (cryotherapy and control) across time (pre-treatment, post-treatment, and 30 min post-treatment). Thirteen healthy volunteers (age 23 ± 4 yrs, ht 1.76 ± 0.09 m, mass 78.8 ± 16.6 kg), with no history of lower extremity joint injury participated in this study. Surface EMG was collected from the peroneus longus (PL) of the dominant leg during an ankle inversion perturbation triggered while walking. Subjects walked the length of a 6.1 m runway 30 times. A trap door mechanism, inducing inversion perturbation, was released at heel contact during six randomly selected trials for each leg. Following baseline measurements, a 1.5 L bag of crushed ice was applied to the lateral ankle of subjects in the treatment group with an elastic wrap. A bag similar in weight and consistency was applied to the lateral ankle of subjects in the control group. A repeated measures ANOVA was used to compare treatment conditions across time (p < 0.05). Maximum inversion range of motion was 28.4 ± 1.8° for all subjects. No overall condition by time difference was detected (p > 0.05) for PL reaction time. Average RMS EMG, normalized to an isometric reference position, increased in the cryotherapy group at the 30 min post-treatment interval relative to the control group (p < 0.05). Joint cooling does not result in deficiencies in reaction time or immediate muscle activation following inversion perturbation compared to a control. Key PointsJoint cooling is used as a treatment intervention prior to activity. Whether ankle cooling

  4. Short-latency afferent inhibition in chronic spinal cord injury

    PubMed Central

    Bailey, Aaron Z.; Mi, Yiqun P.; Nelson, Aimee J.

    2015-01-01

    Background Short-latency afferent inhibition (SAI) results when somatosensory afferent input inhibits the corticospinal output from primary motor cortex (M1). The present study examined SAI in the flexor carpi radialis (FCR) muscle in individuals with spinal cord injury (SCI) and uninjured controls. Methods Short-latency afferent inhibition (SAI) was evoked by stimulating the median nerve at the elbow at intervals of 15, 20 and 25 ms in advance of a transcranial magnetic stimulation (TMS) pulse over M1. SAI was tested with the FCR at rest and also during ~20% of maximum voluntary contraction. Corticospinal output was assessed through measuring both motor thresholds and motor evoked potential (MEP) recruitment curves. The afferent volley was assessed via the N20–P25 amplitude of the somatosensory evoked potential (SEP) and the amplitude of sensory nerve action potentials (SNAP) recorded over the median nerve at the elbow. Results SAI is reduced in SCI in both the contracted and non-contracted FCR muscle. MEP recruitment curves and thresholds were decreased in SCI only in the active state and not the resting state. N20–P25 amplitude was similar between groups in both the resting and active states although SNAP was significantly reduced in SCI at rest. Conclusions We conclude that reduced SAI in SCI is likely attributed to neuroplasticity altering the intrinsic M1 circuitry mediating SAI and/or reduced afferent input traversing a direct thalamocortical route to M1. These data provide a new avenue of research aimed at identifying therapeutic approaches to alter SAI to improve upper limb function in individuals with SCI. PMID:28123808

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. New results in fault latency modelling. [in redundant flight control system

    NASA Technical Reports Server (NTRS)

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

    1983-01-01

    The test design and results from assessment of the performance of the self-test program and the extent of fault latency in a redundant flight control system (FCS) are reported. Assembly language programming generated gate-level faults directed to every avionics component. Details of the fault-simulation software are described, noting the input needed to match the five control-surface parameters managed by the FCS. Most faults were immediately detected, and component-level faults, occurring at pins, were more easily noted than gate-level faults. The results indicated that a 200-word self-test program is sufficient to obtain a fault coverage of 85 percent. Minor hardware changes are required to reach levels over 90 percent.

  10. 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.

  11. 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.

  12. Detection of a Gene Cluster That Is Dispensable for Human Herpesvirus 6 Replication and Latency

    PubMed Central

    Kondo, Kazuhiro; Nozaki, Hideo; Shimada, Kazuya; Yamanishi, Koichi

    2003-01-01

    The U3-U7 gene cluster of human herpesvirus 6 (HHV-6) was replaced with an enhanced green fluorescent protein-puromycin gene cassette containing the cytomegalovirus major immediate-early promoter. Neither viral replication in T cells nor latency and reactivation in macrophages was impaired. During HHV-6 latency, the cytomegalovirus promoter used the transcription start sites employed in cytomegalovirus latency. PMID:12970461

  13. 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.

  14. 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

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

    PubMed

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

    2015-03-01

    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.

  16. 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

  17. Soy isoflavones increase latency of spontaneous mammary tumors in mice.

    PubMed

    Jin, Zeming; MacDonald, Ruth S

    2002-10-01

    Soy protein, with and without isoflavones, is being added to foods by manufacturers in response to the Food and Drug Administration (FDA)-approved health claim for cardiovascular protection. Furthermore, soy isoflavones are increasingly consumed by women in the United States as an alternative to hormone replacement therapy. The role of these phytoestrogens in breast cancer is controversial. Although exposure of rodents to soy isoflavones during the perinatal period appears to reduce mammary cancer formation, exposure in utero or during adulthood may increase tumor growth. The mouse mammary tumor virus (MMTV)-neu mouse spontaneously develops mammary tumors due to overexpression of the ErbB-2/neu/HER2 oncogene. This model is comparable with human breast cancer because overexpression of the neu oncogene occurs in 20-40% of human breast cancers. We fed MMTV-neu mice AIN-93G diets containing no isoflavones, 250 mg/kg genistein, 250 mg/kg daidzein or an isoflavone mixture (NovaSoy, equivalent to 250 mg genistein/kg) from 7 wk of age. Mammary tumor latency was significantly delayed in mice fed isoflavones compared with the control. Once tumors formed, however, the isoflavones did not reduce the number or size of tumors such that at 34 wk of age there were no differences in tumor burden among the treatment groups. Hence, in the MMTV-neu mouse, soy isoflavones delayed mammary tumorigenesis. Further studies are warranted to define the cellular mechanisms through which these compounds affect mammary tumorigenesis in this model.

  18. 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.

  19. Developmental Context Determines Latency of MYC-Induced Tumorigenesis

    PubMed Central

    Beer, Shelly; Zetterberg, Anders; Ihrie, Rebecca A; McTaggart, Ryan A; Yang, Qiwei; Bradon, Nicole; Arvanitis, Constadina; Attardi, Laura D; Feng, Sandy; Ruebner, Boris; Cardiff, Robert D

    2004-01-01

    One of the enigmas in tumor biology is that different types of cancers are prevalent in different age groups. One possible explanation is that the ability of a specific oncogene to cause tumorigenesis in a particular cell type depends on epigenetic parameters such as the developmental context. To address this hypothesis, we have used the tetracycline regulatory system to generate transgenic mice in which the expression of a c-MYC human transgene can be conditionally regulated in murine hepatocytes. MYC's ability to induce tumorigenesis was dependent upon developmental context. In embryonic and neonatal mice, MYC overexpression in the liver induced marked cell proliferation and immediate onset of neoplasia. In contrast, in adult mice MYC overexpression induced cell growth and DNA replication without mitotic cell division, and mice succumbed to neoplasia only after a prolonged latency. In adult hepatocytes, MYC activation failed to induce cell division, which was at least in part mediated through the activation of p53. Surprisingly, apoptosis is not a barrier to MYC inducing tumorigenesis. The ability of oncogenes to induce tumorigenesis may be generally restrained by developmentally specific mechanisms. Adult somatic cells have evolved mechanisms to prevent individual oncogenes from initiating cellular growth, DNA replication, and mitotic cellular division alone, thereby preventing any single genetic event from inducing tumorigenesis. PMID:15455033

  20. 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.

  1. 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.

  2. Onset Latency of Motor Evoked Potentials in Motor Cortical Mapping with Neuronavigated Transcranial Magnetic Stimulation.

    PubMed

    Kallioniemi, Elisa; Pitkänen, Minna; Säisänen, Laura; Julkunen, Petro

    2015-01-01

    Cortical motor mapping in pre-surgical applications can be performed using motor evoked potential (MEP) amplitudes evoked with neuronavigated transcranial magnetic stimulation. The MEP latency, which is a more stable parameter than the MEP amplitude, has not so far been utilized in motor mapping. The latency, however, may provide information about the stress in damaged motor pathways, e.g. compression by tumors, which cannot be observed from the MEP amplitudes. Thus, inclusion of this parameter could add valuable information to the presently used technique of MEP amplitude mapping. In this study, the functional cortical representations of first dorsal interosseous (FDI), abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles were mapped in both hemispheres of ten healthy righthanded volunteers. The cortical muscle representations were evaluated by the area and centre of gravity (CoG) by using MEP amplitudes and latencies. As expected, the latency and amplitude CoGs were congruent and were located in the centre of the maps but in a few subjects, instead of a single centre, several loci with short latencies were observed. In conclusion, MEP latencies may be useful in distinguishing the cortical representation areas with the most direct pathways from those pathways with prolonged latencies. However, the potential of latency mapping to identify stressed motor tract connections at the subcortical level will need to be verified in future studies with patients.

  3. Latencies of Stimulus-Driven Eye Movements Are Shorter in Dyslexic Subjects

    ERIC Educational Resources Information Center

    Bednarek, Dorota B.; Tarnowski, Adam; Grabowska, Anna

    2006-01-01

    Eye movements latencies toward peripherally presented stimuli were measured in 10-year-old dyslexic and control children. Dyslexic subjects, previously found to be oversensitive to stimulation of the magnocellular channel, showed reduced latencies as compared to normally reading controls. An attention shifting task was also used which showed no…

  4. 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;…

  5. 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…

  6. 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).

  7. 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…

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Optimal measurements of hemodynamic response latency in fNIRS using the jackknife approach.

    PubMed

    Maheux, Manon; Bisaillon-Sicotte, Étienne; Tabrizi, Shirin; Armony, Jorge L; Lina, Jean-Marc; Jolicoeur, Pierre

    2017-01-01

    Functional near-infrared spectroscopy (fNIRS) permits measurements of changes in the concentration of oxygenated and deoxygenated hemoglobin, typically with a higher sampling rate than with other imaging methods based on the hemodynamic response. We examined the potential of the fNIRS technique to estimate variations in the latency of hemodynamic responses to experimental events and sought optimal methods to maximize the reliability and reproducibility of latency effects. We used Monte Carlo simulations using subsamples of real fNIRS measures to estimate the statistical power of different approaches (such as fixed threshold, percent of peak, fractional-area latency, for both individual-subject estimates and estimates from jackknife averages) to detect a known simulated latency shift. The simulations used measures of hemodynamic responses in the temporal lobe from two groups of young adult participants who listened to auditory stimuli, one with a blocked presentation design and one with an event-related design. We estimated the relative sensitivity of different latency measures and approaches to the measurement of latency effects of different magnitudes using realistic noise and signal-to-noise characteristics. In general, the jackknife approach provided the greatest statistical power to detect a known latency shift, without inflation of Type I error.

  16. Studying HIV latency by modeling the interaction between HIV proteins and the innate immune response.

    PubMed

    Aguilera, Luis U; Rodríguez-González, Jesús

    2014-11-07

    HIV infection leads to two cell fates, the viral productive state or viral latency (a reversible non-productive state). HIV latency is relevant because infected active CD4+ T-lymphocytes can reach a resting memory state in which the provirus remains silent for long periods of time. Despite experimental and theoretical efforts, the causal molecular mechanisms responsible for HIV latency are only partially understood. Studies have determined that HIV latency is influenced by the innate immune response carried out by cell restriction factors that inhibit the postintegration steps in the virus replication cycle. In this study, we present a mathematical study that combines deterministic and stochastic approaches to analyze the interactions between HIV proteins and the innate immune response. Using wide ranges of parameter values, we observed the following: (1) a phenomenological description of the viral productive and latent cell phenotypes is obtained by bistable and bimodal dynamics, (2) biochemical noise reduces the probability that an infected cell adopts the latent state, (3) the effects of the innate immune response enhance the HIV latency state, (4) the conditions of the cell before infection affect the latent phenotype, i.e., the existing expression of cell restriction factors propitiates HIV latency, and existing expression of HIV proteins reduces HIV latency.

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

    PubMed

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

    2015-08-06

    Auditory evoked potential (AEP) is an effective index for the effects of general anesthetics. However, it's unknown if AEP can differentiate the effects of general anesthetics on nerve fibers and synapses. Presently, we investigated AEP latency and amplitude changes to different acoustic intensities during pentobarbital anesthesia. Latency more regularly changed than amplitude during anesthesia. AEP Latency monotonically decreased with acoustic intensity increase (i.e., latency-intensity curve) and could be fitted to an exponential decay equation, which showed two components, the theoretical minimum latency and stimulus-dependent delay. From the latency-intensity curves, the changes of these two components (∆L and ∆I) were extracted during anesthesia. ∆L and ∆I monitored the effect of pentobarbital on nerve fibers and synapses. Pentobarbital can induce anesthesia, and two side effects, hypoxemia and hypothermia. The hypoxemia was not related with ∆L and ∆I. However, ∆L was changed by the hypothermia, whereas ∆I was changed by the hypothermia and anesthesia. Therefore, we conclude that, AEP latency is superior to amplitude for the effects of general anesthetics, ∆L monitors the effect of hypothermia on nerve fibers, and ∆I monitors a combined effect of anesthesia and hypothermia on synapses. When eliminating the temperature factor, ∆I monitors the anesthesia effect on synapses.

  18. 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.

  19. 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

  20. Short-term physical training alters cardiovascular autonomic response amplitude and latencies.

    PubMed

    Sharma, Rajesh K; Deepak, K K; Bijlani, R L; Rao, P S

    2004-04-01

    This study reports the results of 15 days of exercise training in 25 adult males on cardiovascular autonomic response amplitude and latencies. A standard battery of autonomic function tests including both activity (tone) and reactivity was used. Parasympathetic activity as evaluated from Heart rate variability (HRV) showed no statistically significant change in both time and frequency domain measures, similarly Sympathetic activity as measured by QT/QS2 ratio showed no statistically significant change, but there was a trend of a decrease in sympathetic activity and an increase in parasympathetic activity. There were no changes in the parameters measuring parasympathetic reactivity. Sympathetic reactivity as evaluated by diastolic blood pressure responses to hand grip test (HGT) and cold pressor test (CPT) showed significant decreases. Time domain assessment of autonomic responses was done by measuring tachycardia and bradycardia latencies during Valsalva maneuver (VM) and lying to standing test (LST). Physical training resulted in a decrease in tachycardia latency during LST and a decrease in bradycardia latency during VM. We conclude from the present study that 15 days of physical training is not enough to alter autonomic activity and PNS reactivity but can result in changes in SNS reactivity and latency parameters. We hypothesize that a decrease in bradycardia latency during VM signifies a faster recovery of heart rate during VM and a decrease in tachycardia latency during LST denotes a delayed activation of the system both of which are favorable cardiovascular responses.

  1. 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

  2. Sleep Fragmentation Does Not Explain Misperception of Latency or Total Sleep Time

    PubMed Central

    Saline, Austin; Goparaju, Balaji; Bianchi, Matt T.

    2016-01-01

    Study Objectives: Perception of sleep-wake times may differ from objective measures, although the mechanisms remain elusive. Quantifying the misperception phenotype involves two operational challenges: defining objective sleep latency and treating sleep latency and total sleep time as independent factors. We evaluated a novel approach to address these challenges and test the hypothesis that sleep fragmentation underlies misperception. Methods: We performed a retrospective analysis on patients with or without obstructive sleep apnea during overnight diagnostic polysomnography in our laboratory (n = 391; n = 252). We compared subjective and objective sleep-wake durations to characterize misperception. We introduce a new metric, sleep during subjective latency (SDSL), which captures latency misperception without defining objective sleep latency and allows correction for latency misperception when assessing total sleep time (TST) misperception. Results: The stage content of SDSL is related to latency misperception, but in the opposite manner as our hypothesis: those with > 20 minutes of SDSL had less N1%, more N3%, and lower transition frequency. After adjusting for misperceived sleep during subjective sleep latency, TST misperception was greater in those with longer bouts of REM and N2 stages (OSA patients) as well as N3 (non-OSA patients), which also did not support our hypothesis. Conclusions: Despite the advantages of SDSL as a phenotyping tool to overcome operational issues with quantifying misperception, our results argue against the hypothesis that light or fragmented sleep underlies misperception. Further investigation of sleep physiology utilizing alternative methods than that captured by conventional stages may yield additional mechanistic insights into misperception. Commentary: A commentary on this article appears in this issue on page 1211. Citation: Saline A, Goparaju B, Bianchi MT. Sleep fragmentation does not explain misperception of latency or total

  3. 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.

  4. Low Latency Sensor Web Integration of Seismic Tomography, InSAR, and Deformation Models

    NASA Astrophysics Data System (ADS)

    Kedar, S.; Masterlark, T.; Lees, J. M.; Lundgren, P.; Song, W.

    2011-12-01

    In the volcanic environment, seismometers are sensitive to high-frequency, brittle failure earthquakes (tectonic-shear and dike intrusion events) and volcanic tremor. Real-time seismic analysis provides epicenter location, fault parameters, and, given enough data, the geometry of magmatic intrusion with short latency. Due to the limits of the seismic frequency response, however, seismic data analysis can only infer magma movement and volume change through their manifestation on changes in the elastic properties of the volcano obtained from tomography, and when possible from tracking earthquake hypocenters. Geodetic measurements (GPS, leveling, InSAR) on the other hand, measure volume changes and surface strain more directly by tracking surface deformation. Geodetic observations, however, lack the sensitivity to distinguish between various sources of surface deformation. In particular, the separation of deformation due to magma migration from all other extraneous sources is a key limitation of geodetic data inversion. We will present a framework in which high-resolution, real-time seismic tomography, calculated by a distributed network of seismic sensor nodes, can be coupled with low-latency InSAR acquisition and processing to constrain three-dimensional(3D) finite element model (FEM) solutions for the volcano deformation sources. The FEM simulates pressurized magma chambers (a deformation source) embedded in domains having a distribution of material properties, determined from seismic tomography models, and the irregular relief of a volcano, according to available digital elevation models (DEMs). The mass and volume estimates thus calculated, are then re-incorporated into the next iteration of the seismic tomography. This is done by first delineating subsurface regions where magma injection is required by the deformation models. Model parameters within these 3D structures are constrained by restricting the range of velocity (or Q) those voxels (model elemets) can

  5. Maternal sensitivity and latency to positive emotion following challenge: pathways through effortful control.

    PubMed

    Conway, Anne; McDonough, Susan C; Mackenzie, Michael; Miller, Alison; Dayton, Carolyn; Rosenblum, Katherine; Muzik, Maria; Sameroff, Arnold

    2014-01-01

    The ability to self-generate positive emotions is an important component of emotion regulation. In this study, we focus on children's latency to express positive emotions following challenging situations and assess whether this ability operates through early maternal sensitivity and children's effortful control. Longitudinal relations between maternal sensitivity, infant negative affect, effortful control, and latency to positive emotion following challenge were examined in 156 children who were 33 months of age. Structural equation models supported the hypothesis that maternal sensitivity during infancy predicted better effortful control and, in turn, shorter latencies to positive emotions following challenge at 33 months. Directions for future research are discussed.

  6. Latency study of the High Performance Time to Digital Converter for the ATLAS Muon Spectrometer trigger upgrade

    NASA Astrophysics Data System (ADS)

    Meng, X. T.; Levin, D. S.; Chapman, J. W.; Li, D. C.; Yao, Z. E.; Zhou, B.

    2017-02-01

    The High Performance Time to Digital Converter (HPTDC), a multi-channel ASIC designed by the CERN Microelectronics group, has been proposed for the digitization of the thin-Resistive Plate Chambers (tRPC) in the ATLAS Muon Spectrometer Phase-1 upgrade project. These chambers, to be staged for higher luminosity LHC operation, will increase trigger acceptance and reduce or eliminate the fake muon trigger rates in the barrel-endcap transition region, corresponding to pseudo-rapidity range 1<|η|<1.3. Low level trigger candidates must be flagged within a maximum latency of 1075 ns, thus imposing stringent signal processing time performance requirements on the readout system in general, and on the digitization electronics in particular. This paper investigates the HPTDC signal latency performance based on a specially designed evaluation board coupled with an external FPGA evaluation board, when operated in triggerless mode, and under hit rate conditions expected in Phase-I. This hardware based study confirms previous simulations and demonstrates that the HPTDC in triggerless operation satisfies the digitization timing requirements in both leading edge and pair modes.

  7. 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

  8. Latency versus persistence or intermittent recurrences: evidence for a latent state of murine cytomegalovirus in the lungs.

    PubMed

    Kurz, S; Steffens, H P; Mayer, A; Harris, J R; Reddehase, M J

    1997-04-01

    The state of cytomegalovirus (CMV) after the resolution of acute infection is an unsolved problem in CMV research. While the term "latency" is in general use to indicate the maintenance of the viral genome, a formal exclusion of low-level persistent productive infection depends on the sensitivity of the assay for detecting infectious virus. We have improved the method for detecting infectivity by combining centrifugal infection of permissive indicator cells in culture, expansion to an infectious focus, and sensitive detection of immediate-early RNA in the infected cells by reverse transcriptase PCR. A limiting-dilution approach defined the sensitivity of this assay. Infectivity was thereby found to require as few as 2 to 9 virion DNA molecules of murine CMV, whereas the standard measure of infectivity, the PFU, is the equivalent of ca. 500 viral genomes. Since murine CMV forms multicapsid virions in most infected tissues, the genome-to-infectivity ratio is necessarily >1. This assay thus sets a new standard for investigating CMV latency. In mice in which acute infection was resolved, the viral DNA load in the lungs, a known organ site of CMV latency and recurrence, was found to be 1 genome per 40 lung cells, or a total of ca. 1 million genomes. Despite this high load of CMV DNA, infectious virus was not detected with the improved assay, but recurrence was inducible. These data provide evidence against a low-level persistent productive infection and also imply that intermittent spontaneous recurrence is not a frequent event in latently infected lungs.

  9. 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.

  10. 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

  11. Latency of the auditory evoked neuromagnetic field components: stimulus dependence and insights toward perception.

    PubMed

    Roberts, T P; Ferrari, P; Stufflebeam, S M; Poeppel, D

    2000-03-01

    This review will focus on investigations of the auditory evoked neuromagnetic field component, the M100, detectable in the magnetoencephalogram recorded during presentation of auditory stimuli, approximately 100 milliseconds after stimulus onset. In particular, the dependence of M100 latency on attributes of the stimulus, such as intensity, pitch and timbre will be discussed, along with evidence relating M100 latency observations to perceptual features of the stimuli. Comparison with investigation of the analogous electrical potential component, the N1, will be made. Parametric development of stimuli from pure tones through complex tones to speech elements will be made, allowing the influence of spectral pitch, virtual pitch and perceptual categorization to be delineated and suggesting implications for the role of such latency observations in the study of speech processing. The final section will deal with potential clinical applications offered by M100 latency measurements, as objective indices of normal and abnormal cortical processing.

  12. 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.

  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. 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.

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

    PubMed

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

    2009-12-01

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

  16. 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.

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

    PubMed Central

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

    2012-01-01

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

  18. 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.

  19. Terminal latency abnormality in amyotrophic lateral sclerosis without split hand syndrome.

    PubMed

    Park, Donghwi; Park, Jin-Sung

    2017-02-10

    Amyotrophic lateral sclerosis (ALS) has a peculiar involvement pattern; clinically it is known as split hand syndrome and electrophysiologically shows abnormalities in the abductor pollicis brevis (APB)/abductor digiti minimi (ADM) ratio. The aim of this study was to find a significant electrophysiological parameter in upper limb onset ALS patients with normal APB/ADM ratio when compared to cervical spondylotic amyotrophy (CSA) and healthy controls. We retrospectively reviewed the electrophysiological results of 47 upper limb onset ALS and 42 CSA cases; 20 healthy individuals were included as controls. We included ALS and CSA patients with normal ADM/APB ratio (≥0.6, and ≤1.7), and the parameters of electrophysiological study were compared. The electrophysiological parameters of statistical significance among ALS, CSA and normal controls were: amplitude of median and ulnar nerves, the terminal latency of median nerve, F-wave latency of median and ulnar nerves, terminal latency ratio of ulnar/median nerves, and F-wave latency ratio of ulnar/median nerves (p < 0.05). Among these parameters, the terminal latency ratio of ulnar/median nerve and terminal latency of median nerve in ALS were significantly different with both of CSA and normal control (p < 0.006). The abnormality in the terminal latency of the median nerve can be partly explained by the distal motor axonal dysfunction due to sodium and potassium channel abnormalities. The hypothesis of distal axonopathy is known to play an important role in the pathogenesis of ALS causing a significant prolongation of the terminal latency in the median nerve and the ulnar/median nerve ratio.

  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. Preventing Active Timing Attacks in Low-Latency Anonymous Communication [Extended Abstract

    DTIC Science & Technology

    2010-07-01

    Preventing Active Timing Attacks in Low-Latency Anonymous Communication [Extended Abstract] Joan Feigenbaum1?, Aaron Johnson2??, and Paul Syverson3...itd.nrl.navy.mil Abstract. Low-latency anonymous communication protocols in gen- eral, and the popular onion-routing protocol in particular, are broken...inserting delays and dropping messages. We present a protocol that provides anonymity against an active adver- sary by using a black-box padding scheme

  3. Low-latency fiber-millimeter-wave system for future mobile fronthauling

    NASA Astrophysics Data System (ADS)

    Tien Dat, Pham; Kanno, Atsushi; Yamamoto, Naokatsu; Kawanishi, Tetsuya

    2016-02-01

    A seamless combination of fiber and millimeter-wave (MMW) systems can be very attractive for future heterogeneous mobile networks such as 5G because of its flexibility and high bandwidth. Analog mobile signal transmission over seamless fiber-MMW systems is very promising to reduce the latency and the required band-width, and to simplify the systems. However, stable and high-performance seamless systems are indispensable to conserve the quality of the analog signal transmission. In this paper, we present several technologies to develop such seamless fiber-MMW systems. In the downlink direction, a high-performance system can be realized using a high-quality optical MMW signal generator and a self-homodyne MMW signal detector. In the uplink direction, a cascade of radio-on-radio and radio-over-fiber systems using a burst-mode optical amplifier can support bursty radio signal transmission. A full-duplex transmission with negligible interference effects can be realized using frequency multiplexing in the radio link and wavelength-division multiplexing in the optical link. A high-spectral efficiency MMW-over-fiber system using an intermediate frequency-over-fiber system and a high-quality remote delivery of a local oscillator signal is highly desirable to reduce the costs.

  4. 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.

  5. 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.

  6. 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

  7. 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.

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

    PubMed

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

    2011-01-01

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

  9. Latency-Related Development of Functional Connections in Cultured Cortical Networks

    PubMed Central

    le Feber, J.; van Pelt, J.; Rutten, W.L.C.

    2009-01-01

    Abstract To study plasticity, we cultured cortical networks on multielectrode arrays, enabling simultaneous recording from multiple neurons. We used conditional firing probabilities to describe functional network connections by their strength and latency. These are abstract representations of neuronal pathways and may arise from direct pathways between two neurons or from a common input. Functional connections based on direct pathways should reflect synaptic properties. Therefore, we searched for long-term potentiation (this mechanism occurs in vivo when presynaptic action potentials precede postsynaptic ones with interspike intervals up to ∼20 ms) in vitro. To investigate if the strength of functional connections showed a similar latency-related development, we selected periods of monotonously increasing or decreasing strength. We observed increased incidence of short latencies (5–30 ms) during strengthening, whereas these rarely occurred during weakening. Furthermore, we saw an increased incidence of 40–65 ms latencies during weakening. Conversely, functional connections tended to strengthen in periods with short latency, whereas strengthening was significantly less than average during long latency. Our data suggest that functional connections contain information about synaptic connections, that conditional firing probability analysis is sensitive enough to detect it and that a substantial fraction of all functional connections is based on direct pathways. PMID:19383487

  10. 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.

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

    PubMed

    Yang, Juan; Qi, Mingming; Guan, Lili

    2014-03-01

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

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

    PubMed

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

    2015-09-01

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

  13. The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?

    PubMed

    Wills, Mark R; Poole, Emma; Lau, Betty; Krishna, Ben; Sinclair, John H

    2015-03-01

    While the host immune response following primary human cytomegalovirus (HCMV) infection is generally effective at stopping virus replication and dissemination, virus is never cleared by the host and like all herpesviruses, persists for life. At least in part, this persistence is known to be facilitated by the ability of HCMV to establish latency in myeloid cells in which infection is essentially silent with, importantly, a total lack of new virus production. However, although the viral transcription programme during latency is much suppressed, a number of viral genes are expressed during latent infection at the protein level and many of these have been shown to have profound effects on the latent cell and its environment. Intriguingly, many of these latency-associated genes are also expressed during lytic infection. Therefore, why the same potent host immune responses generated during lytic infection to these viral gene products are not recognized during latency, thereby allowing clearance of latently infected cells, is far from clear. Reactivation from latency is also a major cause of HCMV-mediated disease, particularly in the immune compromised and immune naive, and is also likely to be a major source of virus in chronic subclinical HCMV infection which has been suggested to be associated with long-term diseases such as atherosclerosis and some neoplasias. Consequently, understanding latency and why latently infected cells appear to be immunoprivileged is crucial for an understanding of the pathogenesis of HCMV and may help to design strategies to eliminate latent virus reservoirs, at least in certain clinical settings.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. Saccadic latency is prolonged in Spinocerebellar Ataxia type 2 and correlates with the frontal-executive dysfunctions.

    PubMed

    Rodríguez-Labrada, Roberto; Velázquez-Pérez, Luis; Seigfried, Carola; Canales-Ochoa, Nalia; Auburger, Georg; Medrano-Montero, Jacqueline; Sánchez-Cruz, Gilberto; Aguilera-Rodríguez, Raúl; Laffita-Mesa, José; Vázquez-Mojena, Yaimeé; Verdecia-Ramirez, Marisleydis; Motta, Maribel; Quevedo-Batista, Yudith

    2011-07-15

    Data on saccadic latency in patients with Spinocerebellar Ataxia 2 (SCA2) are sparse and contradictory. In order to determine whether saccadic latency is definitely prolonged, identify its possible determinants and evaluate it as disease biomarker we assessed the saccadic latency by electronystagmography in 110 SCA2 patients and their paired controls. Mean saccadic latencies were significantly longer in patients when compared to controls for all tested target displacements. Forty-six percent of SCA2 patients had saccadic latencies above the normal range. Reciprobit plots of saccadic latency demonstrated a skewed distribution in the direction of longer latencies for the patients compared to controls. As saccadic latency increased, the velocity and amplitude of saccades significantly decreased in SCA2 subjects but not in controls. Saccadic latency was not influenced by any demographical, clinical or molecular SCA2 variables, but it showed a significant correlation with the performance of the Stroop test, the verbal fluency test and the Wisconsin Card Sorting Test in SCA2 patients. This paper demonstrated that saccadic latency is prolonged in SCA2 patients and it significantly correlates with the performance of frontal-executive functions, thus this parameter could be a useful biomarker to evaluate the efficiency of future therapeutical options on these dysfunctions.

  19. 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.

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

    PubMed

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

    2016-06-24

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

  1. HIV-1 Tat and Viral Latency: What We Can Learn from Naturally Occurring Sequence Variations.

    PubMed

    Kamori, Doreen; Ueno, Takamasa

    2017-01-01

    Despite the effective use of antiretroviral therapy, the remainder of a latently HIV-1-infected reservoir mainly in the resting memory CD4(+) T lymphocyte subset has provided a great setback toward viral eradication. While host transcriptional silencing machinery is thought to play a dominant role in HIV-1 latency, HIV-1 protein such as Tat, may affect both the establishment and the reversal of latency. Indeed, mutational studies have demonstrated that insufficient Tat transactivation activity can result in impaired transcription of viral genes and the establishment of latency in cell culture experiments. Because Tat protein is one of highly variable proteins within HIV-1 proteome, it is conceivable that naturally occurring Tat mutations may differentially modulate Tat functions, thereby influencing the establishment and/or the reversal of viral latency in vivo. In this mini review, we summarize the recent findings of Tat naturally occurring polymorphisms associating with host immune responses and we highlight the implication of Tat sequence variations in relation to HIV latency.

  2. HIV-1 Tat and Viral Latency: What We Can Learn from Naturally Occurring Sequence Variations

    PubMed Central

    Kamori, Doreen; Ueno, Takamasa

    2017-01-01

    Despite the effective use of antiretroviral therapy, the remainder of a latently HIV-1-infected reservoir mainly in the resting memory CD4+ T lymphocyte subset has provided a great setback toward viral eradication. While host transcriptional silencing machinery is thought to play a dominant role in HIV-1 latency, HIV-1 protein such as Tat, may affect both the establishment and the reversal of latency. Indeed, mutational studies have demonstrated that insufficient Tat transactivation activity can result in impaired transcription of viral genes and the establishment of latency in cell culture experiments. Because Tat protein is one of highly variable proteins within HIV-1 proteome, it is conceivable that naturally occurring Tat mutations may differentially modulate Tat functions, thereby influencing the establishment and/or the reversal of viral latency in vivo. In this mini review, we summarize the recent findings of Tat naturally occurring polymorphisms associating with host immune responses and we highlight the implication of Tat sequence variations in relation to HIV latency. PMID:28194140

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

    PubMed

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

    1988-01-01

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

  4. Classifier-based latency estimation: a novel way to estimate and predict BCI accuracy

    NASA Astrophysics Data System (ADS)

    Thompson, David E.; Warschausky, Seth; Huggins, Jane E.

    2013-02-01

    Objective. Brain-computer interfaces (BCIs) that detect event-related potentials (ERPs) rely on classification schemes that are vulnerable to latency jitter, a phenomenon known to occur with ERPs such as the P300 response. The objective of this work was to investigate the role that latency jitter plays in BCI classification. Approach. We developed a novel method, classifier-based latency estimation (CBLE), based on a generalization of Woody filtering. The technique works by presenting the time-shifted data to the classifier, and using the time shift that corresponds to the maximal classifier score. Main results. The variance of CBLE estimates correlates significantly (p < 10-42) with BCI accuracy in the Farwell-Donchin BCI paradigm. Additionally, CBLE predicts same-day accuracy, even from small datasets or datasets that have already been used for classifier training, better than the accuracy on the small dataset (p < 0.05). The technique should be relatively classifier-independent, and the results were confirmed on two linear classifiers. Significance. The results suggest that latency jitter may be an important cause of poor BCI performance, and methods that correct for latency jitter may improve that performance. CBLE can also be used to decrease the amount of data needed for accuracy estimation, allowing research on effects with shorter timescales.

  5. ScriptingRT: A Software Library for Collecting Response Latencies in Online Studies of Cognition

    PubMed Central

    Schubert, Thomas W.; Murteira, Carla; Collins, Elizabeth C.; Lopes, Diniz

    2013-01-01

    ScriptingRT is a new open source tool to collect response latencies in online studies of human cognition. ScriptingRT studies run as Flash applets in enabled browsers. ScriptingRT provides the building blocks of response latency studies, which are then combined with generic Apache Flex programming. Six studies evaluate the performance of ScriptingRT empirically. Studies 1–3 use specialized hardware to measure variance of response time measurement and stimulus presentation timing. Studies 4–6 implement a Stroop paradigm and run it both online and in the laboratory, comparing ScriptingRT to other response latency software. Altogether, the studies show that Flash programs developed in ScriptingRT show a small lag and an increased variance in response latencies. However, this did not significantly influence measured effects: The Stroop effect was reliably replicated in all studies, and the found effects did not depend on the software used. We conclude that ScriptingRT can be used to test response latency effects online. PMID:23805326

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

    PubMed Central

    Lykouras, Dimosthenis; Rees, Kate

    2016-01-01

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

  7. Anxiety mediates the relationship between sleep onset latency and emotional eating in minority children.

    PubMed

    Nguyen-Rodriguez, Selena T; McClain, Arianna D; Spruijt-Metz, Donna

    2010-12-01

    This study examined associations between sleep onset latency and emotional eating in a minority sample of children. A cross-sectional school-based study of sleep, psychological constructs, diet and physical activity was conducted in 6 public and private schools in Los Angeles County. An ethnically diverse sample of 356 third through fifth graders completed confidential self-report surveys. Multilevel regression (MLM) analyses were conducted to study associations while controlling for gender, ethnicity, and the random effect of school. Girls made up 57% of the total sample, which was predominantly Latino (42.6%), followed by African Americans (21.6%) and Asians (19.2%). MLM revealed that there were significant associations between sleep onset latency and emotional eating (p=.030), depressive symptomology (p<.0001) and trait anxiety (p<.0001). Sobel's test for mediation showed that trait anxiety (p=.011) but not depressive symptomology (p=.141) was a mediator of the relationship between sleep onset latency and emotional eating. Thereby providing a mechanism through which sleep onset latency is related to emotional eating. These findings suggest that sleep onset latency is associated with increased anxiety, depressive symptoms, and emotional eating. Although causal inferences cannot be drawn from this cross-sectional data, future studies should examine the possibility that problems falling asleep could lead to emotional dysregulation that in turn leads to emotional eating. Emotional eating may be one avenue by which sleep disturbances lead to overweight and obesity.

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

    PubMed

    Li, Zichong; Lu, Huasong; Zhou, Qiang

    2016-02-01

    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.

  9. Antidromic latency of magnocellular, parvocellular, and koniocellular (Blue-ON) geniculocortical relay cells in marmosets.

    PubMed

    Cheong, Soon Keen; Johannes Pietersen, Alexander Nicolaas

    2014-05-01

    We studied the functional connectivity of cells in the lateral geniculate nucleus (LGN) with the primary visual cortex (V1) in anesthetized marmosets (Callithrix jacchus). The LGN sends signals to V1 along parallel visual pathways called parvocellular (P), magnocellular (M), and koniocellular (K). To better understand how these pathways provide inputs to V1, we antidromically activated relay cells in the LGN by electrically stimulating V1 and measuring the conduction latencies of P (n = 7), M (n = 14), and the "Blue-ON" (n = 5) subgroup of K cells (K-BON cells). We found that the antidromic latencies of K-BON cells were similar to those of P cells. We also measured the response latencies to high contrast visual stimuli for a subset of cells. We found the LGN cells that have the shortest latency of response to visual stimulation also have the shortest antidromic latencies. We conclude that Blue color signals are transmitted directly to V1 from the LGN by K-BON cells.

  10. 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

  11. Relationship of P3b single-trial latencies and response times in one, two, and three-stimulus oddball tasks.

    PubMed

    Walsh, Matthew M; Gunzelmann, Glenn; Anderson, John R

    2017-02-01

    The P300 is one of the most widely studied components of the human event-related potential. According to a longstanding view, the P300, and particularly its posterior subcomponent (i.e., the P3b), is driven by stimulus categorization. Whether the P3b relates to tactical processes involved in immediate responding or strategic processes that affect future behavior remains controversial, however. It is difficult to determine whether variability in P3b latencies relates to variability in response times because of limitations in the methods currently available to quantify the latency of the P3b during single trials. In this paper, we report results from the Psychomotor Vigilance Task (PVT), the Hitchcock Radar Task, and a 3-Stimulus Oddball Task. These represent variants of the one-, two-, and three-stimulus oddball paradigms commonly used to study the P3b. The PVT requires simple detection, whereas the Hitchcock Radar Task and the 3-Stimulus Task require detection and categorization. We apply a novel technique that combines hidden semi-Markov models and multi-voxel pattern analysis (HSMM-MVPA) to data from the three experiments. HSMM-MVPA revealed a processing stage in each task corresponding to the P3b. Trial-by-trial variability in the latency of the processing stage correlated with response times in the Hitchcock Radar Task and the 3-Stimulus Task, but not the PVT. These results indicate that the P3b reflects a stimulus categorization process, and that its latency is strongly associated with response times when the stimulus must be categorized before responding. In addition to those theoretical insights, the ability to detect the onset of the P3b and other components on a single-trial basis using HSMM-MVPA opens the door for new uses of mental chronometry in cognitive neuroscience.

  12. Potential Role for a β-Catenin Coactivator (High-Mobility Group AT-Hook 1 Protein) during the Latency-Reactivation Cycle of Bovine Herpesvirus 1.

    PubMed

    Zhu, Liqian; Workman, Aspen; Jones, Clinton

    2017-03-01

    The latency-related (LR) RNA encoded by bovine herpesvirus 1 (BoHV-1) is abundantly expressed in latently infected sensory neurons. Although the LR gene encodes several products, ORF2 appears to mediate important steps during the latency-reactivation cycle because a mutant virus containing stop codons at the amino terminus of ORF2 does not reactivate from latency in calves. We recently found that the Wnt/β-catenin signaling pathway is regulated during the BoHV-1 latency-reactivation cycle (Y. Liu, M. Hancock, A. Workman, A. Doster, and C. Jones, J Virol 90:3148-3159, 2016). In the present study, a β-catenin coactivator, high-mobility group AT-hook 1 protein (HMGA1), was detected in significantly more neurons in the trigeminal ganglia of latently infected calves than in those of uninfected calves. Consequently, we hypothesized that HMGA1 cooperates with ORF2 and β-catenin to maintain latency. In support of this hypothesis, coimmunoprecipitation studies demonstrated that ORF2 stably interacts with a complex containing β-catenin and/or HMGA1 in transfected mouse neuroblastoma (Neuro-2A) cells. Confocal microscopy provided evidence that ORF2 was relocalized by HMGA1 and β-catenin in Neuro-2A cells. ORF2 consistently enhanced the ability of HMGA1 to stimulate β-catenin-dependent transcription, suggesting that interactions between ORF2 and a complex containing β-catenin and HMGA1 have functional significance. An ORF2 stop codon mutant, an ORF2 nuclear localization mutant, or a mutant lacking the 5 protein kinase A or C phosphorylation sites interfered with its ability to stimulate β-catenin-dependent transcription. Since the canonical Wnt/β-catenin signaling pathway promotes neurogenesis (synapse formation and remodeling) and inhibits neurodegeneration, interactions between ORF2, HMGA1, and β-catenin may be important for certain aspects of the latency-reactivation cycle.IMPORTANCE The lifelong latency of bovine herpesvirus 1 (BoHV-1) requires that significant

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

    SciTech Connect

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

    1988-11-01

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

  14. 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.

  15. 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.

  16. 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.

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

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Woodbury, Michael H.; Shin, Kang G.

    1990-01-01

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

  19. Using homogeneous primary neuron cultures to study fundamental aspects of HSV-1 latency and reactivation.

    PubMed

    Kim, Ju Youn; Shiflett, Lora A; Linderman, Jessica A; Mohr, Ian; Wilson, Angus C

    2014-01-01

    We describe a primary neuronal culture system suitable for molecular characterization of herpes simplex virus type 1 (HSV-1) infection, latency, and reactivation. While several alternative models are available, including infections of live animal and explanted ganglia, these are complicated by the presence of multiple cell types, including immune cells, and difficulties in manipulating the neuronal environment. The highly pure neuron culture system described here can be readily manipulated and is ideal for molecular studies that focus exclusively on the relationship between the virus and host neuron, the fundamental unit of latency. As such it allows for detailed investigations of both viral and neuronal factors involved in the establishment and maintenance of HSV-1 latency and in viral reactivation induced by defined stimuli.

  20. Fictitious inhibitory differences: how skewness and slowing distort the estimation of stopping latencies.

    PubMed

    Verbruggen, Frederick; Chambers, Christopher D; Logan, Gordon D

    2013-03-01

    The stop-signal paradigm is a popular method for examining response inhibition and impulse control in psychology, cognitive neuroscience, and clinical domains because it allows the estimation of the covert latency of the stop process: the stop-signal reaction time (SSRT). In three sets of simulations, we examined to what extent SSRTs that were estimated with the popular mean and integration methods were influenced by the skew of the reaction time distribution and the gradual slowing of the response latencies. We found that the mean method consistently overestimated SSRT. The integration method tended to underestimate SSRT when response latencies gradually increased. This underestimation bias was absent when SSRTs were estimated with the integration method for smaller blocks of trials. Thus, skewing and response slowing can lead to spurious inhibitory differences. We recommend that the mean method of estimating SSRT be abandoned in favor of the integration method.

  1. Use of a latency-based demand assessment to identify potential demands for functional analyses.

    PubMed

    Call, Nathan A; Miller, Sarah J; Mintz, Joslyn Cynkus; Mevers, Joanna Lomas; Scheithauer, Mindy C; Eshelman, Julie E; Beavers, Gracie A

    2016-12-01

    Unlike potential tangible positive reinforcers, which are typically identified for inclusion in functional analyses empirically using preference assessments, demands are most often selected arbitrarily or based on caregiver report. The present study evaluated the use of a demand assessment with 12 participants who exhibited escape-maintained problem behavior. Participants were exposed to 10 demands, with aversiveness measured by average latency to the first instance of problem behavior. In subsequent functional analyses, results of a demand condition that included the demand with the shortest latency to problem behavior resulted in identification of an escape function for 11 of the participants. In contrast, a demand condition that included the demand with the longest latency resulted in identification of an escape function for only 5 participants. The implication of these findings is that for the remaining 7 participants, selection of the demand for the functional analysis without using the results of the demand assessment could have produced a false-negative finding.

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

    SciTech Connect

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

    2008-12-20

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

  3. The influence of target angular velocity on visual latency difference determined using the rotating Pulfrich effect.

    PubMed

    Nickalls, R W

    1996-09-01

    Visual latency difference was determined directly in normal volunteers, using the rotating Pulfrich technique described by Nickalls [Vision Research, 26, 367-372 (1986)]. Subjects fixated a black vertical rod rotating clockwise on a horizontal turntable turning with constant angular velocity (16.6,33.3 or 44.7 revs/min) with a neutral density filter (OD 0.7 or 1.5) in front of the right eye. For all subjects the latency difference associated with the 1.5 OD filter was significantly greater (P < 0.001) with the rod rotating at 16.6 rev/min than at 33.3 revs/min. The existence of an inverse relationship between latency difference and angular velocity is hypothesized.

  4. 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

  5. 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.

  6. Middle latency auditory evoked potentials during total intravenous anesthesia with droperidol, ketamine and fentanyl.

    PubMed

    Kudoh, A; Matsuki, A

    1999-04-01

    We investigated whether total intravenous anesthesia with ketamine, fentanyl and droperidol would affect middle latency auditory evoked potentials and explicit memory, and whether dreams during the anesthesia are related to plasma concentrations of fentanyl and the infusion technique. A total number of 40 patients were the subjects for this study. Twenty patients (group A) were maintained with intravenous ketamine 2 mg kg-1 hr-1 and fentanyl 5 micrograms kg-1 hr-1 for the first 60 min and 3 micrograms kg-1 hr-1 for the next 90 min, and droperidol 0.1 mg kg-1. The remaining 20 patients (group B) were maintained with intravenous ketamine 2 mg kg-1 hr-1, droperidol 0.1 mg kg-1 and fentanyl 50-100 micrograms in a bolus intermittently as needed by vital signs such as increases in heart rate and arterial blood pressure. Middle latency auditory evoked potentials, plasma fentanyl and ketamine levels were measured; explicit memory and dreams were also estimated. There were no patients who recollected explicit memories of intraoperative events in both groups. The middle latency auditory evoked potentials were not significantly changed during the anesthesia in both groups. We could find no significant differences in latencies and amplitudes of the middle latency auditory evoked potentials between the both groups. Plasma fentanyl levels of group B patients were significantly lower than those of group A patients and the incidence of the dreams was significantly higher in group B patients. We conclude that the anesthesia with ketamine, fentanyl and droperidol is not associated with the explicit memories, though the middle latency auditory evoked potentials were not significantly changed as compared with those in the waking state. In addition, dreams during the anesthesia may correlate with plasma fentanyl concentrations or the infusion technique.

  7. Role of latency jittering correction in motion-onset VEP amplitude decay during prolonged visual stimulation.

    PubMed

    Kremláček, J; Hulan, M; Kuba, M; Kubová, Z; Langrová, J; Vít, F; Szanyi, J

    2012-06-01

    Visual evoked potentials to motion-onset stimulation (M-VEPs) gradually attenuate in amplitude during examination. The observed decline in averaged responses can be caused by decreases in single response magnitudes and/or increased variability in a response delays, that is, latency jittering. To illuminate the origins of the suppression of M-VEPs during stimuli repetition, we used correlation technique to estimate an upper bound of possible latency jittering of single sweeps and we evaluated the effect of its correction on the amplitudes of three M-VEP dominant peaks P1, N2 and P3. During prolonged visual motion stimulation, the variability of corrective latency shifts in the occipital region increased (r = 0.35: 0.44) and the number of single responses corresponding to the average curve declined in occipital and parietal derivations (r = -0.48: -0.62). While the P1 peak amplitude did not exhibit any time-specific behaviour, the N2 amplitude exhibited a significant decay of 29.4% that was partially reduced to 16.6% in the central occipital derivation by the latency jitter and non-correspondence corrections. The strongest attenuation (32.7%) was observed in the P3 amplitude and was less sensitive to the corrections, dropping only to 27.9%. The main part of the response suppression to repeated motion stimulation was caused by amplitude drop and represents non-stationary process that likely correspond to a fatigue model. The rise of variability in latency jitter correction and the reduction in single responses correlated with the M-VEP were significant factors associated with prolonged motion stimulation. The relation of these parameters to a hypothetical veridical response is ambiguous and can be caused by a time shift of the response or by a change of signal-to-noise ratio. Using selective averaging and latency jitter correction, the effect of response suppression was partially removed.

  8. Use of latency to problem behavior to evaluate demands for inclusion in functional analyses.

    PubMed

    Call, Nathan A; Pabico, Ryan S; Lomas, Joanna E

    2009-01-01

    Few direct-assessment procedures are designed to identify potential negative reinforcers (e.g., including demands in the escape condition of functional analyses). Two participants were systematically exposed to a series of demands nominated by caregivers as potential negative reinforcers. Sessions ended following the first instance of problem behavior, and a hierarchy of demand aversiveness was created based on the latency to the first problem behavior. Subsequent functional analyses confirmed the predictive value of the hierarchy, with shorter latency demands consistently producing more differentiated functional analysis outcomes.

  9. 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.

  10. Low latency, area, and energy efficient Hybrid Photonic Plasmonic on-chip Interconnects (HyPPI)

    NASA Astrophysics Data System (ADS)

    Sun, Shuai; Badaway, Abdel-Hameed A.; Narayana, Vikram; El-Ghazawi, Tarek; Sorger, Volker J.

    2016-03-01

    In this paper we benchmark various interconnect technologies including electrical, photonic, and plasmonic options. We contrast them with hybridizations where we consider plasmonics for active manipulation devices, and photonics for passive propagation integrated circuit elements, and further propose another novel hybrid link that utilizes an on chip laser for intrinsic modulation thus bypassing electro-optic modulation. Link benchmarking proves that hybridization can overcome the shortcomings of both pure photonic and plasmonic links. We show superiority in a variety of performance parameters such as point-to-point latency, energy efficiency, capacity, ability to support wavelength division multiplexing, crosstalk coupling length, bit flow density and Capability-to-Latency-Energy-Area Ratio.

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

    SciTech Connect

    Canavan, G.H.

    1998-12-31

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

  12. 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.

  13. USE OF LATENCY TO PROBLEM BEHAVIOR TO EVALUATE DEMANDS FOR INCLUSION IN FUNCTIONAL ANALYSES

    PubMed Central

    Call, Nathan A; Pabico, Ryan S; Lomas, Joanna E

    2009-01-01

    Few direct-assessment procedures are designed to identify potential negative reinforcers (e.g., including demands in the escape condition of functional analyses). Two participants were systematically exposed to a series of demands nominated by caregivers as potential negative reinforcers. Sessions ended following the first instance of problem behavior, and a hierarchy of demand aversiveness was created based on the latency to the first problem behavior. Subsequent functional analyses confirmed the predictive value of the hierarchy, with shorter latency demands consistently producing more differentiated functional analysis outcomes. PMID:20190935

  14. 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.

  15. 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

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

    PubMed

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

    2016-10-26

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    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.

  18. 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.

  19. 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

  20. PIM1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

    DTIC Science & Technology

    2008-10-31

    CA 92S54. USA "Department of Biochemistry and Microbiology. Ijjma Linda University School of Medicine. Ijima Undo. CA 92354. USA ’Department of...372-378, 1987. 13. Devlin J, Devlin P, Myambo K, Lilly M, Rado T, Warren K: Isolation and expression of a cDNA encoding a human granulcyte colony...stimulating factor. J Leukocyte Biol 41:302-306, 1987. 14. Lilly M, Devlin J, Devlin P, Rado T: Production of granulocyte colony-stimulating factor by

  1. Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test.

    PubMed

    Littner, Michael R; Kushida, Clete; Wise, Merrill; Davila, David G; Morgenthaler, Timothy; Lee-Chiong, Teofilo; Hirshkowitz, Max; Daniel, L Loube; Bailey, Dennis; Berry, Richard B; Kapen, Sheldon; Kramer, Milton

    2005-01-01

    Characterization of excessive sleepiness is an important task for the sleep clinician, and assessment requires a thorough history and in many cases, objective assessment in the sleep laboratory. These practice parameters were developed to guide the sleep clinician on appropriate clinical use of the Multiple Sleep Latency Test (MSLT), and the Maintenance of Wakefulness Test (MWT). These recommendations replace those published in 1992 in a position paper produced by the American Sleep Disorders Association. A Task Force of content experts was appointed by the American Academy of Sleep Medicine to perform a comprehensive review of the scientific literature and grade the evidence regarding the clinical use of the MSLT and the MWT. Practice parameters were developed based on this review and in most cases evidence based methods were used to support recommendations. When data were insufficient or inconclusive, the collective opinion of experts was used to support recommendations. These recommendations were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. The MSLT is indicated as part of the evaluation of patients with suspected narcolepsy and may be useful in the evaluation of patients with suspected idiopathic hypersomnia. The MSLT is not routinely indicated in the initial evaluation and diagnosis of obstructive sleep apnea syndrome, or in assessment of change following treatment with nasal continuous positive airway pressure (CPAP). The MSLT is not routinely indicated for evaluation of sleepiness in medical and neurological disorders (other than narcolepsy), insomnia, or circadian rhythm disorders. The MWT may be indicated in assessment of individuals in whom the inability to remain awake constitutes a safety issue, or in patients with narcolepsy or idiopathic hypersomnia to assess response to treatment with medications. There is little evidence linking mean sleep latency on

  2. 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.

  3. 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.…

  4. 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.

  5. Human Short-Latency Somatosensory Evoked Potentials in Impact Acceleration Research: Equipment, Procedures and Techniques

    DTIC Science & Technology

    1990-10-01

    Instrumentation Data Sheet .......................... 10 Figure 8. Human Physiology Screen One ....................................... 1I1 Figure 9. Human ... Physiology Screen Two...................................... 12 Figure 10. Human Physiology Screen Three ..................................... 12 Figure...Short-Latency Somatosensory Evoked Potentials in Impact Acceleration Research ***** HUMAN PHYSIOLOGY SCREEN***** Please Read First To move from one

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

    ERIC Educational Resources Information Center

    Allnutt, Louise

    2010-01-01

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

  7. 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…

  8. 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.…

  9. Latency and Accuracy Characteristics of Saccades and Corrective Saccades in Children and Adults.

    ERIC Educational Resources Information Center

    Cohen, Mark E.; Ross, Leonard E.

    1978-01-01

    Examines the latency and the accuracy of adult's and children's saccades under optimal warning and no-warning conditions. Subjects were nine adults (mean age =23.7) and nine elementary school students (mean age =8.5). (Author/MP)

  10. 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…

  11. Global gene expression profiling of Marek's disease virus during cytolytic and latency infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD), a lymphoproliferative disease of domestic chickens, is caused by an avian alpha-herpesvirus, Marek’s disease virus (MDV). MDV causes an early cytolytic infection in B cells followed by a latency infection in CD4+ T cells. The transcriptional analysis of a limited number of MD...

  12. 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…

  13. 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...

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

    ERIC Educational Resources Information Center

    Koriat, Asher; Ackerman, Rakefet

    2010-01-01

    Research with adults indicates that confidence in the correctness of an answer decreases as a function of the amount of time it takes to reach that answer, suggesting that people use response latency as a mnemonic cue for subjective confidence. Experiment 1 extended investigation to 2nd, 3rd and 5th graders. When children chose the answer to…

  15. An Examination of Dysfunctional Latency Age Children of Alcoholic Parents and Problems in Intervention.

    ERIC Educational Resources Information Center

    Morehouse, Ellen R.; Richards, Tarpley

    1982-01-01

    Describes how parental functions essential to children's growth and development are damaged or destroyed by alcoholism and examines interpersonal problems of latency age children of alcoholic parents. Also describes therapist's problems in working with such children and offers recommendations for helping them work through faulty relationship…

  16. 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.

  17. Auditory brainstem response and late latency response in individuals with tinnitus having normal hearing

    PubMed Central

    Konadath, Sreeraj; Manjula, Puttabasappa

    2016-01-01

    Summary Tinnitus is a commonly encountered complaint in routine audiology practice. The pathophysiology and exact generation site of tinnitus is not precisely established. Auditory brainstem response (ABR) and late latency response (LLR) findings in individuals with tinnitus show mixed results in the literature. Majority of studies have focused on individuals having tinnitus with peripheral hearing loss. The present study explores ABR and LLR characteristics among tinnitus patients with normal audiometric presentation; with no direct indication of any cochlear lesion. This study aims at characterizing the ABR and LLR findings in individuals with tinnitus having normal audiometric presentation. ABR and LLR waveform characteristics were recorded and compared between participants with tinnitus (Group 1) and those without tinnitus (Group 2). The ABR analysis indicated no significant differences in latency and amplitude between Groups 1 and 2. However, patients with tinnitus showed abnormally reduced absolute amplitudes of peaks I and V. LLR analysis indicated no significant differences in latency and amplitude between Groups 1 and 2 except enhanced amplitude of P1. The reduced amplitude of peaks I and V along with normal absolute latencies of peaks I, III and V indicate that the origin of tinnitus is possibly due to reduced excitation of auditory nerve fibres arising from a peripheral hearing loss beyond 8 kHz. The P1 amplitude enhancement could be attributed to mechanism explaining central gain model; which suggests that central auditory structures recalibrates the mean firing rate, considering the reduced output from sensory structures, generating neural noise perceived as tinnitus. PMID:27904821

  18. Variability of Response Latency in Paired Associate Learning as a Function of Training Procedure.

    ERIC Educational Resources Information Center

    Judd, Wilson A.; Glaser, Robert

    Two procedures were investigated in an attempt to decrease the variability of overlearning response latencies in a study-test paradigm, paired-associate task matching CVC's with response keys: (1) self-pacing the task by presenting test trial stimuli whenever the subject pressed a "home" key; and (2) instructing and shaping subjects to keep home…

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

    PubMed

    Sarek, Grzegorz; Järviluoma, Annika; Moore, Henna M; Tojkander, Sari; Vartia, Salla; Biberfeld, Peter; Laiho, Marikki; Ojala, Päivi M

    2010-03-19

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

  20. Vocalization Latencies of Skilled and Less Skilled Comprehenders for Words Written in Hiragana and Kanji.

    ERIC Educational Resources Information Center

    Kuhara-Kojima, Keiko; And Others

    1996-01-01

    Finds that Japanese fifth graders' naming speed was a good indicator of the automaticity of the lexical access for both syllabaries and morphograms, but that skilled/less-skilled differences in vocalization latencies were greater for real words than for pseudowords for both hiragana and kanji. Discusses the applicability of C. A. Perfetti's verbal…

  1. The Middle Latency Response (MLR) and Steady State Evoked Potential (SSEP) in Neonates.

    DTIC Science & Technology

    1985-05-01

    antibiotics, intracranial hemorrhage, and congenital malformations . Unfortunately, the items in this list often occur in combination rather than in isolation...JOURNAL OF THE AMERICAN AUDITORY SOCIETY 5: 156-162, 1979. Yamada, 0., Kodera, K. and Yagi, T. Cochlear processes affecting wave V latency of the

  2. 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…

  3. 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)…

  4. Structural equation modeling for estimating the identification accuracy and detection time latency of English monosyllabic words

    NASA Astrophysics Data System (ADS)

    Takayanagi, Sumiko; Bernstein, Lynne E.; Auer, Edward T.

    2003-10-01

    Structural equation modeling (SEM) was used to examine the statistical structure among sets of experiential (word age of acquisition and subjective familiarity) and lexical similarity (lexical equivalence class size and neighborhood density) variables for word identification and reaction time latency tasks. Stimuli were 240 vocoded monosyllabic English words with reduced intelligibility and altered similarity relationships. Participants detected a target word following a prime and on every trial reported the prime. The identification accuracy was estimated by words and phonemes correct, and detection latency was estimated by trimmed and harmonic mean RTs. A parsimonious SEM was chosen in terms of the chi-square and model fit indices that determine whether the models adequately described the particular associations of variables/interfactor relationships. The variable/factor error variances were constrained to be uncorrelated with each other in order to evaluate effects independently. A bootstrapping technique indicated that the regression weights of the top-down and bottom-up factors were small, but they were significant in the model. The variance accounted for (VAF) by the model was 7.1% for identification accuracy, and 5.2% for RT latency. The model also indicated that RT latency was highly influenced by prime identification accuracy (15% VAF). [Work supported by NIH/NIDCD00695.

  5. Effect of color of flash stimulus on variability of flash visual evoked potential latencies.

    PubMed

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

    2012-01-01

    Visual Evoked Potentials (VEPs) are evoked potentials generated in response to visual stimuli. The flash VEP (FVEP) is used less frequently than pattern-reversal VEP (PR-VEP) because; it shows great variations in both latency and amplitude in normal subjects. The advantage of FVEP is its feasibility in non-cooperative subjects, which circumvents the major limitation of PR-VEP. The present study was undertaken to assess the effect of change of color of flashlight on variability of FVEP latencies. Healthy subjects in the age group of 18-30 years underwent the standard stimulus using white light, followed by altered stimuli done with red and blue light. 2 trials were given for each eye, for each type of stimulus. The same set of studies was repeated at the same clock time the following day. The inter-individual and intra-individual variability in the peak latency of P2 and N2 waveforms was assessed using coefficient of variation (COV). Both inter-individual and intra-individual variability was less when monochromatic light was used. Between red and blue FVEP, inter-individual variability was less in blue FVEP and the results of intra-individual variability was inconclusive. Monochromatic stimulation preferably with blue light reduced both inter-individual and intra-individual variability seen in latency of P2 and N2 waveforms in FVEP and hence recommended in preference to standard white stimulus for FVEP recording.

  6. 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

  7. On the spatial distribution of the reflection sources of different latency components of otoacoustic emissions

    PubMed Central

    Sisto, Renata; Moleti, Arturo; Shera, Christopher A.

    2015-01-01

    The experimental observation of long- and short-latency components in both stimulus-frequency and transient-evoked otoacoustic emissions admits a comprehensive explanation within the coherent reflection mechanism, in a linear active transmission-line cochlear model. A local complex reflectivity function associated with roughness was defined and analyzed by varying the tuning factor of the model, systematically showing, for each frequency, a multiple-peak spatial structure, compatible with the observed multiple-latency structure of otoacoustic emissions. Although this spatial pattern and the peak relative intensity changes with the chosen random roughness function, the multiple-peak structure is a reproducible feature of different “digital ears,” in good agreement with experimental data. If one computes the predicted transmission delays as a function of frequency and position for each source, one gets a good match to the latency-frequency patterns that are directly computed from synthesized otoacoustic spectra using time-frequency analysis. This result clarifies the role of the spatial distribution of the otoacoustic emission sources, further supporting the interpretation of different-latency otoacoustic components as due to reflection sources localized at different places along the basilar membrane. PMID:25698011

  8. In vitro effects of the small-molecule protein kinase C agonists on HIV latency reactivation

    PubMed Central

    Brogdon, Jessica; Ziani, Widade; Wang, Xiaolei; Veazey, Ronald S.; Xu, Huanbin

    2016-01-01

    The persistence of latently HIV-infected cellular reservoirs represents the major obstacle to virus eradication in patients under antiretroviral therapy (ART). Cure strategies to eliminate these reservoirs are thus needed to reactivate proviral gene expression in latently infected cells. In this study, we tested optimal concentrations of PKC agonist candidates (PEP005/Ingenol-3-angelate, prostratin, bryostatin-1, and JQ1) to reactivate HIV latency in vitro, and examined their effects on cell survival, activation and epigenetic histone methylation after treatment alone or in combination in cell line and isolated CD4 T cells from SIV-infected macaques. The results showed that PKC agonists increased cell activation with different degrees of latency reactivation, concomitant with reduced levels of histone methylation. With increasing concentrations, prostratin and byrostain-1 treatment rapidly reduced cell survival and cell activation. The PKC agonist combinations, or in combination with JQ1, led to modest levels of synergistic reactivation of HIV. Remarkably, PEP005 treatment alone caused marked reactivation of HIV latency, similar to PMA stimulation. These findings suggested that PEP005 alone, as indicated its lower cytotoxicity and lower effective dose inducing maximal reactivation, might be a candidate for effectively reactivating HIV latency as part of a therapeutic strategy for HIV infection. PMID:27941949

  9. Global stability for a class of mass action systems allowing for latency in tuberculosis

    NASA Astrophysics Data System (ADS)

    McCluskey, C. Connell

    2008-02-01

    A very general compartmental model of the spread of an infectious disease with mass action incidence is given. The global stability of this system is completely determined using Lyapunov functions. The general system exhibits the traditional threshold behaviour. The dimension of the system is arbitrary, allowing, in particular, for detailed modelling of the distribution of latency times for tuberculosis.

  10. Short and long latency jaw-opening reflex responses elicited by mechanical stimulation in man.

    PubMed

    Yamada, Y; Stohler, C S; Shimada, K; Ash, M M

    1985-01-01

    Jaw-opening reflex responses elicited by tapping the chin during maximum clenching in incisal edge-to-edge contact position were studied in 10 healthy subjects. Stimuli were also delivered during weak clenching on a rubber stamp, separating the incisors by approx. 10 mm and protruding the mandible to the edge-to-edge incisor relationship. All four central incisors were stimulated simultaneously. With weak stimuli, there was a short-latency (9.5 ms) digastric response which may have had a disynaptic pathway. Taps of moderate strength produced long-latency (20 ms) responses, and sometimes a short-latency (9.5 ms) component as well. Strong (non-painful) taps produced an even longer-latency digastric response, 30 ms or more following the stimulus with less synchronization than earlier responses. Jaw-jerk reflexes occurred 8.5 ms following the tap, independently of the magnitude of the stimulus. Local anaesthesia of the upper and lower incisors abolished the digastric muscle response. Thus large periodontal afferents may be responsible for the early digastric reflex activity and smaller fibres for later effects. Temporal summation of the reflex response probably occurred when all incisors were stimulated simultaneously.

  11. Functional organization of human auditory cortex: Investigation of response latencies through direct recordings

    PubMed Central

    McMurray, Bob; Kovach, Christopher K.; Oya, Hiroyuki; Kawasaki, Hiroto; Howard, Matthew A.

    2015-01-01

    The model for functional organization of human auditory cortex is in part based on findings in non-human primates, where the auditory cortex is hierarchically delineated into core, belt and parabelt fields. This model envisions that core cortex directly projects to belt, but not to parabelt, whereas belt regions are a major source of direct input for auditory parabelt. In humans, the posteromedial portion of Heschl’s gyrus (HG) represents core auditory cortex, whereas the anterolateral portion of HG and the posterolateral superior temporal gyrus (PLST) are generally interpreted as belt and parabelt, respectively. In this scheme, response latencies can be hypothesized to progress in serial fashion from posteromedial to anterolateral HG to PLST. We examined this hypothesis by comparing response latencies to multiple stimuli, measured across these regions using simultaneous intracranial recordings in neurosurgical patients. Stimuli were 100 Hz click trains and the speech syllable /da/. Response latencies were determined by examining event-related band power in the high gamma frequency range. The earliest responses in auditory cortex occurred in posteromedial HG. Responses elicited from sites in anterolateral HG were neither earlier in latency from sites on PLST, nor more robust. Anterolateral HG and PLST exhibited some preference for speech syllable stimuli compared to click trains. These findings are not supportive of a strict serial model envisioning principal flow of information along HG to PLST. In contrast, data suggest that a portion of PLST may represent a relatively early stage in the auditory cortical hierarchy. PMID:25019680

  12. Reliability and efficacy of the long-latency stretch reflex in the human thumb.

    PubMed

    Marsden, C D; Merton, P A; Morton, H B; Rothwell, J C; Traub, M M

    1981-07-01

    1. The amount of positional compensation afforded by the long-latency reflex in the flexor pollicis longus has been investigated in ten normal human subjects. 2. The interphalangeal joint of the thumb was extended by between 2 and 40 degrees at up to 900 deg/s by suddenly increasing the standing force applied to the lever against which the subject was pressing with the pad of the thumb. 3. Electromyographic (e.m.g.) responses at spinal-latency were very small or absent for stretches of this magnitude. The long-latency stretch reflex produced an average positional correction of about 50% for disturbances in the range of 5-25 degrees. The response began to saturate for disturbances of greater than 25 degrees. 4. The e.m.g. response was pulsatile, lasting only some 50 ms, even during continuously increasing disturbances; frequently it terminated despite a remaining positional error. 5. There was a large variation from subject to subject in the average amount of positional correction provided by the stretch reflex. Examination of single responses to the same stretch in individual subjects showed an even greater variation from trial to trial. 6. Variation in the compensation produced by the long-latency stretch reflex from trial to trial could not be explained by the slight variation in size or maximum velocity of the individual stretches.

  13. The effects of parental divorce: experiences of the child in early latency.

    PubMed

    Kelly, J B; Wallerstein, J S

    1976-01-01

    This paper discusses the impact of divorce on 26 children in early latency, as observed shortly after the initial parental separation and one year later. The material is part of a larger clinical study, begun in 1970, of 131 children and adolescents from 60 divorcing families.

  14. The effects of parental divorce: experiences of the child in later latency.

    PubMed

    Wallerstein, J S; Kelly, J B

    1976-04-01

    This paper discusses the impact of divorce on 31 children in later latency, as observed shortly after the initial parental separation and one year later. The material is part of an on-going clinical study, begun in 1970, of 131 children and adolescents from 60 divorcing families in Northern California.

  15. Convergence of Kaposi's sarcoma-associated herpesvirus reactivation with Epstein-Barr virus latency and cellular growth mediated by the notch signaling pathway in coinfected cells.

    PubMed

    Spadavecchia, Sophia; Gonzalez-Lopez, Olga; Carroll, Kyla Driscoll; Palmeri, Diana; Lukac, David M

    2010-10-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphoma (PEL). All PEL cell lines are infected with KSHV, and 70% are coinfected with Epstein-Barr virus (EBV). KSHV reactivation from latency requires promoter-specific transactivation by the KSHV Rta protein through interactions with RBP-Jk (CSL), the cellular DNA-binding component of the Notch signal transduction pathway. EBV transformation of primary B cells requires EBV nuclear antigen 2 (EBNA-2) to interact with RBP-Jk to direct the latent viral and cellular gene expression program. Although KSHV Rta and EBV EBNA-2 both require RBP-Jk for transactivation, previous studies have suggested that RBP-Jk-dependent transactivators do not function identically. We have found that the EBV latent protein LMP-1 is expressed in less than 5% of KSHV(+)/EBV(+) PEL cells but is induced in an Rta-dependent fashion when KSHV reactivates. KSHV Rta transactivates the EBV latency promoters in an RBP-Jk-dependent fashion and forms a ternary complex with RBP-Jk on the promoters. In B cells that are conditionally transformed by EBV alone, we show that KSHV Rta complements a short-term EBNA-2 growth deficiency in an autocrine/paracrine manner. Complementation of EBNA-2 deficiency by Rta depends on RBP-Jk and LMP-1, and Rta transactivation is required for optimal growth of KSHV(+)/EBV(+) PEL lines. Our data suggest that Rta can contribute to EBV-driven cellular growth by transactivating RBP-Jk-dependent EBV latency genes. However, our data also suggest that EBNA-2 and Rta induce distinct alterations in the cellular proteomes that contribute to the growth of infected cells.

  16. BET-Inhibitors Disrupt Rad21-Dependent Conformational Control of KSHV Latency

    PubMed Central

    Chen, Horng-Shen; De Leo, Alessandra; Kerekovic, Andrew; Hills, Robert

    2017-01-01

    Kaposi’s Sarcoma-associated Herpesvirus (KSHV) establishes stable latent infection in B-lymphocytes and pleural effusion lymphomas (PELs). During latency, the viral genome persists as an epigenetically constrained episome with restricted gene expression programs. To identify epigenetic regulators of KSHV latency, we screened a focused small molecule library containing known inhibitors of epigenetic factors. We identified JQ1, a Bromodomain and Extended Terminal (BET) protein inhibitor, as a potent activator of KSHV lytic reactivation from B-cells carrying episomal KSHV. We validated that JQ1 and other BET inhibitors efficiently stimulated reactivation of KSHV from latently infected PEL cells. We found that BET proteins BRD2 and BRD4 localize to several regions of the viral genome, including the LANA binding sites within the terminal repeats (TR), as well as at CTCF-cohesin sites in the latent and lytic control regions. JQ1 did not disrupt the interaction of BRD4 or BRD2 with LANA, but did reduce the binding of LANA with KSHV TR. We have previously demonstrated a cohesin-dependent DNA-loop interaction between the latent and lytic control regions that restrict expression of ORF50/RTA and ORF45 immediate early gene transcripts. JQ1 reduced binding of cohesin subunit Rad21 with the CTCF binding sites in the latency and lytic control regions. JQ1 also reduced DNA-loop interaction between latent and lytic control regions. These findings implicate BET proteins BRD2 and BRD4 in the maintenance of KSHV chromatin architecture during latency and reveal BET inhibitors as potent activators of KSHV reactivation from latency. PMID:28107481

  17. Channel noise effects on first spike latency of a stochastic Hodgkin-Huxley neuron

    NASA Astrophysics Data System (ADS)

    Maisel, Brenton; Lindenberg, Katja

    2017-02-01

    While it is widely accepted that information is encoded in neurons via action potentials or spikes, it is far less understood what specific features of spiking contain encoded information. Experimental evidence has suggested that the timing of the first spike may be an energy-efficient coding mechanism that contains more neural information than subsequent spikes. Therefore, the biophysical features of neurons that underlie response latency are of considerable interest. Here we examine the effects of channel noise on the first spike latency of a Hodgkin-Huxley neuron receiving random input from many other neurons. Because the principal feature of a Hodgkin-Huxley neuron is the stochastic opening and closing of channels, the fluctuations in the number of open channels lead to fluctuations in the membrane voltage and modify the timing of the first spike. Our results show that when a neuron has a larger number of channels, (i) the occurrence of the first spike is delayed and (ii) the variation in the first spike timing is greater. We also show that the mean, median, and interquartile range of first spike latency can be accurately predicted from a simple linear regression by knowing only the number of channels in the neuron and the rate at which presynaptic neurons fire, but the standard deviation (i.e., neuronal jitter) cannot be predicted using only this information. We then compare our results to another commonly used stochastic Hodgkin-Huxley model and show that the more commonly used model overstates the first spike latency but can predict the standard deviation of first spike latencies accurately. We end by suggesting a more suitable definition for the neuronal jitter based upon our simulations and comparison of the two models.

  18. Tap Arduino: An Arduino microcontroller for low-latency auditory feedback in sensorimotor synchronization experiments.

    PubMed

    Schultz, Benjamin G; van Vugt, Floris T

    2016-12-01

    Timing abilities are often measured by having participants tap their finger along with a metronome and presenting tap-triggered auditory feedback. These experiments predominantly use electronic percussion pads combined with software (e.g., FTAP or Max/MSP) that records responses and delivers auditory feedback. However, these setups involve unknown latencies between tap onset and auditory feedback and can sometimes miss responses or record multiple, superfluous responses for a single tap. These issues may distort measurements of tapping performance or affect the performance of the individual. We present an alternative setup using an Arduino microcontroller that addresses these issues and delivers low-latency auditory feedback. We validated our setup by having participants (N = 6) tap on a force-sensitive resistor pad connected to the Arduino and on an electronic percussion pad with various levels of force and tempi. The Arduino delivered auditory feedback through a pulse-width modulation (PWM) pin connected to a headphone jack or a wave shield component. The Arduino's PWM (M = 0.6 ms, SD = 0.3) and wave shield (M = 2.6 ms, SD = 0.3) demonstrated significantly lower auditory feedback latencies than the percussion pad (M = 9.1 ms, SD = 2.0), FTAP (M = 14.6 ms, SD = 2.8), and Max/MSP (M = 15.8 ms, SD = 3.4). The PWM and wave shield latencies were also significantly less variable than those from FTAP and Max/MSP. The Arduino missed significantly fewer taps, and recorded fewer superfluous responses, than the percussion pad. The Arduino captured all responses, whereas at lower tapping forces, the percussion pad missed more taps. Regardless of tapping force, the Arduino outperformed the percussion pad. Overall, the Arduino is a high-precision, low-latency, portable, and affordable tool for auditory experiments.

  19. 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

  20. 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…

  1. 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…

  2. Restricted TET2 Expression in Germinal Center Type B Cells Promotes Stringent Epstein-Barr Virus Latency.

    PubMed

    Wille, Coral K; Li, Yangguang; Rui, Lixin; Johannsen, Eric C; Kenney, Shannon C

    2017-03-01

    Epstein-Barr virus (EBV) latently infects normal B cells and contributes to the development of certain human lymphomas. Newly infected B cells support a highly transforming form (type III) of viral latency; however, long-term EBV infection in immunocompetent hosts is limited to B cells with a more restricted form of latency (type I) in which most viral gene expression is silenced by promoter DNA methylation. How EBV converts latency type is unclear, although it is known that type I latency is associated with a germinal center (GC) B cell phenotype, and type III latency with an activated B cell (ABC) phenotype. In this study, we have examined whether expression of TET2, a cellular enzyme that initiates DNA demethylation by converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates EBV latency type in B cells. We found that TET2 expression is inhibited in normal GC cells and GC type lymphomas. In contrast, TET2 is expressed in normal naive B cells and ABC type lymphomas. We also demonstrate that GC type cell lines have increased 5mC levels and reduced 5hmC levels in comparison to those of ABC type lines. Finally, we show that TET2 promotes the ability of the EBV transcription factor EBNA2 to convert EBV-infected cells from type I to type III latency. These findings demonstrate that TET2 expression is repressed in GC cells independent of EBV infection and suggest that TET2 promotes type III EBV latency in B cells with an ABC or naive phenotype by enhancing EBNA2 activation of methylated EBV promoters.IMPORTANCE EBV establishes several different types of viral latency in B cells. However, cellular factors that determine whether EBV enters the highly transforming type III latency, versus the more restricted type I latency, have not been well characterized. Here we show that TET2, a cellular enzyme that initiates DNA demethylation by converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates EBV latency type in B cells by

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

    PubMed

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

    2016-08-01

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

  4. 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

  5. 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

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

    PubMed

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

    2015-07-01

    Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephalitis; however, a third of the cases of HSV-1 encephalitis are associated with HSV-1 primary infection. Primary VZV infection causes varicella (chickenpox) following which latent virus may reactivate decades later to produce herpes zoster (shingles), as well as an increasingly recognized number of subacute, acute and chronic neurological conditions. Following primary infection, both viruses establish a latent infection in neuronal cells in human peripheral ganglia. However, the detailed mechanisms of viral latency and reactivation have yet to be unravelled. In both cases latent viral DNA exists in an 'end-less' state where the ends of the virus genome are joined to form structures consistent with unit length episomes and concatemers, from which viral gene transcription is restricted. In latently infected ganglia, the most abundantly detected HSV-1 RNAs are the spliced products originating from the primary latency associated transcript (LAT). This primary LAT is an 8.3 kb unstable transcript from which two stable (1.5 and 2.0 kb) introns are spliced. Transcripts mapping to 12 VZV genes have been detected in human ganglia removed at autopsy; however, it is difficult to ascribe these as transcripts present during latent infection as early-stage virus reactivation may have transpired in the post-mortem time period in the ganglia. Nonetheless, low-level transcription of VZV ORF63 has been repeatedly detected in multiple ganglia removed as close to death as possible. There is increasing

  7. Dynamic chromatin boundaries delineate a latency control region of Epstein-Barr virus.

    PubMed

    Chau, Charles M; Lieberman, Paul M

    2004-11-01

    The oncogenic potential of latent Epstein-Barr virus (EBV) can be regulated by epigenetic factors controlling LMP1 and EBNA2 gene transcription. The EBV latency control region (LCR) constitutes approximately 12 kb of viral sequence spanning the divergent promoters of LMP1 and EBNA2 and encompasses the EBV latent replication origin OriP and RNA polymerase III-transcribed EBV-encoded RNA genes. We have used the chromatin immunoprecipitation assay to examine the chromatin architecture of the LCR in different types of EBV latency programs. We have found that histone H3 K4 methylation (H3mK4) was enriched throughout a large domain that extended from internal repeat 1 (IR1) to the terminal repeat in type III latency where EBNA2 and LMP1 genes are expressed. In type I latency where EBNA2 and LMP1 genes are transcriptionally silent, the H3mK4 domain contracts and does not enter the EBNA2 or LMP1 promoters. In contrast, histone H3 K9 methylation (H3mK9), associated with silent heterochromatin, was enriched in the EBNA2 and LMP1 upstream control regions in type I but not type III cells. MTA [5'-deoxy-5'(methylthio)adenosine], a pharmacological inhibitor of protein methylation, globally reduced histone H3mK4 and inhibited EBNA2 transcription in type III cells. 5'-Azacytidine, an inhibitor of DNA methylation that derepresses EBNA2 transcription in type I latency, caused H3mK4 expansion and a corresponding loss of H3mK9 at IR1. The chromatin boundary protein and transcription repressor CCCTC-binding factor was enriched at the EBNA2 transcription control region in type I but not type III cells. We also present evidence that OriP binding factors EBNA1 and ORC2 can interact with sequences outside of OriP including a region within IR1 that may influence EBNA2 transcription status. These results indicate that types I and III latency programs have distinct histone methylation patterns in the LCR and suggest that chromatin architecture coordinates gene expression of LMP1 and EBNA2.

  8. Hyperreactivity to weak acoustic stimuli and prolonged acoustic startle latency in children with autism spectrum disorders

    PubMed Central

    2014-01-01

    Background People with autism spectrum disorders (ASD) are known to have enhanced auditory perception, however, acoustic startle response to weak stimuli has not been well documented in this population. The objectives of this study are to evaluate the basic profile of acoustic startle response, including peak startle latency and startle magnitude to weaker stimuli, in children with ASD and typical development (TD), and to evaluate their relationship to ASD characteristics. Methods We investigated acoustic startle response with weak and strong acoustic stimuli in 12 children with ASD and 28 children with TD, analyzing the relationship between startle measures and quantitative autistic traits assessed with the Social Responsiveness Scale (SRS). The electromyographic activity of the left orbicularis oculi muscle to acoustic stimuli of 65 to 115 dB sound pressure level (SPL), in increments of 5 dB, was measured to evaluate acoustic startle response. The average eyeblink magnitude for each acoustic stimuli intensity and the average peak startle latency of acoustic startle response were evaluated. Results The magnitude of the acoustic startle response to weak stimuli (85 dB or smaller) was greater in children with ASD. The peak startle latency was also prolonged in individuals with ASD. The average magnitude of the acoustic startle response for stimulus intensities greater than 85 dB was not significantly larger in the ASD group compared with the controls. Both greater startle magnitude in response to weak stimuli (particularly at 85 dB) and prolonged peak startle latency were significantly associated with total scores, as well as several subscales of the SRS in the whole sample. We also found a significant relationship between scores on the social cognition subscale of the SRS and the average magnitude of the acoustic startle response for stimulus intensities of 80 and 85 dB in the TD group. Conclusions Children with ASD exhibited larger startle magnitude to weak

  9. Peri-threshold encoding of stimulus frequency and intensity in the M100 latency.

    PubMed

    Stufflebeam, S M; Poeppel, D; Rowley, H A; Roberts, T P

    1998-01-05

    Recent work has suggested that, in addition to spatial tonotopy, pitch and timbre information may be encoded in the temporal activity of the auditory cortex. Specifically, the post-stimulus latency of the maximal cortical evoked neuromagnetic field (M100 or N1m) is a function of stimulus frequency. We investigated the additional effect of varying the stimulus intensity on the M100 response. A 37-channel biomagnetometer recorded neuromagnetic fields over the temporal lobe of healthy volunteers in response to monaurally presented tones. The frequency dependence of the M100 latency remained remarkably invariant even at low stimulus intensity. Thus, for peri-threshold stimuli, frequency information appears encoded in the temporal form of the evoked response.

  10. 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

  11. 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

  12. 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.

  13. Stimulus intensity affects the latency but not the amplitude of the N2pc.

    PubMed

    Brisson, Benoit; Robitaille, Nicolas; Jolicoeur, Pierre

    2007-10-08

    The N2pc component of the event-related potential (ERP) is an index of visual-spatial attention. It is not clear whether the N2pc reflects pure top-down attentional activity or an interaction of top-down activity with bottom-up sensory activity. Here, we manipulated stimulus intensity of the items composing the target display. Although the amplitude of the P1 component increased monotonically with increasing stimulus intensity, the amplitude of the N2pc did not vary with stimulus intensity. Instead, the onset latency of the N2pc was delayed for weaker stimuli, suggesting that the strength of the selection cue (target color) influenced the moment at which attention was deployed. The results reveal one way in which early sensory ERP amplitude differences are converted into later latency differences.

  14. VEP in neglect patients have longer latencies for luminance but not for chromatic patterns.

    PubMed

    Spinelli, D; Angelelli, P; De Luca, M; Burr, D C

    1996-02-29

    In patients with unilateral neglect, visual evoked potentials (VEP) to stimuli displayed in the left visual field are delayed compared with responses to right visual field stimuli. In the present study, 10 patients with right brain damage and neglect were tested with contrast-reversed sinusoidal gratings, modulated either in luminance or in chromaticity. For gratings of luminance contrast modulated over relatively high temporal frequencies (4-10.5 Hz), latencies of VEP were about 30 ms longer for stimuli presented to the contralesional (left) visual field than to the field ipsilateral to the lesion. For equiluminant stimuli modulated at relatively low temporal frequencies (1-4 Hz), however, latency was the same for both hemifields. As this condition activates predominately the parvocellular pathway the results are consistent with our previous suggestion that the delay observed with luminance stimuli in neglect patients results from selective disruption of the faster response of the magnocellular pathway.

  15. Long-latency components of somatosensory evoked potentials during passive tactile perception of gratings.

    PubMed

    Genna, C; Artoni, F; Fanciullacci, C; Chisari, C; Oddo, C M; Micera, S

    2016-08-01

    Perception of tactile stimuli elicits Somatosensory Evoked Potentials (SEPs) that can be recorded via non-invasive electroencephalography (EEG). However, it is not yet clear how SEPs localization, shape and latency are modulated by different stimuli during mechanical tactile stimulation of fingertips. The aim of this work is thus to characterize SEPs generated by the tactile perception of gratings during dynamic passive stimulation of the dominant fingertip by means of a mechatronic platform. Results show that a random sequence of stimuli elicited SEPs with two long-latency components: (i) a negative deflection around 140 ms located in the frontal-central-parietal side in the contralateral hemisphere; (ii) a positive deflection around 250 ms located in the frontal-central midline. Time-frequency analysis revealed significant continuous bilateral desynchronization in the alpha band throughout the passive stimulation. These results are a fundamental step towards building a model of brain responses during perception of tactile stimuli for future benchmarking studies.

  16. 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.

  17. 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.

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

    PubMed Central

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

    2014-01-01

    The neural correlates of intraindividual response variability were investigated in a serial choice reaction time (CRT) task. Reaction times (RTs) from the faster and slower portions of the RT distribution for the task were separately aggregated and associated P300 event-related potentials computed. Independent behavioral measures of executive function and IQ were also recorded. Across frontal, fronto-central, central, centro-parietal and parietal scalp regions, P300 amplitudes were significantly greater for faster relative to slower behavioral responses. However, P300 peak amplitude latencies did not differ according to the speed of the behavioral RT. Importantly, controlling for select independent measures of executive function attenuated shared variance in P300 amplitude for faster and slower trials. The findings suggest that P300 amplitude rather than latency is associated with the speed of behavioral RTs, and the possibility that fluctuations in executive control underlie variability in speeded responding. PMID:25120458

  19. Treatment of high-latency microcapsules containing an aluminium complex with an epoxy-functionalised trialkoxysilane.

    PubMed

    Kamiya, Kazunobu; Suzuki, Noboru

    2016-12-01

    Some aluminium complexes are excellent catalysts of cationic polymerisation and are used for low-temperature and fast-curing adhesive, used in electronic part mounting. Microencapsulation is a suitable technique for getting high latency of the catalysts and long shelf life of the adhesives. For the higher latency in a cycloaliphatic epoxy compound, the microcapsule surface which retained small amount of aluminium complex was coated with epoxy polymer and the effect was examined. From the X-ray photoelectron spectroscopic results, the surface was recognised to be sufficiently coated and the differential scanning calorimetric analyses showed that the coating did not significantly affect the low-temperature and fast-curing properties of adhesive. After storing the mixture of cycloaliphatic epoxy compound, coated microcapsules, triphenylsilanol and silane coupling agent for 48 h at room temperature, the increase in viscosity was only 0.01 Pa s, resulting in the excellent shelf life.

  20. 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

  1. Effect of stimulus intensity level on auditory middle latency response brain maps in human adults.

    PubMed

    Tucker, D A; Dietrich, S; McPherson, D L; Salamat, M T

    2001-05-01

    Auditory middle latency response (AMLR) brain maps were obtained in 11 young adults with normal hearing. AMLR waveforms were elicited with monaural clicks presented at three stimulus intensity levels (50, 70, and 90 dB nHL). Recordings were made for right and left ear stimulus presentations. All recordings were obtained in an eyes open/awake status for each subject. Peak-to-peak amplitudes and absolute latencies of the AMLR Pa and Pb waveforms were measured at the Cz electrode site. Pa and Pb waveforms were present 100 percent of the time in response to the 90 dB nHL presentation. The prevalence of Pa and Pb to the 70 dB nHL presentation varied from 86 to 95 percent. The prevalence of Pa and Pb to the 50 dB nHL stimulus never reached 100 percent, ranging in prevalence from 77 to 68 percent. No significant ear effect was seen for amplitude or latency measures of Pa or Pb. AMLR brain maps of the voltage field distributions of Pa and Pb waveforms showed different topographic features. Scalp topography of the Pa waveform was altered by a reduction in stimulus intensity level. At 90 dB nHL, the Pa brain map showed a large positivity midline over the frontal and central scalp areas. At lower stimulus intensity levels, frontal positivity was reduced, and scalp negativity over occipital regions was increased. Pb scalp topography was also altered by a reduction in stimulus intensity level. Varying the stimulus intensity significantly altered Pa and Pb distributions of amplitude and latency measures. Pa and Pb distributions were skewed regardless of stimulus intensity.

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

    NASA Technical Reports Server (NTRS)

    Park, Won J.; Crampton, George H.

    1988-01-01

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

  3. 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…

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

    NASA Technical Reports Server (NTRS)

    Chren, William A., Jr.

    1993-01-01

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

  5. 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.

  6. 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

  7. L-Tryptophan: Effects on Daytime Sleep Latency and the Waking EEG

    DTIC Science & Technology

    1982-10-22

    TRYPTOPHAN: EFFECTS ON DAYTIME SLEEP LATENCY AND THE WAKING EEG pr Cheryl L. Slinweber, Reidun Ursin, 1 Raymond P. Hilbert and Richard L. Hilderbrand 2 p...Gessa, 1973; Curzon & Knott , 1974; Gessa & Tagliamonte, 1974), and it has been previously suggested that 1-tryptophan may have hyp- notic effects...Curzon, G. & Knott , P.J. Fatty acids in the disposition of tryptophan. In: Aromatic Amino Acids in the Brain, Ciba Foundation Symposium 22, Elsevier

  8. 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.

  9. 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.

  10. 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

  11. Intranasal Infection with Chlamydia abortus Induces Dose-Dependent Latency and Abortion in Sheep

    PubMed Central

    Longbottom, David; Livingstone, Morag; Maley, Stephen; van der Zon, Arjan; Rocchi, Mara; Wilson, Kim; Wheelhouse, Nicholas; Dagleish, Mark; Aitchison, Kevin; Wattegedera, Sean; Nath, Mintu; Entrican, Gary; Buxton, David

    2013-01-01

    Background Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus. Methodology/Principal Findings Three groups of sheep (groups 1, 2 and 3) were experimentally infected with different doses of C. abortus (5×103, 5×105 and 5×107 inclusion forming units (IFU), respectively) prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b) or were inoculated subcutaneously on day 70 of gestation with 2×106 IFU C. abortus (group 5). Animals in groups 1, 2 and 5 experienced an abortion rate of 50–67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium. Conclusions/Significance The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and vaccines for

  12. 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.

  13. Light adaptation increases response latency of alpha ganglion cells via a threshold-like nonlinearity.

    PubMed

    Chang, L; He, S

    2014-01-03

    Adaptation is an important process of sensory systems to adjust sensitivity to ensure the appropriate information encoding. Sensitivity and kinetics of retinal ganglion cell (RGC) responses have been studied extensively using a brief flash superimposed on different but steady backgrounds. However, it is still unclear if light adaptation exerts any effect on more complex response properties, such as response nonlinearity. In this study, we found that the latency of spike responses to a repeated flashing spot stimulation increased by 30 ms in the mouse ON α RGCs (An ON-type RGC is excited when a spot is turned on in the center of its receptive field). A single dimming event preceding the test flash on a steady adapting background could also produce similar effect in increasing latency of light responses. A simple computational model with a linear transformation of the light stimulus and a threshold-like nonlinearity could account for the experimental data. Moreover, the strength of the measured nonlinearity and the response latency were affected by the duration of light adaptation. The possible biological processes underlying this nonlinearity were explored. Voltage clamp recording revealed the presence of the increase in latency and threshold-like nonlinearity in the excitatory input of RGCs. However, no comparable nonlinearity was observed in the light responses of the ON cone bipolar cells. We further excluded GABAergic and glycinergic inhibition, N-methyl-D-aspartate receptor rectification and voltage-gated Na(+) channels as potential sources of this nonlinearity by pharmacological experiments. Our results indicate the bipolar cell terminals as the potential site of nonlinearity. Computational modeling constrained by experimental data supports that conclusion and suggests the voltage-sensitive Ca(++) channels and Ca(++)-dependent vesicle release in the bipolar cell terminals as mechanistic basis.

  14. 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.

  15. HIVed, a knowledgebase for differentially expressed human genes and proteins during HIV infection, replication and latency

    PubMed Central

    Li, Chen; Ramarathinam, Sri H.; Revote, Jerico; Khoury, Georges; Song, Jiangning; Purcell, Anthony W.

    2017-01-01

    Measuring the altered gene expression level and identifying differentially expressed genes/proteins during HIV infection, replication and latency is fundamental for broadening our understanding of the mechanisms of HIV infection and T-cell dysfunction. Such studies are crucial for developing effective strategies for virus eradication from the body. Inspired by the availability and enrichment of gene expression data during HIV infection, replication and latency, in this study, we proposed a novel compendium termed HIVed (HIV expression database; http://hivlatency.erc.monash.edu/) that harbours comprehensive functional annotations of proteins, whose genes have been shown to be dysregulated during HIV infection, replication and latency using different experimental designs and measurements. We manually curated a variety of third-party databases for structural and functional annotations of the protein entries in HIVed. With the goal of benefiting HIV related research, we collected a number of biological annotations for all the entries in HIVed besides their expression profile, including basic protein information, Gene Ontology terms, secondary structure, HIV-1 interaction and pathway information. We hope this comprehensive protein-centric knowledgebase can bridge the gap between the understanding of differentially expressed genes and the functions of their protein products, facilitating the generation of novel hypotheses and treatment strategies to fight against the HIV pandemic. PMID:28358052

  16. 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.

  17. 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.

  18. 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

  19. Rat mandibular distraction osteogenesis: latency, rate, and rhythm determine the adaptive response.

    PubMed

    Paccione, M F; Mehrara, B J; Warren, S M; Greenwald, J A; Spector, J A; Luchs, J S; Longaker, M T

    2001-03-01

    Distraction osteogenesis is a well-established technique of endogenous tissue engineering. The biomechanical factors thought to affect the quality of the distraction regenerate include the latency, rate, rhythm, and consolidation period. In an effort to understand the impact of these parameters on regenerate bone formation, this study was designed to decipher the most adaptive response in a rat model of mandibular distraction osteogenesis. Ninety-six adult Sprague-Dawley rats were divided into 16 subgroups (n = 6 per subgroup) based on variations in the distraction parameters (i.e., latency, rate, and rhythm). After a 28-day consolidation period, the mandibles were harvested, decalcified, and sectioned. A standardized histologic ranking system was used to evaluate the effect of each protocol on the adaptive response of the regenerate bone. In this study, we have demonstrated that the latency period dramatically affects the success of distraction osteogenesis. Furthermore, distraction rates up to 0.50 mm per day stimulated excellent regenerate bone formation, whereas greater distraction rates produced a fibrous union. Finally, higher frequency distraction (i.e., increased rhythm) appeared to accelerate regenerate bone formation. We believe that defining the critical parameters of this model will improve future analysis of gene expression during rat mandibular distraction osteogenesis and may facilitate the development of biologically based strategies designed to enhance regenerate bone formation.

  20. The role of conditioned stimulus termination in short-latency avoidance responding in cats.

    PubMed

    Zieliński, K; Plewako, M

    1980-10-01

    The behavioral effects of two procedures for bar-pressing avoidance training in cats were studied. In one procedure conditioned stimulus (CS) termination was response-contingent on both shock and non-shock trials; in the other the minimal duration of the CS was equal to the CS-US (unconditioned stimulus) interval. When avoidance responses did not terminate the CS short-latency avoidance responses were not acquired, the cats made more intertrial responses, and removal of the proreal and orbital gyri interfered more with avoidance responding than was observed in the other group. Abolition of shock application and introduction of a fixed duration of the CS resulted in extinction of the avoidance responses, which was more rapid in cats trained under the response contingent CS termination procedure. The data suggest that responses performed during the CS-US interval should be divided into two subclasses: short-latency responses which not only avoid pain but also avoid fear conditioned to the CS, and long-latency responses which avoid pain and escape from the fear state.

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

    PubMed

    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.

  2. Visual attention in adults with developmental dyslexia: evidence from manual reaction time and saccade latency.

    PubMed

    Judge, Jeannie; Caravolas, Markéta; Knox, Paul C

    2007-05-01

    Two studies were conducted to investigate visual attention deficits in dyslexia. In Experiment 1, adults with dyslexia and age- and IQ-matched controls completed a simple cueing task; participants responded to briefly presented (20 ms) eccentric targets (3 degrees , 6 degrees , or 9 degrees ) with a key press. In Experiment 2, the same participants completed a saccade version of the task, and saccade amplitude, accuracy, and latency were measured. The results revealed comparable performance between the groups on the manual reaction time task. The groups also performed similarly in saccade accuracy and latency. Moreover, neither group showed a visual field asymmetry in their performance, with the exception that adults with dyslexia showed longer saccade latency for 9 degrees targets presented to their left visual field than did controls. However, on the latter measure, the majority (78%) of those with dyslexia performed within the range of the control group. Correlational analyses revealed associations between reading and phoneme awareness in both groups, but phoneme awareness was not associated with visual attention in adult dyslexics. Together, the results are not compatible with a visual attention deficit in adult dyslexia, while they provide support for the phonological deficit hypothesis.

  3. Mapping and correction of vascular hemodynamic latency in the BOLD signal.

    PubMed

    Chang, Catie; Thomason, Moriah E; Glover, Gary H

    2008-10-15

    Correlation and causality metrics can be applied to blood-oxygen level-dependent (BOLD) signal time series in order to infer neural synchrony and directions of information flow from fMRI data. However, the BOLD signal reflects both the underlying neural activity and the vascular response, the latter of which is governed by local vasomotor physiology. The presence of potential vascular latency differences thus poses a confound in the detection of neural synchrony as well as inferences about the causality of neural processes. In the present study, we investigate the use of a breath holding (BH) task for characterizing and correcting for voxel-wise neurovascular latency differences across the whole brain. We demonstrate that BH yields reliable measurements of relative timing differences between voxels, and further show that a BH-derived latency correction can impact both functional connectivity maps of the resting-state default-mode network and activation maps of an event-related working memory (WM) task.

  4. The Relationship between Parameters of Long-Latency Evoked Potentials in a Multisensory Design.

    PubMed

    Hernández, Oscar H; García-Martínez, Rolando; Monteón, Victor

    2016-10-01

    In previous papers, we have shown that parameters of the omitted stimulus potential (OSP), which occurs at the end of a train of sensory stimuli, strongly depend on the modality. A train of stimuli also produces long-latency evoked potentials (LLEP) at the beginning of the train. This study is an extension of the OSP research, and it tested the relationship between parameters (ie, rate of rise, amplitude, and peak latency) of the P2 waves when trains of auditory, visual, or somatosensory stimuli were applied. The dynamics of the first 3 potentials in the train, related to habituation, were also studied. Twenty healthy young college volunteers participated in the study. As in the OSP, the P2 was faster and higher for auditory than for visual or somatosensory stimuli. The first P2 was swifter and higher than the second and the third potentials. The strength of habituation depends on the sensory modality and the parameter used. All these findings support the view that many long-latency brain potentials could share neural mechanisms related to wave generation.

  5. Adaptive and innate transforming growth factor beta signaling impact herpes simplex virus 1 latency and reactivation.

    PubMed

    Allen, Sariah J; Mott, Kevin R; Wechsler, Steven L; Flavell, Richard A; Town, Terrence; Ghiasi, Homayon

    2011-11-01

    Innate and adaptive immunity play important protective roles by combating herpes simplex virus 1 (HSV-1) infection. Transforming growth factor β (TGF-β) is a key negative cytokine regulator of both innate and adaptive immune responses. Yet, it is unknown whether TGF-β signaling in either immune compartment impacts HSV-1 replication and latency. We undertook genetic approaches to address these issues by infecting two different dominant negative TGF-β receptor type II transgenic mouse lines. These mice have specific TGF-β signaling blockades in either T cells or innate cells. Mice were ocularly infected with HSV-1 to evaluate the effects of restricted innate or adaptive TGF-β signaling during acute and latent infections. Limiting innate cell but not T cell TGF-β signaling reduced virus replication in the eyes of infected mice. On the other hand, blocking TGF-β signaling in either innate cells or T cells resulted in decreased latency in the trigeminal ganglia of infected mice. Furthermore, inhibiting TGF-β signaling in T cells reduced cell lysis and leukocyte infiltration in corneas and trigeminal ganglia during primary HSV-1 infection of mice. These findings strongly suggest that TGF-β signaling, which generally functions to dampen immune responses, results in increased HSV-1 latency.

  6. Autophagy Genes Enhance Murine Gammaherpesvirus 68 Reactivation From Latency by Preventing Virus-induced Systemic Inflammation

    PubMed Central

    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.

    2016-01-01

    SUMMARY Host genes that regulate systemic inflammation upon chronic viral infection are incompletely understood. Murine γ-herpesvirus 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

  7. 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.

  8. 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

  9. Short-latency tachycardia evoked by stimulation of muscle and cutaneous afferents.

    PubMed

    Gelsema, A J; Bouman, L N; Karemaker, J M

    1985-04-01

    The short-latency effect on heart rate of peripheral nerve stimulation was studied in decerebrate cats. Selective activation (17-40 microA, 100 Hz, 1 s long) of low-threshold fibers in the nerves to the triceps surae muscle yielded isometric contractions of maximal force that were accompanied by a cardiac cycle length shortening within 0.4 s from the start of stimulation. This effect was abolished by pharmacologically induced neuromuscular blockade. The cardiac cycle length shortening during paralysis reappeared after a 6- to 10-fold increase of the stimulation strength. Cutaneous (sural) nerve stimulation (15-25 microA, 100 Hz, 1 s long) elicited reflex contractions in the stimulated limb, which were also accompanied by a cardiac acceleration with similar latency. Paralysis prevented the reflex contractions and reduced the cardiac response in some cats and abolished it in others. The response reappeared in either case after a 5- to 10-fold increase of the stimulus strength. It is concluded that muscle nerve and cutaneous nerve activity both cause a similar cardiac acceleration with a latency of less than 0.4 s. The response to muscle nerve stimulation is elicited by activity in group III afferents. It is excluded that the cardiac response to nerve stimulation is secondary to a change in the respiratory pattern.

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

    PubMed

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

    2016-04-01

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

  11. Mismatch field latency, but not power, may mark a shared autistic and schizotypal trait phenotype.

    PubMed

    Ford, Talitha C; Woods, Will; Crewther, David P

    2017-02-21

    The auditory mismatch negativity (MMN), a preattentive processing potential, and its magnetic counterpart (MMF) are consistently reported as reduced in schizophrenia and autism spectrum disorders. This study investigates whether MMF characteristics differ between subclinically high and low scorers on the recently discovered shared autism and schizophrenia phenotype, Social Disorganisation. A total of 18 low (10 females) and 19 high (9 females) Social Disorganisation scorers underwent magnetoencephalography (MEG) during a MMF paradigm of 50ms standard (1000Hz, 85%) and 100ms duration deviant tones. MMF was measured from the strongest active magnetometer over the right and left hemispheres (consistent across groups) after 100ms. No differences in MMF power were found, however there was a significant delay in the MMF peak (p=0.007). The P3am (following the MMF) was significantly reduced across both hemispheres for the high Social Disorganisation group (p=0.025), there were no specific hemispheric differences in P3am power or latency. Right MMF peak latency increased with higher scores on the schizotypal subscales Odd Speech, Odd Behaviour and Constricted Affect. Findings suggest that MMF peak latency delay marks a convergence of the autism and schizophrenia spectra at a subclinical. These findings have significant implications for future research methodology, as well as clinical practice.

  12. 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.

  13. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.

    PubMed

    Archin, N M; Liberty, A L; Kashuba, A D; Choudhary, S K; Kuruc, J D; Crooks, A M; Parker, D C; Anderson, E M; Kearney, M F; Strain, M C; Richman, D D; Hudgens, M G; Bosch, R J; Coffin, J M; Eron, J J; Hazuda, D J; Margolis, D M

    2012-07-25

    Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.

  14. 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

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

    PubMed Central

    Zhang, Q; Gutsch, D; Kenney, S

    1994-01-01

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

  16. Test-Retest of Long Latency Auditory Evoked Potentials (P300) with Pure Tone and Speech Stimuli.

    PubMed

    Perez, Ana Paula; Ziliotto, Karin; Pereira, Liliane Desgualdo

    2017-04-01

    Introduction Long latency auditory evoked potentials, especially P300, have been used for clinical evaluation of mental processing. Many factors can interfere with Auditory Evoked Potential - P300 results, suggesting large intra and inter-subject variations. Objective The objective of the study was to identify the reliability of P3 components (latency and amplitude) over 4-6 weeks and the most stable auditory stimulus with the best test-retest agreement. Methods Ten normal-hearing women participated in the study. Only subjects without auditory processing problems were included. To determine the P3 components, we elicited long latency auditory evoked potential (P300) by pure tone and speech stimuli, and retested after 4-6 weeks using the same parameters. We identified P300 latency and amplitude by waveform subtraction. Results We found lower coefficient of variation values in latency than in amplitude, with less variability analysis when speech stimulus was used. There was no significant correlation in latency measures between pure tone and speech stimuli, and sessions. There was a significant intrasubject correlation between measures of latency and amplitude. Conclusion These findings show that amplitude responses are more robust for the speech stimulus when compared with its pure tone counterpart. The P300 indicated stability for latency and amplitude measures when the test-retest was applied. Reliability was higher for amplitude than for latency, with better agreement when the pure tone stimulus was used. However, further research with speech stimulus is needed to clarify how these stimuli are processed by the nervous system.

  17. Test-Retest of Long Latency Auditory Evoked Potentials (P300) with Pure Tone and Speech Stimuli

    PubMed Central

    Perez, Ana Paula; Ziliotto, Karin; Pereira, Liliane Desgualdo

    2016-01-01

    Introduction Long latency auditory evoked potentials, especially P300, have been used for clinical evaluation of mental processing. Many factors can interfere with Auditory Evoked Potential - P300 results, suggesting large intra and inter-subject variations. Objective The objective of the study was to identify the reliability of P3 components (latency and amplitude) over 4–6 weeks and the most stable auditory stimulus with the best test-retest agreement. Methods Ten normal-hearing women participated in the study. Only subjects without auditory processing problems were included. To determine the P3 components, we elicited long latency auditory evoked potential (P300) by pure tone and speech stimuli, and retested after 4–6 weeks using the same parameters. We identified P300 latency and amplitude by waveform subtraction. Results We found lower coefficient of variation values in latency than in amplitude, with less variability analysis when speech stimulus was used. There was no significant correlation in latency measures between pure tone and speech stimuli, and sessions. There was a significant intrasubject correlation between measures of latency and amplitude. Conclusion These findings show that amplitude responses are more robust for the speech stimulus when compared with its pure tone counterpart. The P300 indicated stability for latency and amplitude measures when the test-retest was applied. Reliability was higher for amplitude than for latency, with better agreement when the pure tone stimulus was used. However, further research with speech stimulus is needed to clarify how these stimuli are processed by the nervous system. PMID:28382119

  18. 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.

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

    PubMed Central

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

    2016-01-01

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

  20. 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

  1. The effects of video-taped feedback on form, accuracy, and latency in an open and closed environment.

    PubMed

    Del Rey, P

    1971-12-01

    40 college women performed a modification of the classical fencing lunge against 2 laterally-arranged targets, under closed and open environmental conditions. Form (rating scale), accuracy (proximity to target center), and response latency were taken to measure the effects of video-taped feedback (VT). Administration of VT with specific instructions to direct S's attention to parts of the display resulted in closer approximation of the externally-imposed form, higher accuracy, and shorter response latency. Performing the skill in the closed environmental condition resulted in less deviation from the imposed form, higher accuracy scores, and longer response latency. No significant correlations were found between imposed form and accuracy.

  2. The relationship between self-reported vividness and latency during mental size scaling of everyday items: phenomenological evidence of different types of imagery.

    PubMed

    D'Angiulli, Amedeo; Reeves, Adam

    2007-01-01

    We examined how the relationship between ratings of vividness (or image strength) and image latency might reflect the concerted action of two visual imagery pathways hypothesized by Kosslyn (1994): the ventral pathway, processing object properties, and the dorsal pathway, processing locative properties of mental images. Participants formed their images at small or large angular display sizes, varying the amount of size scaling needed. In Experiment 1, display size varied between participants, and images were trial unique. The higher the vividness, the faster the generation of small images (requiring size scaling of less than 10 degrees), which would recruit mainly the ventral pathway. This vivid-is-fast relationship changed for large images (requiring size scaling of 10 degrees or more), which would recruit mainly the dorsal pathway. The size-dependent alteration of the vivid-is-fast relationship was replicated in the first block of Experiment 2. However, when repeated over 3 consecutive blocks, image generation sped up, and gradually the vivid-is-fast relationship tended to occur for all display sizes until complete automatization of image generation occurred. The findings suggest that differential patterns of vividness-latency relationship can reflect the types of images involved, their relative ventral and dorsal contributions, and the involvement of working memory.

  3. 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

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

    PubMed Central

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

    2011-01-01

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

  5. Outcomes of a NASA Workshop to Develop a Portfolio of Low Latency Datasets for Time-Sensitive Applications

    NASA Technical Reports Server (NTRS)

    Davies, Diane K.; Brown, Molly E.; Green, David S.; Michael, Karen A.; Murray, John J.; Justice, Christopher O.; Soja, Amber J.

    2016-01-01

    It is widely accepted that time-sensitive remote sensing data serve the needs of decision makers in the applications communities and yet to date, a comprehensive portfolio of NASA low latency datasets has not been available. This paper will describe the NASA low latency, or Near-Real Time (NRT), portfolio, how it was developed and plans to make it available online through a portal that leverages the existing EOSDIS capabilities such as the Earthdata Search Client (https:search.earthdata.nasa.gov), the Common Metadata Repository (CMR) and the Global Imagery Browse Service (GIBS). This paper will report on the outcomes of a NASA Workshop to Develop a Portfolio of Low Latency Datasets for Time-Sensitive Applications (27-29 September 2016 at NASA Langley Research Center, Hampton VA). The paper will also summarize findings and recommendations from the meeting outlining perceived shortfalls and opportunities for low latency research and application science.

  6. 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.

  7. HIV latency is influenced by regions of the viral genome outside of the long terminal repeats and regulatory genes.

    PubMed

    Marsden, Matthew D; Burke, Bryan P; Zack, Jerome A

    2011-09-01

    We have previously described an in vitro primary thymocyte model for HIV latency that recapitulates several important aspects of latently infected cells obtained from patients. Our original model included a truncated HIV genome expressing only Tat, Rev, and Vpu along with a reporter gene. We have now expanded these studies to include reporter viruses encoding more complete viral genomes. We show here that regions of the viral genome outside of the long terminal repeat promoter and Tat/Rev regulatory genes can substantially affect both the basal level of HIV transcription prior to stimulation, and also the level of viral expression following costimulation via CD3 and CD28 ligation. These differences in latency phenotype between truncated and more complete HIV genomes demonstrate the importance of accessory genes in the context of HIV latency and indicate that care should be taken when interpreting data derived from heavily modified HIV genomes in latency models.

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

    PubMed Central

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

    2015-01-01

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

  9. Relationship between measures of HIV reactivation and the decline of latent reservoir under latency-reversing agents.

    PubMed

    Petravic, Janka; Rasmussen, Thomas A; Lewin, Sharon R; Kent, Stephen J; Davenport, Miles P

    2017-02-15

    Antiretroviral-free HIV remission requires substantial reduction of the number of latently infected cells and enhanced immune control of viremia. Latency-reversing agents (LRA) aim to eliminate latently infected cells by increasing the rate of reactivation of HIV transcription, which exposes these cells to killing by the immune system. As LRA are explored in clinical trials, it becomes increasingly important to assess the effect of increased HIV reactivation rate on the decline of latently infected cells, and estimate LRA efficacy in increasing virus reactivation. However, whether the extent of HIV reactivation is a good predictor of the rate of decline of the number of latently infected cells is dependent on a number of factors. Our modeling shows that mechanisms of maintenance and clearance of the reservoir, lifespan of cells with reactivated HIV and other factors may significantly impact the relationship between measures of HIV reactivation and the decline of the number of latently infected cells.The usual measures of HIV reactivation are the increase in cell-associated HIV RNA (CA RNA) and/or plasma HIV RNA soon after administration. We analyze two recent studies where CA RNA was used to estimate the impact of two novel LRAs, panobinostat and romidepsin. Both drugs increased the CA RNA level 3-4 fold in clinical trials. However, cells with panobinostat-reactivated HIV appeared long-lived (half-life > month), suggesting that HIV reactivation rate increased approximately by 8%. With romidepsin, the lifespan of cells that reactivated HIV was short (2 days), suggesting that HIV reactivation rate may have doubled under treatment.Importance Long-lived latently infected cells that persist on antiretroviral treatment (ART) are thought to be the source of viral rebound soon after ART interruption. The elimination of latently infected cells is an important step to achieving antiretroviral-free HIV remission. Latency-reversing agents (LRA) aim to activate HIV expression

  10. Sensory Feedback in Interlimb Coordination: Contralateral Afferent Contribution to the Short-Latency Crossed Response during Human Walking

    PubMed Central

    Gervasio, Sabata; Voigt, Michael; Kersting, Uwe G.; Farina, Dario; Sinkjær, Thomas

    2017-01-01

    A constant coordination between the left and right leg is required to maintain stability during human locomotion, especially in a variable environment. The neural mechanisms underlying this interlimb coordination are not yet known. In animals, interneurons located within the spinal cord allow direct communication between the two sides without the need for the involvement of higher centers. These may also exist in humans since sensory feedback elicited by tibial nerve stimulation on one side (ipsilateral) can affect the muscles activation in the opposite side (contralateral), provoking short-latency crossed responses (SLCRs). The current study investigated whether contralateral afferent feedback contributes to the mechanism controlling the SLCR in human gastrocnemius muscle. Surface electromyogram, kinematic and kinetic data were recorded from subjects during normal walking and hybrid walking (with the legs moving in opposite directions). An inverse dynamics model was applied to estimate the gastrocnemius muscle proprioceptors’ firing rate. During normal walking, a significant correlation was observed between the magnitude of SLCRs and the estimated muscle spindle secondary afferent activity (P = 0.04). Moreover, estimated spindle secondary afferent and Golgi tendon organ activity were significantly different (P ≤ 0.01) when opposite responses have been observed, that is during normal (facilitation) and hybrid walking (inhibition) conditions. Contralateral sensory feedback, specifically spindle secondary afferents, likely plays a significant role in generating the SLCR. This observation has important implications for our understanding of what future research should be focusing on to optimize locomotor recovery in patient populations. PMID:28060839

  11. 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.

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

    PubMed Central

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

    2017-01-01

    Primary effusion lymphoma (PEL) is an incurable malignancy that develops in immunodeficient patients as a consequence of latent infection of B-cells with Kaposi's sarcoma-associated herpes virus (KSHV). Malignant growth of KSHV-infected B cells requires the activity of the transcription factor nuclear factor (NF)-κB, which controls maintenance of viral latency and suppression of the viral lytic program. Here we show that the KSHV proteins K13 and K15 promote NF-κB activation via the protease mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1), a key driver of NF-κB activation in lymphocytes. Inhibition of the MALT1 protease activity induced a switch from the latent to the lytic stage of viral infection, and led to reduced growth and survival of PEL cell lines in vitro and in a xenograft model. These results demonstrate a key role for the proteolytic activity of MALT1 in PEL, and provide a rationale for the pharmacological targeting of MALT1 in PEL therapy. PMID:27538487

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

    PubMed

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

    2017-03-01

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

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

    PubMed

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

    2004-04-16

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

  15. Ribosomal Protein S6 Interacts with the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus ▿

    PubMed Central

    Chen, Wuguo; Dittmer, Dirk P.

    2011-01-01

    The latency-associated nuclear antigen (LANA) is central to the maintenance of Kaposi's sarcoma-associated herpesvirus (KSHV) and to the survival of KSHV-carrying tumor cells. In an effort to identify interaction partners of LANA, we purified authentic high-molecular-weight complexes of LANA by conventional chromatography followed by immunoprecipitation from the BC-3 cell line. This is the first analysis of LANA-interacting partners that is not based on forced ectopic expression of LANA. Subsequent tandem mass spectrometry (MS/MS) analysis identified many of the known LANA-interacting proteins. We confirmed LANA's interactions with histones. Three classes of proteins survived our stringent four-step purification procedure (size, heparin, anion, and immunoaffinity chromatography): two heat shock proteins (Hsp70 and Hsp96 precursor), signal recognition particle 72 (SRP72), and 10 different ribosomal proteins. These proteins are likely involved in structural interactions within LANA high-molecular-weight complexes. Here, we show that ribosomal protein S6 (RPS6) interacts with LANA. This interaction is mediated by the N-terminal domain of LANA and does not require DNA or RNA. Depletion of RPS6 from primary effusion lymphoma (PEL) cells dramatically decreases the half-life of full-length LANA. The fact that RPS6 has a well-established nuclear function beyond its role in ribosome assembly suggests that RPS6 (and by extension other ribosomal proteins) contributes to the extraordinary stability of LANA. PMID:21734034

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

    PubMed Central

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

    2015-01-01

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

  17. Protein expression from unintegrated HIV-1 DNA introduces bias in primary in vitro post-integration latency models.

    PubMed

    Bonczkowski, Pawel; De Scheerder, Marie-Angélique; Malatinkova, Eva; Borch, Alexandra; Melkova, Zora; Koenig, Renate; De Spiegelaere, Ward; Vandekerckhove, Linos

    2016-12-02

    To understand the persistence of latently HIV-1 infected cells in virally suppressed infected patients, a number of in vitro models of HIV latency have been developed. In an attempt to mimic the in vivo situation as closely as possible, several models use primary cells and replication-competent viruses in combination with antiretroviral compounds to prevent ongoing replication. Latency is subsequently measured by HIV RNA and/or protein production after cellular activation. To discriminate between pre- and post-integration latency, integrase inhibitors are routinely used, preventing novel integrations upon cellular activation. Here, we show that this choice of antiretrovirals may still cause a bias of pre-integration latency in these models, as unintegrated HIV DNA can form and directly contribute to the levels of HIV RNA and protein production. We further show that the addition of reverse transcriptase inhibitors effectively suppresses the levels of episomal HIV DNA (as measured by 2-LTR circles) and decreases the levels of HIV transcription. Consequently, we show that latency levels described in models that only use integrase inhibitors may be overestimated. The inclusion of additional control conditions, such as 2-LTR quantification and the addition of reverse transcriptase inhibitors, is crucial to fully elucidate the actual levels of post-integration latency.

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

    PubMed

    Shinya, Masahiro; Kawashima, Noritaka; Nakazawa, Kimitaka

    2016-01-01

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

  19. Protein expression from unintegrated HIV-1 DNA introduces bias in primary in vitro post-integration latency models

    PubMed Central

    Bonczkowski, Pawel; De Scheerder, Marie-Angélique; Malatinkova, Eva; Borch, Alexandra; Melkova, Zora; Koenig, Renate; De Spiegelaere, Ward; Vandekerckhove, Linos

    2016-01-01

    To understand the persistence of latently HIV-1 infected cells in virally suppressed infected patients, a number of in vitro models of HIV latency have been developed. In an attempt to mimic the in vivo situation as closely as possible, several models use primary cells and replication-competent viruses in combination with antiretroviral compounds to prevent ongoing replication. Latency is subsequently measured by HIV RNA and/or protein production after cellular activation. To discriminate between pre- and post-integration latency, integrase inhibitors are routinely used, preventing novel integrations upon cellular activation. Here, we show that this choice of antiretrovirals may still cause a bias of pre-integration latency in these models, as unintegrated HIV DNA can form and directly contribute to the levels of HIV RNA and protein production. We further show that the addition of reverse transcriptase inhibitors effectively suppresses the levels of episomal HIV DNA (as measured by 2-LTR circles) and decreases the levels of HIV transcription. Consequently, we show that latency levels described in models that only use integrase inhibitors may be overestimated. The inclusion of additional control conditions, such as 2-LTR quantification and the addition of reverse transcriptase inhibitors, is crucial to fully elucidate the actual levels of post-integration latency. PMID:27910923

  20. Relating the variability of tone-burst otoacoustic emission and auditory brainstem response latencies to the underlying cochlear mechanics

    NASA Astrophysics Data System (ADS)

    Verhulst, Sarah; Shera, Christopher A.

    2015-12-01

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

  1. [Left ventricular electromechanical latency period is an additional indicator to upgrade from right to biventricular DDD pacing].

    PubMed

    Ismer, B; Körber, T; von Knorre, G H; Voss, W; Burska, D; Nienaber, C A

    2006-01-01

    In DDD pacing, the left-ventricular electromechanical latency period defines the duration between premature ventricular stimulation and the prematurely ending left-atrial contribution to left-ventricular filling. It has to be considered in diastolic AV delay optimization. Individual duration of this parameter seemed to reflect the ventricular function. Therefore, we compared the left-ventricular electromechanical latency period due to right ventricular stimulus with the documented ejection fraction of two groups, 33 congestive heart failure patients carrying biventricular systems and 13 right ventricular paced bradycardia patients. A mean latency period of 168+/-26 ms was found in the heart failure patients (ejection fraction: 25+/-5%) which was significantly longer (p=0.0039) compared to the bradycardia patients (ejection fraction: 51+/-12%) with a mean latency of 119+/-13 ms. Thus, an increasing latency period during right ventricular DDD pacing therapy indicates decreasing ejection fraction. A cut-off interval of 135 ms allowed the discrimination of 93% of our patients as having an individual ejection fraction of either up to 35% or above. Thus, the left ventricular electromechanical latency period can be used as an additional parameter indicating the necessity to upgrade from right to biventricular DDD pacing.

  2. 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.

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

    PubMed

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

    2016-04-01

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

  4. [Multiple sleep latency test, maintenance of wakefulness test and suggestive immobilization test].

    PubMed

    Tanaka, Haruhito

    2015-06-01

    In clinical practice, assessment usually involves self-report; however, objective measures are available. The multiple sleep latency test(MSLT) is performed during the main period of wakefulness and is designed to determine a patient's propensity to fall asleep. To be valid, the MSLT should be performed the day after nocturnal polysomnography (PSG). It is the standard test for the assessment of objective sleepiness and diagnosis of narcolepsy, that is a mean sleep latency equal to or under 8 minutes and equal to or greater than two sleep onset REM periods (SOREMPs). As opposed to the MSLT, the maintenance of wakefulness test (MWT) is designed to test the patient's ability to stay awake. The MWT is a 40-minutes protocol consisting of four trials separated by 2-hour intervals and is performed in much the same way as the MSLT. The MWT may be indicated in assessment of individuals in whom the inability to remain awake constitutes a safety issue, or in patients with narcolepsy or idiopathic hypersomnia to assess response to treatment with medications. There is little evidence linking mean sleep latency on the MWT with risk of accidents in real world circumstances. The suggestive immobilization test(SIT) was designed during which sensor and motor symptoms of restless legs syndrome are quantified during a period of immobility taking place in the evening before PSG. The patient is instructed to avoid moving voluntary for the entire duration of the test, which is designed to last 1 hour. The subjective leg discomfort evaluation and periodic leg movement by surface electromyograms from right and left anterior tibialis support diagnosis for restless legs syndrome. Many factors, such as clinical setting, pretest condition or aging effects etc. can alter the findings of the test and considerable clinical judgment is needed to avoid an error in interpretation. Above those three sleep-wake related tests provide us useful information.

  5. 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.

  6. 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

  7. Factors associated with severity of occupational asthma with a latency period at diagnosis

    PubMed Central

    Descatha, Alexis; Leproust, Hélène; Choudat, Dominique; Garnier, Robert; Pairon, Jean-Claude; Ameille, Jacques

    2007-01-01

    Background Severity of occupational asthma at diagnosis is an important prognostic factor. The aim of this study was to determine which factors affect the severity of occupational asthma with latency period at diagnosis. Methods The study population consisted of 229 consecutive subjects with occupational asthma with latency period recruited by four occupational health departments and divided into two groups according to the severity of the disease at diagnosis. The moderate-severe (FEV1 < 70% predicted, or PD20 methacholine ≤300 μg; n=101) and mild (FEV1 ≥70% predicted and PD20 methacholine > 300 μg, n=128) groups were compared in terms of clinical and demographic parameters. Multivariate analysis using logistic regressions was performed to examine factors associated with asthma severity. Results Duration of symptoms before diagnosis was significantly longer in the moderate-severe group (mean ± SD: 6.3 ± 6.8 years versus 3.4 ± 4.4 years, p<0.001). Sex ratio, age, atopy, smoking habits, duration of exposure before symptoms, and molecular weight of the causal agent were not significantly different between the two groups. On multivariate analysis, only duration of symptoms before diagnosis was associated with asthma severity (aOR=1.12, 95% CI 1.05–1.18, p<0.001). Conclusions Severity of occupational asthma with latency period at diagnosis was associated with duration of symptoms before diagnosis, but not with the type of causal agent. This finding emphasizes the need for early diagnosis and avoidance of exposure. PMID:17573728

  8. 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.

  9. MicroRNA regulation of viral immunity, latency, and carcinogenesis of selected tumor viruses and HIV.

    PubMed

    Wang, Ling; Li, Guangyu; Yao, Zhi Q; Moorman, Jonathan P; Ning, Shunbin

    2015-09-01

    MicroRNAs (miRNAs) function as key regulators in immune responses and cancer development. In the contexts of infection with oncogenic viruses, miRNAs are engaged in viral persistence, latency establishment and maintenance, and oncogenesis. In this review, we summarize the potential roles and mechanisms of viral and cellular miRNAs in the host-pathogen interactions during infection with selected tumor viruses and HIV, which include (i) repressing viral replication and facilitating latency establishment by targeting viral transcripts, (ii) evading innate and adaptive immune responses via toll-like receptors, RIG-I-like receptors, T-cell receptor, and B-cell receptor pathways by targeting signaling molecules such as TRAF6, IRAK1, IKKε, and MyD88, as well as downstream targets including regulatory cytokines such as tumor necrosis factor α, interferon γ, interleukin 10, and transforming growth factor β, (iii) antagonizing intrinsic and extrinsic apoptosis pathways by targeting pro-apoptotic or anti-apoptotic gene transcripts such as the Bcl-2 family and caspase-3, (iv) modulating cell proliferation and survival through regulation of the Wnt, PI3K/Akt, Erk/MAPK, and Jak/STAT signaling pathways, as well as the signaling pathways triggered by viral oncoproteins such as Epstein-Barr Virus LMP1, by targeting Wnt-inhibiting factor 1, SHIP, pTEN, and SOCSs, and (v) regulating cell cycle progression by targeting cell cycle inhibitors such as p21/WAF1 and p27/KIP1. Further elucidation of the interaction between miRNAs and these key biological events will facilitate our understanding of the pathogenesis of viral latency and oncogenesis and may lead to the identification of miRNAs as novel targets for developing new therapeutic or preventive interventions.

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

    PubMed

    Murphy, P R; Hammond, G R

    1992-01-01

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

  11. 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.

  12. 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.

  13. ’Short-Latency’ Somatosensory Evoked Potentials during Experimentally Induced Biodynamic Stress in Humans.

    DTIC Science & Technology

    1985-12-01

    BP, a negative-going * ."" near-field wave originating in the brachial plexus, the A and B waves of Chiappa , et a]. (1980), and the NI, N2, and P2...1981) and by Chiappa , et al. (1980). Table 2 shows the baseline means and standard deviations of the SSEP peaks for all five Ss, derived from the loose...Head and Spine. Charles Thomas, Springfield, 1982, 324-378. Chiappa , K.H., Choi, S.K. and Young, R.R. Short latency somatosensory evoked potentials

  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. 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

  16. Latency-aged children with attachment disturbances: a conjoint treatment model.

    PubMed

    Shiller, Virginia M

    2011-01-01

    Psychoanalytic theory and practice has increasingly accepted the importance of attachment relationships in psychic development. However, there have been only very limited efforts to develop psychoanalytically informed interventions for older adopted and foster children who show significant disturbances in attachment. This paper reviews theory and research that lays groundwork for a framework for conceptualizing treatment needs for attachment disordered children. Two cases of conjoint work with parents and their latency age sons are presented. The treatment cases highlight the importance of work to increase parents' reflective functioning capacities and the need to challenge children's defensively excluded early internal working models of self and caregivers.

  17. 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.

  18. A new set of 299 pictures for psycholinguistic studies: French norms for name agreement, image agreement, conceptual familiarity, visual complexity, image variability, age of acquisition, and naming latencies.

    PubMed

    Bonin, Patrick; Peereman, Ronald; Malardier, Nathalie; Méot, Alain; Chalard, Marylène

    2003-02-01

    Pictures are often used as stimuli in studies of perception, language, and memory. Since performances on different sets of pictures are generally contrasted, stimulus selection requires the use of standardized material to match pictures across different variables. Unfortunately, the number of standardized pictures available for empirical research is rather limited. The aim of the present study is to provide French normative data for a new set of 299 black-and-white drawings. Alario and Ferrand (1999) were closely followed in that the pictures were standardized on six variables name agreement, image agreement, conceptual familiarity, visual complexity, image variability, and age of acquisition. Objective frequency measures are also provided for themost common names associated with the pictures. Comparative analyses between our results and the norms obtained in other, similar studies are reported. Finally, naming latencies corresponding to the set of pictures were also collected from French native speakers, and correlational/multiple-regression analyses were performed on naming latencies. This new set of standardized pictures is available on the Internet (http://leadserv.u-bourgogne.fr/bases/pictures/) and should be of great use to researchers when they select pictorial stimuli.

  19. NEDDylation Is Essential for Kaposi’s Sarcoma-Associated Herpesvirus Latency and Lytic Reactivation and Represents a Novel Anti-KSHV Target

    PubMed Central

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

    2015-01-01

    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. PMID:25794275

  20. Kaposi sarcoma herpes virus latency associated nuclear antigen protein release the G2/M cell cycle blocks by modulating ATM/ATR mediated checkpoint pathway.

    PubMed

    Kumar, Amit; Sahu, Sushil Kumar; Mohanty, Suchitra; Chakrabarti, Sudipta; Maji, Santanu; Reddy, R Rajendra; Jha, Asutosh K; Goswami, Chandan; Kundu, Chanakya N; Rajasubramaniam, Shanmugam; Verma, Subhash C; Choudhuri, Tathagata

    2014-01-01

    The Kaposi's sarcoma-associated herpesvirus infects the human population and maintains latency stage of viral life cycle in a variety of cell types including cells of epithelial, mesenchymal and endothelial origin. The establishment of latent infection by KSHV requires the expression of an unique repertoire of genes among which latency associated nuclear antigen (LANA) plays a critical role in the replication of the viral genome. LANA regulates the transcription of a number of viral and cellular genes essential for the survival of the virus in the host cell. The present study demonstrates the disruption of the host G2/M cell cycle checkpoint regulation as an associated function of LANA. DNA profile of LANA expressing human B-cells demonstrated the ability of this nuclear antigen in relieving the drug (Nocodazole) induced G2/M checkpoint arrest. Caffeine suppressed nocodazole induced G2/M arrest indicating involvement of the ATM/ATR. Notably, we have also shown the direct interaction of LANA with Chk2, the ATM/ATR signalling effector and is responsible for the release of the G2/M cell cycle block.

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

    PubMed

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

    2014-07-01

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

  2. Latency and persistence of respiratory syncytial virus despite T cell immunity.

    PubMed

    Schwarze, Jurgen; O'Donnell, Diarmund R; Rohwedder, Angela; Openshaw, Peter J M

    2004-04-01

    Respiratory syncytial virus (RSV) causes bronchiolitis in infants, which is associated with recurrent wheezing in later childhood. There is mounting evidence that the virus becomes latent or persists in vivo, but little is known about the mechanisms of its latency, persistence, and immune evasion. We therefore infected BALB/c mice intranasally with human RSV, analyzed sequential tissue samples by direct culture and polymerase chain reaction for viral and messenger RNA, and monitored antiviral immune responses. Virus could not be detected in bronchoalveolar lavage samples beyond Day 14, but viral genomic and messenger RNA was present in lung homogenates for 100 days or more; combined depletion of CD4 and CD8 T cells allowed infective virus to be recovered. Neutralizing antibody and memory cytotoxic T cell responses were intact in mice with latent infections, and latent viral genome contained an authentic nonmutated M2 82-91 K(d) cytotoxic T lymphocyte epitope. A mutation of this epitope, detected in one clone, did not assist evasion. We suggest that RSV latency depends on persistence in privileged sites rather than on viral mutation.

  3. 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

  4. Evaluation of packet latency in single and multi-hop WiFi wireless networks

    NASA Astrophysics Data System (ADS)

    Anna, Kiran; Bassiouni, Mostafa

    2006-05-01

    In this paper, we evaluate the packet latency performance of a new scheduler-based scheme that we have implemented on top of the p-persistent 802.11 MAC layer. We extended Cali's dynamic p-persistent 802.11 protocol from single class to multiple classes by means of a weighted fair queuing scheduler built on top of the MAC p-persistent layer. We used the NS2 simulator in the implementation and testing of our multiple-class scheduler and incorporated the scheduler-based architecture by modifying the NS2's 802.11 DCF implementation and the protocol stack of the wireless node. Our tests showed that AEDCF cannot maintain the same throughput differentiation ratios among different traffic classes under different loads. In contrast, the p-persistent Scheduler scheme maintains the desired differentiation ratios under different loads, gives higher total network throughput and provides easier tuning. We present detailed performance results of the scheduler-based architecture in terms of QoS differentiation and packet latency. All tests were implemented in NS2. The paper concentrates on single hop wireless networks and compares the scheduler-based scheme with AEDCF. The paper is concluded by a discussion on how to extend the evaluation to multi-hop wireless networks and examine the role of the routing layer and the MAC layer.

  5. Jumping the gun: Faster response latencies to deceptive questions in a realistic scenario.

    PubMed

    Mapala, Tessa; Warmelink, Lara; Linkenauger, Sally A

    2017-03-13

    Most theories of lie detection assume that lying increases cognitive load, resulting in longer response latencies during questioning. However, the studies supporting this theory are typically laboratory-based, in settings with no specific validity in security contexts. Consequently, using virtual reality (VR), we investigated how response latencies were influenced in an ecologically valid environment of interest to security professionals. In a highly realistic airport security terminal presented in VR, a security officer asked participants yes/no questions about their belongings. We found that liars actually responded more quickly to questions on which they were lying than to questions on which they were telling the truth. A control group, who answered the same questions but were not lying, answered equally quickly for all questions. We argue that this decrease in response time is possibly an unconscious reaction to questions on which individuals must answer deceptively. These results call into question the generalizability of previous research and highlight the importance of ecological validity when researching lie detection. These findings also uncover a new potential tool for enhancing lie detection in real-world scenarios.

  6. Effects of leg pedaling on early latency cutaneous reflexes in upper limb muscles.

    PubMed

    Sasada, Syusaku; Tazoe, Toshiki; Nakajima, Tsuyoshi; Zehr, E Paul; Komiyama, Tomoyoshi

    2010-07-01

    The functional coupling of neural circuits between the upper and lower limbs involving rhythmic movements is of interest to both motor control research and rehabilitation science. This coupling can be detected by examining the effect of remote rhythmic limb movement on the modulation of reflex amplitude in stationary limbs. The present study investigated the extent to which rhythmic leg pedaling modulates the amplitude of an early latency (peak 30-70 ms) cutaneous reflex (ELCR) in the upper limb muscles. Thirteen neurologically intact volunteers performed leg pedaling (60 or 90 rpm) while simultaneously contracting their arm muscles isometrically. Control experiments included isolated isometric contractions and discrete movements of the leg. ELCRs were evoked by stimulation of the superficial radial nerve with a train of rectangular pulses (three pulses at 333 Hz, intensity 2.0- to 2.5-fold perceptual threshold). Reflex amplitudes were significantly increased in the flexor carpi radialis and posterior deltoid and significantly decreased in the biceps brachii muscles during leg pedaling compared with that during stationary isometric contraction of the lower leg muscles. This effect was also sensitive to cadence. No significant modulation was seen during the isometric contractions or discrete movements of the leg. Additionally, there was no phase-dependent modulation of the ELCR. These findings suggest that activation of the rhythm generating system of the legs affects the excitability of the early latency cutaneous reflex pathways in the upper limbs.

  7. 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.

  8. 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

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

    SciTech Connect

    Rahayu, Retno; Ohsaki, Eriko; Omori, Hiroko; Ueda, Keiji

    2016-09-15

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

  10. Short-latency crossed inhibitory responses in extensor muscles during locomotion in the cat.

    PubMed

    Frigon, Alain; Rossignol, Serge

    2008-02-01

    During locomotion, contacting an obstacle generates a coordinated response involving flexion of the stimulated leg and activation of extensors contralaterally to ensure adequate support and forward progression. Activation of motoneurons innervating contralateral muscles (i.e., crossed extensor reflex) has always been described as an excitation, but the present paper shows that excitatory responses during locomotion are almost always preceded by a short period of inhibition. Data from seven cats chronically implanted with bipolar electrodes to record electromyography (EMG) of several hindlimb muscles bilaterally were used. A stimulating cuff electrode placed around the left tibial and left superficial peroneal nerves at the level of the ankle in five and two cats, respectively, evoked cutaneous reflexes during locomotion. During locomotion, short-latency ( approximately 13 ms) inhibitory responses were frequently observed in extensors of the right leg (i.e., contralateral to the stimulation), such as gluteus medius and triceps surae muscles, which were followed by excitatory responses ( approximately 25 ms). Burst durations of the left sartorius (Srt), a hip flexor, and ankle extensors of the right leg increased concomitantly in the mid- to late-flexion phases of locomotion with nerve stimulation. Moreover, the onset and offset of Srt and ankle extensor bursts bilaterally were altered in specific phases of the step cycle. Short-latency crossed inhibition in ankle extensors appears to be an integral component of cutaneous reflex pathways in intact cats during locomotion, which could be im