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Sample records for triple virally reduced

  1. Poly(A) Tail Recognition by a Viral RNA Element Through Assembly of a Triple Helix

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    M Mitton-Fry; S DeGregorio; J Wang; T Steitz; J Steitz

    2011-12-31

    Kaposi's sarcoma-associated herpesvirus produces a highly abundant, nuclear noncoding RNA, polyadenylated nuclear (PAN) RNA, which contains an element that prevents its decay. The 79-nucleotide expression and nuclear retention element (ENE) was proposed to adopt a secondary structure like that of a box H/ACA small nucleolar RNA (snoRNA), with a U-rich internal loop that hybridizes to and protects the PAN RNA poly(A) tail. The crystal structure of a complex between the 40-nucleotide ENE core and oligo(A){sub 9} RNA at 2.5 angstrom resolution reveals that unlike snoRNAs, the U-rich loop of the ENE engages its target through formation of a major-groove triple helix. A-minor interactions extend the binding interface. Deadenylation assays confirm the functional importance of the triple helix. Thus, the ENE acts as an intramolecular RNA clamp, sequestering the PAN poly(A) tail and preventing the initiation of RNA decay.

  2. The Healthy Workplace Project: Reduced Viral Exposure in an Office Setting

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    Reynolds, Kelly A.; Beamer, Paloma I.; Plotkin, Kevin R.; Sifuentes, Laura Y.; Koenig, David W.; Gerba, Charles P.

    2015-01-01

    Viral illnesses like gastroenteritis and the common cold create a substantial burden in the workplace due to reduced productivity, increased absenteeism, and increased health care costs. Behaviors in the workplace contribute to the spread of human viruses via direct contact between hands, contaminated surfaces and the mouth, eyes, and/or nose. This study assessed whether implementation of the Healthy Workplace Project (HWP) (providing hand sanitizers, disinfecting wipes, facial tissues, and use instructions) would reduce viral loads in an office setting of approximately 80 employees after seeding fomites and the hands of volunteer participants with an MS-2 phage tracer. The HWP significantly reduced viable phage detected on participants’ hands, communal fomites, and personal fomites (p≤0.010) in office environments and presents a cost-effective method for reducing the health and economic burden associated with viral illnesses in the workplace. PMID:26066784

  3. Does a Negative Triple Test Reduce the Rate of Negative Appendectomy in Adults?

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    Mahmoud F. Sakr

    2012-08-01

    Results: Sixty-seven patients (65.9% were female and 35 (34.1% were male. Their ages ranged between 16 and 49 years (mean 27.5 years. Most patients (87.3% had their symptoms for 12-36 hours before hospital admission. The mean values for TLC, NP, and CRP were 7,573/ and micro;L, 54.53%, and 0.61 mg/L, respectively. Of the 102 patients with NTT, 101 (99% proved not to have appendiceal inflammation (NPV=99%. Only 39 patients were operated upon, of whom 38 (97.4% had a normal appendix, and the remaining 63 patients were either discharged (n=47 or referred to other specialties (n=16. There were significantly more women (76.3%, 29/38 with negative appendectomy than men (24.7%, 9/38 (X2= 21.1, p=0.0001. Gynecological causes were the most common (60.5%, 23/38 and in 11 cases, the exact etiology could not be identified. Conclusions: From the data presented, it may be concluded that TLC, NP and CRP blood levels (triple test should be measured upon hospital admission of adult patients with clinically suspected acute appendicitis. If used judiciously, they may spare the group of patients with an NTT an unnecessary surgical operation, hence markedly reducing the NAR with its potential risks. [Arch Clin Exp Surg 2012; 1(4.000: 229-236

  4. Baseline characteristics of the 3096 patients recruited into the 'Triple Antiplatelets for Reducing Dependency after Ischemic Stroke' trial

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    Bath, Philip Mw; Appleton, Jason P; Beridze, Maia

    2017-01-01

    antiplatelets for reducing dependency after ischemic stroke was a large trial of intensive/triple antiplatelet therapy in acute ischemic stroke and transient ischemic attack, and included participants from four predominantly Caucasian countries who were representative of patients in many western stroke services.......Background The risk of recurrence following ischemic stroke or transient ischemic attack is highest immediately after the event. Antiplatelet agents are effective in reducing the risk of recurrence and two agents are superior to one in the early phase after ictus. Design The triple antiplatelets...... for reducing dependency after ischemic stroke trial was an international multicenter prospective randomized open-label blinded-endpoint trial that assessed the safety and efficacy of short-term intensive antiplatelet therapy with three agents (combined aspirin, clopidogrel and dipyridamole) as compared...

  5. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

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    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet

    2007-01-01

    human SP-D multimers as well as reduced hemagglutination inhibiting activity against several strains of IAV. Natural SP-D trimers also had different interactions with human neutrophil peptide defensins (HNPs) in viral neutralization assays as compared to multimeric SP-D. CONCLUSION: These studies...

  6. Baseline characteristics of the 3096 patients recruited into the 'Triple Antiplatelets for Reducing Dependency after Ischemic Stroke' trial.

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    Bath, Philip Mw; Appleton, Jason P; Beridze, Maia; Christensen, Hanne; Dineen, Robert A; Duley, Lelia; England, Timothy J; Heptinstall, Stan; James, Marilyn; Krishnan, Kailash; Markus, Hugh S; Pocock, Stuart; Ranta, Annemarei; Robinson, Thompson G; Flaherty, Katie; Scutt, Polly; Venables, Graham S; Woodhouse, Lisa J; Sprigg, Nikola

    2017-07-01

    Background The risk of recurrence following ischemic stroke or transient ischemic attack is highest immediately after the event. Antiplatelet agents are effective in reducing the risk of recurrence and two agents are superior to one in the early phase after ictus. Design The triple antiplatelets for reducing dependency after ischemic stroke trial was an international multicenter prospective randomized open-label blinded-endpoint trial that assessed the safety and efficacy of short-term intensive antiplatelet therapy with three agents (combined aspirin, clopidogrel and dipyridamole) as compared with guideline treatment in acute ischemic stroke or transient ischemic attack. The primary outcome was stroke recurrence and its severity, measured using the modified Rankin Scale at 90 days. Secondary outcomes included recurrent vascular events, functional measures (cognition, disability, mood, quality of life), and safety (bleeding, death, serious adverse events). Data are number (%) or mean (standard deviation, SD). Results Recruitment ran from April 2009 to March 2016; 3096 patients were recruited from 106 sites in four countries (Denmark 1.6%, Georgia 2.7%, New Zealand 0.2%, UK 95.4%). Randomization characteristics included: age 69.0 (10.1) years; male 1945 (62.8%); time onset to randomization 29.4 (11.9) h; stroke severity (National Institutes for Health Stroke Scale) 2.8 (3.6); blood pressure 143.5 (18.2)/79.5 (11.4) mmHg; IS 2143 (69.2%), transient ischemic attack 953 (30.8%). Conclusion Triple antiplatelets for reducing dependency after ischemic stroke was a large trial of intensive/triple antiplatelet therapy in acute ischemic stroke and transient ischemic attack, and included participants from four predominantly Caucasian countries who were representative of patients in many western stroke services.

  7. Triple Negative Breast Cancers Have a Reduced Expression of DNA Repair Genes

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    Andreis, Daniele; Bertoni, Ramona; Giardini, Roberto; Fox, Stephen B.; Broggini, Massimo; Bottini, Alberto; Zanoni, Vanessa; Bazzola, Letizia; Foroni, Chiara; Generali, Daniele; Damia, Giovanna

    2013-01-01

    DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia) in paraffin embedded samples of triple negative breast cancer (TNBC) compared to luminal A breast cancer (LABC). Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects. PMID:23825533

  8. A Humanin Derivative Reduces Amyloid Beta Accumulation and Ameliorates Memory Deficit in Triple Transgenic Mice

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    Niikura, Takako; Sidahmed, Elkhansa; Hirata-Fukae, Chiho; Aisen, Paul S.; Matsuoka, Yasuji

    2011-01-01

    Humanin (HN), a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD)-related cytotoxicities, including exposure to amyloid beta (Abeta), in vitro. We previously demonstrated that the injection of S14G-HN, a highly potent HN derivative, into brain ameliorated memory loss in an Abeta-injection mouse model. To fully understand HN's functions under AD-associated pathological conditions, we examined the effect of S14G-HN on triple transgenic mice harboring APPswe, tauP310L, and PS-1M146V that show the age-dependent development of multiple pathologies relating to AD. After 3 months of intranasal treatment, behavioral analyses showed that S14G-HN ameliorated cognitive impairment in male mice. Moreover, ELISA and immunohistochemical analyses showed that Abeta levels in brains were markedly lower in S14G-HN-treated male and female mice than in vehicle control mice. We also found the expression level of neprilysin, an Abeta degrading enzyme, in the outer molecular layer of hippocampal formation was increased in S14G-HN-treated mouse brains. NEP activity was also elevated by S14G-HN treatment in vitro. These findings suggest that decreased Abeta level in these mice is at least partly attributed to S14G-HN-induced increase of neprilysin level. Although HN was identified as an anti-neuronal death factor, these results indicate that HN may also have a therapeutic effect on amyloid accumulation in AD. PMID:21264226

  9. A humanin derivative reduces amyloid beta accumulation and ameliorates memory deficit in triple transgenic mice.

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    Takako Niikura

    Full Text Available Humanin (HN, a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD-related cytotoxicities, including exposure to amyloid beta (Abeta, in vitro. We previously demonstrated that the injection of S14G-HN, a highly potent HN derivative, into brain ameliorated memory loss in an Abeta-injection mouse model. To fully understand HN's functions under AD-associated pathological conditions, we examined the effect of S14G-HN on triple transgenic mice harboring APP(swe, tau(P310L, and PS-1(M146V that show the age-dependent development of multiple pathologies relating to AD. After 3 months of intranasal treatment, behavioral analyses showed that S14G-HN ameliorated cognitive impairment in male mice. Moreover, ELISA and immunohistochemical analyses showed that Abeta levels in brains were markedly lower in S14G-HN-treated male and female mice than in vehicle control mice. We also found the expression level of neprilysin, an Abeta degrading enzyme, in the outer molecular layer of hippocampal formation was increased in S14G-HN-treated mouse brains. NEP activity was also elevated by S14G-HN treatment in vitro. These findings suggest that decreased Abeta level in these mice is at least partly attributed to S14G-HN-induced increase of neprilysin level. Although HN was identified as an anti-neuronal death factor, these results indicate that HN may also have a therapeutic effect on amyloid accumulation in AD.

  10. Reduced risk of axillary lymphatic spread in triple-negative breast cancer

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    Holm-Rasmussen, Emil Villiam; Jensen, Maj-Britt; Balslev, Eva

    2015-01-01

    We examined the association between the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status of women with primary breast cancer and the risk of axillary lymph node (ALN) involvement at the time of diagnosis. Information on 20,009 women diagnosed with primary breast...... cancer between 2008 and 2012 was retrieved from the Danish Breast Cancer Cooperative Group database. The associations between clinical and pathological variables and ALN involvement at the time of diagnosis were evaluated in univariate and multivariate regression analyses, as well as the significance...... of tumor subtypes in ALN involvement. The risk of ALN metastases at the time of diagnosis was significantly reduced in HR-negative patients compared to HR-positive patients [adjusted odds ratio (OR) 0.69; 95 % CI 0.63-0.76; P = 0.0009]. A HER2-positive status was associated with an increased risk of ALN...

  11. Pre- and postoperative dexamethasone does not reduce bleaching-induced tooth sensitivity: A randomized, triple-masked clinical trial.

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    Rezende, Márcia; Bonafé, Elize; Vochikovski, Laína; Farago, Paulo Vitor; Loguercio, Alessandro Dourado; Reis, Alessandra; Kossatz, Stella

    2016-01-01

    Tooth sensitivity (TS) is the most common side effect of dental bleaching therapies. Dexamethasone has been used with tooth bleaching to reduce TS. The efficacy of dexamethasone for this purpose has not been well studied. The authors conducted a triple-masked, randomized, clinical trial with a parallel design involving 63 healthy participants who received either a placebo or dexamethasone. The placebo or dexamethasone (8 milligrams) was administered 1 hour before the in-office bleaching (35% hydrogen peroxide) and extra doses of 4 mg were administered every 6 hours for a total of 48 hours. TS was recorded on 2 scales: visual analog scale (0-10) and numeric rating scale (0-4) in different periods. The color evaluations were performed before and 1 month after dental bleaching with visual shade guides VITA Classical (VITA Zahnfabrik) and VITA Bleachedguide 3D-MASTER (VITA Zahnfabrik), and for a shade guide evaluation, the authors used a digital spectrophotometer, VITA Easyshade (VITA Zahnfabrik). The absolute risk of TS was evaluated by a Fisher exact test. Data of TS intensity using the NRS scale for the 2 groups were compared with Mann-Whitney and Friedman tests, whereas data from the visual analog scale were evaluated by 2-way repeated measures analysis of variance. The color changes between groups were compared using a t test (α = .05). In both groups, the authors detected a high risk of TS, which was approximately 90%. No significant difference was observed in terms of TS intensity. A whitening of approximately 3 shade guide units of the VITA Classical was detected in both groups, which were statistically similar. The use of dexamethasone before bleaching did not reduce the risk and intensity of bleaching-induced TS. The use of the steroidal anti-inflammatory agent dexamethasone was not capable of preventing TS arising from in-office dental bleaching. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

  12. Proteasome inhibitors induce apoptosis and reduce viral replication in primary effusion lymphoma cells

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    Saji, Chiaki [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812 (Japan); Higashi, Chizuka; Niinaka, Yasufumi [Faculty of Medicine, University of Yamanashi, Chuoh-shi 409-3898 (Japan); Yamada, Koji [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812 (Japan); Noguchi, Kohji [Faculty of Pharmacy, Keio University, 1-5-30 Shiba-koen, Minato-ku, Tokyo 105-8512 (Japan); Fujimuro, Masahiro, E-mail: fuji2@mb.kyoto-phu.ac.jp [Department of Cell Biology, Kyoto Pharmaceutical University, Misasagi-Shichonocho 1, Yamashinaku, Kyoto 607-8412 (Japan)

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Constitutive NF-{kappa}B signaling is essential for the survival and growth of PEL cells. Black-Right-Pointing-Pointer NF-{kappa}B signaling is upregulated by the proteasome-dependent degradation of I{kappa}B{alpha}. Black-Right-Pointing-Pointer Proteasome inhibitors suppress NF-{kappa}B signaling and induce apoptosis in PEL cells through stabilization of I{kappa}B{alpha}. Black-Right-Pointing-Pointer Proteasome inhibitors suppress viral replication in PEL cells during lytic KSHV infection. -- Abstract: Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV). This study provides evidence that proteasomal activity is required for both survival of PEL cells stably harboring the KSHV genome and viral replication of KSHV. We evaluated the cytotoxic effects of proteasome inhibitors on PEL cells. The proteasome inhibitors MG132, lactacystin, and proteasome inhibitor I dramatically inhibited cell proliferation and induced apoptosis of PEL cells through the accumulation of p21 and p27. Furthermore, proteasome inhibitors induced the stabilization of NF-{kappa}B inhibitory molecule (I{kappa}B{alpha}) and suppressed the transcriptional activity of NF-{kappa}B in PEL cells. The NF-{kappa}B specific inhibitor BAY11-7082 also induced apoptosis in PEL cells. The constitutive activation of NF-{kappa}B signaling is essential for the survival and growth of B cell lymphoma cells, including PEL cells. NF-{kappa}B signaling is upregulated by proteasome-dependent degradation of I{kappa}B{alpha}. The suppression of NF-{kappa}B signaling by proteasome inhibitors may contribute to the induction of apoptosis in PEL cells. In addition, proteasome activity is required for KSHV replication in KSHV latently infected PEL cells. MG132 reduced the production of progeny virus from PEL cells at low concentrations, which do not affect PEL cell growth. These findings suggest that proteasome

  13. THE ROLE OF INTERFERON ALPHA-2b IN REDUCING OF VIRAL LOAD IN HPV INFECTED WOMEN

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    Кристина Владимировна Марочко

    2017-05-01

    Conclusion. Mono-infection was prevalent among HPV infected women HPV 16 is the most frequently detected hrHPV. The use of the drug interferon alfa-2b in the study group, contributed to viral load reduction.

  14. Reducing anxiety levels in preschool children undergoing cryotherapy for cutaneous viral warts: use of a portable video player.

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    Tey, Hong Liang; Tan, Eugene Sern Ting; Tan, Felicia Geok Ching; Tan, Kim Lian; Lim, Irene Siew Heok; Tan, Andy Soon Leong

    2012-09-01

    To determine if watching a children's program on a portable video player reduces anxiety levels in preschool children before cryotherapy for cutaneous viral warts. Nonblinded before-after trial. General dermatology clinic. Consecutive patients aged 2 to 6 years who underwent cryotherapy for cutaneous viral warts. Patients were shown a children's program on a portable video player before cryotherapy. Mean score difference on the modified Yale Preoperative Anxiety Scale between children treated during the 10 weeks before vs the 10 weeks after the intervention was implemented. Ninety-nine cryotherapy sessions performed among 35 children were evaluated. Fifteen children underwent cryotherapy during the preintervention phase only, and 13 children underwent cryotherapy during the intervention phase only. The mean modified Yale Preoperative Anxiety Scale scores were 58.4 during the preintervention phase and 37.7 during the intervention phase (P = .005). The percentages of children with a high anxiety score (≥30) were 100% (15 of 15) during the preintervention phase and 38% (5 of 13) during the intervention phase (P video player significantly reduced preprocedural anxiety levels in preschool children undergoing cryotherapy for cutaneous viral warts.

  15. Reducing uncertainty in within-host parameter estimates of influenza infection by measuring both infectious and total viral load.

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    Stephen M Petrie

    Full Text Available For in vivo studies of influenza dynamics where within-host measurements are fit with a mathematical model, infectivity assays (e.g. 50% tissue culture infectious dose; TCID50 are often used to estimate the infectious virion concentration over time. Less frequently, measurements of the total (infectious and non-infectious viral particle concentration (obtained using real-time reverse transcription-polymerase chain reaction; rRT-PCR have been used as an alternative to infectivity assays. We investigated the degree to which measuring both infectious (via TCID50 and total (via rRT-PCR viral load allows within-host model parameters to be estimated with greater consistency and reduced uncertainty, compared with fitting to TCID50 data alone. We applied our models to viral load data from an experimental ferret infection study. Best-fit parameter estimates for the "dual-measurement" model are similar to those from the TCID50-only model, with greater consistency in best-fit estimates across different experiments, as well as reduced uncertainty in some parameter estimates. Our results also highlight how variation in TCID50 assay sensitivity and calibration may hinder model interpretation, as some parameter estimates systematically vary with known uncontrolled variations in the assay. Our techniques may aid in drawing stronger quantitative inferences from in vivo studies of influenza virus dynamics.

  16. Statins reduce the risk of liver decompensation and death in chronic viral hepatitis: a propensity score weighted landmark analysis.

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    Wong, J C-T; Chan, H L-Y; Tse, Y-K; Yip, T C-F; Wong, V W-S; Wong, G L-H

    2017-11-01

    Decompensated liver disease due to portal hypertension leads to significant morbidity and mortality. Statins can modulate intrahepatic vascular tone, but the clinical significance remains uncertain. To determine the effects of statin use on the risk of liver decompensation and death among patients with chronic viral hepatitis. We conducted a population wide cohort study using a hospital based database from the Hong Kong Hospital Authority. Adults with chronic viral hepatitis without prior liver decompensation were identified from 2000 to 2012 by International Classification of Diseases, Ninth Revision, Clinical Modification, diagnostic codes. Statin use was defined as a cumulative defined daily dose of >28. Landmark analysis was used to overcome immortal time bias. Propensity score weighting was further performed to minimise baseline confounders. Primary outcome was a composite of portal hypertension related liver decompensation events, with adjustment for death as a competing risk. A total of 69 184 patients with chronic viral hepatitis (2053 statin users and 67 131 statin non-users) were identified for the 2-year landmark analysis. After propensity score weighting of 23 baseline covariates, statin use was associated with a significant reduction in composite liver decompensation events (HR: 0.55; 95% CI: 0.36-0.83; P = .005), ascites (HR: 0.57; 95% CI: 0.36-0.92; P = .02), and a dose-dependent decrease in death (HR: 0.87; 95% CI: 0.76-0.99; P = .035) relative to no statin use. Patients with chronic viral hepatitis who used statins have a reduced risk of liver decompensation and death compared to non-users in this propensity score weighted landmark analysis. © 2017 John Wiley & Sons Ltd.

  17. Early phase viral kinetics of chronic hepatitis C patients receiving telaprevir-based triple therapy: a comparison of two real-time PCR assays.

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    Ogawa, Eiichi; Furusyo, Norihiro; Murata, Masayuki; Toyoda, Kazuhiro; Eiraku, Kunimitsu; Shimizu, Motohiro; Harada, Yuji; Mitsumoto, Fujiko; Takayama, Koji; Okada, Kyoko; Kainuma, Mosaburo; Hayashi, Jun

    2013-08-01

    Monitoring hepatitis C virus (HCV) kinetics during antiviral treatment is recommended for determining the best form of treatment management. We compared the measurement of HCV RNA by two Real-time PCR assays during the first 12weeks phase of telaprevir in combination with pegylated interferon α2b and ribavirin treatment for chronic hepatitis C patients. The viral kinetics of 65 patients with HCV genotype 1b was assessed. HCV RNA was tested at baseline, on day 3, and every week from 1 to 12 by both the first-generation Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV (CAP/CTM) assay and the Abbott RealTime HCV (ART) assay. A total of 910 serum samples were obtained from the 65 patients. Of these, 168 (28.5%) of the 590 samples HCV RNA negative by CAP/CTM were positive by ART. In contrast, 17 (3.9%) of the 439 samples HCV RNA negative by ART were positive by CAP/CTM. The rates of HCV RNA negativity by ART at weeks 3, 4, and 5 were significantly lower than those by CAP/CTM (21.5% vs. 50.8%, 36.9% vs. 70.8% and 44.6% vs. 81.5%; PHCV RNA negativity, the predictive value of detectable HCV RNA for non-sustained virological response (non-SVR) by CAP/CTM is higher than by ART at weeks 4, 6, and 8. We also found that 16 (24.6%) by CAP/CTM and 28 (43.1%) by ART had a reappearance of residual HCV RNA during the telaprevir treatment period. However, the reappearance of residual HCV RNA was not associated with non-SVR. In conclusion, a significant difference was found between the two real-time PCR assays for the assessment of virological response based on undetectable HCV RNA. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. High Maternal HIV-1 Viral Load During Pregnancy Is Associated With Reduced Placental Transfer of Measles IgG Antibody

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    Farquhar, Carey; Nduati, Ruth; Haigwood, Nancy; Sutton, William; Mbori-Ngacha, Dorothy; Richardson, Barbra; John-Stewart, Grace

    2012-01-01

    Background Studies among HIV-1–infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population. Methods To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1–infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed. Maternal CD4 count, HIV-1 viral load, and HIV-1–specific gp41 antibody concentrations were measured antenatally and at delivery. Measles IgG concentrations were assayed in maternal blood and infant cord blood obtained during delivery to calculate placental antibody transfer. Results Among 40 women (73%) with positive measles titers, 30 (75%) were found to have abnormally low levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32 weeks’ gestation and at delivery was associated with reductions in placental transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High maternal HIV-1–specific gp41 antibody titer was also highly correlated with both decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001). Conclusions This is the first study to evaluate the relationship between maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive immunity among HIV-1–exposed infants. These data support the hypothesis that high HIV-1 viral load during the last trimester may impair maternofetal transfer of IgG and increases risk of measles and other serious infections among HIV-1–exposed infants. PMID:16280707

  19. Overcoming Triple Segregation

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    Gandara, Patricia

    2010-01-01

    Latinos are, after whites, the most segregated student group in the United States, and their segregation is closely tied to poor academic outcomes. Latinos experience a triple segregation: by race/ethnicity, poverty, and language. Racial segregation perpetuates negative stereotypes, reduces the likelihood of a strong teaching staff, and is often…

  20. Reducing viral contamination from finger pads: handwashing is more effective than alcohol-based hand disinfectants

    NARCIS (Netherlands)

    Tuladhar, E.; Hazeleger, W.C.; Koopmans, M.; Zwietering, M.H.; Duizer, E.

    2015-01-01

    Background - Hand hygiene is important for interrupting transmission of viruses through hands. Effectiveness of alcohol-based hand disinfectant has been shown for bacteria but their effectiveness in reducing transmission of viruses is ambiguous. Aim - To test efficacy of alcohol hand disinfectant

  1. The Recombinant Maize Ribosome-Inactivating Protein Transiently Reduces Viral Load in SHIV89.6 Infected Chinese Rhesus Macaques

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    Rui-Rui Wang

    2015-01-01

    Full Text Available Ribosome inactivating proteins (RIPs inhibit protein synthesis by depurinating the large ribosomal RNA and some are found to possess anti-human immunodeficiency virus (HIV activity. Maize ribosome inactivating protein (RIP has an internal inactivation loop which is proteolytically removed for full catalytic activity. Here, we showed that the recombinant active maize RIP protected chimeric simian-human immunodeficiency virus (SHIV 89.6-infected macaque peripheral blood mononuclear cells from lysis ex vivo and transiently reduced plasma viral load in SHIV89.6-infected rhesus macaque model. No evidence of immune dysregulation and other obvious side-effects was found in the treated macaques. Our work demonstrates the potential development of maize RIP as an anti-HIV agent without impeding systemic immune functions.

  2. Redox Fluctuation Influences Viral Abundance in the Reduced Zone of a Shallow Alluvial Aquifer in Rifle, CO

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    Pan, D.; Williams, K. H.; Robbins, M.; Weber, K. A.

    2014-12-01

    Naturally reduced zones (NRZs) within alluvial aquifers contain naturally elevated concentrations of organic carbon (OC) and can play a role in controlling the fate of redox-active contaminants. OC in NRZs stimulates microbial activity through coupling of OC oxidation to reduction of subsurface electron acceptors. Stimulation of the indigenous microbial community also results in the stimulation of the viral community. Viruses are the most abundant biological entity on Earth and can indirectly influence carbon cycling by infecting and lysing host cells, resulting in release of OC bound in biomass. In the alluvial aquifer near Rifle, CO, prior acetate injection resulted in reductive immobilization of U and a reduced zone simulating a NRZ, with elevated ferrous iron and sulfide (53.2-62.5 µM and 0.2-3.1 µM, respectively). To study the effects of redox fluctuations in a RZ, oxygenated groundwater was injected. Prior to injection, groundwater was suboxic (0.05-0.11 mg/L). Amended O2 was immediately consumed in the RZ. While cell numbers didn't significantly increase, viruses increased from 1.1x106-2.1x106 mL-1 to 2.3x106-4.6x106 mL-1. VCR increased 1.8-3.4 fold from 3.9-10.1 to 11.0-17.9, demonstrating microbial activity. These changes were associated with large fluctuations of groundwater dissolved OC, suggesting viral release of OC from cellular biomass. Groundwater ORP decreased from an initial -146 mV - -132 mV to -317 mV - -304 mV, indicating an increase in the supply of available electron donors. Thus, rather than expected oxidative solubilization of U following amendment of O2, soluble U decreased, suggesting likely U reduction in the RZ. Fe and S fluctuated, but changes were not associated with aqueous U. Across the whole floodplain, viral abundance is correlated to groundwater dissolved OC, suggesting that viruses may be contributing to the liberalization of dissolved OC from biomass in NRZs, allowing turnover of carbon and reduction of contaminants of

  3. Reduced host cell invasiveness and oxidative stress tolerance in double and triple csp gene family deletion mutants of Listeria monocytogenes.

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    Loepfe, Chantal; Raimann, Eveline; Stephan, Roger; Tasara, Taurai

    2010-07-01

    The cold shock protein (Csp) family comprises small, highly conserved proteins that bind nucleic acids to modulate various bacterial gene expressions. In addition to cold adaptation functions, this group of proteins is thought to facilitate various cellular processes to promote normal growth and stress adaptation responses. Three proteins making up the Listeria monocytogenes Csp family (CspA, CspB, and CspD) promote both cold and osmotic stress adaptation functions in this bacterium. The contribution of these three Csps in the host cell invasion processes of L. monocytogenes was investigated based on human Caco-2 and murine macrophage in vitro cell infection models. The DeltacspB, DeltacspD, DeltacspAB, DeltacspAD, DeltacspBD, and DeltacspABD strains were all significantly impaired in Caco-2 cell invasion compared with the wild-type strain, whereas in the murine macrophage infection assay only, the double (DeltacspBD) and triple (DeltacspABD) csp mutants were also significantly impaired in cell invasion compared with the wild-type strain. The DeltacspBD and DeltacspABD mutants displayed the most severely impaired invasion phenotypes. The invasion ability of these two mutant strains was also further analyzed using cold-stress-exposed organisms. In both cell infection models a significant reduction in invasiveness was observed after cold stress exposure of Listeria organisms. The negative impact of cold stress on subsequent cell invasion ability was, however, more severe in cold-sensitive csp mutants (DeltacspBD and DeltacspABD) compared with the wild type. The impaired macrophage invasion and intracellular growth of DeltacspBD and DeltacspABD also led us to examine oxidative stress resistance capacity in these two mutant strains. Both strains also displayed higher oxidative stress sensitivity relative to the wild-type strain. Our data indicate that besides cold and osmotic stress adaptation roles, Csp family proteins also promote efficient host cell invasion and

  4. Reduced-complexity multi-site rainfall generation: one million years over night using the model TripleM

    Science.gov (United States)

    Breinl, Korbinian; Di Baldassarre, Giuliano; Girons Lopez, Marc

    2017-04-01

    We assess uncertainties of multi-site rainfall generation across spatial scales and different climatic conditions. Many research subjects in earth sciences such as floods, droughts or water balance simulations require the generation of long rainfall time series. In large study areas the simulation at multiple sites becomes indispensable to account for the spatial rainfall variability, but becomes more complex compared to a single site due to the intermittent nature of rainfall. Weather generators can be used for extrapolating rainfall time series, and various models have been presented in the literature. Even though the large majority of multi-site rainfall generators is based on similar methods, such as resampling techniques or Markovian processes, they often become too complex. We think that this complexity has been a limit for the application of such tools. Furthermore, the majority of multi-site rainfall generators found in the literature are either not publicly available or intended for being applied at small geographical scales, often only in temperate climates. Here we present a revised, and now publicly available, version of a multi-site rainfall generation code first applied in 2014 in Austria and France, which we call TripleM (Multisite Markov Model). We test this fast and robust code with daily rainfall observations from the United States, in a subtropical, tropical and temperate climate, using rain gauge networks with a maximum site distance above 1,000km, thereby generating one million years of synthetic time series. The modelling of these one million years takes one night on a recent desktop computer. In this research, we first start the simulations with a small station network of three sites and progressively increase the number of sites and the spatial extent, and analyze the changing uncertainties for multiple statistical metrics such as dry and wet spells, rainfall autocorrelation, lagged cross correlations and the inter-annual rainfall

  5. A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection.

    Science.gov (United States)

    Troupin, Andrea; Londono-Renteria, Berlin; Conway, Michael J; Cloherty, Erin; Jameson, Samuel; Higgs, Stephen; Vanlandingham, Dana L; Fikrig, Erol; Colpitts, Tonya M

    2016-09-01

    Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Aedes aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated. Ubiquitin proteins have multiple functions in insects, including marking proteins for proteasomal degradation, regulating apoptosis and mediating innate immune signaling. We used qRT-PCR to quantify gene expression and infection, and RNAi to reduce Ub3881 expression. Mosquitoes were infected with DENV through blood feeding. We transfected DENV protein expression constructs to examine the effect of Ub3881 on protein degradation. We used site-directed mutagenesis and transfection to determine what amino acids are involved in Ub3881-mediated protein degradation. Immunofluorescence, Co-immunoprecipitation and Western blotting were used to examine protein interactions and co-localization. The overexpression of Ub3881, but not related ubiquitin proteins, decreased DENV infection in mosquito cells and live Ae. aegypti. The Ub3881 protein was demonstrated to be involved in DENV envelope protein degradation and reduce the number of infectious virions released. We conclude that Ub3881 has several antiviral functions in the mosquito, including specific viral protein degradation. Our data highlights Ub3881 as a target for future DENV prevention strategies in the mosquito transmission vector. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Tajima, Shigeru [Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640 (Japan); Hikono, Hirokazu; Saito, Takehiko [Influenza and Prion Disease Research Center, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan); Aida, Yoko, E-mail: aida@riken.jp [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

    2014-07-18

    Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC{sub 50} values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets.

  7. Inhibition of viral replication reduces regulatory T cells and enhances the antiviral immune response in chronic hepatitis B.

    Science.gov (United States)

    Stoop, Jeroen N; van der Molen, Renate G; Kuipers, Ernst J; Kusters, Johannes G; Janssen, Harry L A

    2007-04-25

    Regulatory T cells (Treg) play a key role in the impaired immune response that is typical for a chronic Hepatitis B virus (HBV) infection. To gain more insight in the mechanism that is responsible for this impaired immune response, the effect of viral load reduction resulting from treatment with the nucleotide analogue adefovir dipivoxil on the percentages of Treg and HBV-specific T-cell responses was analyzed. Peripheral blood mononuclear cells (PBMC) of 12 patients were collected at baseline and during treatment. In parallel to the decline in viral load, we found a decline in circulating Treg, combined with an increase in HBV core antigen-specific IFN-gamma production and proliferation. The production of IL10 did not decrease during therapy. In conclusion, adefovir induced viral load reduction results in a decline of circulating Treg together with a partial recovery of the immune response.

  8. Inhibition of viral replication reduces regulatory T cells and enhances the antiviral immune response in chronic hepatitis B

    International Nuclear Information System (INIS)

    Stoop, Jeroen N.; Molen, Renate G. van der; Kuipers, Ernst J.; Kusters, Johannes G.; Janssen, Harry L.A.

    2007-01-01

    Regulatory T cells (Treg) play a key role in the impaired immune response that is typical for a chronic Hepatitis B virus (HBV) infection. To gain more insight in the mechanism that is responsible for this impaired immune response, the effect of viral load reduction resulting from treatment with the nucleotide analogue adefovir dipivoxil on the percentages of Treg and HBV-specific T-cell responses was analyzed. Peripheral blood mononuclear cells (PBMC) of 12 patients were collected at baseline and during treatment. In parallel to the decline in viral load, we found a decline in circulating Treg, combined with an increase in HBV core antigen-specific IFN-γ production and proliferation. The production of IL10 did not decrease during therapy. In conclusion, adefovir induced viral load reduction results in a decline of circulating Treg together with a partial recovery of the immune response

  9. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load

    DEFF Research Database (Denmark)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P

    2009-01-01

    -68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential......-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral...... vectors encoding both M2 and M3. Additionally we show that M3 immunization prevented the usual development of virus-induced splenomegaly at 2-3 weeks post-infection. This is the first time that immunization with a non-replicating vaccine has lead to a significantly reduced viral load at time points beyond...

  10. Preemptive CD8 T-cell immunotherapy of acute cytomegalovirus infection prevents lethal disease, limits the burden of latent viral genomes, and reduces the risk of virus recurrence.

    Science.gov (United States)

    Steffens, H P; Kurz, S; Holtappels, R; Reddehase, M J

    1998-03-01

    In the immunocompetent host, primary cytomegalovirus (CMV) infection is resolved by the immune response without causing overt disease. The viral genome, however, is not cleared but is maintained in a latent state that entails a risk of virus recurrence and consequent organ disease. By using murine CMV as a model, we have shown previously that multiple organs harbor latent CMV and that reactivation occurs with an incidence that is determined by the viral DNA load in the respective organ (M. J. Reddehase, M. Balthesen, M. Rapp, S. Jonjic, I. Pavic, and U. H. Koszinowski. J. Exp. Med. 179:185-193, 1994). This predicts that a therapeutic intervention capable of limiting the load of latent viral genome should also reduce the risk of virus recurrence. Here we demonstrate the benefits and the limits of a preemptive CD8 T-cell immunotherapy of CMV infection in the immunocompromised bone marrow transplantation recipient. Antiviral CD8 T cells prevented CMV disease and accelerated the resolution of productive infection. The therapy also resulted in a lower load of latent CMV DNA in organs and consequently reduced the incidence of recurrence. The data thus provide a further supporting argument for clinical trials of preemptive cytoimmunotherapy of human CMV disease with CD8 T cells. However, CD8 T cells failed to clear the viral DNA. The therapy-susceptible portion of the DNA load differed between organs and was highest in the lungs. The existence of an invariant, therapy-resistant load suggests a role for immune system evasion mechanisms in the establishment of CMV latency.

  11. Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA

    Directory of Open Access Journals (Sweden)

    Ristic Natalia

    2010-09-01

    Full Text Available Abstract Background The viral genome of HIV-1 contains several secondary structures that are important for regulating viral replication. The stem-loop 1 (SL1 sequence in the 5' untranslated region directs HIV-1 genomic RNA dimerization and packaging into the virion. Without SL1, HIV-1 cannot replicate in human T cell lines. The replication restriction phenotype in the SL1 deletion mutant appears to be multifactorial, with defects in viral RNA dimerization and packaging in producer cells as well as in reverse transcription of the viral RNA in infected cells. In this study, we sought to characterize SL1 mutant replication restrictions and provide insights into the underlying mechanisms of compensation in revertants. Results HIV-1 lacking SL1 (NLΔSL1 did not replicate in PM-1 cells until two independent non-synonymous mutations emerged: G913A in the matrix domain (E42K on day 18 postinfection and C1907T in the SP1 domain (P10L on day 11 postinfection. NLΔSL1 revertants carrying either compensatory mutation showed enhanced infectivity in PM-1 cells. The SL1 revertants produced significantly more infectious particles per nanogram of p24 than did NLΔSL1. The SL1 deletion mutant packaged less HIV-1 genomic RNA and more cellular RNA, particularly signal recognition particle RNA, in the virion than the wild-type. NLΔSL1 also packaged 3- to 4-fold more spliced HIV mRNA into the virion, potentially interfering with infectious virus production. In contrast, both revertants encapsidated 2.5- to 5-fold less of these HIV-1 mRNA species. Quantitative RT-PCR analysis of RNA cross-linked with Gag in formaldehyde-fixed cells demonstrated that the compensatory mutations reduced the association between Gag and spliced HIV-1 RNA, thereby effectively preventing these RNAs from being packaged into the virion. The reduction of spliced viral RNA in the virion may have a major role in facilitating infectious virus production, thus restoring the infectivity of NLΔSL1

  12. Viral Polymerases

    Science.gov (United States)

    Choi, Kyung H.

    2016-01-01

    Viral polymerases play a central role in viral genome replication and transcription. Based on the genome type and the specific needs of particular virus, RNA-dependent RNA polymerase, RNA-dependent DNA polymerase, DNA-dependent RNA polymerase, and DNA-dependent RNA polymerases are found in various viruses. Viral polymerases are generally active as a single protein capable of carrying out multiple functions related to viral genome synthesis. Specifically, viral polymerases use variety of mechanisms to recognize initial binding sites, ensure processive elongation, terminate replication at the end of the genome, and also coordinate the chemical steps of nucleic acid synthesis with other enzymatic activities. This review focuses on different viral genome replication and transcription strategies, and the polymerase interactions with various viral proteins that are necessary to complete genome synthesis. PMID:22297518

  13. Proteomics approach to understand reduced clearance of mycobacteria and high viral titers during HIV-mycobacteria co-infection.

    Science.gov (United States)

    Ganji, Rakesh; Dhali, Snigdha; Rizvi, Arshad; Sankati, Swetha; Vemula, Mani Harika; Mahajan, Gaurang; Rapole, Srikanth; Banerjee, Sharmistha

    2016-03-01

    Environmental mycobacteria, highly prevalent in natural and artificial (including chlorinated municipal water) niches, are emerging as new threat to human health, especially to HIV-infected population. These seemingly harmless non-pathogenic mycobacteria, which are otherwise cleared, establish as opportunistic infections adding to HIV-associated complications. Although immune-evading strategies of pathogenic mycobacteria are known, the mechanisms underlying the early events by which opportunistic mycobacteria establish infection in macrophages and influencing HIV infection are unclear. Proteomics of phagosome-enriched fractions from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) mono-infected and HIV-M. bovis BCG co-infected THP-1 cells by LC-MALDI-MS/MS revealed differential distribution of 260 proteins. Validation of the proteomics data showed that HIV co-infection helped the survival of non-pathogenic mycobacteria by obstructing phagosome maturation, promoting lipid biogenesis and increasing intracellular ATP equivalents. In turn, mycobacterial co-infection up-regulated purinergic receptors in macrophages that are known to support HIV entry, explaining increased viral titers during co-infection. The mutualism was reconfirmed using clinically relevant opportunistic mycobacteria, Mycobacterium avium, Mycobacterium kansasii and Mycobacterium phlei that exhibited increased survival during co-infection, together with increase in HIV titers. Additionally, the catalogued proteins in the study provide new leads that will significantly add to the understanding of the biology of opportunistic mycobacteria and HIV coalition. © 2015 John Wiley & Sons Ltd.

  14. Triple-axis spectrometer

    International Nuclear Information System (INIS)

    Toeroek, Gy.

    2001-01-01

    A triple-axis spectrometer has been designed for structural and dynamical studies of condensed matter. Because of the limited number of other operational equipment the triple axis spectrometer was used in a multi purpose regime, e.g. high resolution diffractometry, strain analysis, reflectometry, quasielastic and inelastic scattering. A polarization setup was also tested on this spectrometer. (R.P.)

  15. Pemasaran ViralViral Marketing

    OpenAIRE

    Situmorang, James Rianto

    2010-01-01

    Viral marketing is an extremely powerful and effective form of internet marketing. Itis a new form of word-of-mouth through internet. In viral marketing, someone passeson a marketing message to someone else and so on. Viral marketing proposes thatmessages can be rapidly disseminated from consumer to consumer leading to largescale market acceptance. The analogy of a virus is used to described the exponentialdiffusion of information in an electronic environment and should not be confusedwith th...

  16. Efficacy of highly active triple antiretroviral therapy in preventing ...

    African Journals Online (AJOL)

    Drug efficacy and safety were assessed by CD4 count, viral load, liver enzymes level, fasting blood sugar level, blood urea and haemoglobin concentration level before and after treatment and the paediatric seroprevalence rate. Highly active triple antiretroviral therapy was associated with maternal immunological ...

  17. Pharyngitis - viral

    Science.gov (United States)

    ... Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Pharyngitis - viral URL of this page: //medlineplus.gov/ency/article/ ...

  18. Viral gastroenteritis

    Science.gov (United States)

    ... Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Viral gastroenteritis (stomach flu) URL of this page: //medlineplus. ...

  19. Neonatal Gene Therapy for Hemophilia B by a Novel Adenovirus Vector Showing Reduced Leaky Expression of Viral Genes.

    Science.gov (United States)

    Iizuka, Shunsuke; Sakurai, Fuminori; Tachibana, Masashi; Ohashi, Kazuo; Mizuguchi, Hiroyuki

    2017-09-15

    Gene therapy during neonatal and infant stages is a promising approach for hemophilia B, a congenital disorder caused by deficiency of blood coagulation factor IX (FIX). An adenovirus (Ad) vector has high potential for use in neonatal or infant gene therapy for hemophilia B due to its superior transduction properties; however, leaky expression of Ad genes often reduces the transduction efficiencies by Ad protein-mediated tissue damage. Here, we used a novel Ad vector, Ad-E4-122aT, which exhibits a reduction in the leaky expression of Ad genes in liver, in gene therapy studies for neonatal hemophilia B mice. Ad-E4-122aT exhibited significantly higher transduction efficiencies than a conventional Ad vector in neonatal mice. In neonatal hemophilia B mice, a single neonatal injection of Ad-E4-122aT expressing human FIX (hFIX) (Ad-E4-122aT-AHAFIX) maintained more than 6% of the normal plasma hFIX activity levels for approximately 100 days. Sequential administration of Ad-E4-122aT-AHAFIX resulted in more than 100% of the plasma hFIX activity levels for more than 100 days and rescued the bleeding phenotypes of hemophilia B mice. In addition, immunotolerance to hFIX was induced by Ad-E4-122aT-AHAFIX administration in neonatal hemophilia B mice. These results indicated that Ad-E4-122aT is a promising gene delivery vector for neonatal or infant gene therapy for hemophilia B.

  20. Enhanced immunogenicity, mortality protection, and reduced viral brain invasion by alum adjuvant with an H5N1 split-virion vaccine in the ferret.

    Directory of Open Access Journals (Sweden)

    Robert Colby Layton

    Full Text Available Pre-pandemic development of an inactivated, split-virion avian influenza vaccine is challenged by the lack of pre-existing immunity and the reduced immunogenicity of some H5 hemagglutinins compared to that of seasonal influenza vaccines. Identification of an acceptable effective adjuvant is needed to improve immunogenicity of a split-virion avian influenza vaccine.Ferrets (N = 118 were vaccinated twice with a split-virion vaccine preparation of A/Vietnam/1203/2004 or saline either 21 days apart (unadjuvanted: 1.9 µg, 7.5 µg, 30 µg, or saline, or 28 days apart (unadjuvanted: 22.5 µg, or alum-adjuvanted: 22.5 or 7.5 µg. Vaccinated animals were challenged intranasally 21 or 28 days later with 10(6 EID(50 of the homologous strain. Immunogenicity was measured by hemagglutination inhibition and neutralization assays. Morbidity was assessed by observed behavior, weight loss, temperature, cytopenias, histopathology, and viral load. No serum antibodies were detected after vaccination with unadjuvanted vaccine, whereas alum-adjuvanted vaccination induced a robust antibody response. Survival after unadjuvanted dose regimens of 30 µg, 7.5 µg and 1.9 µg (21-day intervals was 64%, 43%, and 43%, respectively, yet survivors experienced weight loss, fever and thrombocytopenia. Survival after unadjuvanted dose regimen of 22.5 µg (28-day intervals was 0%, suggesting important differences in intervals in this model. In contrast to unadjuvanted survivors, either dose of alum-adjuvanted vaccine resulted in 93% survival with minimal morbidity and without fever or weight loss. The rarity of brain inflammation in alum-adjuvanted survivors, compared to high levels in unadjuvanted vaccine survivors, suggested that improved protection associated with the alum adjuvant was due to markedly reduced early viral invasion of the ferret brain.Alum adjuvant significantly improves efficacy of an H5N1 split-virion vaccine in the ferret model as measured by

  1. Triple Point Topological Metals

    Directory of Open Access Journals (Sweden)

    Ziming Zhu

    2016-07-01

    Full Text Available Topologically protected fermionic quasiparticles appear in metals, where band degeneracies occur at the Fermi level, dictated by the band structure topology. While in some metals these quasiparticles are direct analogues of elementary fermionic particles of the relativistic quantum field theory, other metals can have symmetries that give rise to quasiparticles, fundamentally different from those known in high-energy physics. Here, we report on a new type of topological quasiparticles—triple point fermions—realized in metals with symmorphic crystal structure, which host crossings of three bands in the vicinity of the Fermi level protected by point group symmetries. We find two topologically different types of triple point fermions, both distinct from any other topological quasiparticles reported to date. We provide examples of existing materials that host triple point fermions of both types and discuss a variety of physical phenomena associated with these quasiparticles, such as the occurrence of topological surface Fermi arcs, transport anomalies, and topological Lifshitz transitions.

  2. Construction and evaluation of a novel triple cell epitopebased ...

    African Journals Online (AJOL)

    Purpose: To construct a novel triple cell epitope-based polypeptide vaccine against cow mastitis induced by Staphylococcus aureus, Escherichia coli and Streptococcus and to reduce the use of antibiotics. Methods: Based on bioinformatics approach, a novel triple epitope-based polypeptide (CM-TEP) was designed and ...

  3. Preemptive CD8 T-Cell Immunotherapy of Acute Cytomegalovirus Infection Prevents Lethal Disease, Limits the Burden of Latent Viral Genomes, and Reduces the Risk of Virus Recurrence

    OpenAIRE

    Steffens, Hans-Peter; Kurz, Sabine; Holtappels, Rafaela; Reddehase, Matthias J.

    1998-01-01

    In the immunocompetent host, primary cytomegalovirus (CMV) infection is resolved by the immune response without causing overt disease. The viral genome, however, is not cleared but is maintained in a latent state that entails a risk of virus recurrence and consequent organ disease. By using murine CMV as a model, we have shown previously that multiple organs harbor latent CMV and that reactivation occurs with an incidence that is determined by the viral DNA load in the respective organ (M. J....

  4. Prevalence of antibodies against measles, mumps, and rubella before and after vaccination of school-age children with three different triple combined viral vaccines, Rio Grande do Sul, Brazil, 1996 Prevalencia de anticuerpos contra sarampión, paperas y rubéola en niños en edad escolar antes y después de la vacunación con tres vacunas triples antivirales combinadas diferentes, Rio Grande do Sul, Brasil, 1996

    Directory of Open Access Journals (Sweden)

    Boaventura Antônio dos Santos

    2006-11-01

    Full Text Available OBJECTIVE: We evaluated the seroprevalence for measles, mumps, and rubella in school-age children (6-12 years old before and after the administration of three triple combined viral vaccines. METHODS: In two municipal schools of Rio Grande do Sul, Brazil, 692 blood samples were collected before vaccination and 636 samples 21 to 30 days after vaccination during 1996. IgG antibody seropositivity was investigated by enzyme-linked immunosorbent assay (measles and mumps with Enzygnost [Behring, Marburg, Germany]; rubella with Rubenostika [Organon Teknica, Boxtel, the Netherlands]. The vaccines compared were: A: E-Zagreb, L-Zagreb, and Wistar RA 27/3 (Tresivac; B: Moraten, J-Lynn, and Wistar RA 27/3 (M-M-R II; and C: Schwarz, Urabe AM-9, and Wistar RA 27/3 (Trimovax. RESULTS: Before vaccination, 79.2% [95% confidence interval (CI = 76.0%-82.2%] of the samples were positive for measles, 69.4% (95% CI = 65.8%-72.8% for mumps, and 55.4% (95% CI = 51.6%-59.2% for rubella. After vaccination with the A, B, and C vaccines, seropositivity was 100.0%, 99.5%, and 100.0%, respectively for measles; 99.5%, 94.5%, and 92.0% for mumps; and 92.6%, 91.3%, and 88.6% for rubella. CONCLUSIONS: About one-fifth (20.8% of the schoolchildren who could have been vaccinated against measles at age 9 months had levels of antibodies insufficient for protection. In the sample of schoolchildren without previous vaccination against mumps and rubella, high proportions of susceptible levels were found. All vaccines were immunogenic, but vaccine A yielded a seroconversion rate of 99.5% for the mumps component, which was significantly higher than the other two vaccines (P OBJETIVO: Se evaluó la seroprevalencia para sarampión, paperas y rubéola en niños en edad escolar (6-12 años antes y después de la administración de tres vacunas triples antivirales combinadas. MÉTODOS: Se colectaron 692 muestras de sangre antes de la vacunación y 636 muestras entre 21 y 30 días después de la

  5. CCR5 Expression Is Reduced in Lymph Nodes of HIV Type 1–Infected Women, Compared With Men, But Does Not Mediate Sex-Based Differences in Viral Loads

    Science.gov (United States)

    Meditz, Amie L.; Folkvord, Joy M.; Lyle, Ngan H.; Searls, Kristina; Lie, Yolanda S.; Coakley, Eoin P.; McCarter, Martin; MaWhinney, Samantha; Connick, Elizabeth

    2014-01-01

    Background. Human immunodeficiency virus type 1 (HIV-1)–infected women have lower viral loads than men but similar rates of disease progression. We hypothesized that sex-based differences in CCR5 expression mediate viral load differences. Methods. CCR5 was analyzed by flow cytometry in disaggregated lymph node cells from untreated HIV-1–infected women (n = 28) and men (n = 27). The frequencies of HIV-1 RNA–producing cells in the lymph node were determined by in situ hybridization. Linear and generalized linear regression models were used. Results. The percentage of CCR5+CD3+CD4+ cells was lower in women (mean, 12%) than men (mean, 16%; P = .034). Neither the percentage of CCR5+CD3+CD4+ cells nor the CCR5 density predicted viral load or HIV-1 RNA–producing lymph node cells (P ≥ .24), after adjusting for CD4+ T-cell count, race, and age. Women had marginally fewer HIV-1 RNA–producing cells (mean, 0.21 cells/mm2) than men (mean, 0.44 cells/mm2; P = .046). After adjusting for the frequency of HIV-1 RNA–producing cells and potential confounders, the viral load in women were 0.46 log10 copies/mL lower than that in men (P = .018). Conclusions. Reduced lymph node CCR5 expression in women did not account for the viral load difference between sexes. CCR5 expression did not predict viral load or frequencies of HIV-1 RNA–producing cells, indicating that physiologic levels of CCR5 do not limit HIV-1 replication in lymph node. Less plasma virus was associated with each HIV-1 RNA–producing cell in women as compared to men, suggesting that women may either produce fewer virions per productively infected cell or more effectively clear extracellular virus. PMID:24179109

  6. Triple gauge boson couplings

    CERN Document Server

    Gounaris, George J; Zeppenfeld, Dieter; Ajaltouni, Ziad J; Arhrib, A; Bella, G; Berends, F A; Bilenky, S M; Blondel, A; Busenitz, J K; Choudhury, D; Clarke, P; Conboy, J E; Diehl, M; Fassouliotis, D; Frère, J M; Georgiopoulos, C H; Gibbs, M; Grünewald, M W; Hansen, J B; Hartmann, C; Jin, B N; Jousset, J; Kalinowski, Jan; Kocian, M L; Lahanas, Athanasios B; Layssac, J; Lieb, E H; Markou, C; Matteuzzi, C; Mättig, P; Moreno, J M; Moultaka, G; Nippe, A; Orloff, J; Papadopoulos, C G; Paschalis, J; Petridou, C; Phillips, H; Podlyski, F; Pohl, M; Renard, F M; Rossignol, J M; Rylko, R; Sekulin, R L; Van Sighem, A; Simopoulou, Errietta; Skillman, A; Spanos, V C; Tonazzo, A; Tytgat, M H G; Tzamarias, S; Verzegnassi, Claudio; Vlachos, N D; Zevgolatakos, E

    1996-01-01

    We present the results obtained by the "Triple Gauge Couplings" working group during the LEP2 Workshop (1994-1995). The report concentrates on the measurement of WW\\gamma and WWZ couplings in e^-e^+\\to W^-W^+ or, more generally, four-fermion production at LEP2. In addition the detection of new interactions in the bosonic sector via other production channels is discussed.

  7. Normalization for triple-target microarray experiments

    Directory of Open Access Journals (Sweden)

    Magniette Frederic

    2008-04-01

    Full Text Available Abstract Background Most microarray studies are made using labelling with one or two dyes which allows the hybridization of one or two samples on the same slide. In such experiments, the most frequently used dyes are Cy3 and Cy5. Recent improvements in the technology (dye-labelling, scanner and, image analysis allow hybridization up to four samples simultaneously. The two additional dyes are Alexa488 and Alexa494. The triple-target or four-target technology is very promising, since it allows more flexibility in the design of experiments, an increase in the statistical power when comparing gene expressions induced by different conditions and a scaled down number of slides. However, there have been few methods proposed for statistical analysis of such data. Moreover the lowess correction of the global dye effect is available for only two-color experiments, and even if its application can be derived, it does not allow simultaneous correction of the raw data. Results We propose a two-step normalization procedure for triple-target experiments. First the dye bleeding is evaluated and corrected if necessary. Then the signal in each channel is normalized using a generalized lowess procedure to correct a global dye bias. The normalization procedure is validated using triple-self experiments and by comparing the results of triple-target and two-color experiments. Although the focus is on triple-target microarrays, the proposed method can be used to normalize p differently labelled targets co-hybridized on a same array, for any value of p greater than 2. Conclusion The proposed normalization procedure is effective: the technical biases are reduced, the number of false positives is under control in the analysis of differentially expressed genes, and the triple-target experiments are more powerful than the corresponding two-color experiments. There is room for improving the microarray experiments by simultaneously hybridizing more than two samples.

  8. Recovery and normalization of triple coincidences in PET

    Energy Technology Data Exchange (ETDEWEB)

    Lage, Eduardo, E-mail: elage@mit.edu; Parot, Vicente; Dave, Shivang R.; Herraiz, Joaquin L. [Madrid-MIT M+Visión Consortium, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Moore, Stephen C.; Sitek, Arkadiusz; Park, Mi-Ae [Division of Nuclear Medicine, Department of Radiology, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts 02115 (United States); Udías, Jose M. [Grupo de Física Nuclear, Departamento de Física Atómica Molecular y Nuclear, Universidad Complutense de Madrid, CEI Moncloa, Madrid 28040 (Spain); Vaquero, Juan J. [Departamento de Ingeniería Biomédica e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Leganés 28911 (Spain)

    2015-03-15

    authors’ method increased peak NEC rates of the scanner by 26.6% and 32% for mouse- and rat-sized objects, respectively. This increase in NEC-rate performance was also reflected in the image-quality metrics. Images reconstructed using double and triple coincidences recovered using their method had better signal-to-noise ratio than those obtained using only double coincidences, while preserving spatial resolution and contrast. Distribution of triple coincidences using an equal-weighting scheme increased apparent system sensitivity but degraded image quality. The performance boost provided by the inclusion of triple coincidences using their method allowed to reduce the acquisition time of standard imaging procedures by up to ∼25%. Conclusions: Recovering triple coincidences with the proposed method can effectively increase the sensitivity of current clinical and preclinical PET systems without compromising other parameters like spatial resolution or contrast.

  9. Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis

    NARCIS (Netherlands)

    Boulle, Andrew; Stephan, Christoph; Miro, Jose M.; Cavassini, Matthias; Chêne, Geneviève; Costagliola, Dominique; Dabis, François; D'Arminio Monforte, Antonella; del Amo, Julia; van Sighem, Ard; Vehreschild, Jörg; Gill, John; Guest, Jodie; Haerry, David Hans-Ulrich; Hogg, Robert; Justice, Amy; Mocroft, Amanda; Obel, Niels; Crane, Heidi; Smith, Colette; Reiss, Peter; Saag, Michael; Sterling, Tim; Teira, Ramon; Williams, Matthew; Zangerle, Robert; Sterne, Jonathan; May, Margaret; Ingle, Suzanne; Trickey, Adam; Ainsworth, Jonathan; Anderson, Jane; Babiker, Abdel; Chadwick, David; Delpech, Valerie; Dunn, David; Fisher, Martin; Gazzard, Brian; Gilson, Richard; Hay, Phillip; Gompels, Mark; Hill, Teresa; Johnson, Margaret; Jose, Sophie; Kegg, Stephen; Leen, Clifford; Mackie, Nicky; Nelson, Mark; Orkin, Chloe; Palfreeman, Adrian; Phillips, Andrew; Pillay, Deenan; Post, Frank; Sabin, Caroline; Sachikonye, Memory; Schwenk, Achim; Walsh, John; Thornton, Alicia; Huntington, Susie; Glabay, Adam; Garrett, Nigel; Lynch, Janet; Hand, James; de Souza, Carl; Perry, Nicky; Tilbury, Stuart; Youssef, Elaney; Churchill, Duncan; Waxman, Matthew; Asboe, David; Mandalia, Sundhiya; Munshi, Sajid; Awosika, Damilola; Korat, Hardik; Taylor, Chris; Gleisner, Zachary; Ibrahim, Fowzia; Campbell, Lucy; Baillie, Kirsty; Cope, Emma; Gibney, Marie; Gibson, Jane; Brima, Nataliya; Williams, Ian; Miller, Sheila; Wood, Chris; Youle, Mike; Lampe, Fiona; Chaloner, Clinton; Winston, Alan; Weber, Jonathan; Ramzan, Farhan; Carder, Mark; Wilson, Alan; Morris, Sheila; Allan, Sue; Moore, Anne; Fox, Lynn; Bojanowski, Josef; Lewszuk, Adam; Main, Paul; Mitchell, N. N.; Hunter, N. N.; Dhillon, Mandip; Martin, Fabiola; Douglas, Sarah; Russell-Sharp, Sarah

    2016-01-01

    To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure. Collaborative analysis of data from eight European and three Canadian cohorts. Adults (N>20 000) who started triple ART between 1996 and 2012 and had data on viral

  10. Up-modulation of PLC-β2 reduces the number and malignancy of triple-negative breast tumor cells with a CD133+/EpCAM+phenotype: a promising target for preventing progression of TNBC.

    Science.gov (United States)

    Brugnoli, Federica; Grassilli, Silvia; Lanuti, Paola; Marchisio, Marco; Al-Qassab, Yasamin; Vezzali, Federica; Capitani, Silvano; Bertagnolo, Valeria

    2017-09-04

    The malignant potential of triple negative breast cancer (TNBC) is also dependent on a sub-population of cells with a stem-like phenotype. Among the cancer stem cell markers, CD133 and EpCAM strongly correlate with breast tumor aggressiveness, suggesting that simultaneous targeting of the two surface antigens may be beneficial in treatment of TNBC. Since in TNBC-derived cells we demonstrated that PLC-β2 induces the conversion of CD133 high to CD133 low cells, here we explored its possible role in down-modulating the expression of both CD133 and EpCAM and, ultimately, in reducing the number of TNBC cells with a stem-like phenotype. A magnetic step-by-step cell isolation with antibodies directed against CD133 and/or EpCAM was performed on the TNBC-derived MDA-MB-231 cell line. In the same cell model, PLC-β2 was over-expressed or down-modulated and cell proliferation and invasion capability were evaluated by Real-time cell assays. The surface expression of CD133, EpCAM and CD44 in the different experimental conditions were measured by multi-color flow cytometry immunophenotyping. A CD133 + /EpCAM + sub-population with high proliferation rate and invasion capability is present in the MDA-MB-231 cell line. Over-expression of PLC-β2 in CD133 + /EpCAM + cells reduced the surface expression of both CD133 and EpCAM, as well as proliferation and invasion capability of this cellular subset. On the other hand, the up-modulation of PLC-β2 in the whole MDA-MB-231 cell population reduced the number of cells with a CD44 + /CD133 + /EpCAM + stem-like phenotype. Since selective targeting of the cells with the highest aggressive potential may have a great clinical importance for TNBC, the up-modulation of PLC-β2, reducing the number of cells with a stem-like phenotype, may be a promising goal for novel therapies aimed to prevent the progression of aggressive breast tumors.

  11. Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388).

    Science.gov (United States)

    Krishnan, Kailash; Beridze, Maia; Christensen, Hanne; Dineen, Rob; Duley, Lelia; Heptinstall, Stan; James, Marilyn; Markus, Hugh S; Pocock, Stuart; Ranta, Annemarei; Robinson, Thompson; Nikola, Nikola; Venables, Graham; Bath, Philip

    2015-10-01

    The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event. Because two antiplatelet agents are superior to one in patients with non-cardioembolic events, more intensive treatment might be even more effective. The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance. Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (ISRCTN47823388) is comparing the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one-month. This international collaborative parallel-group prospective randomized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack. Randomization and data collection are performed over a secure Internet site with real-time data validation and concealment of allocation. Outcomes, serious adverse events, and neuroimaging are adjudicated centrally with blinding to treatment allocation. The primary outcome is stroke recurrence and its severity ('ordinal recurrence' based on modified Rankin Scale) at 90 days, with masked assessment centrally by telephone. Secondary outcomes include vascular events, functional measures (disability, mood, cognition, quality of life), and safety (bleeding, death, serious adverse events). The trial has recruited more than 50% of its target sample size (latest number: 2399) and is running in 104 sites in 4 countries. One-third of patients presented with a transient ischemic attack. © 2015 The Author. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

  12. Abacavir-based triple nucleoside regimens for maintenance therapy in patients with HIV.

    Science.gov (United States)

    Cruciani, Mario; Mengoli, Carlo; Serpelloni, Giovanni; Parisi, Saverio G; Malena, Marina; Bosco, Oliviero

    2013-06-05

    Regimen simplification can be defined as a change in established effective therapy to reduce pill burden and dosing frequency, to enhance tolerability, or to decrease specific food and fluid requirements. Many patients on suppressive antiretroviral therapy may be considered candidates for a simplification strategy and, among them, those who have achieved virologic suppression. Several clinical trials have evaluated the efficacy of triple nucleoside combination as a simplification therapy in patients who achieved virologic suppression The aim of this review is to combine randomised, controlled trials to examine whether in patients with undetectable viraemia on a Protease inhibitor (PI) based regimen simplification treatment with abacavir (ABC)-based triple-nucleoside combinations has similar rates of efficacy and tolerability compared with a PI regimen or simplification with a NNRTIs (efavirenz-EFV- or nevirapine-NVP) containing regimen. Studies were included if they had at least two of the three interventions, including one 3NRTI arm. Electronic databases and conference proceedings were searched (1996-2012) with relevant search terms without limits to language. Randomised controlled trials (RCTs) only are included in this review. Patients population is represented by HIV-infected adult patients treated with a PI-containing regimen (PI or boosted PI),  with undetectable viral load. Patients on a PI-containing regimen had three possibilities: continue the PI regimen or switch to a simplification maintenance regimen, including switch to a NNRTI (EFV or NVP) containing regimen, or switch to a triple-NRTI regimen (ABC-zidovudine-lamivudine) The primary outcomes were: proportion of patients discontinuing or switching antiretroviral therapy due to virologic failure or to adverse events; death (all cause) and AIDS defining illness; occurrence of myocardial infarction and cardiovascular disease. Secondary outcomes  were: proportion of patients maintaining an undetectable

  13. On split Lie triple systems

    Indian Academy of Sciences (India)

    We also introduced in [1] techniques of connection of roots in the framework of split Lie algebras. In the present paper we extend these techniques to the framework of split Lie triple systems so as to obtain a generalization of the results in [1]. We consider the wide class of split Lie triple systems (which contains the class of.

  14. Harmonic analysis on triple spaces

    DEFF Research Database (Denmark)

    Danielsen, Thomas Hjortgaard

    In this thesis we study examples of triple spaces, both their structure theory, their invariant differential operators as well as analysis on them. The first major results provide us with some examples of triple spaces which are strongly spherical, i.e. satisfy some conditions reminiscent...

  15. On split Lie triple systems

    Indian Academy of Sciences (India)

    Lie triple system; system of roots; root space; split Lie algebra; structure theory. 1. Introduction and previous definitions. Throughout this paper, Lie triple systems T are considered of arbitrary dimension and over an arbitrary field K. It is worth to mention that, unless otherwise stated, there is not any restriction on dim Tα or {k ...

  16. Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada

    DEFF Research Database (Denmark)

    Obel, Niels

    2016-01-01

    OBJECTIVES: To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure. DESIGN: Collaborative analysis of data from eight European and three Canadian cohorts. METHODS: Adults (N>20 000) who started triple ART between 199...

  17. Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus.

    Science.gov (United States)

    Morgan, Sophie B; Hemmink, Johanneke D; Porter, Emily; Harley, Ross; Shelton, Holly; Aramouni, Mario; Everett, Helen E; Brookes, Sharon M; Bailey, Michael; Townsend, Alain M; Charleston, Bryan; Tchilian, Elma

    2016-06-15

    Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate. Copyright © 2016 The Authors.

  18. Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

    Directory of Open Access Journals (Sweden)

    Pahar Bapi

    2012-08-01

    Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

  19. Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial.

    Science.gov (United States)

    Pulido, Federico; Ribera, Esteban; Lagarde, María; Pérez-Valero, Ignacio; Palacios, Rosario; Iribarren, José A; Payeras, Antoni; Domingo, Pere; Sanz, José; Cervero, Miguel; Curran, Adrián; Rodríguez-Gómez, Francisco J; Téllez, María J; Ryan, Pablo; Barrufet, Pilar; Knobel, Hernando; Rivero, Antonio; Alejos, Belén; Yllescas, María; Arribas, José R

    2017-11-29

    Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for maintenance of human immunodeficiency virus type 1 (HIV-1) suppression. This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA dual- and triple-therapy arms was 88.9% (112/126) and 92.7% (114/123; difference, -3.8%; 95% confidence interval, -11.0 to 3.4), respectively. Four participants in the dual-therapy arm and 2 in the triple-therapy arm developed protocol-defined virological failure. Switching to dual therapy was associated with a significant increase in total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, but not in the total-to-HDL cholesterol ratio. Serious adverse events and study drug discontinuations due to adverse events occurred in 4.8% vs 4.9%P = .97) and in 0.8% (1/126) vs 1.6% P = .55) in dual therapy vs triple therapy, respectively. Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability compared to triple therapy. NCT02159599. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  20. Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses.

    Science.gov (United States)

    Pham, Hanh T; Mesplède, Thibault; Wainberg, Mark A

    2016-04-30

    Recommended regimens for HIV-positive individuals include the co-administration of dolutegravir (DTG) with two reverse transcriptase inhibitors (RTIs). Although rare, emerging resistance against DTG is often associated with the R263K substitution in integrase. In-vitro-selected R263K was associated with impaired viral replication capacity, DNA integration, and integrase strand-transfer activity, especially when accompanied by the secondary mutation H51Y. Given the reduced fitness of RTI-resistant viruses, we investigated potential impacts on viral replication of combining R263K and H51Y/R263K with major RTI-resistance substitutions including K65R, L74V, K103N, E138K, and M184I/V. We combined the R263K or H51Y/R263K with RTI-resistance mutations into the proviral plasmid pNL4.3 and measured the resulting viral infectiousness, replication capacity, and ability to integrate viral DNA into host cells. Infectiousness was determined by luciferase assay in TZM-bl cells. Replicative capacity was monitored over 7 days and viral DNA integration was studied by real-time Alu-qPCR in PM1 cells. We found that viral infectiousness, replication capacities and integration levels were greatly reduced in triple mutants, i.e. H51Y/R263K plus a RT mutation, and moderately reduced in double mutants, i.e. R263K plus a RT mutation, compared to wild-type and single RT-mutant viruses. Our findings help to explain the absence of RTI mutations in individuals who experienced DTG-treatment failure.

  1. Viral Advertising: Branding Effects from Consumers’ Perspectives

    OpenAIRE

    Jiang, Yueqing

    2012-01-01

    Viral advertising is popular for its high viral transmission results online. Its increased impacts on the social media users have been noticed by the author. At the same time, viewers’ negative attitudes toward traditional advertisements become obvious which can be regarded as the phenomenon of advertisement avoidance. It arouses author’s interests to know how the viral advertising reduces the viewers’ negative emotions and its performances in branding online. This paper is going to look into...

  2. Beyond viral suppression of HIV

    DEFF Research Database (Denmark)

    Lazarus, Jeffrey V.; Safreed-Harmon, Kelly; Barton, Simon E

    2016-01-01

    BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed......, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target...... for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV...

  3. Topical herpes simplex virus 2 (HSV-2) vaccination with human papillomavirus vectors expressing gB/gD ectodomains induces genital-tissue-resident memory CD8+ T cells and reduces genital disease and viral shedding after HSV-2 challenge.

    Science.gov (United States)

    Çuburu, Nicolas; Wang, Kening; Goodman, Kyle N; Pang, Yuk Ying; Thompson, Cynthia D; Lowy, Douglas R; Cohen, Jeffrey I; Schiller, John T

    2015-01-01

    No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8(+) T cells that were able to secrete gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8(+) T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection. Genital herpes is a highly prevalent chronic disease caused by

  4. Twin and triple peaks papilledema.

    Science.gov (United States)

    Mehta, Jodhbir S; Plant, Gordon T; Acheson, James F

    2005-07-01

    To describe 2 adult patients who presented with papilledema after band atrophy (i.e., twin and triple peaks papilledema). Retrospective small case series. Two outpatients. Observations made on 2 patients whose cases were reviewed in the neuro-ophthalmology clinic. The first patient had a pituitary tumor presenting with papilledema, causing a triple peaks clinical sign. Color photographs, optical coherence tomograms, and magnetic resonance images are shown. The second patient developed twin peaks papilledema due to a chiasmal glioma causing secondary raised intracranial pressure. Twin peaks papilledema is a rare clinical sign that may develop in adults as well as in children. The first report and optical coherence tomography features of triple peaks papilledema illustrate a new clinical sign.

  5. Viral eradication reduces all-cause mortality, including non-liver-related disease, in patients with progressive hepatitis C virus-related fibrosis.

    Science.gov (United States)

    Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Kiriyama, Seiki; Tanikawa, Makoto; Hisanaga, Yasuhiro; Kanamori, Akira; Kitabatake, Shusuke; Yama, Tsuyoki; Tanaka, Junko

    2017-03-01

    Eradication of hepatitis C virus (HCV) with interferon (IFN)-based therapy has been reported to reduce all-cause mortality in patients with chronic HCV infection. However, the impact of HCV eradication on non-liver-related mortality and causes of death has not been sufficiently investigated in patients with progressive HCV-related fibrosis. We enrolled 784 chronic HCV patients with progressive liver fibrosis (aspartate aminotransferase to platelet ratio index >1). Cause of death, incidence of hepatocellular carcinoma, and all-cause mortality including non-liver-related mortality were analyzed. Of these 784 patients, 170 achieved sustained virological response (SVR) (eradication of HCV) with IFN-based therapy (IFN-SVR), and 614 did not receive IFN-based therapy (non-IFN patients, chronic HCV infection). The median follow-up duration was 10.3 years. Two hundred seventy-three patients died during follow-up (liver-related death, n = 171; non-liver-related death, n = 102). The mortality rate from non-liver-related disease was 63.6% (7/11) in IFN-SVR patients and 36.3% (95/262) in non-IFN patients, respectively. In multivariate analysis, the eradication of HCV associated with not only hepatocellular carcinoma incidence (hazard ratio (HR), 0.162; 95% confidence interval (CI), 0.092-0.284), and all-cause mortality (HR, 0.094; 95% CI, 0.047-0.187), but non-liver-related mortality (HR, 0.286; 95% CI, 0.127-0.644) as well. Eradication of HCV reduced both liver-related and non-liver-related mortality in patients with progressive HCV-related fibrosis. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  6. Solution Patterns Predicting Pythagorean Triples

    Science.gov (United States)

    Ezenweani, Ugwunna Louis

    2013-01-01

    Pythagoras Theorem is an old mathematical treatise that has traversed the school curricula from secondary to tertiary levels. The patterns it produced are quite interesting that many researchers have tried to generate a kind of predictive approach to identifying triples. Two attempts, namely Diophantine equation and Brahmagupta trapezium presented…

  7. Harmonic analysis on triple spaces

    DEFF Research Database (Denmark)

    Danielsen, Thomas Hjortgaard

    of properties of symmetric spaces. The algebras of invariant differential operators for these spaces are studied and the conclusion is that most of them are non-commutative. Finally, we restrict our attention to a single triple space, giving a specific polar decomposition and corresponding integration formula......, and studying the relations between open orbits of parabolic subgroups, multiplicities and distribution vectors....

  8. On split Lie triple systems

    Indian Academy of Sciences (India)

    The key tool in this job is the notion of connection of roots in the framework of split Lie triple systems. Author Affiliations. Antonio J Calderón Martín1. Departamento de Matemáticas, Universidad de Cádiz, 11510 Puerto Real, Cádiz, Spain. Dates. Manuscript received: 25 January 2008. Proceedings – Mathematical Sciences.

  9. Triple antiviral therapy in hepatitis C virus infection with or without mixed cryoglobulinaemia: a prospective, controlled pilot study.

    Science.gov (United States)

    Gragnani, Laura; Fabbrizzi, Alessio; Triboli, Elisa; Urraro, Teresa; Boldrini, Barbara; Fognani, Elisa; Piluso, Alessia; Caini, Patrizio; Ranieri, Jessica; Monti, Monica; Laffi, Giacomo; Zignego, Anna Linda

    2014-09-01

    Mixed cryoglobulinaemia is strongly related to hepatitis C virus infection. Treatment with peg-interferon and ribavirin has been indicated as first-line therapy for mild/moderate hepatitis C virus-related mixed cryoglobulinaemia. To evaluate the safety and efficacy of triple boceprevir-based antiviral therapy in patients with or without mixed cryoglobulinaemia previously treated with peg-interferon and ribavirin, and with advanced liver disease. Thirty-five hepatitis C virus-positive patients (17 with asymptomatic mixed cryoglobulinaemia, 5 with symptomatic mixed cryoglobulinaemia, and 11 without mixed cryoglobulinaemia) were treated with triple boceprevir-based antiviral therapy. In 19/22 cryoglobulinaemic subjects (86%), the addition of boceprevir induced cryocrit disappearance. Cryocrit behaviour was related to virological response, with improvement of symptoms upon undetectable viraemia and reappearance after virological breakthrough. The rate of sustained virological response was lower in cryoglobulinaemic patients than in patients without mixed cryoglobulinaemia (23.8% vs 70% respectively, p=0.01). Boceprevir-based therapy was safe and effective in cryoglobulinaemic patients. The correlation between direct inhibition of hepatitis C virus replication and clinical improvement in mixed cryoglobulinaemic patients is definitive proof of the key pathogenetic role played by viral replication. Further studies are needed to confirm and clarify the reduced virological response in patients with mixed cryoglobulinaemia. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  10. On split Lie triple systems II

    Indian Academy of Sciences (India)

    Lie triple system with a coherent 0-root space is the direct sum of the family of its minimal ideals, each one being a simple split Lie triple system, and the simplicity of T is characterized. In the present paper we extend these results to arbitrary split Lie triple systems with no restrictions on their 0-root spaces. Keywords.

  11. Bovine leukemia virus reduces anti-viral cytokine activities and NK cytotoxicity by inducing TGF-β secretion from regulatory T cells.

    Science.gov (United States)

    Ohira, Kosuke; Nakahara, Ayako; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Maekawa, Naoya; Ikebuchi, Ryoyo; Kohara, Junko; Murata, Shiro; Ohashi, Kazuhiko

    2016-03-01

    CD4(+)CD25(high)Foxp3(+) T cells suppress excess immune responses that lead to autoimmune and/or inflammatory diseases, and maintain host immune homeostasis. However, CD4(+)CD25(high)Foxp3(+) T cells reportedly contribute to disease progression by over suppressing immune responses in some chronic infections. In this study, kinetic and functional analyses of CD4(+)CD25(high)Foxp3(+) T cells were performed in cattle with bovine leukemia virus (BLV) infections, which have reported immunosuppressive characteristics. In initial experiments, production of the Th1 cytokines IFN-γ and TNF-α was reduced in BLV-infected cattle compared with uninfected cattle, and numbers of IFN-γ or TNF-α producing CD4(+) T cells decreased with disease progression. In contrast, IFN-γ production by NK cells was inversely correlated with BLV proviral loads in infected cattle. Additionally, during persistent lymphocytosis disease stages, NK cytotoxicity was depressed as indicated by low expression of the cytolytic protein perforin. Concomitantly, total CD4(+)CD25(high)Foxp3(+) T cell numbers and percentages of TGF-β(+) cells were increased, suggesting that TGF-β plays a role in the functional declines of CD4(+) T cells and NK cells. In further experiments, recombinant bovine TGF-β suppressed IFN-γ and TNF-α production by CD4(+) T cells and NK cytotoxicity in cultured cells. These data suggest that TGF-β from CD4(+)CD25(high)Foxp3(+) T cells is immunosuppressive and contributes to disease progression and the development of opportunistic infections during BLV infection.

  12. Reduced Maximal Inhibition in Phenotypic Susceptibility Assays Indicates that Viral Strains Resistant to the CCR5 Antagonist Maraviroc Utilize Inhibitor-Bound Receptor for Entry▿

    Science.gov (United States)

    Westby, Mike; Smith-Burchnell, Caroline; Mori, Julie; Lewis, Marilyn; Mosley, Michael; Stockdale, Mark; Dorr, Patrick; Ciaramella, Giuseppe; Perros, Manos

    2007-01-01

    Maraviroc is a CCR5 antagonist in clinical development as one of a new class of antiretrovirals targeting human immunodeficiency virus type 1 (HIV-1) coreceptor binding. We investigated the mechanism of HIV resistance to maraviroc by using in vitro sequential passage and site-directed mutagenesis. Serial passage through increasing maraviroc concentrations failed to select maraviroc-resistant variants from some laboratory-adapted and clinical isolates of HIV-1. However, high-level resistance to maraviroc was selected from three of six primary isolates passaged in peripheral blood lymphocytes (PBL). The SF162 strain acquired resistance to maraviroc in both treated and control cultures; all resistant variants were able to use CXCR4 as a coreceptor. In contrast, maraviroc-resistant virus derived from isolates CC1/85 and RU570 remained CCR5 tropic, as evidenced by susceptibility to the CCR5 antagonist SCH-C, resistance to the CXCR4 antagonist AMD3100, and an inability to replicate in CCR5 Δ32/Δ32 PBL. Strain-specific mutations were identified in the V3 loop of maraviroc-resistant CC1/85 and RU570. The envelope-encoding region of maraviroc-resistant CC1/85 was inserted into an NL4-3 background. This recombinant virus was completely resistant to maraviroc but retained susceptibility to aplaviroc. Reverse mutation of gp120 residues 316 and 323 in the V3 loop (numbering from HXB2) to their original sequence restored wild-type susceptibility to maraviroc, while reversion of either mutation resulted in a partially sensitive virus with reduced maximal inhibition (plateau). The plateaus are consistent with the virus having acquired the ability to utilize maraviroc-bound receptor for entry. This hypothesis was further corroborated by the observation that a high concentration of maraviroc blocks the activity of aplaviroc against maraviroc-resistant virus. PMID:17182681

  13. Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry.

    Science.gov (United States)

    Westby, Mike; Smith-Burchnell, Caroline; Mori, Julie; Lewis, Marilyn; Mosley, Michael; Stockdale, Mark; Dorr, Patrick; Ciaramella, Giuseppe; Perros, Manos

    2007-03-01

    Maraviroc is a CCR5 antagonist in clinical development as one of a new class of antiretrovirals targeting human immunodeficiency virus type 1 (HIV-1) coreceptor binding. We investigated the mechanism of HIV resistance to maraviroc by using in vitro sequential passage and site-directed mutagenesis. Serial passage through increasing maraviroc concentrations failed to select maraviroc-resistant variants from some laboratory-adapted and clinical isolates of HIV-1. However, high-level resistance to maraviroc was selected from three of six primary isolates passaged in peripheral blood lymphocytes (PBL). The SF162 strain acquired resistance to maraviroc in both treated and control cultures; all resistant variants were able to use CXCR4 as a coreceptor. In contrast, maraviroc-resistant virus derived from isolates CC1/85 and RU570 remained CCR5 tropic, as evidenced by susceptibility to the CCR5 antagonist SCH-C, resistance to the CXCR4 antagonist AMD3100, and an inability to replicate in CCR5 Delta32/Delta32 PBL. Strain-specific mutations were identified in the V3 loop of maraviroc-resistant CC1/85 and RU570. The envelope-encoding region of maraviroc-resistant CC1/85 was inserted into an NL4-3 background. This recombinant virus was completely resistant to maraviroc but retained susceptibility to aplaviroc. Reverse mutation of gp120 residues 316 and 323 in the V3 loop (numbering from HXB2) to their original sequence restored wild-type susceptibility to maraviroc, while reversion of either mutation resulted in a partially sensitive virus with reduced maximal inhibition (plateau). The plateaus are consistent with the virus having acquired the ability to utilize maraviroc-bound receptor for entry. This hypothesis was further corroborated by the observation that a high concentration of maraviroc blocks the activity of aplaviroc against maraviroc-resistant virus.

  14. Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets.

    Directory of Open Access Journals (Sweden)

    S K Rosendahl Huber

    Full Text Available Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP, polymerase basic protein 1 (PB1 and matrix protein 1 (M1. C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.

  15. Origins and challenges of viral dark matter.

    Science.gov (United States)

    Krishnamurthy, Siddharth R; Wang, David

    2017-07-15

    The accurate classification of viral dark matter - metagenomic sequences that originate from viruses but do not align to any reference virus sequences - is one of the major obstacles in comprehensively defining the virome. Depending on the sample, viral dark matter can make up from anywhere between 40 and 90% of sequences. This review focuses on the specific nature of dark matter as it relates to viral sequences. We identify three factors that contribute to the existence of viral dark matter: the divergence and length of virus sequences, the limitations of alignment based classification, and limited representation of viruses in reference sequence databases. We then discuss current methods that have been developed to at least partially circumvent these limitations and thereby reduce the extent of viral dark matter. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 immune checkpoint inhibitors

    Science.gov (United States)

    Loi, Sherene; Dushyanthen, Sathana; Beavis, Paul A; Salgado, Roberto; Denkert, Carsten; Savas, Peter; Combs, Susan; Rimm, David L.; Giltnane, Jennifer M.; Estrada, Monica V.; Sánchez, Violeta; Sanders, Melinda E.; Cook, Rebecca S.; Pilkinton, Mark A.; Mallal, Simon A.; Wang, Kai; Miller, Vincent A.; Stephens, Phil J.; Yelensky, Roman; Doimi, Franco D.; Gómez, Henry; Ryzhov, Sergey V.; Darcy, Phillip K.; Arteaga, Carlos L.; Balko, Justin M.

    2015-01-01

    Purpose Tumor-infiltrating lymphocytes (TILs) in the residual disease (RD) of triple-negative breast cancers (TNBCs) after neoadjuvant chemotherapy (NAC) are associated with improved survival, but insight into tumor cell-autonomous molecular pathways affecting these features are lacking. Experimental Design We analyzed TILs in the RD of clinically and molecularly characterized TNBCs after NAC and explored therapeutic strategies targeting combinations of MEK inhibitors with PD-1/PD-L1-targeted immunotherapy in mouse models of breast cancer. Results Presence of TILs in the RD was significantly associated with improved prognosis. Genetic or transcriptomic alterations in Ras/MAPK signaling were significantly correlated with lower TILs. MEK inhibition up-regulated cell-surface major histocompatibility complex (MHC) expression and PD-L1 in TNBC cells both in vivo and in vitro. Moreover, combined MEK and PDL-1/PD-1 inhibition enhanced anti-tumor immune responses in mouse models of breast cancer. Conclusions These data suggest the possibility that Ras/MAPK pathway activation promotes immune-evasion in TNBC, and support clinical trials combining MEK- and PD-L1-targeted therapies. Furthermore, Ras/MAPK activation and MHC expression may be predictive biomarkers of response to immune checkpoint inhibitors. PMID:26515496

  17. Triple assessment of breast lump

    International Nuclear Information System (INIS)

    Ahmed, I.; Nazir, R.; Chaudhary, M.Y.

    2007-01-01

    To determine the sensitivity, specificity, positive and negative predictive values of triple test (T T) consisting of physical examination (PE), mammography, fine needle aspiration cytology (FNAC) in the evaluation and characterization of palpable breast lump. Secondly, whether this can be employed as an alternative for tru cut/ excisional biopsy. It comprised of 35 consecutive females presenting in the breast clinic with palpable lump. Females below 35 years of age were excluded due to low sensitivity of the mammography in depiction of focal breast lesions resulting from glandular parenchyma. Patients with acute inflammatory signs, fungating masses, pregnant ladies as well as those with cystic lesions, as confirmed by ultrasound, were also excluded from the study. Number, size and recurrent masses did not influence the inclusion criterion. Detailed history and physical examination was carried out as per established protocol. It was followed by mammography and FNAC. All cases underwent excisional biopsy irrespective of the results of the triple test. The patients age ranged from 35 to 75 years with mean age of 45.97. Amongst these, 19 cases were benign (54.28 %) and 16 cases (45.71 %) were malignant. The triple test (T T) was scored as concordant if the elements had either all malignant or all benign results. The triple test was non-concordant if the elements had neither all malignant nor all benign results. The T T was concordant in 19 cases (54.28 %) i.e all the benign cases detected by the triple test were benign on final biopsy (100 % specificity and NPV), all the malignant lesions detected by T T turned out to be malignant on final biopsy (100 % sensitivity and PPV). Triple test was nonconcordant in 16 cases (45.71 %). Triple Test was scored as benign or malignant based upon the combined results of two elements amongst three components. Out of these, 11 cases were malignant and 5 were benign. In 4 cases, the components of the triple test were suspicious i

  18. An iron-capped metal-organic polyyne: {[Fe](C[triple bond]C)2[W][triple bond]CC[triple bond]CC[triple bond][W](C[triple bond]C)2[Fe]}.

    OpenAIRE

    Semenov Sergey N; Taghipourian Shiva F; Blacque Olivier; Fox Thomas; Venkatesan Koushik; Berke Heinz

    2010-01-01

    The organometallic conjugated complex H(C[triple bond]C)(2)[W][triple bond]CC[triple bond]CC[triple bond][W](C[triple bond]C)(2)H {[W] = W(dppe)(2); dppe = 12 bis(diphenylphosphino)ethane} containing a ditungstenatetradecaheptayne unit was synthesized by utilizing a new and efficient coupling method. The stannylated derivative was converted to the tetranuclear complex which exhibits efficient long range electron transfer.

  19. Crop-associated virus reduces the rooting depth of non-crop perennial native grass more than non-crop-associated virus with known viral suppressor of RNA silencing (VSR).

    Science.gov (United States)

    Malmstrom, Carolyn M; Bigelow, Patrick; Trębicki, Piotr; Busch, Anna K; Friel, Colleen; Cole, Ellen; Abdel-Azim, Heba; Phillippo, Colin; Alexander, Helen M

    2017-09-15

    stunted annual Avena sativa L. (oats). These findings suggest that some of the diversity in grass-infecting Luteoviridae reflects viral capacity to modulate defenses in different host types. Intriguingly, while all virus treatments also reduced root production in both host species, only crop-associated BYDV-PAV (or co-infection) reduced rooting depths. Such root effects may increase host susceptibility to drought, and indicate that BYDV-PAV pathogenicity is determined by something other than a P0 VSR. These findings contribute to growing evidence that pathogenic crop-associated viruses may harm native species as well as crops. Critical next questions include the extent to which crop-associated selection pressures drive viral pathogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Viral Haemorrhagic Septicaemia Virus

    DEFF Research Database (Denmark)

    Olesen, Niels Jørgen; Skall, Helle Frank

    2013-01-01

    This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus.......This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus....

  1. [Emergent viral infections

    NARCIS (Netherlands)

    Galama, J.M.D.

    2001-01-01

    The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic

  2. Discovering hidden viral piracy.

    Science.gov (United States)

    Kim, Eddo; Kliger, Yossef

    2005-12-01

    Viruses and developers of anti-inflammatory therapies share a common interest in proteins that manipulate the immune response. Large double-stranded DNA viruses acquire host proteins to evade host defense mechanisms. Hence, viral pirated proteins may have a therapeutic potential. Although dozens of viral piracy events have already been identified, we hypothesized that sequence divergence impedes the discovery of many others. We developed a method to assess the number of viral/human homologs and discovered that at least 917 highly diverged homologs are hidden in low-similarity alignment hits that are usually ignored. However, these low-similarity homologs are masked by many false alignment hits. We therefore applied a filtering method to increase the proportion of viral/human homologous proteins. The homologous proteins we found may facilitate functional annotation of viral and human proteins. Furthermore, some of these proteins play a key role in immune modulation and are therefore therapeutic protein candidates.

  3. Energy Efficient Triple IG Automation EEE (Triple-E)

    Energy Technology Data Exchange (ETDEWEB)

    McGlinchy, Timothy B

    2013-02-28

    GED Integrated Solutions collaborated with US window and door manufactures to investigate, design and verify technical and cost feasibility for producing high performance, high volume, low material and labor cost window, utilizing a modified window design containing a triple insulating glass unit (IGU). This window design approach when combined with a high volume IGU manufacturing system, can produce R5 rated windows for an approximate additional consumer cost of only $4 per square foot when compared to conventional Low-E argon dual pane IG windows, resulting in a verify practical, reliable and affordable high performance window for public use.

  4. Hepatitis viral aguda

    OpenAIRE

    Héctor Rubén Hernández Garcés; René F. Espinosa Álvarez

    1998-01-01

    Se realizó una revisión bibliográfica de las hepatitis virales agudas sobre aspectos vinculados a su etiología. Se tuvieron en cuenta además algunos datos epidemiológicos, las formas clínicas más importantes, los exámenes complementarios con especial énfasis en los marcadores virales y el diagnóstico positivoA bibliographical review of acute viral hepatitis was made taking into account those aspects connected with its etiology. Some epidemiological markers, the most important clinical forms, ...

  5. Viral Gastroenteritis (Stomach Flu)

    Science.gov (United States)

    ... Viral gastroenteritis (stomach flu) Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  6. Hepatitis viral aguda

    Directory of Open Access Journals (Sweden)

    Héctor Rubén Hernández Garcés

    1998-10-01

    Full Text Available Se realizó una revisión bibliográfica de las hepatitis virales agudas sobre aspectos vinculados a su etiología. Se tuvieron en cuenta además algunos datos epidemiológicos, las formas clínicas más importantes, los exámenes complementarios con especial énfasis en los marcadores virales y el diagnóstico positivoA bibliographical review of acute viral hepatitis was made taking into account those aspects connected with its etiology. Some epidemiological markers, the most important clinical forms, and the complementary examinations with special emphasis on the viral markers and the positive diagnosis were also considered

  7. Viral pathogenesis in diagrams

    National Research Council Canada - National Science Library

    Tremblay, Michel; Berthiaume, Laurent; Ackermann, Hans-Wolfgang

    2001-01-01

    .... The 268 diagrams in Viral Pathogenesis in Diagrams were selected from over 800 diagrams of English and French virological literature, including one derived from a famous drawing by Leonardo da Vinci...

  8. Triple dividends of water consumption charges in South Africa

    Science.gov (United States)

    Letsoalo, Anthony; Blignaut, James; de Wet, Theuns; de Wit, Martin; Hess, Sebastiaan; Tol, Richard S. J.; van Heerden, Jan

    2007-05-01

    The South African government is exploring ways to address water scarcity problems by introducing a water resource management charge on the quantity of water used in sectors such as irrigated agriculture, mining, and forestry. It is expected that a more efficient water allocation, lower use, and a positive impact on poverty can be achieved. This paper reports on the validity of these claims by applying a computable general equilibrium model to analyze the triple dividend of water consumption charges in South Africa: reduced water use, more rapid economic growth, and a more equal income distribution. It is shown that an appropriate budget-neutral combination of water charges, particularly on irrigated agriculture and coal mining, and reduced indirect taxes, particularly on food, would yield triple dividends, that is, less water use, more growth, and less poverty.

  9. Pursuing the Triple Aim: The First 7 Years.

    Science.gov (United States)

    Whittington, John W; Nolan, Kevin; Lewis, Ninon; Torres, Trissa

    2015-06-01

    POLICY POINTS: In 2008, researchers at the Institute for Healthcare Improvement (IHI) proposed the Triple Aim, strategic organizing principles for health care organizations and geographic communities that seek, simultaneously, to improve the individual experience of care and the health of populations and to reduce the per capita costs of care for populations. In 2010, the Triple Aim became part of the US national strategy for tackling health care issues, especially in the implementation of the Patient Protection and Affordable Care Act (ACA) of 2010. Since that time, IHI and others have worked together to determine how the implementation of the Triple Aim has progressed. Drawing on our 7 years of experience, we describe 3 major principles that guided the organizations and communities working on this endeavor: creating the right foundation for population management, managing services at scale for the population, and establishing a learning system to drive and sustain the work over time. In 2008, researchers at the Institute for Healthcare Improvement (IHI) described the Triple Aim as simultaneously "improving the individual experience of care; improving the health of populations; and reducing the per capita costs of care for populations." IHI and its close colleagues had determined that both individual and societal changes were needed. In 2007, IHI began recruiting organizations from around the world to participate in a collaborative to implement what became known as the Triple Aim. The 141 participating organizations included health care systems, hospitals, health care insurance companies, and others closely tied to health care. In addition, key groups outside the health care system were represented, such as public health agencies, social services groups, and community coalitions. This collaborative provided a structure for observational research. By noting the contrasts between the contexts and structures of those sites in the collaborative that progressed and

  10. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

    The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

  11. Neuroanatomy goes viral!

    Science.gov (United States)

    Nassi, Jonathan J.; Cepko, Constance L.; Born, Richard T.; Beier, Kevin T.

    2015-01-01

    The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist’s toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic spread, and

  12. Neuroanatomy goes viral!

    Directory of Open Access Journals (Sweden)

    Jonathan eNassi

    2015-07-01

    Full Text Available The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist's toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic

  13. On Spectral Triples in Quantum Gravity I

    DEFF Research Database (Denmark)

    Aastrup, Johannes; M. Grimstrup, Jesper; Nest, Ryszard

    2009-01-01

    This paper establishes a link between Noncommutative Geometry and canonical quantum gravity. A semi-finite spectral triple over a space of connections is presented. The triple involves an algebra of holonomy loops and a Dirac type operator which resembles a global functional derivation operator. ...

  14. Holonomy loops, spectral triples and quantum gravity

    DEFF Research Database (Denmark)

    Johannes, Aastrup; Grimstrup, Jesper Møller; Nest, Ryszard

    2009-01-01

    We review the motivation, construction and physical interpretation of a semi-finite spectral triple obtained through a rearrangement of central elements of loop quantum gravity. The triple is based on a countable set of oriented graphs and the algebra consists of generalized holonomy loops...

  15. Spectral triples and the geometry of fractals

    DEFF Research Database (Denmark)

    Christensen, Erik; Ivan, Cristina; Schroe, Elmar

    2012-01-01

    It is shown that one can construct a spectral triple for the Sierpinski gasket such that it represents any given K-homology class, On the other hand if the geodesic distance and the dimension has to be part of the data from the triple, there are certain restriction....

  16. Sums of two-dimensional spectral triples

    DEFF Research Database (Denmark)

    Christensen, Erik; Ivan, Cristina

    2007-01-01

    We study countable sums of two dimensional modules for the continuous complex functions on a compact metric space and show that it is possible to construct a spectral triple which gives the original metric back. This spectral triple will be finitely summable for any positive parameter. We also co...

  17. Jordan triple systems by the grid approach

    CERN Document Server

    Neher, Erhard

    1987-01-01

    Grids are special families of tripotents in Jordan triple systems. This research monograph presents a theory of grids including their classification and coordinization of their cover. Among the applications given are - classification of simple Jordan triple systems covered by a grid, reproving and extending most of the known classification theorems for Jordan algebras and Jordan pairs - a Jordan-theoretic interpretation of the geometry of the 27 lines on a cubic surface - structure theories for Hilbert-triples and JBW*-triples, the Jordan analogues of Hilbert-triples and W*-algebras which describe certain symmetric Banach manifolds. The notes are essentially self-contained and independent of the structure theory of Jordan algebras and Jordan pairs. They can be read by anyone with a basic knowledge in algebraic geometry or functional analysis. The book is intended to serve both as a reference for researchers in Jordan theory and as an introductory textbook for newcomers to the subject.

  18. Does Viral Marketing really Effective?

    OpenAIRE

    Chien, Ho-shen

    2012-01-01

    Abstract In this article, we examine the effectiveness of viral marketing toward young adults since the majority of Internet users are in this age group. It is also noted that we will only focus on video type of viral messages, which is the most common way to utilized viral marketing for firms. We will discuss how viral video influence consumer behavior in terms of brand images, brand choice, user experience and working memory in this paper. Our results illustrated viral video helps major...

  19. Concepts in viral pathogenesis II

    Energy Technology Data Exchange (ETDEWEB)

    Notkins, A.L.; Oldstone, M.B.A.

    1986-01-01

    This paper contains papers divided among 10 sections. The section titles are: Viral Structure and Function; Viral Constructs; Oncogenes, Transfection, and Differentiation; Viral Tropism and Entry into Cells; Immune Recognition of Viruses; Evolving Concepts in Viral Pathogenesis Illustrated by Selected Plant and Animal Models; Evolving Concepts in Viral Pathogenesis Illustrated by Selected Diseases in Humans; New Trends in Diagnosis and Epidemiology; and Vaccines and Antiviral Therapy.

  20. Viral mechanisms of immune evasion.

    Science.gov (United States)

    Alcami, A; Koszinowski, U H

    2000-09-01

    During the millions of years they have coexisted with their hosts, viruses have learned how to manipulate host immune control mechanisms. Viral gene functions provide an overview of many relevant principles in cell biology and immunology. Our knowledge of viral gene functions must be integrated into virus-host interaction networks to understand viral pathogenesis, and could lead to new anti-viral strategies and the ability to exploit viral functions as tools in medicine.

  1. Mixed Hyperlipidemia Associated with Triple X Syndrome (A Case Report

    Directory of Open Access Journals (Sweden)

    Anton-Pǎduraru Dana-Teodora

    2014-06-01

    Full Text Available Lipid metabolism abnormalities in children may be hereditary or secondary to certain diseases (obesity, type 2 diabetes mellitus. Often elevated triglycerides values are associated with high cholesterol values, playing a major role on atherosclerosis. The triple X syndrome also called “the superfemale syndrome” is not a rare condition, but it is usually undiagnosed or occasionally diagnosed when other investigations are done. The authors present the case of a child admitted in the 3rd Clinic of Pediatrics -“Sf. Maria” Children’s Emergency Hospital, Iaşi -Romania for the continuation of her lipid metabolism investigations, being diagnosed on this occasion with the triple X syndrome. We conclude that the investigation of lipid metabolism, early identification of lipid abnormalities and proper treatment significantly reduce the prevalence of cardiovascular disease in adults. We cannot specify the impact of the presence of the chromosomal anomaly, as it is an accidental association

  2. Triple A syndrome: two novel mutations in the AAAS gene.

    Science.gov (United States)

    Thümmler, Susanne; Huebner, Angela; Baechler-Sadoul, Elisabeth

    2009-01-01

    Triple A syndrome is a rare disease of autosomal recessive inheritance. It was first described in 1978. The typical triad includes adrenocorticotrophic-hormone-resistant glucocorticoid insufficiency, reduced or absent tearing (alacrima) and achalasia. But clinical symptoms can be extremely heterogeneous and of variable clinically expression. This report describes a 7-year-old boy with a 1 year history of fatigue and muscle weakness. Physical examination showed skin and mucosal hyperpigmentation, and hormonal analysis revealed isolated glucocorticoid function. Medical history was marked by megaoesophagus and achalasia. The absence of tears when crying had been noted since birth. In the presence of the classical triad, triple A syndrome was diagnosed. Clinical diagnosis was confirmed by molecular analysis of the AAAS gene on chromosome 12q13. The novel compound heterozygous mutation c.1304delA and c.1292-1294delTTCinsA was found.

  3. Toxic Anterior Segment Syndrome following a Triple Descemet’s Stripping Automated Endothelial Keratoplasty Procedure

    Directory of Open Access Journals (Sweden)

    Nir Sorkin

    2012-11-01

    Full Text Available Purpose: To present a unique case of a 58-year-old female with toxic anterior segment syndrome (TASS, following a triple procedure: Descemet’s stripping automated endothelial keratoplasty (DSAEK, phacoemulsification and posterior chamber intraocular lens implantation. Methods: The patient was treated with topical dexamethasone sodium phosphate 0.1% and topical atropine sulfate 1%. Due to a slow improvement in her clinical status, oral prednisone 1 mg/kg/day was added. Results: The anterior chamber reaction improved gradually, with tapering down of topical and oral treatment, until a complete resolution of the anterior chamber reaction was observed. Conclusions: Taking into account the estimated volume of DSAEK triple procedures performed worldwide, we would expect an annual incidence of several TASS cases, following triple DSAEK procedures. However, we were unable to find any such previous reports in the literature. This fact raises questions regarding the cause of reduced TASS incidence following triple DSAEK procedures.

  4. Current status and strategies for viral hepatitis control in Korea

    Directory of Open Access Journals (Sweden)

    Dong Hyun Sinn

    2017-09-01

    Full Text Available Viral hepatitis is one of major global health challenges with increasing disease burden worldwide. Hepatitis B virus and hepatitis C virus infections are major causes of chronic liver diseases. They can lead to cirrhosis, hepatocellular carcinoma, and death in significant portion of affected people. Transmission of hepatitis B virus can be blocked by vaccination. Progression of hepatitis B virus-related liver diseases can be prevented by long-term viral suppression with effective drugs. Although vaccine for hepatitis C virus is currently unavailable, hepatitis C virus infection can be eradicated by oral direct antiviral agents. To eliminate viral hepatitis, World Health Organization (WHO has urged countries to develop national goals and targets through reducing 90% of new infections and providing universal access to key treatment services up to 80%. This can lead to 65% reduction of viral hepatitis-related mortality. Here, we discuss some key features of viral hepatitis, strategies to control viral hepatitis suggested by WHO, and current status and strategies for viral hepatitis control in South Korea. To achieve the goal of viral hepatitis elimination by 2030 in South Korea, an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention (CDC needs to be established to organize and execute comprehensive strategy for the management of viral hepatitis in South Korea.

  5. Experience with Hepatitis B viral load testing in Nigeria | Okwuraiwe ...

    African Journals Online (AJOL)

    Background: Quantification of the viral burden is an important laboratory tool in the management of hepatitis B virus (HBV)-infected patients. However, widespread use of assays is still hampered by the high cost. Treatment reduces viral load to undetectable levels. HBV infected patients tend to have high HBV DNA levels, ...

  6. 101 . experience with hepatitis b viral load testing in nigeria

    African Journals Online (AJOL)

    User

    ABSTRACT. Background: Quantification of the viral burden is an important laboratory tool in the management of hepatitis B virus. (HBV)-infected patients. However, widespread use of assays is still hampered by the high cost. Treatment reduces viral load to undetectable levels. HBV infected patients tend to have high HBV ...

  7. The zebrafish galectins Drgal1-L2 and Drgal3-L1 bind in vitro to the infectious hematopoietic necrosis virus (IHNV) glycoprotein and reduce viral adhesion to fish epithelial cells

    Digital Repository Service at National Institute of Oceanography (India)

    Nita-Lazar, M.; Mancini, J.; Feng, C.; Gonzalez-Montalban, N.; Ravindran, C.; Jackson, S.; Heras-Sanchez, A.D.L.; Giomarelli, B.; Ahmed, H.; Haslam, S.M.; Wu, G.; Dell, A.; Ammayappan, A.; Vakharia, V.N.; Vasta, G.R.

    of the key roles played by protein-carbohydrate interactions between host lectins and virion envelope glycoproteins in modulating viral adhesion and infectivity. Galectins, which constitute a conserved and ubiquitous lectin family defined by a unique amino... have been defined based on their envelope protein sequence similarity, designated as the U, M, and L genogroups. The M genogroup is endemic in the rainbow trout farming region in Idaho, where phylogenetically distinct sub-groups, designated MA...

  8. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2007-01-01

    Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness.......Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness....

  9. Triple X Syndrome: Symptoms and Causes

    Science.gov (United States)

    ... help determine the cause and suggest appropriate action. Causes Although triple X syndrome is genetic, it's usually not inherited — it's due to a random genetic error. Normally, people have 46 chromosomes in each cell, ...

  10. Triple X Syndrome: Symptoms and Causes

    Science.gov (United States)

    ... girls and women with triple X syndrome have intelligence in the normal range, but possibly slightly lower ... school, social and relationship problems Anxiety and other emotional problems, such as attention-deficit/hyperactivity disorder (ADHD) ...

  11. Viral Marketing and Academic Institution

    OpenAIRE

    Koktová, Silvie

    2010-01-01

    This bachelor thesis examines modern and constantly developing kind of internet marketing -- the so called viral marketing. It deals with its origin, principle, process, advantages and disadvantages, types of viral marketing and presumptions of creating successful viral campaign. The aim of the theoretical part is especially the understanding of viral marketing as one of the effective instruments of contemporary marketing. In this theoretical part the thesis also elaborates a marketing school...

  12. Effectiveness of the Triple P Positive Parenting Program on behavioral problems in children: a meta-analysis.

    Science.gov (United States)

    de Graaf, Ireen; Speetjens, Paula; Smit, Filip; de Wolff, Marianne; Tavecchio, Louis

    2008-09-01

    The Triple P Positive Parenting Program is a multilevel parenting program to prevent and offer treatment for severe behavioral, emotional, and developmental problems in children. The aim of this meta-analysis is to assess the effectiveness of Triple P Level 4 interventions in the management of behavioral problems in children by pooling the evidence from relevant literature that included Level 4 Triple P interventions. Level 4 intervention is indicated if the child has multiple behavior problems in a variety of settings and there are clear deficits in parenting skills. Results indicate that Level 4 of Triple P interventions reduced disruptive behaviors in children. These improvements were maintained well over time, with further improvements in long-term follow-up. These effects support the widespread adoption and implementation of Triple P that is taking place in an increasing number of countries in quite diverse cultural contexts around the world.

  13. Molecular imaging of oncolytic viral therapy

    Directory of Open Access Journals (Sweden)

    Dana Haddad

    2014-01-01

    Full Text Available Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy.

  14. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  15. Viral membrane fusion

    International Nuclear Information System (INIS)

    Harrison, Stephen C.

    2015-01-01

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism

  16. Hepatitis viral C

    Directory of Open Access Journals (Sweden)

    Pedro A. Poma

    2011-12-01

    Full Text Available El virus de la hepatitis C se trasmite por contacto directo con la sangre de la persona infectada. La mayoría de los pacientes no presenta síntomas en la fase aguda o crónica de la hepatitis. Dos a tres décadas después, algunos pacientes progresan a la cirrosis compensada, que también es asintomática. En un examen de sangre, los anticuerpos se presentan como una sorpresa, porque no se les relaciona con un episodio de contagio. Un embarazo ocasiona la posibilidad de efectos negativos de la infección en la madre o el niño. El tratamiento actual no ofrece la certeza de cura, dependiendo del genotipo viral, y presenta efectos adversos que pueden ser severos. La cirrosis descompensada causa la mayoría de muertes relacionadas con esta infección; algunos de estos pacientes desarrollan carcinoma hepatocelular. La reproducción viral causa partículas virales diferentes del virus original, característica que ha impedido el desarrollo de una vacuna. Actualmente, la prevención consiste en evitar el contacto con sangre infectada. Este artículo revisa la infección con el virus de la hepatitis C, incluyendo los últimos progresos en tratamiento. Es necesario educar a la comunidad acerca de los efectos de este virus en la salud pública.

  17. [History of viral hepatitis].

    Science.gov (United States)

    Fonseca, José Carlos Ferraz da

    2010-01-01

    The history of viral hepatitis goes back thousands of years and is a fascinating one. When humans were first infected by such agents, a natural repetitive cycle began, with the capacity to infect billions of humans, thus decimating the population and causing sequelae in thousands of lives. This article reviews the available scientific information on the history of viral hepatitis. All the information was obtained through extensive bibliographic review, including original and review articles and consultations on the internet. There are reports on outbreaks of jaundice epidemics in China 5,000 years ago and in Babylon more than 2,500 years ago. The catastrophic history of great jaundice epidemics and pandemics is well known and generally associated with major wars. In the American Civil War, 40,000 cases occurred among Union troops. In 1885, an outbreak of catarrhal jaundice affected 191 workers at the Bremen shipyard (Germany) after vaccination against smallpox. In 1942, 28,585 soldiers became infected with hepatitis after inoculation with the yellow fever vaccine. The number of cases of hepatitis during the Second World War was estimated to be 16 million. Only in the twentieth century were the main agents causing viral hepatitis identified. The hepatitis B virus was the first to be discovered. In this paper, through reviewing the history of major epidemics caused by hepatitis viruses and the history of discovery of these agents, singular peculiarities were revealed. Examples of this include the accidental or chance discovery of the hepatitis B and D viruses.

  18. Viral impacts on microbial carbon cycling in thawing permafrost soils

    Science.gov (United States)

    Trubl, G. G.; Roux, S.; Bolduc, B.; Jang, H. B.; Emerson, J. B.; Solonenko, N.; Li, F.; Solden, L. M.; Vik, D. R.; Wrighton, K. C.; Saleska, S. R.; Sullivan, M. B.; Rich, V. I.

    2017-12-01

    Permafrost contains 30-50% of global soil carbon (C) and is rapidly thawing. While the fate of this C is unknown, it will be shaped in part by microbes and their associated viruses, which modulate host activities via mortality and metabolic control. To date, viral research in soils has been outpaced by that in aquatic environments, due to the technical challenges of accessing viruses as well as the dramatic physicochemical heterogeneity in soils. Here, we describe advances in soil viromics from our research on permafrost-associated soils, and their implications for associated terrestrial C cycling. First, we optimized viral resuspension-DNA extraction methods for a range of soil types. Second, we applied cutting-edge viral-specific informatics methods to recover viral populations, define their gene content, connect them to potential hosts, and analyze their relationships to environmental parameters. A total of 781 viral populations were recovered from size-fractionated virus samples of three soils along a permafrost thaw gradient. Ecological analyses revealed endemism as recovered viral populations were largely unique to each habitat and unlike those in aquatic communities. Genome- and network-based classification assigned these viruses into 226 viral clusters (VCs; genus-level taxonomy), 55% of which were novel. This increases the number of VCs by a third and triples the number of soil viral populations in the RefSeq database (currently contains 256 VCs and 316 soil viral populations). Genomic analyses revealed 85% of the genes were functionally unknown, though 5% of the annotatable genes contained C-related auxiliary metabolic genes (AMGs; e.g. glycoside hydrolases). Using sequence-based features and microbial population genomes, we were able to in silico predict hosts for 30% of the viral populations. The identified hosts spanned 3 phyla and 6 genera but suggested these viruses have species-specific host ranges as >80% of hosts for a given virus were in the same

  19. [Acute hemorrhagic viral conjunctivitis].

    Science.gov (United States)

    Haicl, P; Vanista, J; Danes, L

    1992-10-01

    Two cases of acute hemorrhagic conjunctivitis are described, in which the enterovirus Coxsackie 24 was found by serological examination to be the etiological agent. The virus was important from Nigeria. The patients suffered by the acute hemorrhagic keratoconjuntivitis with transient iritic irritation without the systemic symptoms. Since now this disease with serological verification was not diagnosed in our country. The question of the viral hemorrhagic conjunctivitis and their treatment is discussed. The necessity of virological investigation in inflammations of the anterior segment is stressed.

  20. Complement and Viral Pathogenesis

    Science.gov (United States)

    Stoermer, Kristina A.; Morrison, Thomas E.

    2011-01-01

    The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection. PMID:21292294

  1. Dengue viral infections

    OpenAIRE

    Gurugama Padmalal; Garg Pankaj; Perera Jennifer; Wijewickrama Ananda; Seneviratne Suranjith

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host...

  2. Drop evaporation and triple line dynamics

    Science.gov (United States)

    Sobac, Benjamin; Brutin, David; Gavillet, Jerome; Université de Provence Team; Cea Liten Team

    2011-03-01

    Sessile drop evaporation is a phenomenon commonly came across in nature or in industry with cooling, paintings or DNA mapping. However, the evaporation of a drop deposited on a substrate is not completely understood due to the complexity of the problem. Here we investigate, with several nano-coating of the substrate (PTFE, SiOx, SiOc and CF), the influence of the dynamic of the triple line on the evaporation process. The experiment consists in analyzing simultaneously the motion of the triple line, the kinetics of evaporation, the internal thermal motion and the heat and mass transfer. Measurements of temperature, heat-flux and visualizations with visible and infrared cameras are performed. The dynamics of the evaporative heat flux appears clearly different depending of the motion of the triple line

  3. Viral marketing as epidemiological model

    OpenAIRE

    Rodrigues, Helena Sofia; Fonseca, Manuel José

    2015-01-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of...

  4. Krein Spectral Triples and the Fermionic Action

    International Nuclear Information System (INIS)

    Dungen, Koen van den

    2016-01-01

    Motivated by the space of spinors on a Lorentzian manifold, we define Krein spectral triples, which generalise spectral triples from Hilbert spaces to Krein spaces. This Krein space approach allows for an improved formulation of the fermionic action for almost-commutative manifolds. We show by explicit calculation that this action functional recovers the correct Lagrangians for the cases of electrodynamics, the electro-weak theory, and the Standard Model. The description of these examples does not require a real structure, unless one includes Majorana masses, in which case the internal spaces also exhibit a Krein space structure.

  5. Relevance Scoring of Triples Using Ordinal Logistic Classification - The Celosia Triple Scorer at WSDM Cup 2017

    OpenAIRE

    Fatma, Nausheen; Chinnakotla, Manoj K.; Shrivastava, Manish

    2017-01-01

    In this paper, we report our participation in the Task 2: Triple Scoring of WSDM Cup challenge 2017. In this task, we were provided with triples of "type-like" relations which were given human-annotated relevance scores ranging from 0 to 7, with 7 being the "most relevant" and 0 being the "least relevant". The task focuses on two such relations: profession and nationality. We built a system which could automatically predict the relevance scores for unseen triples. Our model is primarily a sup...

  6. Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

    Science.gov (United States)

    Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

    2012-01-01

    Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

  7. [Responses to triple viral and tetanus vaccination in HIV-infected children].

    Science.gov (United States)

    Echeverría Lecuona, J; Aldamiz-Echevarría Azuara, L; Cilla Eguiluz, G; Pérez Trallero, E

    1996-04-01

    Our objective was to study the antibody response to the parotiditis, rubella, measles and tetanus vaccines in HIV infected children. Forty-four children of HIV positive mothers, of which 14 were infected (SG) and 33 HIV negative (CG) were studied when they were between 2 and 3 years of age. Their response to vaccinations of four doses of tetanus toxoid and one dose of measles, rubella and parotiditis vaccines was assessed. Children in the SG were tested at the age of 5-6 years to study the evolution of the response. At the age of 2-3 years, all children had optimal protection against tetanus toxoid. The response to measles, parotiditis and rubella was poor (adequate levels of antibodies in 50%, 25% and 21%, respectively) in infected children and good (93%, 75% and 90%, respectively) in the CG. At 5-6 years of age, a decreased level of antitetanus antibodies were found in the SG, maintaining low protection levels. There was no evidence of any changes in the response to measles, while the number of cases with a good response to parotiditis and rubella increased. Further results are necessary to know the effectiveness of the booster. We conclude that: 1) The immunological response to vaccination is poor in HIV infected children. 2) There was no evidence of side effects or changes in the HIV symptoms after vaccination.

  8. Triple Bioluminescence Imaging for In Vivo Monitoring of Cellular Processes

    Directory of Open Access Journals (Sweden)

    Casey A Maguire

    2013-01-01

    Full Text Available Bioluminescence imaging (BLI has shown to be crucial for monitoring in vivo biological processes. So far, only dual bioluminescence imaging using firefly (Fluc and Renilla or Gaussia (Gluc luciferase has been achieved due to the lack of availability of other efficiently expressed luciferases using different substrates. Here, we characterized a codon-optimized luciferase from Vargula hilgendorfii (Vluc as a reporter for mammalian gene expression. We showed that Vluc can be multiplexed with Gluc and Fluc for sequential imaging of three distinct cellular phenomena in the same biological system using vargulin, coelenterazine, and D-luciferin substrates, respectively. We applied this triple imaging system to monitor the effect of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL delivered using an adeno-associated viral vector (AAV on brain tumors in mice. Vluc imaging showed efficient sTRAIL gene delivery to the brain, while Fluc imaging revealed a robust antiglioma therapy. Further, nuclear factor-κB (NF-κB activation in response to sTRAIL binding to glioma cells death receptors was monitored by Gluc imaging. This work is the first demonstration of trimodal in vivo bioluminescence imaging and will have a broad applicability in many different fields including immunology, oncology, virology, and neuroscience.

  9. Triple-axis spectrometer DruechaL

    International Nuclear Information System (INIS)

    Buehrer, W.; Keller, P.

    1996-01-01

    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs

  10. Designing Broadband Access Networks with Triple Redundancy

    DEFF Research Database (Denmark)

    Pedersen, Jens Myrup; Riaz, Muhammad Tahir; Knudsen, Thomas Phillip

    2005-01-01

    An architecture is proposed for designing broadband access networks, which offer triple redundancy to the end users, resulting in networks providing connectivity even in case of any two independent node or line failures. Two physically independent connections are offered by fiber, and the last...

  11. Inclusive photoproduction and the triple Regge formula

    International Nuclear Information System (INIS)

    Gandsman, J.

    The inclusive reactions γp→π + or π - + anything and γn→π + or π - + anything at the photon energy of 7.5GeV were studied. The high π + /π - ratio observed in the target fragmentation region is explained by applying the triple Regge formalism. The inclusive photoproduction of the Δ ++ and rho 0 resonances is also investigated [fr

  12. Triple-axis spectrometer DruechaL

    Energy Technology Data Exchange (ETDEWEB)

    Buehrer, W.; Keller, P. [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs.

  13. Systolic triple-matrix product calculations

    Science.gov (United States)

    Caulfield, H. J.; Verber, C. M.; Stermer, R. L.

    1984-01-01

    In order to handle arbitrary-sized matrices with fixed-sized optical matrix processors, it is necessary to expand or contract the problem to fit the processor. This preprocessing is examined. It is applied to the type of triple-matrix product calculation needed for Kalman filtering. Emphasis will be placed on systolic-type processors.

  14. Discovering Steiner Triple Systems through Problem Solving

    Science.gov (United States)

    Sriraman, Bharath

    2004-01-01

    An attempt to implement problem solving as a teacher of ninth grade algebra is described. The problems selected were not general ones, they involved combinations and represented various situations and were more complex which lead to the discovery of Steiner triple systems.

  15. Clinicopathological comparison of triple negative breast cancers ...

    African Journals Online (AJOL)

    Conclusion: Triple negative breast cancer represented 34.4% which is higher than the range normally reported in the literature. TNBC are associated with younger age, large tumor size, high‑grade tumors, and a higher rate of axillary lymph node metastasis. Key words: Basal subtype, estrogen receptor, hormone receptors, ...

  16. Dual and triple therapy to prevent mother-to-child transmission of ...

    African Journals Online (AJOL)

    Objective. To determine outcomes of pregnant women and their infants at McCord Hospital in Durban, South Africa, where dual and triple therapy to reduce HIV vertical transmission have been used since 2004 despite national guidelines recommending simpler regimens. Method. We retrospectively examined records of all ...

  17. Prevalence of papillomaviruses, polyomaviruses, and herpesviruses in triple-negative and inflammatory breast tumors from algeria compared with other types of breast cancer tumors.

    Directory of Open Access Journals (Sweden)

    Marilys Corbex

    Full Text Available The possible role of viruses in breast cancer etiology remains an unresolved question. We hypothesized that if some viruses are involved, it may be in a subgroup of breast cancers only. Epidemiological arguments drove our interest in breast cancer subgroups that are more frequent in Africa, namely inflammatory breast cancer (IBC and triple-negative breast cancer. We tested whether viral prevalence was significantly higher in these subgroups.One hundred fifty-five paraffin-embedded malignant breast tumors were randomly selected at the pathology laboratory of the University Hospital of Annaba (Algeria to include one third of IBC and two thirds of non-IBC. They were tested for the presence of DNA from 61 viral agents (46 human papillomaviruses, 10 polyomaviruses, and 5 herpesviruses using type-specific multiplex genotyping assays, which combine multiplex PCR and bead-based Luminex technology.Viral DNA was found in 22 (17.9% of 123 tumors. The most prevalent viruses were EBV1 and HPV16. IBC tumors carried significantly more viruses (any type than non-IBC tumors (30% vs. 13%, p<0.04. Similarly, triple-negative tumors displayed higher virus-positivity than non-triple-negative tumors (44% vs. 14%, p<0.009.Our results suggest an association between the presence of viral DNA and aggressive breast cancer phenotypes (IBC, triple-negative. While preliminary, they underline the importance of focusing on subgroups when studying viral etiology in breast cancer. Further studies on viruses in breast cancer should be conducted in much larger samples to confirm these initial findings.

  18. Norovirus Polymerase Fidelity Contributes to Viral Transmission In Vivo

    DEFF Research Database (Denmark)

    Arias Esteban, Armando; Thorne, Lucy; Ghurburrun, Elsa

    2016-01-01

    viral pathogenesis using the murine norovirus model, as increasing viral mutation frequency using a mutagenic nucleoside resulted in clearance of a persistent infection in mice. Given the role of replication fidelity and genetic diversity in pathogenesis, we have now investigated whether polymerase...... and that maintaining diversity is important for the establishment of infection. This work supports the hypothesis that the reduced polymerase fidelity of the pandemic GII.4 human norovirus isolates may contribute to their global dominance....

  19. Triple antiplatelet therapy for preventing vascular events: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Bath Philip MW

    2010-06-01

    Full Text Available Abstract Background Dual antiplatelet therapy is usually superior to mono therapy in preventing recurrent vascular events (VEs. This systematic review assesses the safety and efficacy of triple antiplatelet therapy in comparison with dual therapy in reducing recurrent vascular events. Methods Completed randomized controlled trials investigating the effect of triple versus dual antiplatelet therapy in patients with ischaemic heart disease (IHD, cerebrovascular disease or peripheral vascular disease were identified using electronic bibliographic searches. Data were extracted on composite VEs, myocardial infarction (MI, stroke, death and bleeding and analysed with Cochrane Review Manager software. Odds ratios (OR and 95% confidence intervals (CI were calculated using random effects models. Results Twenty-five completed randomized trials (17,383 patients with IHD were included which involving the use of intravenous (iv GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban, aspirin, clopidogrel and/or cilostazol. In comparison with aspirin-based therapy, triple therapy using an intravenous GP IIb/IIIa inhibitor significantly reduced composite VEs and MI in patients with non-ST elevation acute coronary syndromes (NSTE-ACS (VE: OR 0.69, 95% CI 0.55-0.86; MI: OR 0.70, 95% CI 0.56-0.88 and ST elevation myocardial infarction (STEMI (VE: OR 0.39, 95% CI 0.30-0.51; MI: OR 0.26, 95% CI 0.17-0.38. A significant reduction in death was also noted in STEMI patients treated with GP IIb/IIIa based triple therapy (OR 0.69, 95% CI 0.49-0.99. Increased minor bleeding was noted in STEMI and elective percutaneous coronary intervention (PCI patients treated with GP IIb/IIIa based triple therapy. Stroke events were too infrequent for us to be able to identify meaningful trends and no data were available for patients recruited into trials on the basis of stroke or peripheral vascular disease. Conclusions Triple antiplatelet therapy based on iv GPIIb/IIIa inhibitors

  20. Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir.

    Science.gov (United States)

    Hensel, Michael T; Marshall, Jason D; Dorwart, Michael R; Heeke, Darren S; Rao, Eileen; Tummala, Padmaja; Yu, Li; Cohen, Gary H; Eisenberg, Roselyn J; Sloan, Derek D

    2017-05-01

    Several prophylactic vaccines targeting herpes simplex virus 2 (HSV-2) have failed in the clinic to demonstrate sustained depression of viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies (NAbs), their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the NAb targets gD and gB and the novel T cell antigen and tegument protein UL40, and we compared this vaccine to a whole-inactivated-virus vaccine (formaldehyde-inactivated HSV-2 [FI-HSV-2]). We evaluated different formulations in combination with several Th1-inducing Toll-like receptor (TLR) agonists in vivo In mice, the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide formulated in a squalene-based oil-in-water emulsion promoted most robust, functional HSV-2 antigen-specific CD8 T cell responses and high titers of neutralizing antibodies, demonstrating its superiority to vaccines adjuvanted by monophosphoryl lipid A (MPL)-alum. We further established that FI-HSV-2 alone or in combination with adjuvants as well as adjuvanted subunit vaccines were successful in the induction of NAbs and T cell responses in guinea pigs. These immunological responses were coincident with a suppression of vaginal HSV-2 shedding, low lesion scores, and a reduction in latent HSV-2 DNA in dorsal root ganglia to undetectable levels. These data support the further preclinical and clinical development of prophylactic HSV-2 vaccines that contain appropriate antigen and adjuvant components responsible for programming elevated CD8 T cell responses. IMPORTANCE Millions of people worldwide are infected with herpes simplex virus 2 (HSV-2), and to date, an efficacious prophylactic vaccine has not met the rigors

  1. Triple tray crown and bridge procedures: a guide to how dental assistants can assist the dentist: part 1.

    Science.gov (United States)

    Mamoun, John S; Javaid, Mariam

    2013-01-01

    The manual dual-arch (or triple tray) technique is an efficient way of making a definitive impression and making temporary provisional restorations for crown and bridge procedures. This article demonstrates how a dental assistant can assist a dentist during triple tray crown and bridge procedures. This is the first part of a two-part article, and explains mixing impression materials, making pre-operative dual-arch impressions, deciding in what situations to use separate arch impressions instead of the triple tray, and introduces the topic of making provisional restorations. In the future, in-office CAD-CAM scanning and milling of restorations, or digital scanning of tooth preparations, followed by e-mailing the scans to a dental laboratory, may reduce the frequency of use of the manual triple tray impression technique. However, its intrinsic efficiency may prevent it from becoming obsolete.

  2. Drug Use and Viral Infections (HIV, Hepatitis)

    Science.gov (United States)

    ... DrugFacts » Drug Use and Viral Infections (HIV, Hepatitis) Drug Use and Viral Infections (HIV, Hepatitis) Email Facebook Twitter Revised April 2018 What's the relationship between drug use and viral infections? People who engage in ...

  3. Surveillance for Viral Hepatitis - United States, 2014

    Science.gov (United States)

    ... and Programs Resource Center Anonymous Feedback Viral Hepatitis Surveillance for Viral Hepatitis – United States, 2014 Recommend on ... demographic characteristics and laboratory tests – Enhanced Viral Hepatitis Surveillance Sites*, 2014 Category MA No. % MI No. % NYS† ...

  4. Viral Innovation, Sustainability, and Excellence

    DEFF Research Database (Denmark)

    Edgeman, Rick; Eskildsen, Jacob Kjær

    Enterprises strive to be economically sustainable. In doing so, they either contribute to or detract from environmental and social sustainability. Sustainability is hence multi-dimensional with formulations that include the familiar triple-bottom-line and BEST models. Any assessment regimen for t...

  5. Encefalitis virales en la infancia

    OpenAIRE

    Monserrat Téllez de Meneses; Miguel T. Vila; Pedro Barbero Aguirre; José F. Montoya

    2013-01-01

    La encefalitis viral es una enfermedad grave que implica el compromiso inflamatorio del parénquima cerebral. Las infecciones virales del SNC ocurren con frecuencia como complicación de infecciones virales sistémicas. Más de 100 virus están implicados como agentes causales, entre los cuales el virus Herpes simplex tipo I, es el agente causal más frecuente de encefalitis no epidémica en todos los grupos poblacionales del mundo; es el responsable de los casos más graves en todas las edades. Much...

  6. Enfermedades virales emergentes y reemergentes

    OpenAIRE

    Jorge Eliécer Ossa Londoño; Ana Isabel Toro Montoya

    1996-01-01

    Los virus no son una excepción al principio de que toda forma de vida de hoyes el producto de la evolución de información gen ética preexistente. Tradicionalmente se ha reconocido que ta expresión clínica de las enfermedades virales cambia con el tiempo; molecularmente se ha demostrado que esos cambios fenotípicos son el producto de variaciones en el genoma viral. La tasa de cambio
    gen ético y fenotípico no es la misma en todos los agentes virales y ello está determinado, principal...

  7. Triple helix interactions for eco-innovation

    DEFF Research Database (Denmark)

    Hermann, Roberto Rivas; Riisgaard, Henrik; Remmen, Arne

    the role of science parks in promoting eco-innovation. This study uses qualitative data gathered in two units of analysis: Panama Canal Authority and City of Knowledge Science Park. The study examines how Triple Helix interactions have built the regional system of eco-innovation at the Panama Canal....... Overall, the research found that the Panamanian national innovation system facilitates eco-innovation by: providing research and development, building competence and financing of innovation processes. The “green maritime route” is an example of institutional eco-innovation promoted by the Panama Canal...... Authority with insights from consultants, universities and donnor agencies. The proximity of the science park to the canal, has hitherto not yielded with the creation of a “green cluster”, which could be a precedent to promote eco-innovations. These findings suggest that, Triple Helix interactions...

  8. Triple Achilles Tendon Rupture: Case Report.

    Science.gov (United States)

    Saxena, Amol; Hofer, Deann

    We present a case report with 1-year follow-up data of a 57-year-old male soccer referee who had sustained an acute triple Achilles tendon rupture injury during a game. His triple Achilles tendon rupture consisted of a rupture of the proximal watershed region, a rupture of the main body (mid-watershed area), and an avulsion-type rupture of insertional calcific tendinosis. The patient was treated surgically with primary repair of the tendon, including tenodesis with anchors. Postoperative treatment included non-weightbearing for 4 weeks and protected weightbearing until 10 weeks postoperative, followed by formal physical therapy, which incorporated an "antigravity" treadmill. The patient was able to return to full activity after 26 weeks, including running and refereeing, without limitations. Copyright © 2017 The American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  9. On Spectral Triples in Quantum Gravity I

    DEFF Research Database (Denmark)

    Aastrup, Johannes; M. Grimstrup, Jesper; Nest, Ryszard

    2009-01-01

    This paper establishes a link between Noncommutative Geometry and canonical quantum gravity. A semi-finite spectral triple over a space of connections is presented. The triple involves an algebra of holonomy loops and a Dirac type operator which resembles a global functional derivation operator....... The interaction between the Dirac operator and the algebra reproduces the Poisson structure of General Relativity. Moreover, the associated Hilbert space corresponds, up to a discrete symmetry group, to the Hilbert space of diffeomorphism invariant states known from Loop Quantum Gravity. Correspondingly......, the square of the Dirac operator has, in terms of canonical quantum gravity, the form of a global area-squared operator. Furthermore, the spectral action resembles a partition function of Quantum Gravity. The construction is background independent and is based on an inductive system of triangulations...

  10. Triple collinear emissions in parton showers

    Energy Technology Data Exchange (ETDEWEB)

    Höche, Stefan; Prestel, Stefan

    2017-10-01

    A framework to include triple collinear splitting functions into parton showers is presented, and the implementation of flavor-changing NLO splitting kernels is discussed as a first application. The correspondence between the Monte-Carlo integration and the analytic computation of NLO DGLAP evolution kernels is made explicit for both timelike and spacelike parton evolution. Numerical simulation results are obtained with two independent implementations of the new algorithm, using the two independent event generation frameworks Pythia and Sherpa.

  11. Resolution of a triple axis spectrometer

    DEFF Research Database (Denmark)

    Nielsen, Mourits; Bjerrum Møller, Hans

    1969-01-01

    A new method for obtaining the resolution function for a triple-axis neutron spectrometer is described, involving a combination of direct measurement and analytical calculation. All factors which contribute to the finite resolution of the instrument may be taken into account, and Gaussian...... or experimentally determined probability distributions may be used. The application to the study of the dispersion relation for excitations in a crystal is outlined...

  12. Triple plasmon resonance of bimetal nanoshell

    Energy Technology Data Exchange (ETDEWEB)

    Shirzaditabar, Farzad [Department of Physics, Razi University, Kermanshah (Iran, Islamic Republic of); Saliminasab, Maryam, E-mail: m.saliminasab@yahoo.com [Young Researchers Club, Kermanshah Branch, Islamic Azad University, Kermanshah (Iran, Islamic Republic of); Arghavani Nia, Borhan [Department of Physics, Kermanshah Branch, Islamic Azad University, Kermanshah (Iran, Islamic Republic of)

    2014-07-15

    In this paper, light absorption spectra properties of a bimetal multilayer nanoshell based on quasi-static approach are investigated. Comparing with silver-dielectric-silver and silver-dielectric-gold nanoshells, gold-dielectric-silver nanoshells have three intense and separated plasmon peaks which are more suitable for multiplex biosensing. Calculations show that relatively small thickness of outer silver shell and large dielectric constant of middle dielectric layer of gold-dielectric-silver nanoshell are suitable to obtain the triple plasmon resonance.

  13. On split Lie triple systems II

    Indian Academy of Sciences (India)

    In the present paper we extend these results to arbitrary split Lie triple systems with no restrictions on their 0-root spaces. Author Affiliations. Antonio J Calderón Martín1 M Forero Piulestán1. Departamento de Matemáticas, Universidad de Cádiz, 11510 Puerto Real, Cádiz, Spain. Dates. Manuscript received: 24 June 2009 ...

  14. Relative orientation of orbits in triple stars

    Science.gov (United States)

    Sterzik, M. F.; Tokovinin, A. A.

    2002-03-01

    Statistical analysis of the relative alignment of inner and outer orbits in triple systems resulting from a dynamical decay of small-N clusters (N le10 ) is presented and compared to the statistics of real multiple stars. The distribution of the relative angle Phi between the angular momentum vectors of inner and outer orbits in triple stars formed by decay is shown to depend on the initial cluster conditions like geometry, mass function, rotational and thermal energy. For a realistic set of initial conditions, a modest alignment of orbital momentum vectors is found, in good agreement with the latest observational data on visual multiple stars exhibiting an average between 67o and 79o. The relation between eccentricities of outer orbits and period ratios for both simulated and real triples is consistent with a slightly adjusted formulation of the stability criterium by Mardling & Aarseth (2001). Dynamical decay can therefore explain the weak correlation of orbital orientations observed in multiple stars. Using modern high-resolution techniques, the observed statistics of Phi should be extended as it will allow one to sensitively constrain properties of initial clusters. Table 4 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/384/1030

  15. Cytotoxic T-lymphocyte escape viral variants: how important are they in viral evasion of immune clearance in vivo?

    Science.gov (United States)

    Borrow, P; Shaw, G M

    1998-08-01

    Although viral variants which are not recognized by epitope-specific cytotoxic T lymphocytes (CTL) have been shown to arise during a number of persistent virus infections, in many cases their significance remains controversial: it has been argued that the immune response is sufficiently plastic to contain their replication. In this review, we describe the mechanisms by which amino acid changes in viral proteins may affect epitope recognition by virus-specific CTL, and discuss the viral and immunological basis for the emergence of viral variants bearing such amino acid changes during infection. We then consider the impact that viral variation may have on the host CTL response and its ability to contain virus replication. We argue that the emergence of a viral variant demonstrates that it must have an in vivo replicative advantage, and that as such, the variant must tip the balance between virus replication and immune control somewhat in favor of the virus. Further, we suggest that although the immune response can evolve to recognize new viral epitopes, the CTL generated following such evolution frequently have a reduced ability to contain virus replication. We conclude that this escape mechanism likely does make a significant contribution to persistence/pathogenesis during a number of different virus infections.

  16. Cytokine determinants of viral tropism

    Science.gov (United States)

    McFadden, Grant; Mohamed, Mohamed R.; Rahman, Masmudur M.; Bartee, Eric

    2015-01-01

    The specificity of a given virus for a ceil type, tissue or species — collectively known as viral tropism — is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine viral tropism has become particularly important. In this Review, we summarize our current understanding of the central role of antiviral and pro-inflammatory cytokines, particularly the interferons and tumour necrosis factor, in dictating viral tropism and how these cytokine pathways can be exploited therapeutically for cancer treatment and to better counter future threats from emerging zoonotic pathogens. PMID:19696766

  17. Viral Evolution Core | FNLCR Staging

    Science.gov (United States)

    Brandon F. Keele, Ph.D. PI/Senior Principal Investigator, Retroviral Evolution Section Head, Viral Evolution Core Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research Frederick, MD 21702-1201 Tel: 301-846-173

  18. Microbiological diagnostics of viral hepatitis

    OpenAIRE

    HASDEMİR, Ufuk

    2016-01-01

    Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

  19. Treatment of Acute Viral Bronchiolitis

    OpenAIRE

    Eber, Ernst

    2011-01-01

    Acute viral bronchiolitis represents the most common lower respiratory tract infection in infants and young children and is associated with substantial morbidity and mortality. Respiratory syncytial virus is the most frequently identified virus, but many other viruses may also cause acute bronchiolitis. There is no common definition of acute viral bronchiolitis used internationally, and this may explain part of the confusion in the literature. Most children with bronchiolitis have a self limi...

  20. Evolution of approaches to viral safety issues for biological products.

    Science.gov (United States)

    Lubiniecki, Anthony S

    2011-01-01

    CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Approaches to viral safety issues for biological products have evolved during the past 50+ years. The first cell culture products (viral vaccines) relied largely on the use of in vitro and in vivo virus screening assays that were based upon infectivity of adventitious viral agents. The use of Cohn fractionation and pasteurization by manufacturers of plasma derivatives introduced the concepts that purification and treatment with physical and chemical agents could greatly reduce the risk of viral contamination of human albumin and immunoglobulin products. But the limitations of such approaches became clear for thermolabile products that were removed early in fractionation such as antihemophilic factors, which transmitted hepatitis viruses and HIV-1 to some product recipients. These successes and limitations were taken into account by the early developers of recombinant DNA (rDNA)-derived cell culture products and by regulatory agencies, leading to the utilization of cloning technology to reduce/eliminate contamination due to human viruses and purification technologies to physically remove and inactivate adventitious and endogenous viruses, along with cell banking and cell bank characterization for adventitious and endogenous viruses, viral screening of biological raw materials, and testing of cell culture harvests, to ensure virus safety. Later development and incorporation of nanofiltration technology in the manufacturing process provided additional assurance of viral clearance for safety of biotechnology products. These measures have proven very effective at preventing iatrogenic infection of recipients of biotechnology products; however, viral contamination of production cell cultures has

  1. Double-membrane triple-electrolyte redox flow battery design

    Energy Technology Data Exchange (ETDEWEB)

    Yushan, Yan; Gu, Shuang; Gong, Ke

    2018-03-13

    A redox flow battery is provided having a double-membrane (one cation exchange membrane and one anion exchange membrane), triple-electrolyte (one electrolyte in contact with the negative electrode, one electrolyte in contact with the positive electrode, and one electrolyte positioned between and in contact with the two membranes). The cation exchange membrane is used to separate the negative or positive electrolyte and the middle electrolyte, and the anion exchange membrane is used to separate the middle electrolyte and the positive or negative electrolyte. This design physically isolates, but ionically connects, the negative electrolyte and positive electrolyte. The physical isolation offers great freedom in choosing redox pairs in the negative electrolyte and positive electrolyte, making high voltage of redox flow batteries possible. The ionic conduction drastically reduces the overall ionic crossover between negative electrolyte and positive one, leading to high columbic efficiency.

  2. Evaluation of a novel triple-channel radiochromic film analysis procedure using EBT2.

    Science.gov (United States)

    van Hoof, Stefan J; Granton, Patrick V; Landry, Guillaume; Podesta, Mark; Verhaegen, Frank

    2012-07-07

    A novel approach to read out radiochromic film was introduced recently by the manufacturer of GafChromic film. In this study, the performance of this triple-channel film dosimetry method was compared against the conventional single-red-channel film dosimetry procedure, with and without inclusion of a pre-irradiation (pre-IR) film scan, using EBT2 film and kilo- and megavoltage photon beams up to 10 Gy. When considering regions of interest averaged doses, the triple-channel method and both single-channel methods produced equivalent results. Absolute dose discrepancies between the triple-channel method, both single-channel methods and the treatment planning system calculated dose values, were no larger than 5 cGy for dose levels up to 2.2 Gy. Signal to noise in triple-channel dose images was found to be similar to signal to noise in single-channel dose images. The accuracy of resulting dose images from the triple- and single-channel methods with inclusion of pre-IR film scan was found to be similar. Results of a comparison of EBT2 data from a kilovoltage depth dose experiment to corresponding Monte Carlo depth dose data produced dose discrepancies of 9.5 ± 12 cGy and 7.6 ± 6 cGy for the single-channel method with inclusion of a pre-IR film scan and the triple-channel method, respectively. EBT2 showed to be energy sensitive at low kilovoltage energies with response differences of 11.9% and 15.6% in the red channel at 2 Gy between 50-225 kVp and 80-225 kVp photon spectra, respectively. We observed that the triple-channel method resulted in non-uniformity corrections of ±1% and consistency values of 0-3 cGy for the batches and dose levels studied. Results of this study indicate that the triple-channel radiochromic film read-out method performs at least as well as the single-channel method with inclusion of a pre-IR film scan, reduces film non-uniformity and saves time with elimination of a pre-IR film scan.

  3. Cellular sensing of viral DNA and viral evasion mechanisms.

    Science.gov (United States)

    Orzalli, Megan H; Knipe, David M

    2014-01-01

    Mammalian cells detect foreign DNA introduced as free DNA or as a result of microbial infection, leading to the induction of innate immune responses that block microbial replication and the activation of mechanisms that epigenetically silence the genes encoded by the foreign DNA. A number of DNA sensors localized to a variety of sites within the cell have been identified, and this review focuses on the mechanisms that detect viral DNA and how the resulting responses affect viral infections. Viruses have evolved mechanisms that inhibit these host sensors and signaling pathways, and the study of these antagonistic viral strategies has provided insight into the mechanisms of these host responses. The field of cellular sensing of foreign DNA is in its infancy, but our currently limited knowledge has raised a number of important questions for study.

  4. [Pathology and viral metagenomics, a recent history].

    Science.gov (United States)

    Bernardo, Pauline; Albina, Emmanuel; Eloit, Marc; Roumagnac, Philippe

    2013-05-01

    Human, animal and plant viral diseases have greatly benefited from recent metagenomics developments. Viral metagenomics is a culture-independent approach used to investigate the complete viral genetic populations of a sample. During the last decade, metagenomics concepts and techniques that were first used by ecologists progressively spread into the scientific field of viral pathology. The sample, which was first for ecologists a fraction of ecosystem, became for pathologists an organism that hosts millions of microbes and viruses. This new approach, providing without a priori high resolution qualitative and quantitative data on the viral diversity, is now revolutionizing the way pathologists decipher viral diseases. This review describes the very last improvements of the high throughput next generation sequencing methods and discusses the applications of viral metagenomics in viral pathology, including discovery of novel viruses, viral surveillance and diagnostic, large-scale molecular epidemiology, and viral evolution. © 2013 médecine/sciences – Inserm.

  5. Targeting Prolyl Peptidases in Triple-Negative Breast Cancer

    Science.gov (United States)

    2017-02-01

    AWARD NUMBER: W81XWH-16-1-0025 TITLE: Targeting Prolyl Peptidases in Triple-Negative Breast Cancer PRINCIPAL INVESTIGATOR: Carl G. Maki, PhD...SUBTITLE Targeting Prolyl Peptidases in Triple-Negative Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0025 5c. PROGRAM ELEMENT NUMBER 6...SUBJECT TERMS Triple negative breast cancer, Prolyl peptidases , Breast cancer treatment, Animal model 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

  6. Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral Infection

    Directory of Open Access Journals (Sweden)

    Haifeng C. Xu

    2017-11-01

    Full Text Available NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV. However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following LCMV infection, and this upregulation was dependent on type I interferons. Absence of Qa-1b resulted in increased NK cell-mediated regulation of anti-viral T cells following viral infection. Consequently, anti-viral T cell immunity was reduced in Qa-1b- and NKG2A-deficient mice, resulting in increased viral replication and immunopathology. NK cell depletion restored anti-viral immunity and virus control in the absence of Qa-1b. Taken together, our findings indicate that lymphocytes limit NK cell activity during viral infection in order to promote anti-viral T cell immunity.

  7. The Triple Axis and SPINS Spectrometers.

    Science.gov (United States)

    Trevino, S F

    1993-01-01

    In this paper are described the triple axis and spin polarized inelastic neutron scattering (SPINS) spectrometers which are installed at the NIST Cold Neutron Research Facility (CNRF). The general principle of operation of these two instruments is described in sufficient detail to allow the reader to make an informed decision as to their usefulness for his needs. However, it is the intention of the staff at the CNRF to provide the expert resources for their efficient use in any given situation. Thus, this work is not intended as a user manual but rather as a guide into the range of applicability of the two instruments.

  8. Triple Pelvic Osteotomy and Double Pelvic Osteotomy.

    Science.gov (United States)

    Guevara, Francisco; Franklin, Samuel P

    2017-07-01

    Triple and double pelvic osteotomy (TPO, DPO) are performed with the goal of increasing acetabular ventro-version, increasing femoral head coverage, and decreasing femoral head subluxation. Since the first descriptions of TPO, there have been modifications in technique, most notably omission of the ischial osteotomy for DPO, and improvements in the implants, including availability of locking TPO/DPO bone plates. Associated complication rates seem to have declined accordingly. The most salient questions regarding these procedures remain what selection criteria should be used to identify candidates and whether halting or preventing osteoarthritis is necessary to consider these surgeries clinically beneficial. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The triple axis and SPINS spectrometers

    International Nuclear Information System (INIS)

    Trevino, S.F.

    1993-01-01

    In this paper are described the triple axis and spin polarized inelastic neutron scattering (SPINS) spectrometers which are installed at the NIST Cold Neutron Research Facility (CNRF). The general principle of operation of these two instruments is described in sufficient detail to allow the reader to make an informed decision as to their usefulness for his needs. However, it is the intention of the staff at the CNRF to provide the expert resources for their efficient use in any given situation. Thus, this work is not intended as a user manual but rather as a guide into the range of applicability of the two instruments

  10. Occurrence of viral pathogens in Penaeus monodon post-larvae from aquaculture hatcheries

    Directory of Open Access Journals (Sweden)

    Toms C. Joseph

    2015-09-01

    Full Text Available Viral pathogens appear to exert the most significant constraints on the growth and survival of crustaceans under culture conditions. The prevalence of viral pathogens White Spot Syndrome Virus (WSSV, Hepatopancreatic Parvo Virus (HPV, Monodon Baculo Virus (MBV and Infectious Hypodermal and Hematopoietic Necrosis Virus (IHHNV in Penaeus monodon post-larvae was studied. Samples collected from different hatcheries and also samples submitted by farmers from Kerala were analyzed. Out of 104 samples collected, WSSV was detected in 12.5% of the post-larvae samples. Prevalence of concurrent infections by HPV, MBV and WSSV (either dual or triple infection was present in 60.6% of the total post-larvae tested. Out of the 51 double positives, 98% showed either HPV or IHHNV infection. HPV or IHHNV was detected in 11 post-larval samples showing triple viral infection. This is the first report of IHHNV from India. Result of this study reveals the lack of efficient screening strategies to eradicate viruses in hatchery reared post-larvae.

  11. DNA-guided hepatitis B treatment: Viral load is insufficient with few exceptions

    OpenAIRE

    Jain, Pankaj

    2009-01-01

    In DNA-guided hepatitis B treatment, viral load is insufficient, and requires other viral markers for treatment of hepatitis B patients as in patients with acute exacerbation of chronic hepatitis B, end-stage renal disease on dialysis, human immunodeficiency virus co-infected patients. There are exceptions to this rule: a residual level hepatitis B virus (HBV) DNA at 24 wk predicts beneficial outcome and reduced resistance at 1 year. The genotypic viral resistance to antiviral agents and occu...

  12. Enfermedades virales emergentes y reemergentes

    Directory of Open Access Journals (Sweden)

    Jorge Eliécer Ossa Londoño

    1996-03-01

    Full Text Available Los virus no son una excepción al principio de que toda forma de vida de hoyes el producto de la evolución de información gen ética preexistente. Tradicionalmente se ha reconocido que ta expresión clínica de las enfermedades virales cambia con el tiempo; molecularmente se ha demostrado que esos cambios fenotípicos son el producto de variaciones en el genoma viral. La tasa de cambio
    gen ético y fenotípico no es la misma en todos los agentes virales y ello está determinado, principalmente, por factores intrínsecos del virus, como la naturaleza de su ácido nucleico, y por la longevidad
    y tasa reproductiva del huésped.

  13. Hepatitis B viral DNA decline at loss of HBeAg is mainly explained by reduced cccDNA load--down-regulated transcription of PgRNA has limited impact.

    Science.gov (United States)

    Malmström, Sebastian; Larsson, Simon B; Hannoun, Charles; Lindh, Magnus

    2012-01-01

    Quantification of hepatitis B virus (HBV) DNA and surface antigen (HBsAg) serum levels have become increasingly important for the assessment of clinical stage and response to treatment for chronic hepatitis B. Effective immune clearance results in reduction of viremia by 4-5 log units and HBsAg levels by 2 log, but these processes are not well understood. Thus, it is uncertain to what extent mechanisms that inhibit transcription of the pregenomic RNA (pgRNA), an RNA intermediate, contribute to suppression of viremia. Likewise, it is unclear if transcriptional regulation is important for the excessive production of surface antigen (HBsAg) that is a hallmark of HBV infection. HBV RNA and cccDNA were quantified in 19 liver biopsies from patients with chronic HBV infection, as well as in transfected Huh7.5 cells and in PLC/PRF/5 cells carrying integrated HBV genome. Patients negative for HBeAg had 2.15 log lower levels of cccDNA in liver tissue, 4.84 log lower serum levels of HBV DNA and 1.45 log lower serum levels of HBsAg, than HBeAg-positive patients. The pgRNA in liver tissue correlated strongly with cccDNA (R(2) = 0.87, ploss of HBeAg was mainly explained by reduced cccDNA load in the liver, whereas the contribution of down-regulation of pgRNA transcription was relatively small. Enhanced transcription of S-RNA does not explain excessive production of HBsAg.

  14. Dispersion cancellation in a triple Laue interferometer

    International Nuclear Information System (INIS)

    Lemmel, Hartmut

    2014-01-01

    The concept of dispersion cancellation has been established in light optics to improve the resolution of interferometric measurements on dispersive media. Odd order dispersion cancellation allows to measure phase shifts without defocusing the interferometer due to wave packet displacements, while even order dispersion cancellation allows to measure time lags without losing resolution due to wave packet spreading. We report that either type of dispersion cancellation can be realized very easily in a triple Laue interferometer. Such interferometers are Mach–Zehnder interferometers based on Bragg diffraction, and are commonly used for neutrons and x-rays. Although the first x-ray interferometer was built nearly five decades ago, the feature of dispersion cancellation hasn't been recognized so far because the concept was hardly known in the neutron and x-ray community. However, it explains right away the surprising decoupling of phase shift and spatial displacement that we have discovered recently in neutron interferometry (Lemmel and Wagh 2010 Phys. Rev. A 82 033626). Furthermore, this article might inspire the light optics community to consider whether a triple Laue interferometer for laser light would be useful and feasible. We explain how dispersion cancellation works in neutron interferometry, and we describe the setup rigorously by solving the Schrödinger equation and by calculating the path integral. We point out, that the latter has to be evaluated with special care since in our setup the beam trajectory moves with respect to the crystal lattice of the interferometer. (paper)

  15. VERITAS: Versatile Triple-Axis Spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Il

    2006-04-15

    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, {approx} 5 m Curved Guide, {approx} 26 m w/ R 1500 m Straight Guide before the Instrument, {approx} 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world.

  16. VERITAS: Versatile Triple-Axis Spectrometer

    International Nuclear Information System (INIS)

    Park, Sung Il

    2006-04-01

    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, ∼ 5 m Curved Guide, ∼ 26 m w/ R 1500 m Straight Guide before the Instrument, ∼ 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world

  17. Functional Role of Infective Viral Particles on Metal Reduction

    Energy Technology Data Exchange (ETDEWEB)

    Coates, John D.

    2014-04-01

    A proposed strategy for the remediation of uranium (U) contaminated sites was based on the immobilization of U by reducing the oxidized soluble U, U(VI), to form a reduced insoluble end product, U(IV). Previous studies identified Geobacter sp., including G. sulfurreducens and G. metallireducens, as predominant U(VI)-reducing bacteria under acetate-oxidizing and U(VI)-reducing conditions. Examination of the finished genome sequence annotation of the canonical metal reducing species Geobacter sulfurreducens strain PCA and G. metallireduceans strain GS-15 as well as the draft genome sequence of G. uraniumreducens strain Rf4 identified phage related proteins. In addition, the completed genome for Anaeromyxobacter dehalogenans and the draft genome sequence of Desulfovibrio desulfuricans strain G20, two more model metal-reducing bacteria, also revealed phage related sequences. The presence of these gene sequences indicated that Geobacter spp., Anaeromyxobacter spp., and Desulfovibrio spp. are susceptible to viral infection. Furthermore, viral populations in soils and sedimentary environments in the order of 6.4×10{sup 6}–2.7×10{sup 10} VLP’s cm{sup -3} have been observed. In some cases, viral populations exceed bacterial populations in these environments suggesting that a relationship may exist between viruses and bacteria. Our preliminary screens of samples collected from the ESR FRC indicated that viral like particles were observed in significant numbers. The objective of this study was to investigate the potential functional role viruses play in metal reduction specifically Fe(III) and U(VI) reduction, the environmental parameters affecting viral infection of metal reducing bacteria, and the subsequent effects on U transport.

  18. A Cell-Permeable Hairpin Peptide Inhibits Hepatitis C Viral Nonstructural Protein 5A Mediated Translation and Virus Production

    Science.gov (United States)

    Khachatoorian, Ronik; Arumugaswami, Vaithilingaraja; Ruchala, Piotr; Raychaudhuri, Santanu; Maloney, Eden M.; Miao, Edna; Dasgupta, Asim; French, Samuel W.

    2012-01-01

    NS5A is a key regulator of hepatitis C virus (HCV) life cycle including RNA replication, assembly, and translation. We and others have shown NS5A to augment HCV IRES-mediated translation. Further, Quercetin treatment and heat shock protein (HSP) 70 knockdown inhibit NS5A-driven augmentation of IRES-mediated translation and infectious virus production. We have also co-immunoprecipitated HSP70 with NS5A and demonstrated cellular colocalization leading to the hypothesis that the NS5A/HSP70 complex formation is important for IRES-mediated translation. Here, we have identified the NS5A region responsible for complex formation through in vitro deletion analyses. Deletion of NS5A domains II and III failed to reduce HSP70 binding, whereas domain I deletion eliminated complex formation. NS5A domain I alone also bound HSP70. Deletion mapping of domain I identified the C-terminal 34 amino acids (C34) to be the interaction site. Further, addition of C34 to domains II and III restored complex formation. C34 expression significantly reduced intracellular viral protein levels, in contrast to same size control peptides from other NS5A domains. C34 also competitively inhibited NS5A-augmented IRES-mediated translation, while controls did not. Triple-alanine scan mutagenesis identified an exposed beta-sheet hairpin in C34 to be primarily responsible for NS5A-augmented IRES-mediated translation. Moreover, treatment with a 10 amino acid peptide derivative of C34 suppressed NS5A-augmented IRES-mediated translation and significantly inhibited intracellular viral protein synthesis, with no associated cytotoxicity. Conclusion: These results support the hypothesis that the NS5A/HSP70 complex augments viral IRES-mediated translation, identify a sequence-specific hairpin element in NS5A responsible for complex formation, and demonstrate the functional significance of C34 hairpin-mediated NS5A/HSP70 interaction. Identification of this element may allow for further interrogation of NS5A

  19. Non-Viral Deoxyribonucleoside Kinases

    DEFF Research Database (Denmark)

    Christiansen, Louise Slot; Munch-Petersen, Birgitte; Knecht, Wolfgang

    2015-01-01

    Deoxyribonucleoside kinases (dNKs) phosphorylate deoxyribonucleosides to their corresponding monophosphate compounds. dNks also phosphorylate deoxyribonucleoside analogues that are used in the treatment of cancer or viral infections. The study of the mammalian dNKs has therefore always been of gr...

  20. Viral Infection and Hepatocellular Carcinoma

    NARCIS (Netherlands)

    J. Li (Juan)

    2017-01-01

    markdownabstractMuch of liver pathology is related to infection with HBV and HCV and it is important to define factors associated with clinical behavior of disease following infection with these viruses. Thus in this thesis I first focus on the natural history of chronic viral diseases associated

  1. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R

    2001-01-01

    expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets....

  2. A Policy Framework for Health Systems to Promote Triple Aim Innovation.

    Science.gov (United States)

    Verma, Amol; Bhatia, Sacha

    2016-01-01

    With the expiry of the Health Accords, provincial governments must face the challenge of improving performance in the context of ageing demographics, increasing multi-morbidity, and real concerns about financial stability. The Institute for Healthcare Improvement Triple Aim articulates fundamental goals that can guide health system transformation: improved population health, enhanced patient experience and reduced or stable per capita costs. Advancing fragmented and costly health systems in pursuit of these goals requires transformative, as opposed to iterative, change. Provincial governments are ideally suited to lead this change by acting as "integrators" who link healthcare organizations and align incentives across the spectrum of delivery. Although there is very limited evidence regarding the effectiveness of system-level reforms, we draw on initiatives from around the world to suggest policies that can promote system-level Triple Aim innovation. We categorize these policies within the classic functions ascribed to health systems: financing, stewardship and resource generation. As healthcare financers, governments should orient procurement policy towards the Triple Aim innovation and reform payment to reward value not volume. As health system stewards, governments should define a Triple Aim vision; measure and report outcomes, patient experience, and costs; integrate across sectors; and facilitate learning from failure and spread of successful innovation. As resource generators, governments should invest in health information technology to exploit "big data" and ensure that professional education equips front-line clinicians with skills necessary to improve systems. There are a number of barriers to system-level Triple Aim innovation. There is a lack of evidence for macro-level policy changes, innovation is costly and complicated, and system reform may not be politically appealing. Triple Aim innovation may also be conflated with organization-level quality

  3. Unexpected Hydration of a Triple Bond During DNA Synthesis

    DEFF Research Database (Denmark)

    Fatthalla, Maha I.; Pedersen, Erik B.

    2016-01-01

    acidic conditions, polarizes the triple bond in the intercalator and this makes hydration of the triple bond possible during the DNA synthesis and an oligonucleotide with 1-(indol-3-yl)-2-(pyren-1-yl)ethanone as the intercalator is formed. Insertion of the unhydrated and hydrated linker systems gave...

  4. Government and Governance of Regional Triple Helix Interactions

    Science.gov (United States)

    Danson, Mike; Todeva, Emanuela

    2016-01-01

    This conceptual paper contributes to the discussion of the role of regional government and regional Triple Helix constellations driving economic development and growth within regional boundaries. The impact of regionalism and subsidiarity on regional Triple Helix constellations, and the questions of governmentality, governance and institutional…

  5. December2004 Results of Triple Arthrodesis in Uganda.

    African Journals Online (AJOL)

    user

    2004-12-02

    Dec 2, 2004 ... triple arthrodesis in children should be deferred until the age of 12 years, for fear of increased failure of fusion ... children and youths aged between 6 and 21 years underwent Triple Athrodesis procedure. However, only 36 ... Complication. No. Of Cases. Good. Fair. Fail. Delayed Wound Healing. 5. 3. 2. 0.

  6. Triple Play Service and IPTV Services Offered within it

    Directory of Open Access Journals (Sweden)

    Dagmar Pajdusakova

    2008-01-01

    Full Text Available This paper deals with Triple Play multimedia service and figures its architecture. Triple Play offers voice, video and data services together in one customer connection. There is offered IPTV (Internet Protocol Television service within this service, where we can include also Video on Demand service and other different additional services. In the paper is described classification of Video on Demand services.

  7. Mast cells in viral infections

    Directory of Open Access Journals (Sweden)

    Piotr Witczak

    2012-04-01

    Full Text Available  There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9, but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus. It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

  8. Viral infections among couples for assisted reproduction in a fertility ...

    African Journals Online (AJOL)

    2012-09-28

    Sep 28, 2012 ... these clients. The males' seminal parameters were analyzed according to World Health Organization (WHO) criteria. ... Two couples had concordant HIV and HBV infections, respectively. ... for the baby) and antiretroviral therapy for HIV-positive partners to reduce the viral load before fertility treatment is.

  9. Viral infections among couples for assisted reproduction in a fertility ...

    African Journals Online (AJOL)

    Apart from separate laboratory and storage facilities, basic principles to minimize transmission are recommended: HBV vaccination in sero‑discordant partners of HBV carriers (and immunoprophylaxis for the baby) and antiretroviral therapy for HIV‑positive partners to reduce the viral load before fertility treatment is ...

  10. Triple-layer smart grid business model

    DEFF Research Database (Denmark)

    Ma, Zheng; Lundgaard, Morten; Jørgensen, Bo Nørregaard

    2016-01-01

    Viewing the smart grid with the theory of business models may open opportunities in understanding and capturing values in new markets. This study tries to discover and map the smart grid ecosystem-based business model framework with two different environments (sub-Saharan Africa and Denmark......), and identifies the parameters for the smart grid solutions to the emerging markets. This study develops a triple-layer business model including the organizational (Niche), environmental (Intermediate), and global (Dominators) factors. The result uncovers an interface of market factors and stakeholders...... in a generic smart grid constellation. The findings contribute the transferability potential of the smart grid solutions between countries, and indicate the potential to export and import smart grid solutions based on the business modeling....

  11. Rooted triple consensus and anomalous gene trees

    Directory of Open Access Journals (Sweden)

    Schmidt Heiko A

    2008-04-01

    Full Text Available Abstract Background Anomalous gene trees (AGTs are gene trees with a topology different from a species tree that are more probable to observe than congruent gene trees. In this paper we propose a rooted triple approach to finding the correct species tree in the presence of AGTs. Results Based on simulated data we show that our method outperforms the extended majority rule consensus strategy, while still resolving the species tree. Applying both methods to a metazoan data set of 216 genes, we tested whether AGTs substantially interfere with the reconstruction of the metazoan phylogeny. Conclusion Evidence of AGTs was not found in this data set, suggesting that erroneously reconstructed gene trees are the most significant challenge in the reconstruction of phylogenetic relationships among species with current data. The new method does however rule out the erroneous reconstruction of deep or poorly resolved splits in the presence of lineage sorting.

  12. RITA-type triple axis spectrometers

    International Nuclear Information System (INIS)

    Roennow, H.M.

    2001-01-01

    The RITA spectrometer at Risoe National Laboratory was the first to incorporate a complete re-thinking of the neutron-path from source, through detector to analysis. Since then, other RITA-type spectrometers such as SPINS at NIST, RITA-II at PSI have been built, and several new spectrometers around the world are adapting the same philosophy. The main novelty of RITA was the introduction of a single back-end tank featuring both an analyser block with multiple individually turnable analyser blades and a 2D position sensitive detector. Several new triple-axis spectrometers are presently being built at existing and future sources, and almost all of them have learnt from the experience with RITA. (R.P.)

  13. Triple T: Tourism, transmodernity and transformative learning

    Directory of Open Access Journals (Sweden)

    Ateljević Irena

    2016-01-01

    Full Text Available This paper brings together 'triple T' of tourism, transmodernity and transformative learning by exposing critical questions of (tourism futures and the sense of direction where are we going as a single humanity. In the current context of overwhelming crisis at all levels - environmentally, socially, economically, politically and culturally, there is an increasing evidence that we cannot continue with 'business as usual'. Hence, natural and social science, economists, political activists, writers, spiritual leaders and successful social entrepreneurs argue that humanity needs (and is actually going through a major global mind change and a paradigm shift in the 2T' century which is often described as the shift towards transmodernity. In exposing so, the paper then connects tourism and transformative learning asa potential catalyst to change the world for the better.

  14. Polarized triple-axis spectrometer TASP

    Energy Technology Data Exchange (ETDEWEB)

    Boeni, P.; Keller, P. [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    The polarized triple-axis spectrometer TASP at SINQ has been optimized for measuring magnetic cross sections in condensed matter. The neutrons are polarized or analyzed either by means of benders or Heusler monochromators. The beam divergence, i.e. the intensity, and the spectral range of the neutrons is rather large because of the supermirror coatings of the feeding neutron guide. The intensity can be further increased at the sample position by means of a focussing monochromator and a focussing anti-trumpet. The end position of TASP allows the tailoring of the neutron beam already before the monochromator and to scatter neutrons over very wide ranges of angles. (author) 6 figs., 1 tab., 8 refs.

  15. Polarized triple-axis spectrometer TASP

    International Nuclear Information System (INIS)

    Boeni, P.; Keller, P.

    1996-01-01

    The polarized triple-axis spectrometer TASP at SINQ has been optimized for measuring magnetic cross sections in condensed matter. The neutrons are polarized or analyzed either by means of benders or Heusler monochromators. The beam divergence, i.e. the intensity, and the spectral range of the neutrons is rather large because of the supermirror coatings of the feeding neutron guide. The intensity can be further increased at the sample position by means of a focussing monochromator and a focussing anti-trumpet. The end position of TASP allows the tailoring of the neutron beam already before the monochromator and to scatter neutrons over very wide ranges of angles. (author) 6 figs., 1 tab., 8 refs

  16. Viral-associated exacerbations of asthma and COPD.

    Science.gov (United States)

    Traves, Suzanne L; Proud, David

    2007-06-01

    Exacerbations of asthma and chronic obstructive pulmonary disease are major burdens on the healthcare system, and contribute significantly to the mortality and morbidity associated with these diseases. Upper respiratory viral infections are associated with the majority of such disease exacerbations. The past few years have seen advances in the mechanisms by which viral infections induce pro-inflammatory chemokine production, and in our understanding of host antiviral and anti-inflammatory defence pathways that might regulate responses to infection. A more comprehensive understanding of the molecular basis of these processes could elucidate new therapeutic approaches to reduce the devastating impact that these exacerbations have on quality of life and healthcare costs.

  17. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

    2016-01-01

    meningitis patients, CSF antibodies are focussed to only one single glycoform peptide of a major viral glycoprotein. Thus, dependent on the viral disease, the serological response may be variable or constant with respect to the number of targeted peptide glycoforms. Mapping of these epitopes relies......Viral envelope glycoproteins are major targets for antibodies that bind to and inactivate viral particles. The capacity of a viral vaccine to induce virus-neutralizing antibodies is often used as a marker for vaccine efficacy. Yet the number of known neutralization target epitopes is restricted...... owing to various viral escape mechanisms. We expand the range of possible viral glycoprotein targets, by presenting a previously unknown type of viral glycoprotein epitope based on a short peptide stretch modified with small O-linked glycans. Besides being immunologically active, these epitopes have...

  18. Triple negative breast cancer: an Indian perspective

    Directory of Open Access Journals (Sweden)

    Akhtar M

    2015-08-01

    Full Text Available Murtaza Akhtar, Subhrajit Dasgupta, Murtuza Rangwala Department of Surgery, NKP Salve Institute of Medical Sciences and Research Centre, Nagpur, Maharashtra, India Introduction: Breast cancer is the most common female cancer in the world. Triple negative breast cancer (TNBC is a recently identified biological variant with aggressive tumor behavior and poor prognosis. Data of hormonal status from the Indian population is scarce due to financial constraints in performing immunohistochemistry evaluation. The present study aims to prospectively analyze receptor status of all breast cancer patients and identify TNBC and compare their clinical profile and short term survival with other non-TNBC group. Materials and methods: All cytologically and histopathologically confirmed cases of carcinoma breast were prospectively enrolled. In a longitudinal study at tertiary care hospital in central India based on the hormonal status, they were further divided into TNBC and other groups. Comparison of risk factors, clinical profile and short-term survival was carried out. Results: A total 85 patients were enrolled and of them 37 (43.7% were TNBC. On comparing risk factors ie, age, age at menarche, total reproductive age, age at first child birth, and menopausal status – no statistical significance was observed between the TNBC and non-TNBC groups. But on comparison of clinical profile TNBC tumors were significantly large with majority of patients presenting as locally advanced breast cancer (83%. No statistical difference was observed in axillary lymph node status between two groups. TNBC tumors were histologically more aggressive (grade 3 compared to other groups. No statistically significant difference was observed in short term overall survival but all three deaths were observed in the TNBC group only and two local recurrences after surgery were observed in the TNBC group. Conclusion: TNBC forms a large proportion of carcinoma breast patients in a central

  19. Fractura triple del complejo suspensorio del hombro

    Directory of Open Access Journals (Sweden)

    Eraclio Delgado Rifá

    2015-06-01

    Full Text Available El complejo suspensorio del hombro es una estructura sumamente importante, compuesta por un anillo de huesos y tejidos blandos. Las lesiones aisladas de este complejo anatómico son frecuentes y no afectan su estabilidad. La interrupción doble conduce a la inestabilidad de esta estructura y usualmente requiere tratamiento quirúrgico. La triple interrupción, por su parte, es sumamente rara y es encontrada en casos de trauma de alta energía a menudo en asociación con otras lesiones. Se presenta una triple lesión del complejo suspensorio del hombro en un paciente de 46 años de edad, con una fractura de la glenoides, del acromion tipo III de Kuhn y de la coracoides tipo II de Ogawa. En este caso, la fractura del acromion fue tratada con fijación percutánea con alambres de Kirschner, por tener asociado lesiones de partes blandas que contraindicaron la reducción abierta. La fractura de la glenoides y de la apófisis coracoides fueron tratadas conservadoramente. Después de 6 meses de evolución, el paciente tuvo un resultado funcional aceptable, con una abducción de 90 grados, los 30 grados de rotación externa y 70 de rotación interna, además asintomático y consolidación de todas las fracturas. A pesar de ser catalogada de una lesión grave del cinturón escapular y estar asociada a otras lesiones se obtuvo un resultado satisfactorio al final del tratamiento.

  20. The "Triple Depreciation Line" instead of the "Triple Bottom Line": Towards a genuine integrated reporting

    OpenAIRE

    Rambaud, Alexandre; Richard, Jacques

    2014-01-01

    The ‘Triple Bottom Line’ (TBL) is a major and increasingly used socio-environmental accounting framework. However, critical academic examinations of this model have been remained scarce and most importantly, no real alternatives have been developed. Thus this theoretical paper provides a contribution to fill this gap. Through a critical analysis of the TBL, we argue that it suffers from severe limitations. In particular, it does not protect human and natural capital (HNC). As an answer to the...

  1. Impact of Stepping Stones Triple P on Parents with a Child Diagnosed with Autism Spectrum Disorder: Implications for School Psychologists

    Science.gov (United States)

    VanVoorhis, Richard W.; Miller, Kenneth L.; Miller, Susan M.; Stull, Judith C.

    2015-01-01

    The Stepping Stones Positive Parenting Program (Stepping Stones Triple P; SSTP) was designed for caregivers of children with disabilities to improve select parental variables such as parenting styles, parental satisfaction, and parental competency, and to reduce parental stress and child problem behaviors. This study focused on SSTP training for…

  2. Comparison of Triple Therapy plus Probiotic Yogurt vs. Standard Triple Therapy on Helicobacter Pylori Eradication

    Directory of Open Access Journals (Sweden)

    Vahid Mirzaee

    2013-04-01

    Full Text Available Background: Treatment of Helicobacter pylori as a major cause of gastric diseases is of utmost concern. We aimed to assess efficacy of triple therapy (amoxicillin, clarithromycin and pantoprazole plus probiotic yogurt (PY on eradication of H. pylori. Materials and Methods: Total 102 H. pylori positive patients were divided to 3 groups equally and randomly. For treatment of each group amoxicillin, clarithromycin and pantoprazole were used. Group A had additional PY and Group B ordinary low fat yogurt in their regimen as well. These groups were compared regarding treatment success.Results: Total number of 88 patients finished the treatment course. The most common experienced side effects were dysgeusia in groups A and B (25.8% and 32.3%, respectively, and dysgeusia with diarrhea and abdominal pain (30.8% in group C. Eradication rate was, respectively, 61.3%, 64.5% and 71.3% in group A, B and C of which difference was not statistically significant. However, the difference between 3 groups in regard to education level was statistically significant (p=0.005.Conclusion: PY enriched triple therapy has decreased side effects of antibiotics consumption; however, this has no impact on eradication of H. pylori. PY and triple therapy can be used concomitantly to increase the patient tolerance.

  3. Viral commercials: the consumer as marketeer

    NARCIS (Netherlands)

    Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

    2010-01-01

    Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers,

  4. Biochemical principles and inhibitors to interfere with viral capping pathways.

    Science.gov (United States)

    Decroly, Etienne; Canard, Bruno

    2017-06-01

    Messenger RNAs are decorated by a cap structure, which is essential for their translation into proteins. Many viruses have developed strategies in order to cap their mRNAs. The cap is either synthetized by a subset of viral or cellular enzymes, or stolen from capped cellular mRNAs by viral endonucleases ('cap-snatching'). Reverse genetic studies provide evidence that inhibition of viral enzymes belonging to the capping pathway leads to inhibition of virus replication. The replication defect results from reduced protein synthesis as well as from detection of incompletely capped RNAs by cellular innate immunity sensors. Thus, it is now admitted that capping enzymes are validated antiviral targets, as their inhibition will support an antiviral response in addition to the attenuation of viral mRNA translation. In this review, we describe the different viral enzymes involved in mRNA capping together with relevant inhibitors, and their biochemical features useful in inhibitor discovery. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Prospects for new viral vaccines.

    Science.gov (United States)

    Marmion, B P

    1980-08-11

    Animal virology has made outstanding contributions to preventive medicine by the development of vaccines for the control of infectious disease in man and animals. Cost-benefit analysis indicates substantial savings in health care costs from the control of diseases such as smallpox, poliomyelitis, yellow fever and measels. Areas for further development include vaccines for influenza (living, attenuated virus), the herpes group (varicella: cytomegalovirus), respiratory syncytial virus, rotavirus and hepatitis A, B, and non A/non B. The general options for vaccine formulation are discussed with particular emphasis on approaches with the use of viral genetics to 'tailor make' vaccine viruses with defined growth potential in laboratory systems, low pathogenicity, and defined antigens. Current progress with the development of an inactivated hepatitis B vaccine is reviewed as a case study in vaccine development. The impact of recent experiments in cloning hepatitis B virus DNA in E. coli on the production of a purified viral polypeptide vaccine is assessed.

  6. Viral diseases and human evolution

    Directory of Open Access Journals (Sweden)

    Leal Élcio de Souza

    2000-01-01

    Full Text Available The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc. are becoming formidable challenges, which may have a direct impact on the fate of our species.

  7. Viral diseases and human evolution.

    Science.gov (United States)

    Leal, E de S; Zanotto, P M

    2000-01-01

    The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effects on human progress. Recently emerged diseases causing massive pandemics (e.g., HIV-1 and HCV, dengue, etc.) are becoming formidable challenges, which may have a direct impact on the fate of our species.

  8. Salicylate •Phenanthroline copper (II) complex induces apoptosis in triple-negative breast cancer cells.

    Science.gov (United States)

    Fan, Limei; Tian, Muyou; Liu, Yunyi; Deng, Ying; Liao, Zhengkai; Xu, Jinhua

    2017-05-02

    In this study, we investigated anti-tumor activity and associated molecular mechanism of action of Salicylate ●Phenanthroline Copper (II) Complex in triple-negative breast cancer. Salicylate ●Phenanthroline Copper (II) Complex inhibited the growth of four breast cancer cell lines (MCF-7, T47D, MDA-MB-231 and BT-20) and induced apoptosis in a concentration-dependent manner. The effect was more profound in MDA-MB-231 and BT-20 triple-negative breast cancer cell lines. Western blot showed that the expression of the apoptosis-related protein Bcl-2, Bcl-xl and survivin was significantly reduced in MDA-MB-231 after treatment with Salicylate ●Phenanthroline Copper (II) Complex. In vivo, Salicylate ●Phenanthroline Copper (II) Complex administration significantly attenuated tumor growth of MDA-MB-231 xenografts, and the expression levels of Bcl-2, Bcl-xL and survivin were reduced as measured by immunohistochemical staining. These data suggest that Salicylate ●Phenanthroline Copper (II) Complex is a promising novel therapeutic drug for triple-negative breast cancer and warrants further study.

  9. Viral diseases and human evolution

    OpenAIRE

    Leal, Elcio de Souza [UNIFESP; Zanotto, Paolo Marinho de Andrade [UNIFESP

    2000-01-01

    The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish l...

  10. Viral exanthems in the tropics.

    Science.gov (United States)

    Carneiro, Sueli Coelho da Silva; Cestari, Tania; Allen, Samuel H; Ramos e-Silva, Marcia

    2007-01-01

    Viral exanthems are a common problem in tropical regions, particularly affecting children. Most exanthems are transient and harmless, but some are potentially very dangerous. Pregnant women and malnourished or immunocompromised infants carry the greatest risk of adverse outcome. In this article, parvovirus B19; dengue and yellow fever; West Nile, Barmah Forest, Marburg, and Ebola viruses, and human herpesviruses; asymmetric periflexural exanthema of childhood; measles; rubella; enteroviruses; Lassa fever; and South American hemorrhagic fevers will be discussed.

  11. Treatment of acute viral bronchiolitis.

    Science.gov (United States)

    Eber, Ernst

    2011-01-01

    Acute viral bronchiolitis represents the most common lower respiratory tract infection in infants and young children and is associated with substantial morbidity and mortality. Respiratory syncytial virus is the most frequently identified virus, but many other viruses may also cause acute bronchiolitis. There is no common definition of acute viral bronchiolitis used internationally, and this may explain part of the confusion in the literature. Most children with bronchiolitis have a self limiting mild disease and can be safely managed at home with careful attention to feeding and respiratory status. Criteria for referral and admission vary between hospitals as do clinical practice in the management of acute viral bronchiolitis, and there is confusion and lack of evidence over the best treatment for this condition. Supportive care, including administration of oxygen and fluids, is the cornerstone of current treatment. The majority of infants and children with bronchiolitis do not require specific measures. Bronchodilators should not be routinely used in the management of acute viral bronchiolitis, but may be effective in some patients. Most of the commonly used management modalities have not been shown to have a clear beneficial effect on the course of the disease. For example, inhaled and systemic corticosteroids, leukotriene receptor antagonists, immunoglobulins and monoclonal antibodies, antibiotics, antiviral therapy, and chest physiotherapy should not be used routinely in the management of bronchiolitis. The potential effect of hypertonic saline on the course of the acute disease is promising, but further studies are required. In critically ill children with bronchiolitis, today there is little justification for the use of surfactant and heliox. Nasal continuous positive airway pressure may be beneficial in children with severe bronchiolitis but a large trial is needed to determine its value. Finally, very little is known on the effect of the various

  12. The Hill stability of triple planets in the Solar system

    Science.gov (United States)

    Liu, Chao; Gong, Shengping

    2017-07-01

    The Hill stability of the nine known triple asteroid systems in the solar system has been investigated in a framework of the three body system. In this paper, the Sun and triple-asteroid system are treated as a four body system to analyze the influence of the Sun on the Hill stability of the triple subsystem. First, the relationship of the total energy and the angular momentum between the four body system and the triple subsystem is derived. It is found that the total energy of this 1-3 configuration four body system is the sum of the energy of the triple subsystem and the energy of a two-body system composed of the Sun and the mass center of the subsystem; so is the angular momentum. Then, the Hill stability of the triple subsystem is reinvestigated using a previous criterion in the four body problem (Gong and Liu in Mon. Not. R. Astron. Soc. 462:547-553, 2016) and the results are compared to those in the three body problem. Among the nine known triple-asteroid systems, 1995 CC and 1999 TC are Hill stable for both models; the others are stable in the three body model while not stable in the four body model. In addition, the exploration of Pluto by New Horizons has attracted great attention in recent years, the Sun-Pluto-Charon-Hydra four body system is investigated in the paper, and it is found that the system is Hill stable.

  13. Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide

    Directory of Open Access Journals (Sweden)

    Singh D

    2017-10-01

    Full Text Available Dave Singh,1 Massimo Corradi,2 Monica Spinola,3 Alberto Papi,4 Omar S Usmani,5 Mario Scuri,3 Stefano Petruzzelli,3 Jørgen Vestbo1 1Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK; 2Department of Medicine and Surgery, University of Parma, Parma, Italy; 3Chiesi Farmaceutici SpA, Parma, Italy; 4Department of Medical Sciences, Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy; 5National Heart and Lung Institute, Imperial College London, London, UK Abstract: The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance. The triple combination therapy of inhaled corticosteroids (ICSs, long-acting beta2 agonists (LABAs, and long-acting muscarinic antagonists (LAMAs has become an option for maintenance treatment of COPD and as a “step-up” therapy from single or double combination treatments. There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations. A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 µg/puff/formoterol fumarate (6 µg/puff/glycopyrronium bromide (12.5 µg/puff has been developed as a hydrofluoroalkane pressurized metered dose inhaler. Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation. This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients. Keywords: COPD, inhaled triple therapy, beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide

  14. Acral manifestations of viral infections.

    Science.gov (United States)

    Adışen, Esra; Önder, Meltem

    Viruses are considered intracellular obligates with a nucleic acid RNA or DNA. They have the ability to encode proteins involved in viral replication and production of the protective coat within the host cells but require host cell ribosomes and mitochondria for translation. The members of the families Herpesviridae, Poxviridae, Papovaviridae, and Picornaviridae are the most commonly known agents for cutaneous viral diseases, but other virus families, such as Adenoviridae, Togaviridae, Parvoviridae, Paramyxoviridae, Flaviviridae, and Hepadnaviridae, can also infect the skin. Herpetic whitlow should be considered under the title of special viral infections of the acral region, where surgical incision is not recommended; along with verruca plantaris with its resistance to treatment and the search for a new group of treatments, including human papillomavirus vaccines; HIV with maculopapular eruptions and palmoplantar desquamation; orf and milker's nodule with its nodular lesions; papular-purpuric gloves and socks syndrome with its typical clinical presentation; necrolytic acral erythema with its relationship with zinc; and hand, foot, and mouth disease with its characteristics of causing infection with its strains, with high risk for complication. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Pediatric Asthma and Viral Infection.

    Science.gov (United States)

    Garcia-Garcia, M Luz; Calvo Rey, Cristina; Del Rosal Rabes, Teresa

    2016-05-01

    Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma. Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.

  16. Neutrophil extracellular traps go viral

    Directory of Open Access Journals (Sweden)

    Günther Schönrich

    2016-09-01

    Full Text Available Neutrophils are the most numerous immune cells. Their importance as a first line of defense against bacterial and fungal pathogens is well described. In contrast, the role of neutrophils in controlling viral infections is less clear. Bacterial and fungal pathogens can stimulate neutrophils to produce extracellular traps (NETs in a process called NETosis. Although NETosis has previously been described as a special form of programmed cell, there are forms of NET production that do not end with the demise of neutrophils. As an end result of NETosis, genomic DNA complexed with microbicidal proteins is expelled from neutrophils. These structures can kill pathogens or at least prevent their local spread within host tissue. On the other hand disproportionate NET formation can cause local or systemic damage. Only recently was it recognized that viruses can also induce NETosis. In this review, we discuss the mechanisms by which NETs are produced in the context of viral infection and how this may contribute to both antiviral immunity and immunopathology. Finally, we shed light on viral immune evasion mechanisms targeting NETs.

  17. On Pythagoras Theorem for Products of Spectral Triples

    Science.gov (United States)

    D'Andrea, Francesco; Martinetti, Pierre

    2013-05-01

    We discuss a version of Pythagoras theorem in noncommutative geometry. Usual Pythagoras theorem can be formulated in terms of Connes' distance, between pure states, in the product of commutative spectral triples. We investigate the generalization to both non-pure states and arbitrary spectral triples. We show that Pythagoras theorem is replaced by some Pythagoras inequalities, that we prove for the product of arbitrary (i.e. non-necessarily commutative) spectral triples, assuming only some unitality condition. We show that these inequalities are optimal, and we provide non-unital counter-examples inspired by K-homology.

  18. ANTI-VIRAL ACTIVITY OF GLYCIRRHETINIC AND GLYCIRRHIZIC ACIDS

    Directory of Open Access Journals (Sweden)

    V. V. Zarubaev

    2016-01-01

    Full Text Available Influenza is a highly contagious human disease. In the course of use of antiviral drugs drug-resistant strains of the virus are formed, resulting in reduced efficiency of the chemotherapy. The review describes the biological activity of glycirrhetinic (GLA and glycirrhizic (GA acids in terms of their use as a therapeutic agent for viral infections. So, these compounds are against a broad spectrum of viruses, including herpes, corona-, alphaand flaviviruses, human immunodeficiency virus, vaccinia virus, poliovirus type I, vesicular stomatitis virus and influenza A virus. These data indicate that anti-viral effect of these compounds is due to several types of activity — direct antiviral effects, effects on cellular proand anti-viral and immunomodulating pathways, in particular by activation of innate immunity system. GA interferes with early steps of the viral reproductive cycle such as virus binding to its receptor, the absorption of the virus by endocytosis or virus decapsidation in the cytoplasm. This is due to the effect of GA-induced reduction of membrane fluidity. Thus, one mechanism for the antiviral activity of GA is that GA molecule increases the rigidity of cellular and viral membranes after incorporation in there. This results in increasing of energy threshold required for the formation of negative curvature at the fusion zones, as well as difficult lateral migration of the virus-receptor complexes. In addition, glycyrrhizin prevents interaction of viral nucleoprotein with cellular protein HMGB1, which is necessary for the viral life cycle. Glycyrrhizin also inhibits the induction of oxidative stress during influenza infection, exhibiting antioxidant properties, which leads to a reduction of virus-induced production of cytokines/chemokines, without affecting the replication of the virus. A wide spectrum of biological activity and effect on various aspects of the viral pathogenesis substantiate the effect of GA and GLA as a component

  19. Uncovering the triple omeron vertex from Wilson line formalism

    International Nuclear Information System (INIS)

    Chirilli, G. A.; Szymanowski, L.; Wallon, S.

    2011-01-01

    We compute the triple omeron vertex from the Wilson line formalism, including both planar and nonplanar contributions, and get perfect agreement with the result obtained in the Extended Generalized Logarithmic Approximation based on Reggeon calculus.

  20. Triple Isotope Water Analyzer for Extraplanetary Studies, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Los Gatos Research (LGR) proposes to employ Off-Axis ICOS to develop triple-isotope water analyzers for lunar and other extraplanetary exploration. This instrument...

  1. Tripled Fixed Point in Ordered Multiplicative Metric Spaces

    Directory of Open Access Journals (Sweden)

    Laishram Shanjit

    2017-06-01

    Full Text Available In this paper, we present some triple fixed point theorems in partially ordered multiplicative metric spaces depended on another function. Our results generalise the results of [6] and [5].

  2. Triple Isotope Water Analyzer for Extraplanetary Studies Project

    Data.gov (United States)

    National Aeronautics and Space Administration — In this Small Business Innovative Research (SBIR) effort, Los Gatos Research (LGR) proposes to develop a miniature, high-resolution, low power, triple-isotope water...

  3. Applications of tripled chaotic maps in cryptography

    International Nuclear Information System (INIS)

    Behnia, S.; Akhshani, A.; Akhavan, A.; Mahmodi, H.

    2009-01-01

    Security of information has become a major issue during the last decades. New algorithms based on chaotic maps were suggested for protection of different types of multimedia data, especially digital images and videos in this period. However, many of them fundamentally were flawed by a lack of robustness and security. For getting higher security and higher complexity, in the current paper, we introduce a new kind of symmetric key block cipher algorithm that is based on tripled chaotic maps. In this algorithm, the utilization of two coupling parameters, as well as the increased complexity of the cryptosystem, make a contribution to the development of cryptosystem with higher security. In order to increase the security of the proposed algorithm, the size of key space and the computational complexity of the coupling parameters should be increased as well. Both the theoretical and experimental results state that the proposed algorithm has many capabilities such as acceptable speed and complexity in the algorithm due to the existence of two coupling parameters and high security. Note that the ciphertext has a flat distribution and has the same size as the plaintext. Therefore, it is suitable for practical use in secure communications.

  4. Triple Hybrid Energy Harvesting Interface Electronics

    Science.gov (United States)

    Uluşan, H.; Chamanian, S.; Pathirana, W. M. P. R.; Zorlu, Ö.; Muhtaroğlu, A.; Külah, H.

    2016-11-01

    This study presents a novel triple hybrid system that combines simultaneously generated power from thermoelectric (TE), vibration-based electromagnetic (EM) and piezoelectric (PZT) harvesters for a relatively high power supply capability. In the proposed solution each harvesting source utilizes a distinct power management circuit that generates a DC voltage suitable for combining the three parallel supplies. The circuits are designed and implemented in 180 nm standard CMOS technology, and are terminated with a schottky diode to avoid reverse current flow. The harvested AC signal from the EM harvester is rectified with a self-powered AC-DC doubler, which utilizes active diode structures to minimize the forward- bias voltage drop. The PZT interface electronics utilizes a negative voltage converter as the first stage, followed by synchronous power extraction and DC-to-DC conversion through internal switches, and an external inductor. The ultra-low voltage DC power harvested by the TE generator is stepped up through a charge-pump driven by an LC oscillator with fully- integrated center-tapped differential inductors. Test results indicate that hybrid energy harvesting circuit provides more than 1 V output for load resistances higher than 100 kΩ (10 μW) where the stand-alone harvesting circuits are not able to reach 1 V output. This is the first hybrid harvester circuit that simultaneously extracts energy from three independent sources, and delivers a single DC output.

  5. Triple echo steady-state (TESS) relaxometry.

    Science.gov (United States)

    Heule, Rahel; Ganter, Carl; Bieri, Oliver

    2014-01-01

    Rapid imaging techniques have attracted increased interest for relaxometry, but none are perfect: they are prone to static (B0 ) and transmit (B1 ) field heterogeneities, and commonly biased by T2 /T1 . The purpose of this study is the development of a rapid T1 and T2 relaxometry method that is completely (T2 ) or partly (T1 ) bias-free. A new method is introduced to simultaneously quantify T1 and T2 within one single scan based on a triple echo steady-state (TESS) approach in combination with an iterative golden section search. TESS relaxometry is optimized and evaluated from simulations, in vitro studies, and in vivo experiments. It is found that relaxometry with TESS is not biased by T2 /T1 , insensitive to B0 heterogeneities, and, surprisingly, that TESS-T2 is not affected by B1 field errors. Consequently, excellent correspondence between TESS and reference spin echo data is observed for T2 in vitro at 1.5 T and in vivo at 3 T. TESS offers rapid T1 and T2 quantification within one single scan, and in particular B1 -insensitive T2 estimation. As a result, the new proposed method is of high interest for fast and reliable high-resolution T2 mapping, especially of the musculoskeletal system at high to ultra-high fields. Copyright © 2013 Wiley Periodicals, Inc.

  6. Performance of a Horizontal Triple Cylinder Type Pulping Machine

    Directory of Open Access Journals (Sweden)

    Sukrisno Widyotomo

    2011-05-01

    Full Text Available Pulping is one important step in wet coffee processing method. Pulping process usually uses a machine which constructed by wood or metal materials. A horizontal single cylinder type of fresh coffee cherries pulping machine is the most popular machine in coffee processing. One of the weaknesses of a horizontal single cylinder type of fresh coffee cherries pulping machine is higher in broken beans. Broken bean is one of mayor aspects in defect system that contribute to low quality. Indonesian Coffee and Cocoa Research Institute has designed and tested a horizontal double cylinder type of fresh coffee cherries pulping machine which resulted in 12.6—21.4% of broken beans. To reduce percentage of broken beans, Indonesian Coffee and Cocoa Research Institute has developed and tested a horizontal triple cylinder type of fresh coffee cherries pulping machine. Material tested was fresh mature Robusta coffee cherries, 60—65% (wet basis moisture content; has classified on 3 levels i.e. unsorted, small and medium, and clean from metal and foreign materials. The result showed that the machine produced 6,340 kg/h in optimal capacity for operational conditions, 1400 rpm rotor rotation speed for unsorted coffee cherries with composition 55.5% whole parchment coffee, 3.66% broken beans, and 1% beans in wet skin.Key words : coffee, pulp, pulper, cylinder, quality.

  7. Optimization of elliptic neutron guides for triple-axis spectroscopy

    International Nuclear Information System (INIS)

    Janoschek, M.; Boeni, P.; Braden, M.

    2010-01-01

    In the last decade the performance of neutron guides for the transport of neutrons has been significantly increased. The most recent developments have shown that elliptic guide systems can be used to focus neutron beams while simultaneously reducing the number of neutron reflections, hence, leading to considerable gains in neutron flux. We have carried out Monte-Carlo simulations for a new triple-axis spectrometer that will be built at the end position of the conventional cold guide NL-1 in the neutron guide hall of the research reactor FRM-II in Munich, Germany. Our results demonstrate that an elliptic guide section at the end of a conventional guide can be used to at least maintain the total neutron flux onto the sample, while significantly improving the energy resolution of the spectrometer. The simulation further allows detailed insight how the defining parameters of an elliptic guide have to be chosen to obtain optimum results. Finally, we show that the elliptic guide limits losses in the neutron flux that generally arise at the gaps, where the monochromator system of the upstream instrument is situated.

  8. Encefalitis virales en la infancia

    Directory of Open Access Journals (Sweden)

    Monserrat Téllez de Meneses

    2013-09-01

    Full Text Available La encefalitis viral es una enfermedad grave que implica el compromiso inflamatorio del parénquima cerebral. Las infecciones virales del SNC ocurren con frecuencia como complicación de infecciones virales sistémicas. Más de 100 virus están implicados como agentes causales, entre los cuales el virus Herpes simplex tipo I, es el agente causal más frecuente de encefalitis no epidémica en todos los grupos poblacionales del mundo; es el responsable de los casos más graves en todas las edades. Muchos de los virus para los cuales existe vacunas también pueden causar encefalitis como: sarampión, paperas, polio, rabia, rubéola, varicela. El virus produce una inflamación del tejido cerebral, la cual puede evolucionar a una destrucción de neuronas, provocar hemorragia y daño cerebral, dando lugar a encefalitis graves, como la encefalitis necrotizante o hemorrágica, con mucho peor pronóstico, produciendo secuelas graves, incluso la muerte. El cuadro clínico, incluye la presencia de cefalea, fiebre y alteración de la conciencia, de rápida progresión. El pronóstico de las encefalitis víricas es variable, algunos casos son leves, con recuperación completa, sin embargo existen casos graves que pueden ocasionar secuelas importantes a nivel cerebral. Es fundamental realizar un diagnóstico lo antes posible, a través de pruebas de laboratorio (bioquímica, PCR, cultivos y de neuroimagen (TAC, RM y ante todo, la instauración de un tratamiento precoz para evitar la evolución del proceso y sus posibles complicaciones. El pronóstico empeora si se retrasa la instauración del tratamiento.

  9. Evaluation of Viral Meningoencephalitis Cases

    Directory of Open Access Journals (Sweden)

    Handan Ilhan

    2012-08-01

    Full Text Available AIM: To evaluate retrospectively adult cases of viral encephalitis. METHOD: Fifteen patients described viral encephalitis hospitalized between the years 2006-2011 follow-up and treatment at the infectious diseases clinic were analyzed retrospectively. RESULTS: Most of the patients (%60 had applied in the spring. Fever (87%, confusion (73%, neck stiffness (73%, headache (73%, nausea-vomiting (33%, loss of consciousness (33%, amnesia (33%, agitation (20%, convulsion (%20, focal neurological signs (13%, Brudzinski-sign (13% were most frequently encountered findings. Electroencephalography test was applied to 13 of 14 patients, and pathological findings compatible with encephalitis have been found. Radiological imaging methods such as CT and MRI were performed in 9 of the 14 patients, and findings consistent with encephalitis were reported. All of initial cerebrospinal fluid (CSF samples were abnormal. The domination of the first examples was lymphocytes in 14 patients; only one patient had an increase in neutrophilic cells have been found. CSF protein level was high in nine patients, and low glucose level was detected in two patients. Herpes simplex virus polymerized chain reaction (PCR analyze was performed to fourteen patients CSF. Only two of them (14% were found positive. One of the patients sample selectively examined was found to be Parvovirus B19 (+, the other patient urine sample Jacobs-creutzfeld virus PCR was found to be positively. Empiric acyclovir therapy was given to all patients. Neuropsychiatric squeal developed at the one patient. CONCLUSION: The cases in the forefront of change in mental status viral meningoencephalitis should be considered and empirical treatment with acyclovir should be started. [TAF Prev Med Bull 2012; 11(4.000: 447-452

  10. A Stakeholder Approach to Triple Bottom Line Accounting: Nigerian Experience

    OpenAIRE

    Okenwa Cy Ogbodo

    2015-01-01

    The broad objective of this study is to determine whether triple bottom line reports has been able to deliver stakeholders with the needed satisfaction when compared to conventional financial reports. To achieve the above objective three research questions were raised, to address the issue of triple bottom line report and stakeholder satisfaction. From these hypotheses were formulated. The descriptive method of research design was employed to generate the required data. The population of were...

  11. Immunohistochemical Characteristics of Triple Negative/Basal-like Breast Cancer

    OpenAIRE

    Emel Ebru PALA; Ümit BAYOL; Süheyla CUMURCU; Elif KESKİN

    2012-01-01

    Objective: Triple-negative-breast-cancer that accounts for 10-20% of all breast carcinomas is defined by the lack of estrogen receptor, progesterone receptor, HER2 expression, and agressive clinical behavior. Triple-negative-breast-cancer is categorized into basal like and other types. The basal-like subtype is characterized by the expression of myoepithelial/basal markers.Material and Method: We studied 41 immunohistochemically triplenegative- breast-cancer patients to determine EGFR, Cytoke...

  12. Targeting histone abnormality in triple negative breast cancer

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-14-1-0238 TITLE: Targeting histone abnormality in triple negative breast cancer PRINCIPAL INVESTIGATOR: Steffi...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting histone abnormality in triple negative breast cancer 5b. GRANT NUMBER W81XWH-14-1-0238 5c...PDXs). In addition, two teams collaborated in studying the functional role of LSD2 in breast cancer progression. The interactive studies between two

  13. Design of intelligent locks based on the triple KeeLoq algorithm

    Directory of Open Access Journals (Sweden)

    Huibin Chen

    2016-04-01

    Full Text Available KeeLoq algorithm with high security was usually used in wireless codec. Its security lack is indicated in this article according to the detailed rationale and the introduction of previous attack researches. Taking examples from Triple Data Encryption Standard algorithm, the triple KeeLoq codec algorithm was first proposed. Experimental results showed that the algorithm would not reduce powerful rolling effect and in consideration of limited computing power of embedded microcontroller three 64-bit keys were suitable to increase the crack difficulties and further improved its security. The method was applied to intelligent door access system for experimental verification. 16F690 extended Bluetooth or WiFi interface was employed to design the lock system on door. Key application was constructed on Android platform. The wireless communication between the lock on door and Android key application employed triple KeeLoq algorithm to ensure the higher security. Due to flexibility and multiformity (an Android key application with various keys of software-based keys, the solution owned overwhelmed advantages of low cost, high security, humanity, and green environmental protection.

  14. On the stability and collisions in triple stellar systems

    Science.gov (United States)

    He, Matthias Y.; Petrovich, Cristobal

    2018-02-01

    A significant fraction of main-sequence (MS) stars are part of a triple system. We study the long-term stability and dynamical outcomes of triple stellar systems using a large number of long-term direct N-body integrations with relativistic precession. We find that the previously proposed stability criteria by Eggleton & Kiseleva and Mardling & Aarseth predict the stability against ejections reasonably well for a wide range of parameters. Assuming that the triple stellar systems follow orbital and mass distributions from FGK binary stars in the field, we find that ˜ 1 per cent and ˜ 0.5 per cent of the triple systems lead to a direct head-on collision (impact velocity ˜ escape velocity) between MS stars and between a MS star and a stellar-mass compact object, respectively. We conclude that triple interactions are the dominant channel for direct collisions involving a MS star in the field with a rate of one event every ˜100 years in the Milky Way. We estimate that the fraction of triple systems that form short-period binaries is up to ˜ 23 per cent with only up to ˜ 13 per cent being the result of three-body interactions with tidal dissipation, which is consistent with previous work using a secular code.

  15. Triple combination as adjuvant to cryotherapy in the treatment of solar lentigines: investigator-blinded, randomized clinical trial.

    Science.gov (United States)

    Hexsel, D; Hexsel, C; Porto, M D; Siega, C

    2015-01-01

    Post-inflammatory hyperpigmentation is a frequent concern when treating solar lentigines. To assess the safety and efficacy of a triple combination cream with fluocinolone acetonide 0.01%, hydroquinone 4% and tretinoin 0.05% as adjuvant to cryotherapy in the treatment of solar lentigines in hands dorsum, and in the prevention of post-inflammatory hyperpigmentation after cryotherapy. This prospective, randomized, controlled, investigator-blinded, single-centre study enrolled 50 patients. Twenty-five patients received a 2-week daily triple combination cream plus sunscreen pre-treatment and 25 received sunscreen alone. After that, cryotherapy was performed in all patients followed by a 3-week recovery period. After this period, patients received the same initial treatment and were followed up for 8 weeks. Melanin and erythema levels of a target and a control lentigo were objectively measured using a narrowband reflectance spectrophotometer. Lentigines count, colour homogeneity and global improvement were also assessed. The number of solar lentigines reduced in the first 2 weeks only in patients who used the triple combination 25 ± 7 vs. 22 ± 8 (P cryotherapy were the reported adverse reactions. Triple combination cream can be used to enhance the resolution of solar lentigines, and to significantly reduce melanin levels and lentigines count, improving treatment results. It was well-tolerated and did not increase the occurrence of neither erythema nor other side-effects after the cryotherapy. © 2014 European Academy of Dermatology and Venereology.

  16. Estimating Initial Viral Levels during Simian Immunodeficiency Virus/Human Immunodeficiency Virus Reactivation from Latency.

    Science.gov (United States)

    Pinkevych, Mykola; Fennessey, Christine M; Cromer, Deborah; Tolstrup, Martin; Søgaard, Ole S; Rasmussen, Thomas A; Keele, Brandon F; Davenport, Miles P

    2018-01-15

    Human immunodeficiency virus (HIV) viremia rebounds rapidly after treatment interruption, and a variety of strategies are being explored to reduce or control viral reactivation posttreatment. This viral rebound arises from reactivation of individual latently infected cells, which spread during ongoing rounds of productive infection. The level of virus produced by the initial individual reactivating cells is not known, although it may have major implications for the ability of different immune interventions to control viral rebound. Here we use data from both HIV and simian immunodeficiency virus (SIV) treatment interruption studies to estimate the initial viral load postinterruption and thereby the initial individual reactivation event. Using a barcoded virus (SIVmac239M) to track reactivation from individual latent cells, we use the observed viral growth rates and frequency of reactivation to model the dynamics of reactivation to estimate that a single reactivated latent cell can produce an average viral load equivalent to ∼0.1 to 0.5 viral RNA (vRNA) copies/ml. Modeling of treatment interruption in HIV suggests an initial viral load equivalent of ∼0.6 to 1 vRNA copies/ml. These low viral loads immediately following latent cell reactivation provide a window of opportunity for viral control by host immunity, before further replication allows viral spread. This work shows the initial levels of viral production that must be controlled in order to successfully suppress HIV reactivation following treatment interruption. IMPORTANCE Current treatment for HIV is able to suppress viral replication and prevent disease progression. However, treatment cannot eradicate infection, because the virus lies silent within latently infected cells. If treatment is stopped, the virus usually rebounds above the level of detection within a few weeks. There are a number of approaches being tested aimed at either eradicating latently infected cells or controlling the virus if it

  17. Triple therapy with pyridoxine, arginine supplementation and dietary lysine restriction in pyridoxine-dependent epilepsy: Neurodevelopmental outcome.

    Science.gov (United States)

    Coughlin, Curtis R; van Karnebeek, Clara D M; Al-Hertani, Walla; Shuen, Andrew Y; Jaggumantri, Sravan; Jack, Rhona M; Gaughan, Sommer; Burns, Casey; Mirsky, David M; Gallagher, Renata C; Van Hove, Johan L K

    2015-01-01

    Pyridoxine-dependent epilepsy (PDE) is an epileptic encephalopathy characterized by response to pharmacologic doses of pyridoxine. PDE is caused by deficiency of α-aminoadipic semialdehyde dehydrogenase resulting in impaired lysine degradation and subsequent accumulation of α-aminoadipic semialdehyde. Despite adequate seizure control with pyridoxine monotherapy, 75% of individuals with PDE have significant developmental delay and intellectual disability. We describe a new combined therapeutic approach to reduce putative toxic metabolites from impaired lysine metabolism. This approach utilizes pyridoxine, a lysine-restricted diet to limit the substrate that leads to neurotoxic metabolite accumulation and L-arginine to compete for brain lysine influx and liver mitochondrial import. We report the developmental and biochemical outcome of six subjects who were treated with this triple therapy. Triple therapy reduced CSF, plasma, and urine biomarkers associated with neurotoxicity in PDE. The addition of arginine supplementation to children already treated with dietary lysine restriction and pyridoxine further reduced toxic metabolites, and in some subjects appeared to improve neurodevelopmental outcome. Dietary lysine restriction was associated with improved seizure control in one subject, and the addition of arginine supplementation increased the objective motor outcome scale in two twin siblings, illustrating the contribution of each component of this treatment combination. Optimal results were noted in the individual treated with triple therapy early in the course of the disease. Residual disease symptoms could be related to early injury suggested by initial MR imaging prior to initiation of treatment or from severe epilepsy prior to diagnosis. This observational study reports the use of triple therapy, which combines three effective components in this rare condition, and suggests that early diagnosis and treatment with this new triple therapy may ameliorate the

  18. Controlling viral outbreaks: Quantitative strategies.

    Science.gov (United States)

    Mummert, Anna; Weiss, Howard

    2017-01-01

    Preparing for and responding to outbreaks of serious livestock infectious diseases are critical measures to safeguard animal health, public health, and food supply. Almost all of the current control strategies are empirical, and mass culling or "stamping out" is frequently the principal strategy for controlling epidemics. However, there are ethical, ecological, and economic reasons to consider less drastic control strategies. Here we use modeling to quantitatively study the efficacy of different control measures for viral outbreaks, where the infectiousness, transmissibility and death rate of animals commonly depends on their viral load. We develop a broad theoretical framework for exploring and understanding this heterogeneity. The model includes both direct transmission from infectious animals and indirect transmission from an environmental reservoir. We then incorporate a large variety of control measures, including vaccination, antivirals, isolation, environmental disinfection, and several forms of culling, which may result in fewer culled animals. We provide explicit formulae for the basic reproduction number, R0, for each intervention and for combinations. We evaluate the control methods for a realistic simulated outbreak of low pathogenic avian influenza on a mid-sized turkey farm. In this simulated outbreak, culling results in more total dead birds and dramatically more when culling all of the infected birds.

  19. Efficacy of the Positive Parenting Program (Triple-P for a Group of Parents of Children with Attention Deficit Hyperactivity Disorder (ADHD

    Directory of Open Access Journals (Sweden)

    Mehdi Tehranidoost

    2008-07-01

    Full Text Available "nObjective: To evaluate the efficacy of the Positive Parenting Program (Triple-P for parents of children with attention deficit hyperactivity disorder (ADHD. "nMethod:  Sixty families who had at least one child with clinically diagnosed ADHD aged between 6 to12 were recruited from the consecutive referrals to a child and adolescent psychiatric clinic. Families were randomly assigned to the intervention group (who participated in an 8- week- group Triple-P, N=30 and a control group (N=30. Parents completed the battery of self-report questionnaires of triple-P at the beginning and after the 8th session. "nResults: There were no significant differences in pre intervention measures between the two groups. Comparing the pre and post intervention data, the Triple- P group was associated with significantly lower levels of parent reported child behavior problems (P=0.001, lower levels of dysfunctional parenting (P=0.001 and greater parental competence (P=0.001 than the control group. The parents the in triple-P group had significant improvement on measures of depression, anxiety and stress, in comparison with the control group (P=0.001. This study did not follow the long term effect which marks its limitation. "nConclusion: The Triple-P program can be recommended for parents of children with ADHD to reduce the problem behavior of their children and to improve their abilities.

  20. Viral Infection in Renal Transplant Recipients

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    Jovana Cukuranovic

    2012-01-01

    Full Text Available Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

  1. T Cell Exhaustion During Persistent Viral Infections

    Science.gov (United States)

    Kahan, Shannon M.; Wherry, E. John; Zajac, Allan J.

    2015-01-01

    Although robust and highly effective anti-viral T cells contribute to the clearance of many acute infections, viral persistence is associated with the development of functionally inferior, exhausted, T cell responses. Exhaustion develops in a step-wise and progressive manner, ranges in severity, and can culminate in the deletion of the anti-viral T cells. This disarming of the response is consequential as it compromises viral control and potentially serves to dampen immune-mediated damage. Exhausted T cells are unable to elaborate typical anti-viral effector functions. They are characterized by the sustained upregulation of inhibitory receptors and display a gene expression profile that distinguishes them from prototypic effector and memory T cell populations. In this review we discuss the properties of exhausted T cells; the virological and immunological conditions that favor their development; the cellular and molecular signals that sustain the exhausted state; and strategies for preventing and reversing exhaustion to favor viral control. PMID:25620767

  2. Viral diversity threshold for adaptive immunity in prokaryotes.

    Science.gov (United States)

    Weinberger, Ariel D; Wolf, Yuri I; Lobkovsky, Alexander E; Gilmore, Michael S; Koonin, Eugene V

    2012-12-04

    (Lamarckian evolution) are predicted. A remarkable recent discovery in microbiology is that bacteria and archaea possess systems conferring immunological memory and adaptive immunity. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (CRISPR-Cas) are genomic sensors that allow prokaryotes to acquire DNA fragments from invading viruses and plasmids. Providing immunological memory, these stored fragments destroy matching DNA in future viral and plasmid invasions. CRISPR-Cas systems also provide adaptive immunity, keeping up with mutating viruses and plasmids by continually acquiring new DNA fragments. Surprisingly, less than 50% of mesophilic bacteria, in contrast to almost 90% of thermophilic bacteria and Archaea, maintain CRISPR-Cas immunity. Using mathematical modeling, we probe this dichotomy, showing how increased viral mutation rates can explain the reduced prevalence of CRISPR-Cas systems in mesophiles. Rapidly mutating viruses outrun CRISPR-Cas immune systems, likely decreasing their prevalence in bacterial populations. Thus, viral adaptability may select against, rather than for, immune adaptability in prokaryotes.

  3. The triple-A supply chain.

    Science.gov (United States)

    Lee, Hau L

    2004-10-01

    Building a strong supply chain is essential for business success. But when it comes to improving their supply chains, few companies take the right approach. Many businesses work to make their chains faster or more cost-effective, assuming that those steps are the keys to competitive advantage. To the contrary: Supply chains that focus on speed and costs tend to deteriorate over time. The author has spent 15 years studying more than 60 companies to gain insight into this and other supply chain dilemmas. His conclusion: Only companies that build supply chains that are agile, adaptable, and aligned get ahead of their rivals. All three components are essential; without any one of them, supply chains break down. Great companies create supply chains that respond to abrupt changes in markets. Agility is critical because in most industries, both demand and supply fluctuate rapidly and widely. Supply chains typically cope by playing speed against costs, but agile ones respond both quickly and cost-efficiently. Great companies also adapt their supply networks when markets or strategies change. The best supply chains allow managers to identify structural shifts early by recording the latest data, filtering out noise, and tracking key patterns. Finally, great companies align the interests of the partners in their supply chains with their own. That's important because every firm is concerned solely with its own interests. If its goals are out of alignment with those of other partners in the supply chain, performance will suffer. When companies hear about the triple-A supply chain, they assume that building one will require increased technology and investment. But most firms already have the infrastructure in place to create one. A fresh attitude alone can go a long way toward making it happen.

  4. Acute Viral Hepatitis in Pediatric Age Groups

    OpenAIRE

    Sudhamshu KC; Dilip Sharma; Nandu Silwal; Bhupendra Kumar Basnet

    2014-01-01

    Introduction: Our clinical experience showed that there has been no decrease in pediatric cases of acute viral hepatitis in Kathmandu. The objective of the study was to analyze the etiology, clinical features, laboratory parameters, sonological findings and other to determine the probable prognostic factors of Acute Viral Hepatitis in pediatric population. Methods: Consecutive patients of suspected Acute Viral Hepatitis, below the age of 15 years, attending the liver clinic between Januar...

  5. Consumers’ attitude towards viral marketing in Pakistan

    OpenAIRE

    Kiani Irshad ZERNIGAH; Kamran SOHAIL

    2012-01-01

    The rapid advancement of technology has opened many costeffective avenues for marketers to promote their products. One of the emerging techniques of products promotion through the use of technology is viral marketing that is becoming a popular direct marketing tool for marketers across the world. Therefore, marketers should understand factors that result in increased acceptance of viral marketing by consumers. The present research was conducted to investigate consumers’ attitude towards viral...

  6. Viral Advertising on Facebook in Vietnam

    OpenAIRE

    Tran, Phuong

    2014-01-01

    The purpose of this thesis is to explore which factors affect the effectiveness of viral advertising on Facebook in Vietnam. The quantitative research method is applied in this research and the sample is Vietnamese Facebook users. After the data analysis stage using SPSS, it became clear that weak ties, perceptual affinity and emotions have an impact on the effectiveness of viral advertising. The results provide a pratical implication of how to make an Ad which can go viral on Facebook. Moreo...

  7. [Workshop on Molecular Epidemiology of Viral Diseases].

    Science.gov (United States)

    Gómez, B; Cabrera, L; Arias, C F

    1997-01-01

    A workshop on viral epidemiology was held on September 29, 1995 at the Medical School of the Universidad Nacional Autónoma de Mexico. The aim of this workshop was to promote interaction among scientists working in viral epidemiology. Eighteen scientists from ten institutions presented their experiences and work. General aspects of the epidemiology of meaningful viral diseases in the country were discussed, and lectures presented on the rota, polio, respiratory syncytial, dengue, papiloma, rabies, VIH and hepatitis viruses.

  8. Hepatitis A through E (Viral Hepatitis)

    Science.gov (United States)

    ... Nutrition Clinical Trials Primary Biliary Cholangitis Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What ...

  9. Silicon control of bacterial and viral diseases in plants

    Directory of Open Access Journals (Sweden)

    Sakr Nachaat

    2016-12-01

    Full Text Available Silicon plays an important role in providing tolerance to various abiotic stresses and augmenting plant resistance against diseases. However, there is a paucity of reports about the effect of silicon on bacterial and viral pathogens of plants. In general, the effect of silicon on plant resistance against bacterial diseases is considered to be due to either physical defense or increased biochemical defense. In this study, the interaction between silicon foliar or soil-treatments and reduced bacterial and viral severity was reviewed. The current review explains the agricultural importance of silicon in plants, refers to the control of bacterial pathogens in different crop plants by silicon application, and underlines the different mechanisms of silicon-enhanced resistance. A section about the effect of silicon in decreasing viral disease intensity was highlighted. By combining the data presented in this study, a better comprehension of the complex interaction between silicon foliar- or soil-applications and bacterial and viral plant diseases could be achieved.

  10. Viral diseases of northern ungulates

    Directory of Open Access Journals (Sweden)

    K. Frölich

    2000-03-01

    Full Text Available This paper describes viral diseases reported in northern ungulates and those that are a potential threat to these species. The following diseases are discussed: bovine viral diarrhoea/mucosal disease (BVD/MD, alphaherpesvirus infections, malignant catarrhal fever (MCF, poxvirus infections, parainfluenza type 3 virus infection, Alvsborg disease, foot-and-mouth disease, epizootic haemorrhage disease of deer and bluetongue disease, rabies, respiratory syncytial virus infection, adenovirus infection, hog-cholera, Aujeszky's disease and equine herpesvirus infections. There are no significant differences in antibody prevalence to BVDV among deer in habitats with high, intermediate and low density of cattle. In addition, sequence analysis from the BVDV isolated from roe deer (Capreolus capreolus showed that this strain was unique within BVDV group I. Distinct BVDV strains might circulate in free-ranging roe deer populations in Germany and virus transmission may be independent of domestic livestock. Similar results have been obtained in a serological survey of alpha-herpesviruses in deer in Germany. Malignant catarrhal fever was studied in fallow deer (Cervus dama in Germany: the seroprevalence and positive PCR results detected in sheep originating from the same area as the antibody-positive deer might indicate that sheep are the main reservoir animals. Contagious ecthyma (CE is a common disease in domestic sheep and goats caused by the orf virus. CE has been diagnosed in Rocky Mountain bighorn sheep (Ovis canadensis, mountain goats (Oreamnos americanus, Dall sheep (Ovis dalli, chamois (Rupkapra rupi-capra, muskox {Ovibos moschatus and reindeer (Rangifer tarandus. Most parainfluenza type 3 virus infections are mild or clinically undetectable. Serological surveys in wildlife have been successfully conducted in many species. In 1985, a new disease was identified in Swedish moose (Alces alces, designated as Alvsborg disease. This wasting syndrome probably

  11. Differential Requirement of Human Cytomegalovirus UL112-113 Protein Isoforms for Viral Replication.

    Science.gov (United States)

    Schommartz, Tim; Tang, Jiajia; Brost, Rebekka; Brune, Wolfram

    2017-09-01

    requirement for HCMV replication. We found that two of the UL112-113 gene products were dispensable for viral replication in human fibroblasts and endothelial cells. In contrast, viral replication was severely reduced or absent when one of the other two gene products was inactivated, indicating that they are of crucial importance for the viral replication cycle. We further showed that the latter two gene products are involved in the recruitment of pUL44, an essential cofactor of the viral DNA polymerase, to specific sites within the cell nucleus that are thought to serve as starting points for viral DNA replication. Copyright © 2017 American Society for Microbiology.

  12. Reduced Frequencies and Activation of Regulatory T Cells After the Treatment of HIV-1-Infected Individuals with the CCR5 Antagonist Maraviroc Are Associated with a Reduction in Viral Loads Rather Than a Direct Effect of the Drug on Regulatory T Cells.

    Science.gov (United States)

    Joedicke, Jara J; Dirks, Miriam; Esser, Stefan; Verheyen, Jens; Dittmer, Ulf

    2016-04-01

    Regulatory T cells (Tregs) play an important role in the pathogenesis of HIV-1 infection and they frequently express the chemokine receptor CCR5. We therefore investigated whether antiretroviral treatment with the CCR5 antagonist Maraviroc affected Tregs in chronically HIV-1-infected individuals. HIV-1-infected patients with high viral loads had elevated frequencies of activated Tregs in the peripheral blood compared with healthy controls. In patients successfully treated with antiretroviral drugs (undetectable viral loads), the frequency and the activation status of Tregs were comparable with healthy controls without any specific effect related to the treatment with Maraviroc. These results indicate that the control of viral replication in general rather than a direct binding of Maraviroc to CCR5-positive Tregs influences Treg responses in successfully treated chronically HIV-1-infected individuals.

  13. Viral ancestors of antiviral systems.

    Science.gov (United States)

    Villarreal, Luis P

    2011-10-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the 'Big Bang' theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  14. Viral Ancestors of Antiviral Systems

    Directory of Open Access Journals (Sweden)

    Luis P. Villarreal

    2011-10-01

    Full Text Available All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  15. Pepino mosaic virus triple gene block protein 1 (TGBp1) interacts with and increases tomato catalase 1 activity to enhance virus accumulation.

    Science.gov (United States)

    Mathioudakis, Matthaios M; Veiga, Rita S L; Canto, Tomas; Medina, Vicente; Mossialos, Dimitris; Makris, Antonios M; Livieratos, Ioannis

    2013-08-01

    Various plant factors are co-opted by virus elements (RNA, proteins) and have been shown to act in pathways affecting virus accumulation and plant defence. Here, an interaction between Pepino mosaic virus (PepMV) triple gene block protein 1 (TGBp1; p26) and tomato catalase 1 (CAT1), a crucial enzyme in the decomposition of toxic hydrogen peroxide (H₂O₂), was identified using the yeast two-hybrid assay, and confirmed via an in vitro pull-down assay and bimolecular fluorescent complementation (BiFC) in planta. Each protein was independently localized within loci in the cytoplasm and nuclei, sites at which their interaction had been visualized by BiFC. Following PepMV inoculation, CAT mRNA and protein levels in leaves were unaltered at 0, 3 and 6 days (locally) and 8 days (systemically) post-inoculation; however, leaf extracts from the last two time points contained increased CAT activity and lower H₂O₂ evels. Overexpression of PepMV p26 in vitro and in planta conferred the same effect, suggesting an additional involvement of TGBp1 in potexvirus pathogenesis. The accumulation of PepMV genomic and subgenomic RNAs and the expression of viral coat protein in noninoculated (systemic) leaves were reduced significantly in CAT-silenced plants. It is postulated that, during PepMV infection, a p26-CAT1 interaction increases H₂O₂ cavenging, thus acting as a negative regulator of plant defence mechanisms to promote PepMV infections. © 2013 BSPP AND JOHN WILEY & SONS LTD.

  16. Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo.

    Science.gov (United States)

    Zhao, Tiejun; Sun, Qiang; del Rincon, Sonia V; Lovato, Amanda; Marques, Maud; Witcher, Michael

    2014-01-01

    Triple-negative breast cancers are associated with poor clinical outcomes and new therapeutic strategies are clearly needed. Gallotannin (Gltn) has been previously demonstrated to have potent anti-tumor properties against cholangiocarcinoma in mice, but little is known regarding its capacity to suppress tumor outgrowth in breast cancer models. We tested Gltn for potential growth inhibitory properties against a variety of breast cancer cell lines in vitro. In particular, triple-negative breast cancer cells display higher levels of sensitivity to Gltn. The loss of proliferative capacity in Gltn exposed cells is associated with slowed cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and further characterized by changes to proliferation related genes, such as cyclin D1 (CcnD1) as determined by Nanostring technology. Importantly, Gltn administered orally or via intraperitoneal (IP) injections greatly reduced tumor outgrowth of triple-negative breast cells from mammary fat pads without signs of toxicity. In conclusion, these data strongly suggest that Gltn represents a novel approach to treat triple-negative breast carcinomas.

  17. Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo.

    Directory of Open Access Journals (Sweden)

    Tiejun Zhao

    Full Text Available Triple-negative breast cancers are associated with poor clinical outcomes and new therapeutic strategies are clearly needed. Gallotannin (Gltn has been previously demonstrated to have potent anti-tumor properties against cholangiocarcinoma in mice, but little is known regarding its capacity to suppress tumor outgrowth in breast cancer models. We tested Gltn for potential growth inhibitory properties against a variety of breast cancer cell lines in vitro. In particular, triple-negative breast cancer cells display higher levels of sensitivity to Gltn. The loss of proliferative capacity in Gltn exposed cells is associated with slowed cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and further characterized by changes to proliferation related genes, such as cyclin D1 (CcnD1 as determined by Nanostring technology. Importantly, Gltn administered orally or via intraperitoneal (IP injections greatly reduced tumor outgrowth of triple-negative breast cells from mammary fat pads without signs of toxicity. In conclusion, these data strongly suggest that Gltn represents a novel approach to treat triple-negative breast carcinomas.

  18. CAXIAS DO SUL TECHNOLOGY INCUBATOR: TECHNOLOGICAL INNOVATION THROUGH THE TRIPLE HELIX

    Directory of Open Access Journals (Sweden)

    Priscila Bresolin Tisott

    2014-09-01

    on investment in the form of registered patents, attracting new students and recognition as a technological, entrepreneurial and innovative university. The perceived benefits for the industrial sector are training and development for businesses and entrepreneurs, while the municipal government perceives the reduced number of businesses failing and the financial returns, in the form of taxes, as benefits. The findings show that the Triple Helix concept developed by Etzkowitz (2009 plays a cooperative and participatory role in the Technology Incubator, even though it could be applied to more segments of society.

  19. Longitudinal Neuropsychological Profile in a Patient with Triple A Syndrome

    Directory of Open Access Journals (Sweden)

    Luigi Mazzone

    2013-01-01

    Full Text Available Triple A syndrome is an autosomal recessive disorder characterized by the triad of adrenocorticotropic hormone resistant adrenal insufficiency, achalasia, and alacrima. Our aim was to describe the neuropsychological characteristics and the cooccurring psychopathological and neurological disorders in an Italian male child suffering from Triple A syndrome at the time of admission (T0 and after one year of follow-up (T1. Many difficulties were observed in the motor domain, as well as in manual dexterity and static/dynamic balance domains of the motor task over time. In sharp contrast with previous literature reports on frequent mild cognitive dysfunction in patients with Triple A syndrome, our child did not show any mental retardation. By contrast, he showed an average IQ at T0 with a slight improvement at T1. To our knowledge, this report is the first describing neuropsychological profile and co-occurring psychopathological problems in a child with Triple A syndrome. Considering that the Triple A syndrome is a progressive disorder which can take years to develop the full-blown clinical picture, these patients require periodical medical controls. Moreover, assessment of neuropsychological and psychopathological features should be performed in patients with this disease, in order to underline the variability of this syndrome.

  20. Heat shock protein-90-beta facilitates enterovirus 71 viral particles assembly

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Robert Y.L., E-mail: yuwang@mail.cgu.edu.tw [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Kuo, Rei-Lin [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Ma, Wei-Chieh [Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Huang, Hsing-I [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Yu, Jau-Song [Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Molecular Medicine Research Center, Chang Gung University, Tao-Yuan 333, Taiwan (China); Yen, Sih-Min [Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Huang, Chi-Ruei [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Shih, Shin-Ru [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China)

    2013-09-01

    Molecular chaperones are reported to be crucial for virus propagation, but are not yet addressed in Human Enterovirus 71 (EV71). Here we describe the specific association of heat shock protein-90-beta (Hsp90β), but not alpha form (Hsp90α), with EV71 viral particles by the co-purification with virions using sucrose density gradient ultracentrifugation, and by the colocalization with viral particles, as assessed by immunogold electron microscopy. The reduction of the Hsp90β protein using RNA interference decreased the correct assembly of viral particles, without affecting EV71 replication levels. Tracking ectopically expressed Hsp90β protein associated with EV71 virions revealed that Hsp90β protein was transmitted to new host cells through its direct association with infectious viral particles. Our findings suggest a new antiviral strategy in which extracellular Hsp90β protein is targeted to decrease the infectivity of EV71 and other enteroviruses, without affecting the broader functions of this constitutively expressed molecular chaperone. - Highlights: • Hsp90β is associated with EV71 virion and is secreted with the release virus. • Hsp90β effects on the correct assembly of viral particles. • Viral titer of cultured medium was reduced in the presence of geldanamycin. • Viral titer was also reduced when Hsp90β was suppressed by siRNA treatment. • The extracellular Hsp90β was also observed in other RNA viruses-infected cells.

  1. Heat shock protein-90-beta facilitates enterovirus 71 viral particles assembly

    International Nuclear Information System (INIS)

    Wang, Robert Y.L.; Kuo, Rei-Lin; Ma, Wei-Chieh; Huang, Hsing-I; Yu, Jau-Song; Yen, Sih-Min; Huang, Chi-Ruei; Shih, Shin-Ru

    2013-01-01

    Molecular chaperones are reported to be crucial for virus propagation, but are not yet addressed in Human Enterovirus 71 (EV71). Here we describe the specific association of heat shock protein-90-beta (Hsp90β), but not alpha form (Hsp90α), with EV71 viral particles by the co-purification with virions using sucrose density gradient ultracentrifugation, and by the colocalization with viral particles, as assessed by immunogold electron microscopy. The reduction of the Hsp90β protein using RNA interference decreased the correct assembly of viral particles, without affecting EV71 replication levels. Tracking ectopically expressed Hsp90β protein associated with EV71 virions revealed that Hsp90β protein was transmitted to new host cells through its direct association with infectious viral particles. Our findings suggest a new antiviral strategy in which extracellular Hsp90β protein is targeted to decrease the infectivity of EV71 and other enteroviruses, without affecting the broader functions of this constitutively expressed molecular chaperone. - Highlights: • Hsp90β is associated with EV71 virion and is secreted with the release virus. • Hsp90β effects on the correct assembly of viral particles. • Viral titer of cultured medium was reduced in the presence of geldanamycin. • Viral titer was also reduced when Hsp90β was suppressed by siRNA treatment. • The extracellular Hsp90β was also observed in other RNA viruses-infected cells

  2. Role of triple fixed combination valsartan, amlodipine and hydrochlorothiazide in controlling blood pressure

    Directory of Open Access Journals (Sweden)

    Monica Doménech

    2010-04-01

    Full Text Available Monica Doménech, Antonio CocaHypertension Unit, Department of Internal Medicine, Institute of Internal Medicine and Dermatology, Hospital Clinic (IDIBAPS, University of Barcelona, SpainAbstract: Hypertension is one of the main risk factors for the development of cardiovascular diseases and the search for new therapeutic strategies aimed at optimizing its control remains an ongoing research and clinical challenge. In recent years, there has been a marked increase in the use of combinations of antihypertensive drugs with complementary mechanisms of action, with the aims of reducing blood pressure levels more rapidly and vigorously than strategies employing monotherapy and improving treatment compliance and adhesion. Therefore, as recommended by the 2009 reappraisal of the European Society of Hypertension/European Society of Cardiology Guidelines, the use of a triple combination that combines a calcium channel blocker, an angiotensin II receptor blocker and a thiazide diuretic seems a reasonable and efficacious combination for the management of hypertensive patients with moderate, high or very high risk. This article reviews the clinical trials carried out with the fixed combination of amlodipine/valsartan/hydrochlorothiazide at the doses recommended for each drug in monotherapy. The data show that this combination achieved greater reductions in mean sitting diastolic and systolic blood pressure than amlodipine, valsartan or hydrochlorothiazide in monotherapy, with favorable pharmacodynamic and pharmacokinetic profiles. The triple combination at high single doses should be used with caution in elderly patients and those with renal or liver failure. Although the tolerability and safety of the triple combination are good, the mostfrequently reported adverse effects were peripheral edema, headache and dizziness. Analytical alterations were consistent with the already-known biochemical effects of amlodipine, valsartan or hydrochlorothiazide in

  3. Acute Pancreatitis in acute viral hepatitis

    Directory of Open Access Journals (Sweden)

    S K.C.

    2011-03-01

    Full Text Available Introduction: The association of acute viral hepatitis and acute pancreatitis is well described. This study was conducted to find out the frequency of pancreatic involvement in acute viral hepatitis in the Nepalese population. Methods: Consecutive patients of acute viral hepatitis presenting with severe abdominal pain between January 2005 and April 2010 were studied. Patients with history of significant alcohol consumption and gall stones were excluded. Acute viral hepatitis was diagnosed by clinical examination, liver function test, ultrasound examination and confirmed by viral serology. Pancreatitis was diagnosed by clinical presentation, biochemistry, ultrasound examination and CT scan. Results: Severe abdominal pain was present in 38 of 382 serologically-confirmed acute viral hepatitis patients. Twenty five patients were diagnosed to have acute pancreatitis. The pancreatitis was mild in 14 and severe in 11 patients. The etiology of pancreatitis was hepatitis E virus in 18 and hepatitis A virus in 7 patients. Two patients died of complications secondary to shock. The remaining patients recovered from both pancreatitis and hepatitis on conservative treatment. Conclusions: Acute pancreatitis occurred in 6.5 % of patients with acute viral hepatitis. Cholelithiasis and gastric ulcers are the other causes of severe abdominal pain. The majority of the patients recover with conservative management. Keywords: acute viral hepatitis, acute pancreatitis, pain abdomen, hepatitis E, hepatitis A, endemic zone

  4. (Npro) protein of bovine viral d

    Indian Academy of Sciences (India)

    Prakash

    Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle and sheep, and causes significant respiratory and reproductive disease worldwide. Bovine viral diarrhoea virus type 1 (BVDV-1), BVDV-2 along with the border disease virus (BDV) and classical swine fever virus (CSFV) belong to the genus ...

  5. Viral reproductive pathogens of dogs and cats.

    Science.gov (United States)

    Decaro, Nicola; Carmichael, Leland E; Buonavoglia, Canio

    2012-05-01

    This article reviews the current literature on the viral agents that cause reproductive failures in domestic carnivores (dogs and cats). A meaningful update is provided on the etiologic, clinical, pathologic, diagnostic, and prophylactic aspects of the viral infections impacting canine and feline reproduction as a consequence of either direct virus replication or severe debilitation of pregnant animals.

  6. Host and viral translational mechanisms during cricket paralysis virus infection.

    Science.gov (United States)

    Garrey, Julianne L; Lee, Yun-Young; Au, Hilda H T; Bushell, Martin; Jan, Eric

    2010-01-01

    The dicistrovirus is a positive-strand single-stranded RNA virus that possesses two internal ribosome entry sites (IRES) that direct translation of distinct open reading frames encoding the viral structural and nonstructural proteins. Through an unusual mechanism, the intergenic region (IGR) IRES responsible for viral structural protein expression mimics a tRNA to directly recruit the ribosome and set the ribosome into translational elongation. In this study, we explored the mechanism of host translational shutoff in Drosophila S2 cells infected by the dicistrovirus, cricket paralysis virus (CrPV). CrPV infection of S2 cells results in host translational shutoff concomitant with an increase in viral protein synthesis. CrPV infection resulted in the dissociation of eukaryotic translation initiation factor 4G (eIF4G) and eIF4E early in infection and the induction of deIF2alpha phosphorylation at 3 h postinfection, which lags after the initial inhibition of host translation. Forced dephosphorylation of deIF2alpha by overexpression of dGADD34, which activates protein phosphatase I, did not prevent translational shutoff nor alter virus production, demonstrating that deIF2alpha phosphorylation is dispensable for host translational shutoff. However, premature induction of deIF2alpha phosphorylation by thapsigargin treatment early in infection reduced viral protein synthesis and replication. Finally, translation mediated by the 5' untranslated region (5'UTR) and the IGR IRES were resistant to impairment of eIF4F or eIF2 in translation extracts. These results support a model by which the alteration of the deIF4F complex contribute to the shutoff of host translation during CrPV infection, thereby promoting viral protein synthesis via the CrPV 5'UTR and IGR IRES.

  7. Neural stem cell-derived exosomes mediate viral entry

    Directory of Open Access Journals (Sweden)

    Sims B

    2014-10-01

    Full Text Available Brian Sims,1,2,* Linlin Gu,3,* Alexandre Krendelchtchikov,3 Qiana L Matthews3,4 1Division of Neonatology, Department of Pediatrics, 2Department of Cell, Developmental, and Integrative Biology, 3Division of Infectious Diseases, Department of Medicine, 4Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, USA *These authors contributed equally to this work Background: Viruses enter host cells through interactions of viral ligands with cellular receptors. Viruses can also enter cells in a receptor-independent fashion. Mechanisms regarding the receptor-independent viral entry into cells have not been fully elucidated. Exosomal trafficking between cells may offer a mechanism by which viruses can enter cells.Methods: To investigate the role of exosomes on cellular viral entry, we employed neural stem cell-derived exosomes and adenovirus type 5 (Ad5 for the proof-of-principle study. Results: Exosomes significantly enhanced Ad5 entry in Coxsackie virus and adenovirus receptor (CAR-deficient cells, in which Ad5 only had very limited entry. The exosomes were shown to contain T-cell immunoglobulin mucin protein 4 (TIM-4, which binds phosphatidylserine. Treatment with anti-TIM-4 antibody significantly blocked the exosome-mediated Ad5 entry.Conclusion: Neural stem cell-derived exosomes mediated significant cellular entry of Ad5 in a receptor-independent fashion. This mediation may be hampered by an antibody specifically targeting TIM-4 on exosomes. This set of results will benefit further elucidation of virus/exosome pathways, which would contribute to reducing natural viral infection by developing therapeutic agents or vaccines. Keywords: neural stem cell-derived exosomes, adenovirus type 5, TIM-4, viral entry, phospholipids

  8. Ethical Considerations in Research Participation Virality.

    Science.gov (United States)

    Ellis-Barton, Carol

    2016-07-01

    This article seeks to commence and encourage discussion around the upcoming ethical challenges of virality in network structures. When the call for participation in a research project on lupus in Ireland went from an advertisement in a newsletter to a meme (unit of transmissible information) on a closed Facebook page, the ethical considerations of virality were raised. The article analyzes the Association of Internet Researchers guidelines, Facebook policies, and the context of privacy in relation to virality. Virality creates the leverage for methodological pluralism. The nature of the inquiry can determine the method rather than the other way around. Viral ethical considerations are evolving due to the cyber world becoming the primary meme of communication, with flexibility in the researcher's protocol providing opportunities for efficient, cost-effective, and diverse recruitment. © The Author(s) 2016.

  9. Immunization with viral antigens: viral diseases of carp and catfish.

    Science.gov (United States)

    Dixon, P

    1997-01-01

    The viral diseases of carp and catfish for which vaccines have been produced are spring viraemia of carp (SVC), grass carp haemorrhage disease (GCHD) and channel catfish virus disease (CCVD). Field trials of a commercially produced injectable vaccine conducted over several years have shown that carp can be protected against SVC. However the supporting data were predominantly qualitative rather than quantitative. Large-scale field trials of an experimental oral attenuated vaccine against SVC virus over a five year period were successful, and no reversion to virulence of the vaccine was recorded. Injectable inactivated and attenuated vaccines against GCHD have predominantly been tested under laboratory conditions, although a small number of field trials have been reported. In such trials of bath and injectable vaccines, survival rates of 50-90% were achieved. In China, commercially available vaccines are being used against GCHD. Only laboratory trials of vaccines against CCVD have been reported. Bath vaccination of eggs of fry with a subunit vaccine and bath immunisation of fingerlings with an attenuated virus vaccine have been successful. Problems with current approaches and areas for research are discussed.

  10. BPS dynamics of the triple (p,q) string junction

    International Nuclear Information System (INIS)

    Rey, S.-J.; Yee, J.-T.

    1998-01-01

    We study the dynamics of the triple junction of (p,q) strings in type IIB string theory. We probe the tension and mass density of (p,q) strings by studying harmonic fluctuations of the triple junction. We show that they agree perfectly with the BPS formula provided a suitable geometric interpretation of the junction is given. We provide a precise statement of the BPS limit and force-balance property. At weak coupling and sufficiently dense limit, we argue that a (p,q) string embedded in the string network is a 'wiggly string', whose low-energy dynamics can be described via a renormalization group evolved, smooth effective non-relativistic string. We also suggest the possibility that, upon type IIB strings being promoted to the M-theory membrane, there can exist 'evanescent' bound-states at the triple junction in the continuum. (orig.)

  11. Asthenospheric flow and lithospheric evolution near the Mendocino Triple Junction

    Science.gov (United States)

    Liu, Kaijian; Levander, Alan; Zhai, Yongbo; Porritt, Robert W.; Allen, Richard M.

    2012-03-01

    The migration of the Mendocino Triple Junction in northern California creates a complicated lithosphere-asthenosphere boundary system at shallow depths (Gorda plate, the joint inversion Vs model further identifies three other young asthenospheres resulting from different partial melting mechanisms. Northward motion of the triple junction causes asthenospheric flow both from under the Gorda plate and from the cooling former mantle wedge left under the Great Valley and Sierra Nevada, imaged from the joint inversion as a relatively deep (> 75 km) low-Vs anomaly. These two mantle flows appear to begin mixing ~ 100 km south of the southern edge of the Gorda plate in the slab window region. We speculate that the latter provides the wedge-type geochemical signature seen in the Coast Range volcanic rocks, reconciling slab window models and volcanic geochemistry. This 'staggered' upwelling model proposed here also explains the ~ 3 Myr delay in onset of volcanism after triple junction migration.

  12. THE ALGOL TRIPLE SYSTEM SPATIALLY RESOLVED AT OPTICAL WAVELENGTHS

    International Nuclear Information System (INIS)

    Zavala, R. T.; Hutter, D. J.; Hummel, C. A.; Boboltz, D. A.; Ojha, R.; Shaffer, D. B.; Tycner, C.; Richards, M. T.

    2010-01-01

    Interacting binaries typically have separations in the milliarcsecond regime, and hence it has been challenging to resolve them at any wavelength. However, recent advances in optical interferometry have improved our ability to discern the components in these systems and have now enabled the direct determination of physical parameters. We used the Navy Prototype Optical Interferometer to produce for the first time images resolving all three components in the well-known Algol triple system. Specifically, we have separated the tertiary component from the binary and simultaneously resolved the eclipsing binary pair, which represents the nearest and brightest eclipsing binary in the sky. We present revised orbital elements for the triple system, and we have rectified the 180 0 ambiguity in the position angle of Algol C. Our directly determined magnitude differences and masses for this triple star system are consistent with earlier light curve modeling results.

  13. The influence of triple bottom line on international operations management

    Directory of Open Access Journals (Sweden)

    Francisco Sperotto Flores

    2017-12-01

    Full Text Available This paper takes a triple bottom line perspective to analyze how the international operations literature integrates economic, social, and environmental issues. Additionally, it shows the main drivers of and barriers to the adoption of triple bottom line practices by companies in an international context. We conducted a literature review in English language journals which publish research of production and operations management and sustainability, resulting in a final sample of 29 papers. Results show that social and legal pressure for companies to adopt a responsible behavior prompts an isomorphic process that leads them to conduct their operations on behalf of triple bottom line goals. Behavioral differences between spin-offs in various countries caused institutions to create mechanisms that can press and change private standards through regulation and enforcement. There is room for progress in studies that seek to analyze the company’s relationships in its international experience and its multi-institutional relations.

  14. CRITICAL CURVES AND CAUSTICS OF TRIPLE-LENS MODELS

    International Nuclear Information System (INIS)

    Daněk, Kamil; Heyrovský, David

    2015-01-01

    Among the 25 planetary systems detected up to now by gravitational microlensing, there are two cases of a star with two planets, and two cases of a binary star with a planet. Other, yet undetected types of triple lenses include triple stars or stars with a planet with a moon. The analysis and interpretation of such events is hindered by the lack of understanding of essential characteristics of triple lenses, such as their critical curves and caustics. We present here analytical and numerical methods for mapping the critical-curve topology and caustic cusp number in the parameter space of n-point-mass lenses. We apply the methods to the analysis of four symmetric triple-lens models, and obtain altogether 9 different critical-curve topologies and 32 caustic structures. While these results include various generic types, they represent just a subset of all possible triple-lens critical curves and caustics. Using the analyzed models, we demonstrate interesting features of triple lenses that do not occur in two-point-mass lenses. We show an example of a lens that cannot be described by the Chang–Refsdal model in the wide limit. In the close limit we demonstrate unusual structures of primary and secondary caustic loops, and explain the conditions for their occurrence. In the planetary limit we find that the presence of a planet may lead to a whole sequence of additional caustic metamorphoses. We show that a pair of planets may change the structure of the primary caustic even when placed far from their resonant position at the Einstein radius

  15. MHC class I cross-presentation by dendritic cells counteracts viral immune evasion

    OpenAIRE

    Nopora, Katrin; Bernhard, Caroline A.; Ried, Christine; Castello, Alejandro A.; Murphy, Kenneth M.; Marconi, Peggy; Koszinowski, Ulrich H.; Brocker, Thomas

    2012-01-01

    DCs very potently activate CD8(+) T cells specific for viral peptides bound to MHC class I molecules. However, many viruses have evolved immune evasion mechanisms, which inactivate infected DCs and might reduce priming of T cells. Then MHC class I crosspresentation of exogenous viral Ag by non-infected DCs may become crucial to assure CD8(+) T cell responses. Although many vital functions of infected DCs are inhibited in vitro by many different viruses, the contributions of cross-presentation...

  16. Quaternary Evolution of Karliova Triple Junction

    Science.gov (United States)

    Sançar, Taylan; Zabcı, Cengiz; Akyüz, H. Serdar

    2013-04-01

    The arguments to explain Quaternary evolution of Karlıova Triple Junction (KTJ) depends upon two different analogue models. The compressional type of Prandtl Cell Model (PCM) and 60 km wide shear zone with concomitant counter clockwise block rotation used to modelled for west and east of the KTJ respectively. The data for the model of west of the KTJ acquired by extensive field studies, and quantified geomorphic features. Compressional PCM put forward that behavior of slip lines controlled by boundary faults. But the model is not enough to explain slip distribution, age relation of them. At west of the KTJ boundary faults presented by eastern most segments of the North Anatolian Fault Zone (NAFZ) and the East Anatolian Fault Zone (EAFZ). Slip lines, however, presented by Bahçeli and Toklular faults. Both field studies and morphometric analyses undisputedly set forth that there are two different fault types between the NAFZ and EAFZ. The most strain loaded fault type, which are positioned near the NAFZ, start as a strike-slip fault and when it turn to SE its sense of motion change to oblique normal due to changing orientation of principal stress axes. The new orientation of stress axes exposed in the field as a special kind of caprock -cuesta-. The younger slip lines formed very close to junction point and accommodate less slip. Even though slip trajectories started from the boundary faults in compressional PCM, at the west of KTJ, right lateral trajectories more clearly formed close the NAFZ and left lateral trajectories, relatively less strain loaded fault type, are poorly formed close the EAFZ . We think that, this differences between KTJ and compressional PCM result from the distinction of velocity of boundary faults. East of the KTJ governed by completely different mechanism. The region controlled two main fault systems. The Varto Fault Zone (VFZ), the eastern branch of the KTJ, and Murat Fault (MF) delimited the region from north and south respectively. The

  17. Tunable Hybrid Qubit in a Triple Quantum Dot

    Science.gov (United States)

    Wang, Bao-Chuan; Cao, Gang; Li, Hai-Ou; Xiao, Ming; Guo, Guang-Can; Hu, Xuedong; Jiang, Hong-Wen; Guo, Guo-Ping

    2017-12-01

    We experimentally demonstrate quantum-coherent dynamics of a triple-dot-based multielectron hybrid qubit. Pulsed experiments show that this system can be conveniently initialized, controlled, measured electrically, and has a good ratio Q ˜29 between the coherence time and gate time. Furthermore, the current multielectron hybrid qubit has an operation frequency that is tunable in a wide range, from 2 to about 15 GHz. We also provide a qualitative understanding of the experimental observations by mapping them onto a three-electron system. The demonstration of the high tunability in a triple dot system could be potentially useful for future quantum control.

  18. Viral triggers of multiple sclerosis.

    Science.gov (United States)

    Kakalacheva, Kristina; Münz, Christian; Lünemann, Jan D

    2011-02-01

    Genetic and environmental factors jointly determine the susceptibility to develop Multiple Sclerosis (MS). Collaborative efforts during the past years achieved substantial progress in defining the genetic architecture, underlying susceptibility to MS. Similar to other autoimmune diseases, HLA-DR and HLA-DQ alleles within the HLA class II region on chromosome 6p21 are the highest-risk-conferring genes. Less-robust susceptibility effects have been identified for MHC class I alleles and for non-MHC regions. The role of environmental risk factors and their interaction with genetic susceptibility alleles are much less well defined, despite the fact that infections have long been associated with MS development. Current data suggest that infectious triggers are most likely ubiquitous, i.e., highly prevalent in the general population, and that they require a permissive genetic trait which predisposes for MS development. In this review article, we illustrate mechanisms of infection-induced immunopathologies in experimental animal models of autoimmune CNS inflammation, discuss challenges for the translation of these experimental data into human immunology research, and provide future perspectives on how novel model systems could be utilized to better define the role of viral pathogens in MS. 2010 Elsevier B.V. All rights reserved.

  19. Viral infections of the folds (intertriginous areas).

    Science.gov (United States)

    Adışen, Esra; Önder, Meltem

    2015-01-01

    Viruses are considered intracellular obligates with a nucleic acid, either RNA or DNA. They have the ability to encode proteins involved in viral replication and production of the protective coat within the host cells but require host cell ribosomes and mitochondria for translation. The members of the families Herpesviridae, Poxviridae, Papovaviridae, and Picornaviridae are the most commonly known agents for the cutaneous viral diseases, but other virus families, such as Adenoviridae, Togaviridae, Parvoviridae, Paramyxoviridae, Flaviviridae, and Hepadnaviridae, can also infect the skin. Though the cutaneous manifestations of viral infections are closely related to the type and the transmission route of the virus, viral skin diseases may occur in almost any part of the body. In addition to friction caused by skin-to-skin touch, skin folds are warm and moist areas of the skin that have limited air circulation. These features provide a fertile breeding ground for many kinds of microorganisms, including bacteria and fungi. In contrast to specific bacterial and fungal agents that have an affinity for the skin folds, except for viral diseases of the anogenital area, which have well-known presentations, viral skin infections that have a special affinity to the skin folds are not known. Many viral exanthems may affect the skin folds during the course of the infection, but here we focus only on the ones that usually affect the fold areas and also on the less well-known conditions or recently described associations. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Developing a dashboard to help measure and achieve the triple aim: a population-based cohort study.

    Science.gov (United States)

    Seow, Hsien-Yeang; Sibley, Lyn M

    2014-08-30

    Health system planners aim to pursue the three goals of Triple Aim: 1) reduce health care costs; 2) improve population health; and 3) improve the care experience. Moreover, they also need measures that can reliably predict future health care needs in order to manage effectively the health system performance. Yet few measures exist to assess Triple Aim and predict future needs at a health system level. The purpose of this study is to explore the novel application of a case-mix adjustment method in order to measure and help improve the Triple Aim of health system performance. We applied a case-mix adjustment method to a population-based analysis to assess its usefulness as a measure of health system performance and Triple Aim. The study design was a retrospective, cohort study of adults from Ontario, Canada using administrative databases: individuals were assigned a predicted illness burden score using a case-mix adjustment system from diagnoses and health utilization data in 2008, and then followed forward to assess the actual health care utilization and costs in the following year (2009). We applied the Johns Hopkins Adjusted Clinical Group (ACG) Case-Mix System to categorize individuals into 60 levels of healthcare need, called ACGs. The outcomes were: 1) Number of individuals per ACG; 2) Total system costs per ACG; and 3) Mean cost per person per ACG, which together formed a health system "dashboard". We identified 11.4 million adults. 16.1% were aged 65 or older, 3.2 million (28%) did not use health care services that year, and 45,000 (0.4%) were in the highest acuity ACG category using 12 times more than an average adult. The sickest 1%, 5% and 15% of the population use about 10%, 30% and 50% of total health system costs respectively. The dashboard measures 2 dimensions of Triple Aim: 1) reduced costs: when total system costs per ACG or when average costs per person is reduced; and 2) improved population health: when more people move into healthier rather than

  1. A Reference Viral Database (RVDB) To Enhance Bioinformatics Analysis of High-Throughput Sequencing for Novel Virus Detection.

    Science.gov (United States)

    Goodacre, Norman; Aljanahi, Aisha; Nandakumar, Subhiksha; Mikailov, Mike; Khan, Arifa S

    2018-01-01

    Detection of distantly related viruses by high-throughput sequencing (HTS) is bioinformatically challenging because of the lack of a public database containing all viral sequences, without abundant nonviral sequences, which can extend runtime and obscure viral hits. Our reference viral database (RVDB) includes all viral, virus-related, and virus-like nucleotide sequences (excluding bacterial viruses), regardless of length, and with overall reduced cellular sequences. Semantic selection criteria (SEM-I) were used to select viral sequences from GenBank, resulting in a first-generation viral database (VDB). This database was manually and computationally reviewed, resulting in refined, semantic selection criteria (SEM-R), which were applied to a new download of updated GenBank sequences to create a second-generation VDB. Viral entries in the latter were clustered at 98% by CD-HIT-EST to reduce redundancy while retaining high viral sequence diversity. The viral identity of the clustered representative sequences (creps) was confirmed by BLAST searches in NCBI databases and HMMER searches in PFAM and DFAM databases. The resulting RVDB contained a broad representation of viral families, sequence diversity, and a reduced cellular content; it includes full-length and partial sequences and endogenous nonretroviral elements, endogenous retroviruses, and retrotransposons. Testing of RVDBv10.2, with an in-house HTS transcriptomic data set indicated a significantly faster run for virus detection than interrogating the entirety of the NCBI nonredundant nucleotide database, which contains all viral sequences but also nonviral sequences. RVDB is publically available for facilitating HTS analysis, particularly for novel virus detection. It is meant to be updated on a regular basis to include new viral sequences added to GenBank. IMPORTANCE To facilitate bioinformatics analysis of high-throughput sequencing (HTS) data for the detection of both known and novel viruses, we have

  2. Vaccines in the Prevention of Viral Pneumonia.

    Science.gov (United States)

    Fraser, Clementine S; Jha, Akhilesh; Openshaw, Peter J M

    2017-03-01

    Pneumonia is of great global public health importance. Viral infections play both direct and indirect parts in its cause across the globe. Influenza is a leading cause of viral pneumonia in both children and adults, and respiratory syncytial virus is increasingly recognized as causing disease at both extremes of age. Vaccination offers the best prospect for prevention but current influenza vaccines do not provide universal and durable protection, and require yearly reformulation. In the future, it is hoped that influenza vaccines will give better and universal protection, and that new vaccines can be found for other causes of viral pneumonia. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Viral Evasion of Natural Killer Cell Activation.

    Science.gov (United States)

    Ma, Yi; Li, Xiaojuan; Kuang, Ersheng

    2016-04-12

    Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

  4. A skeptical look at viral immune evasion.

    Science.gov (United States)

    Davis, I A; Rouse, B T

    1997-12-01

    In the past several years, many viral gene products have been found to encode proteins which interfere with immune defense mechanisms. Whether these interactions between virus and immune system components are actually evasion mechanisms used during viral infections in their natural hosts remains to be proven. In vitro studies do, however, reveal several tactics which may aid viral replication and dissemination by interfering with components of both the innate and adaptive immune systems. In this manuscript, we discuss the more intensively studied of these putative in vitro evasion tactics and ponder their relevance in in vivo situations.

  5. HSV usurps eukaryotic initiation factor 3 subunit M for viral protein translation: novel prevention target.

    Directory of Open Access Journals (Sweden)

    Natalia Cheshenko

    2010-07-01

    Full Text Available Prevention of genital herpes is a global health priority. B5, a recently identified ubiquitous human protein, was proposed as a candidate HSV entry receptor. The current studies explored its role in HSV infection. Viral plaque formation was reduced by approximately 90% in human cells transfected with small interfering RNA targeting B5 or nectin-1, an established entry receptor. However, the mechanisms were distinct. Silencing of nectin-1 prevented intracellular delivery of viral capsids, nuclear transport of a viral tegument protein, and release of calcium stores required for entry. In contrast, B5 silencing had no effect on these markers of entry, but inhibited viral protein translation. Specifically, viral immediate early genes, ICP0 and ICP4, were transcribed, polyadenylated and transported from the nucleus to the cytoplasm, but the viral transcripts did not associate with ribosomes or polysomes in B5-silenced cells. In contrast, immediate early gene viral transcripts were detected in polysome fractions isolated from control cells. These findings are consistent with sequencing studies demonstrating that B5 is eukaryotic initiation factor 3 subunit m (eIF3m. Although B5 silencing altered the polysome profile of cells, silencing had little effect on cellular RNA or protein expression and was not cytotoxic, suggesting that this subunit is not essential for host cellular protein synthesis. Together these results demonstrate that B5 plays a major role in the initiation of HSV protein translation and could provide a novel target for strategies to prevent primary and recurrent herpetic disease.

  6. The triple synergy of ethylmethylhydroxypyridine succinate, magnesium, and vitamin B6: Molecular mechanisms

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2017-01-01

    Full Text Available Objective: to evaluate the triple effect of ethylmethylhydroxypyridine succinate (EMHPS, organic magnesium salt (magnesium lactate, and vitamin B6 (pyridoxine.Material and methods. A systematic analysis of the molecular mechanisms of the triple synergic action of EMHPS, magnesium, and vitamin B6 was carried out. For chemoinformational analysis, the investigators developed a new mathematical method based on the combinatorial theory of solvability, which allows one to obtain quantitative estimates of the affinity constants of proteome proteins.Results. The pharmacological effects of the EMHPS molecule characterized by nootropic and antioxidant properties are shown to work in synergy with magnesium and vitamin B6. A systematic analysis of synergy interactions indicated 46 biological roles, in which the synergy of EMHPS, magnesium, and pyridoxine could be manifested. The main goals of this synergy are to protect neurons from damage, by combating excitotoxicity in the cells and to neutralize excess homocysteine (to reduce the risk of ischemic and thrombotic stroke, myocardial infarction, and coronary heart disease; to improve cognitive functions and neuromuscular transmission, to reduce anxiety, by activating acetylcholine, GABA, and dopamine receptors; to normalize lipid and glucose metabolism, by lowering hyperglycemia and improving the processing of fats.

  7. Viral Marketing -­ How can a campaign succeed in going viral? What are the pros and cons of viral marketing?

    OpenAIRE

    Guyot, Maëlle

    2016-01-01

    This research contains an in-­depth analysis of viral marketing used by modern firms as a tool to advertise their offerings and increase brand exposure. Initially, the current marketing environment has been analyzed, in order to understand modern consumer behavior and what is trending (or not) in terms of marketing techniques. Subsequently, the relevant theory about viral marketing was explored, to have a deep understanding of the phenomenon (of its characteristics, forms and objectives). ...

  8. Applying Triple-Matrix Masking for Privacy Preserving Data Collection and Sharing in HIV Studies.

    Science.gov (United States)

    Pei, Qinglin; Chen, Shigang; Xiao, Yao; Wu, Samuel S

    2016-01-01

    Many HIV research projects are plagued by the high missing rate of selfreported information during data collection. Also, due to the sensitive nature of the HIV research data, privacy protection is always a concern for data sharing in HIV studies. This paper applies a data masking approach, called triple-matrix masking [1], to the context of HIV research for ensuring privacy protection during the process of data collection and data sharing. Using a set of generated HIV patient data, we show step by step how the data are randomly transformed (masked) before leaving the patients' individual data collection device (which ensures that nobody sees the actual data) and how the masked data are further transformed by a masking service provider and a data collector. We demonstrate that the masked data retain statistical utility of the original data, yielding the exactly same inference results in the planned logistic regression on the effect of age on the adherence to antiretroviral therapy and in the Cox proportional hazard model for the age effect on time to viral load suppression. Privacy-preserving data collection method may help resolve the privacy protection issue in HIV research. The individual sensitive data can be completely hidden while the same inference results can still be obtained from the masked data, with the use of common statistical analysis methods.

  9. EXPERIMENTAL LIPOSOMAL VIRAL VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Romanova OA

    2016-12-01

    Full Text Available Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay;b lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase.Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France, "Inflexal V" (Biotech Ltd. Berne, Switzerland and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane. Liposomes 2.2 - the adjuvant

  10. Triple negative breast cancer: the role of metabolic pathways.

    Science.gov (United States)

    Dean, S J R; Rhodes, A

    2014-12-01

    The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area.

  11. The scalar spectrum of the triple seesaw mechanism

    International Nuclear Information System (INIS)

    Caetano, Wellington; Pires, Carlos

    2011-01-01

    Full text: The Triple seesaw mechanism provides an expression to the neutrino masses which get suppressed by high-scale M 3 in its denominator. Thus, we have a seesaw mechanism which works naturally at TeV scale, presenting, in this way, a great potential of being probed at LHC. In order to generate the small left-handed neutrino masses, the triple seesaw mechanism also requires only heavy right-handed neutrinos as extra fermionic content as the type I seesaw. The minimum Higgs sector required by the mechanism is composed by the standard Higgs doublet plus another Higgs doublet and a Higgs singlet. In this work we obtain the mass spectrum and the eigenvectors of the scalar sector that realizes the Triple seesaw mechanism. As our results, we recover the standard Higgs boson with mass in a region at 116 H < 151 GeV. We analyzed the expression given in the Triple seesaw mechanism for the neutrino mass in a scenario that is consistent with the small mass from the neutrino oscillation data and compatible with the requirements for a WIMP (weakly interacting massive particles) candidate. Finally, we obtain, as our main result, a neutral pseudoscalar with mass around 8-10 GeV which is stable and can be a possible WIMP dark matter candidate. (author)

  12. An improved computer controlled triple-axis neutron spectrometer

    International Nuclear Information System (INIS)

    Cooper, M.J.; Hall, J.W.; Hutchings, M.T.

    1975-07-01

    A description is given of the computer-controlled triple-axis neutron spectrometer installed at the PLUTO reactor at Harwell. The reasons for an nature of recent major improvements are discussed. Following a general description of the spectrometer, details are then given of the new computerised control system, including the functions of the various programs which are now available to the user. (author)

  13. Simulation of triple junction motion with arbitrary surface tensions

    Czech Academy of Sciences Publication Activity Database

    Shofianah, N.; Muhammad, R. Z.; Švadlenka, Karel

    2015-01-01

    Roč. 45, č. 3 (2015), s. 235-244 ISSN 1992-9978 Institutional support: RVO:67985840 Keywords : triple junction motion * mean curvature flow * surface tension Subject RIV: BA - General Mathematics http://www.iaeng.org/IJAM/issues_v45/issue_3/IJAM_45_3_09.pdf

  14. Hybrid Steepest Descent Viscosity Method for Triple Hierarchical Variational Inequalities

    Directory of Open Access Journals (Sweden)

    L.-C. Ceng

    2012-01-01

    Full Text Available We consider a triple hierarchical variational inequality problem (in short, THVIP. By combining hybrid steepest descent method, viscosity method, and projection method, we propose an approximation method to compute the approximate solution of THVIP. We also study the strong convergence of the sequences generated by the proposed method to a solution of THVIP.

  15. Boundary triples for Schrodinger operators with singular interactions on hypersurfaces

    Czech Academy of Sciences Publication Activity Database

    Behrndt, J.; Langer, M.; Lotoreichik, Vladimir

    2016-01-01

    Roč. 7, č. 2 (2016), s. 290-302 ISSN 2220-8054 R&D Projects: GA ČR(CZ) GA14-06818S Institutional support: RVO:61389005 Keywords : boundary triple * Weyl function * Schrodinger operator * singular potential * delta-interaction * hypersurface Subject RIV: BE - Theoretical Physics

  16. The principle of relativity and the special relativity triple

    International Nuclear Information System (INIS)

    Guo Hanying; Wu Hongtu; Zhou Bin

    2009-01-01

    Based on the principle of relativity and the postulate on universal invariant constants (c,l) as well as Einstein's isotropy conditions, three kinds of special relativity form a triple with a common Lorentz group as isotropy group under full Umov-Weyl-Fock-Lorentz transformations among inertial motions

  17. Subtalar versus triple arthrodesis after intra-articular calcaneal fractures

    NARCIS (Netherlands)

    T. Schepers (Tim); B.C.T. Kieboom (Brenda); J.H.J.M. Bessems (Gert); L.M.M. Vogels (Lucas); E.M.M. van Lieshout (Esther); P. Patka (Peter)

    2010-01-01

    textabstractDepending upon initial treatment, between 2 and 30% of patients with a displaced intra-articular calcaneal fracture require a secondary arthrodesis. The aim of this study was to investigate the effect of subtalar versus triple arthrodesis on functional outcome. A total of 33 patients

  18. Subtalar versus triple arthrodesis after intra-articular calcaneal fractures

    NARCIS (Netherlands)

    Schepers, Tim; Kieboom, Brenda C. T.; Bessems, Gert H. J. M.; Vogels, Lucas M. M.; van Lieshout, Esther M. M.; Patka, Peter

    2010-01-01

    Depending upon initial treatment, between 2 and 30% of patients with a displaced intra-articular calcaneal fracture require a secondary arthrodesis. The aim of this study was to investigate the effect of subtalar versus triple arthrodesis on functional outcome. A total of 33 patients with 37

  19. Chemical application of positron annihilation through triple coincidence measurement

    International Nuclear Information System (INIS)

    Yegnasubramanian, S.; Gangadharan, S.

    1982-01-01

    This report summarises the work on the application of triple coincidence measurement of annihilation radiation for providing chemical state information; the observations have been corroborated by angular correlation and Doppler broadening measurements and supplemented by the magnetic quenching in the angular correlation and peak-to-valley ratio in the Ge(Li) singles spectrum for the 511 keV line. (author)

  20. Triple A syndrome presenting with myopathy: An Egyptian patient ...

    African Journals Online (AJOL)

    In this paper we report a 13 year old boy with Allgrove syndrome presenting with muscular weakness that was confi rmed by EMG studies. To our knowledge, muscle disease in Allogrove syndrome was not reported before. Keywords: Allgrove syndrome, triple A syndrome, alacrmia, cardiac achalasia, adrenal insufficiency.

  1. Patriarchy, Women's Triple Roles and Development in Southwest ...

    African Journals Online (AJOL)

    Patriarchy, Women's Triple Roles and Development in Southwest Nigeria. ... AFRREV IJAH: An International Journal of Arts and Humanities ... the social relations of production and, indeed, the whole super-structure of the society could however be changed gradually through the use of the social reproductive role of women ...

  2. The Triple Helix Model and the Knowledge-Based Economy

    NARCIS (Netherlands)

    Leydesdorff, L.; Meyer, M.

    2010-01-01

    The Triple Helix model of university-industry-government relations can be generalized from a neo-institutional model of networks of relations to a neo-evolutionary model of how three selection environments operate upon one another. Two selection mechanisms operating upon each other can mutually

  3. Living Labs as boundary-spanners between Triple Helix actors

    NARCIS (Netherlands)

    van Geenhuizen, M.S.

    2016-01-01

    Living labs are an increasingly popular methodology to enhance innovation. Living labs aim to span boundaries between different organizations, among others Triple helix actors, by acting as a network organization typically in a real-life environment to foster co-creation by user-groups. This paper

  4. A triple GEM detector with two-dimensional readout

    International Nuclear Information System (INIS)

    Ziegler, M.; Sievers, P.; Straumann, U.

    2001-01-01

    For the LHCb experiment a micropattern gas detector has been proposed as a possible technology for the inner tracking. A prototype triple GEM detector was built for this purpose. Here, the performance of this detector in a hadronic beam is presented

  5. Quality of the spare triple-GEM detectors

    CERN Document Server

    Lenci, Rosario; Paoletti, Emiliano; Pasquali, Luigi; Pinci, Davide; Piscitelli, Carmelo; Poli Lener, Marco; Sciubba, Adalberto; Tskhadadze, Edisher

    2017-01-01

    Triple-GEM chambers equip the inner region of the M1 muon station. In order to provide spare detectors in case of problems in the operating ones, new chambers have been assembled at the Frascati National Laboratories of the INFN. This note summarizes the results of the quality tests performed at the end of the production procedure.

  6. The EU must triple its energy saving policy effect

    NARCIS (Netherlands)

    Wesselink, B.; Eichhammer, W.; Harmsen, R.

    2010-01-01

    The impact of EU energy savings policy must triple to achieve the bloc’s 2020 energy savings goal. But such efforts could get a much better foundation if European leaders set a binding energy consumption target, rather than the current indicative savings target. The evidence for such

  7. Behavior of Triple Langmuir Probes in Non-Equilibrium Plasmas

    Science.gov (United States)

    Polzin, Kurt A.; Ratcliffe, Alicia C.

    2018-01-01

    The triple Langmuir probe is an electrostatic probe in which three probe tips collect current when inserted into a plasma. The triple probe differs from a simple single Langmuir probe in the nature of the voltage applied to the probe tips. In the single probe, a swept voltage is applied to the probe tip to acquire a waveform showing the collected current as a function of applied voltage (I-V curve). In a triple probe three probe tips are electrically coupled to each other with constant voltages applied between each of the tips. The voltages are selected such that they would represent three points on the single Langmuir probe I-V curve. Elimination of the voltage sweep makes it possible to measure time-varying plasma properties in transient plasmas. Under the assumption of a Maxwellian plasma, one can determine the time-varying plasma temperature T(sub e)(t) and number density n(sub e)(t) from the applied voltage levels and the time-histories of the collected currents. In the present paper we examine the theory of triple probe operation, specifically focusing on the assumption of a Maxwellian plasma. Triple probe measurements have been widely employed for a number of pulsed and timevarying plasmas, including pulsed plasma thrusters (PPTs), dense plasma focus devices, plasma flows, and fusion experiments. While the equilibrium assumption may be justified for some applications, it is unlikely that it is fully justifiable for all pulsed and time-varying plasmas or for all times during the pulse of a plasma device. To examine a simple non-equilibrium plasma case, we return to basic governing equations of probe current collection and compute the current to the probes for a distribution function consisting of two Maxwellian distributions with different temperatures (the two-temperature Maxwellian). A variation of this method is also employed, where one of the Maxwellians is offset from zero (in velocity space) to add a suprathermal beam of electrons to the tail of the

  8. Tectonic pattern of the Azores spreading centre and triple junction

    Science.gov (United States)

    Searle, Roger

    1980-12-01

    The major tectonic elements of the Azores triple junction have been mapped using long-range side-scan sonar. The data enable the Mid-Atlantic Ridge axis to be located with a precision of a few kilometres. Major faults and other tectonic and volcanic elements of the ridge maintain their regional trend of 010° to 020° past the triple junction area. There is no oblique spreading, and only minor transform offsets of the Mid-Atlantic Ridge occur here. The main effect of the triple junction or Azores hot spot is to diminish the amplitude of the median valley to 200 m or less. There is no axial high: a topographic high seen on several profiles is located to the east of the Mid-Atlantic Ridge spreading axis and does not appear to have any fundamental significance. The third arm of the triple junction includes the Azores srreading centre which appears to have developed as a series of en echelon rifted basins (the Terceira Rift) extending from Formigas Trough at 36.8°N, 24.5°W to a point near 39.3°N, 28.8°W. There are indications that recent activity in the spreading centre may be concentrated in a series of ridges which flank the older rifted basins. Until recently the northwest end of the Terceira Rift was connected to the Mid-Atlantic Ridge axis either directly at an RRR junction, or via a transform fault. The triple junction has probably moved south during the last 6 Ma to a positin on the Mid-Atlantic Ridge near 38.7°N. Initiation of the Azores spreading centre may have occurred during the 36 Ma B.P. rearrangement of poles, with an RFF triple junction north from the East Azores fracture zone to the North Azores fracture zone and transferring a wedge of European plate to the African plate. The tectonic elements revealed by this study are in good agreement with inferred earthquake mechanisms and with the RM2 plate tectonic model of Minster and Jordan, but east-west motion between North America and Africa does not seem to be compatible with the other motions at the

  9. Triple positivity of HBsAg, anti-HCV antibody, and HIV and their ...

    African Journals Online (AJOL)

    Background: Few studies exist on hospital-based seroprevalence of triple positivity of HIV/HBV/HCV in Nigeria. Objectives: The study aimed at determining the triple positivity of HIV, HBsAg and HCV among HIV-infected individuals in Abeokuta, Nigeria and defining the influence of these triple infections on CD4+ counts of ...

  10. Compact printed high rejection triple band-notch UWB antenna with multiple wireless applications

    Directory of Open Access Journals (Sweden)

    Manish Sharma

    2016-09-01

    Full Text Available In this paper, small printed urn-shape triple notch ultra-wideband (UWB monopole antenna with diverse wireless applications is presented. Notch bands include WiMAX (IEEE802.16 3.30–3.80 GHz, WLAN IEEE802.11a/h/j/n (5.15–5.35 GHz, 5.25–5.35 GHz, 5.47–5.725 GHz, 5.725–5.825 GHz, and X-band downlink satellite system (7.25–7.75 GHz and other multiple wireless services as close range radar (8–12 GHz in X-band & satellite communication (12–18 GHz in Ku-band. By including T-shape stub and etching two C-shaped slots on the radiating patch, triple band-notch function is obtained with measured high band rejection (VSWR = 16.54 at 3.60 GHz, VSWR = 22.35 at 5.64 GHz and VSWR = 6.38 at 7.64 GHz and covers a wide useable fractional bandwidth of 154.56% (2.49–19.41 GHz. In short the antenna offers triple band-notch UWB systems as a compact multifunctional antenna to reduce the number of antennas installed in wireless devices for accessing multiple wireless networks with wide radiation pattern.

  11. NNDSS - Table II. Hepatitis (viral, acute) C

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) C - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  12. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases but...

  13. NNDSS - Table II. Hepatitis (viral, acute) C

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) C - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  14. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  15. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year),...

  16. Effects of Demographics on the Antihypertensive Efficacy of Triple Therapy With Amlodipine, Valsartan, and Hydrochlorothiazide for Moderate to Severe Hypertension

    Science.gov (United States)

    Calhoun, David A.; Lacourci00E8;re, Yves; Crikelair, Nora; Jia, Yan; Glazer, Robert D.

    2014-01-01

    Objective To compare the antihypertensive efficacy and safety of once-daily triple therapy with amlodipine (Aml) 10 mg, valsartan (Val) 320 mg, and hydrochlorothiazide (HCTZ) 25 mg versus dual-therapy combinations of these components in patients with moderate to severe hypertension. Research design Subgroup analysis of a multinational, randomized, double-blind, parallel-group, active-controlled trial. Methods After antihypertensive washout and a placebo run-in of up to 4 weeks, 2271 patients were randomly allocated in a 1:1:1:1 ratio to receive Aml/Val/HCTZ triple therapy or dual therapy with Val/HCTZ, Aml/Val, or Aml/HCTZ for 8 weeks. Forced titration to the full dose was done over the first 2 weeks of treatment. Efficacy and safety parameters were determined by age group (<65 vs. ≥65 years), gender, race (White vs. Black), ethnicity (Hispanic/Latino vs. non-Hispanic/Latino), and body mass index (BMI, <30 vs. ≥30 kg/m2). Main outcome measures Change from baseline to endpoint in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP); blood pressure (BP) control rate <140/90 mmHg. Results Triple therapy was numerically superior and, for the majority of comparisons, statistically superior to each dual therapy in reducing MSSBP and MSDBP and in improving BP control rates in all subgroups. Across subgroups, triple therapy reduced MSSBP by 5.7–10.7 mmHg more than Val/HCTZ, 3.4–8.3 mmHg more than Aml/Val, and 4.4–9.4 mmHg more than Aml/HCTZ. Triple therapy was well tolerated across all subgroups. Limitations of our analysis included the lack of stratification of patients by subgroup at randomization and the small sample size of some subgroups (eg, Blacks, elderly). Conclusions Triple therapy with Aml/Val/HCTZ is effective and well tolerated in patients with moderate to severe hypertension regardless of age, gender, race, ethnicity, or BMI. PMID:23721363

  17. Dynamical Implications of Viral Tiling Theory

    OpenAIRE

    ElSawy, K. M.; Taormina, A.; Twarock, R.; Vaughan, L.

    2007-01-01

    The Caspar–Klug classification of viruses whose protein shell, called viral capsid, exhibits icosahedral symmetry, has recently been extended to incorporate viruses whose capsid proteins are exclusively organised in pentamers. The approach, named ‘Viral Tiling Theory’, is inspired by the theory of quasicrystals, where aperiodic Penrose tilings enjoy 5-fold and 10-fold local symmetries. This paper analyses the extent to which this classification approach informs dynamical properties of the vir...

  18. Rapid and highly fieldable viral diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    McKnight, Timothy E.

    2016-12-20

    The present invention relates to a rapid, highly fieldable, nearly reagentless diagnostic to identify active RNA viral replication in a live, infected cells, and more particularly in leukocytes and tissue samples (including biopsies and nasal swabs) using an array of a plurality of vertically-aligned nanostructures that impale the cells and introduce a DNA reporter construct that is expressed and amplified in the presence of active viral replication.

  19. [Liver hemosiderosis study in chronic viral hepatitis].

    Science.gov (United States)

    Cojocariu, Camelia; Trifan, Anca; Mihailovici, Maria Sultana; Danciu, M; Stanciu, C

    2008-01-01

    In chronic viral hepatitis the histopathological exam can reveal the presence of liver iron deposits in 10 to 73% of patients. Iron deposits are usually found in Kupffer cells, in endothelial cells and portal macrophages, and extremely rarely in hepatocytes. To evaluate the incidence of hepatic hemosiderosis in chronic viral hepatitis. 549 morphopathological features of liver biopsy specimens performed in the Gastroenterology and Hepatology Institute IaSi, between January 1 2003 and December 31 2007 have been analyzed. Semiquantitative assessment of the degree of hepatic iron overload was performed and the localization of haemosiderin deposits: at the level of hepatocytes, the reticuloendothelial system or mixedly. The same anatomopathologist examined the blades and interpreted the results. The medium age of patients who underwent liver biopsy was 45.08 years +/- 10.045. Positive iron staining was found in 22.8% of cases, more frequently in males (31%), and in 91.82% of cases iron deposits were grade 1-2. The association of alcoholic etiology did not influence the incidence of hemosiderosis: 23% in patients with hepatitis and no ethanol exposure vs 25% in cases of strictly viral etiology. Deposits of haemosiderin were more frequent in viral hepatitis B (38.6%) than in viral hepatitis C (26.9%). In 34% of cases stainable iron was found only in reticuloendothelial system and in 46% of cases both in Kupffer cells and hepatocytes. Almost a quarter of chronic viral hepatitis cases are associated with liver deposits of haemosiderin, with features of secondary iron overload (deposits localized in the mesenchymal areas or mixedly). There is a higher risk of hemosiderosis in men, especially for those between 30 and 50. Liver iron overload levels in chronic viral hepatitis are, in most cases, low or medium, and the association with an alcoholic etiology does not influence the incidence of hemosiderosis in chronic viral hepatitis.

  20. The fecal viral flora of wild rodents.

    OpenAIRE

    Tung G Phan; Beatrix Kapusinszky; Chunlin Wang; Robert K Rose; Howard L Lipton; Eric L Delwart

    2011-01-01

    The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat) collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae...

  1. Institute of Medicine's Report on Viral Hepatitis

    Centers for Disease Control (CDC) Podcasts

    2010-05-18

    In this podcast, Dr. John Ward, Director of CDC’s Division of Viral Hepatitis, discusses the 2010 report, Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C, from the Institute of Medicine.  Created: 5/18/2010 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 5/18/2010.

  2. Viral Oncolytic Therapeutics for Neoplastic Meningitis

    Science.gov (United States)

    2014-09-01

    Award Number: W81XWH-11-1-0387 TITLE: Viral Oncolytic Therapeutics for Neoplastic Meningitis PRINCIPAL INVESTIGATOR: Mikhail Papisov, PhD...SUBTITLE Viral Oncolytic Therapeutics for Neoplastic Meningitis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0387 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...for neoplastic meningitis ( meningeal metastasis of breast cancer). The proposed therapy will be based on direct (intrathecal) administration of

  3. [Viral interactions with the host's immune system].

    Science.gov (United States)

    Humlová, Z

    2001-01-01

    Viruses are obligatory intracellular parasites, which differ in their structure and strategy of replication. The establishment of an antiviral state in uninfected cells and the elimination of virally infected cells are critical tasks in the host defence. Against the extensive array of immune modalities, viruses have successfully learned how to manipulate host immune control mechanisms. The study of viral strategies of immune evasion can provide insights into host-virus interactions and also illuminates essential functions of the immune system.

  4. Triple-Error-Correcting Codec ASIC

    Science.gov (United States)

    Jones, Robert E.; Segallis, Greg P.; Boyd, Robert

    1994-01-01

    Coder/decoder constructed on single integrated-circuit chip. Handles data in variety of formats at rates up to 300 Mbps, correcting up to 3 errors per data block of 256 to 512 bits. Helps reduce cost of transmitting data. Useful in many high-data-rate, bandwidth-limited communication systems such as; personal communication networks, cellular telephone networks, satellite communication systems, high-speed computing networks, broadcasting, and high-reliability data-communication links.

  5. mTOR in breast cancer: differential expression in triple-negative and non-triple-negative tumors.

    LENUS (Irish Health Repository)

    Walsh, S

    2012-04-01

    Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptors (ER), progesterone receptors (PR) and overexpression of HER2. Targeted therapy is currently unavailable for this subgroup of breast cancer patients. mTOR controls cancer cell growth, survival and invasion and is thus a potential target for the treatment of patients with TNBC. Using immunohistochemistry, mTOR and p-mTOR were measured in 89 TNBCs and 99 non-TNBCs. While mTOR expression was confined to tumor cell cytoplasm, p-mTOR staining was located in the nucleus, perinuclear area and in the cytoplasm. Potentially important, was our finding that nuclear p-mTOR was found more frequently in triple-negative than non triple-negative cancers (p < 0.001). These results suggest that mTOR may play a more important role in the progression of TNBC compared to non-TNBC. Based on these findings, we conclude that mTOR may be a new target for the treatment of triple-negative breast cancer.

  6. Pediatric knowledge about acute viral hepatitis

    Directory of Open Access Journals (Sweden)

    Rita Franca

    Full Text Available Knowledge about hepatotropic viruses is crucial for pediatricians because of the high prevalence of viral hepatitis during childhood. The multiplicity of hepatotropic viruses, the spectrum of acute and chronic infections, and the sequels of viral hepatitis result in a need for physicians to better understand the clinical and epidemiological context of patients with viral hepatitis, as well as the importance of prevention measures for hepatitis. A descriptive cross-sectional study was made of pediatrician's knowledge about viral hepatitis, through questionnaires to 574 pediatricians, with no obligation of identification. The pediatricians were recruited among those who attended a national Congress of Pediatrics in Brasília, Brazil. Among these pediatricians, 50.1% frequently treated cases of hepatitis, and 74.7% indicated that they had knowledge of the existence of five hepatotropic viruses; 14.5% knew about at least four types of hepatitis complications, while only 7.7% and 4.3% were able to correctly diagnose viral hepatitis A and B, respectively. Many (28.4% did not know how to treat the patients adequately. Only 37.5% had already recommended vaccination against hepatitis B. Only 50.2% of the pediatricians had been vaccinated against hepatitis B. We concluded that it is crucial to make pediatricians more knowledgeable about viral hepatitis, through continued education programs, especially emphasizing prevention procedures.

  7. Generating viral metagenomes from the coral holobiont

    Directory of Open Access Journals (Sweden)

    Karen Dawn Weynberg

    2014-05-01

    Full Text Available Reef-building corals comprise multipartite symbioses where the cnidarian animal is host to an array of eukaryotic and prokaryotic organisms, and the viruses that infect them. These viruses are critical elements of the coral holobiont, serving not only as agents of mortality, but also as potential vectors for lateral gene flow, and as elements encoding a variety of auxiliary metabolic functions. Consequently, understanding the functioning and health of the coral holobiont requires detailed knowledge of the associated viral assemblage and its function. Currently, the most tractable way of uncovering viral diversity and function is through metagenomic approaches, which is inherently difficult in corals because of the complex holobiont community, an extracellular mucus layer that all corals secrete, and the variety of sizes and structures of nucleic acids found in viruses. Here we present the first protocol for isolating, purifying and amplifying viral nucleic acids from corals based on mechanical disruption of cells. This method produces at least 50% higher yields of viral nucleic acids, has very low levels of cellular sequence contamination and captures wider viral diversity than previously used chemical-based extraction methods. We demonstrate that our mechanical-based method profiles a greater diversity of DNA and RNA genomes, including virus groups such as Retro-transcribing and ssRNA viruses, which are absent from metagenomes generated via chemical-based methods. In addition, we briefly present (and make publically available the first paired DNA and RNA viral metagenomes from the coral Acropora tenuis.

  8. Viral Metagenomics: MetaView Software

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, C; Smith, J

    2007-10-22

    The purpose of this report is to design and develop a tool for analysis of raw sequence read data from viral metagenomics experiments. The tool should compare read sequences of known viral nucleic acid sequence data and enable a user to attempt to determine, with some degree of confidence, what virus groups may be present in the sample. This project was conducted in two phases. In phase 1 we surveyed the literature and examined existing metagenomics tools to educate ourselves and to more precisely define the problem of analyzing raw read data from viral metagenomic experiments. In phase 2 we devised an approach and built a prototype code and database. This code takes viral metagenomic read data in fasta format as input and accesses all complete viral genomes from Kpath for sequence comparison. The system executes at the UNIX command line, producing output that is stored in an Oracle relational database. We provide here a description of the approach we came up with for handling un-assembled, short read data sets from viral metagenomics experiments. We include a discussion of the current MetaView code capabilities and additional functionality that we believe should be added, should additional funding be acquired to continue the work.

  9. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  10. Viral inoculum dose impacts memory T-cell inflation.

    Science.gov (United States)

    Redeker, Anke; Welten, Suzanne P M; Arens, Ramon

    2014-04-01

    Memory T-cell inflation develops during certain persistent viral infections and is characterized by the accumulation and maintenance of large numbers of effector-memory T cells, albeit with varying degrees in size and phenotype among infected hosts. The underlying mechanisms that control memory T-cell inflation are not yet fully understood. Here, we dissected CMV-specific memory T-cell formation and its connection to the initial infectious dose by varying the inoculum size. After low dose inoculum with mouse CMV, the accumulation of inflationary memory T cells was severely hampered and correlated with reduced reservoirs of latent virus in nonhematopoietic cells and diminished antigen-driven T-cell proliferation. Moreover, lowering of the initial viral dose turned the characteristic effector memory-like inflationary T cells into more central memory-like cells as evidenced by the cell-surface phenotype of CD27(high) , CD62L(+) , CD127(+) , and KLRG1(-) , and by improved secondary expansion potential. These data show the impact of the viral inoculum on the degree of memory T-cell inflation and provide a rationale for the observed variation of human CMV-specific T-cell responses in terms of magnitude and phenotype. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. CRISPR/Cas9-mediated viral interference in plants

    KAUST Repository

    Ali, Zahir

    2015-11-11

    Background The CRISPR/Cas9 system provides bacteria and archaea with molecular immunity against invading phages and conjugative plasmids. Recently, CRISPR/Cas9 has been used for targeted genome editing in diverse eukaryotic species. Results In this study, we investigate whether the CRISPR/Cas9 system could be used in plants to confer molecular immunity against DNA viruses. We deliver sgRNAs specific for coding and non-coding sequences of tomato yellow leaf curl virus (TYLCV) into Nicotiana benthamiana plants stably overexpressing the Cas9 endonuclease, and subsequently challenge these plants with TYLCV. Our data demonstrate that the CRISPR/Cas9 system targeted TYLCV for degradation and introduced mutations at the target sequences. All tested sgRNAs exhibit interference activity, but those targeting the stem-loop sequence within the TYLCV origin of replication in the intergenic region (IR) are the most effective. N. benthamiana plants expressing CRISPR/Cas9 exhibit delayed or reduced accumulation of viral DNA, abolishing or significantly attenuating symptoms of infection. Moreover, this system could simultaneously target multiple DNA viruses. Conclusions These data establish the efficacy of the CRISPR/Cas9 system for viral interference in plants, thereby extending the utility of this technology and opening the possibility of producing plants resistant to multiple viral infections.

  12. MOOCs: Hope and Hype in Viral Technologies and Policies

    Directory of Open Access Journals (Sweden)

    Maureen W. McClure

    2014-01-01

    Full Text Available Massive open online courses (MOOCs have emerged in the last couple of years as Internet-based vehicles providinglow cost global access to quality education. They come in two basic forms: expert and self-organizing. Thedominant expert model provides access to expertise through centralized software platforms with expert-designedshort lecture videos, free online reading materials, discussion forums and a strong emphasis on measurable assessments.Self-organizing models focus on problems that may be too new for well-developed expertise, but are tooimportant to ignore. Their rapid (viral growth has resulted in related “viral policies” created by administrators andothers who feel under competitive pressure to act quickly. MOOC interest is growing in many countries, openingnew opportunities for international education partnerships. Backlashes have taken the form of: (a unresolvedproblems with course perseverance, (b assessment procedures to reduce cheating and improve peer review, and (cfaculty resistance to viral governance. While low course completion rates remains problematic, rapidly developingtechnologies and competitive networks are likely to influence higher education institutional policy for some timeto come.

  13. Adsorption of viral particles from the blood plasma of patients with viral hepatitis on nanodiamonds.

    Science.gov (United States)

    Baron, A V; Osipov, N V; Yashchenko, S V; Kokotukha, Yu A; Baron, I J; Puzyr, A P; Olkhovskiy, I A; Bondar, V S

    2016-07-01

    Adsorption of viral particles from the blood plasma of patients with viral hepatitis B and C on modified nanodiamonds (MNDs) was shown in the in vitro experiments. PCR method showed the treatment of plasma with MNDs leads to a decrease in the viral load by 2-3 orders of magnitude or more in both cases studied. These results make it possible to predict the applicability of MNDs for the development of new technologies of hemodialysis and plasmapheresis for binding and removal of viral particles from the blood of infected patients.

  14. An Odyssey to Viral Pathogenesis.

    Science.gov (United States)

    Oldstone, Michael B A

    2016-05-23

    polishing by Karl Habel (a superb senior virologist who left the National Institutes of Health and came to Scripps), and the gifted postdoctoral fellows who joined my laboratory over four decades form the log of my scientific voyage. The strong friendships and collaborations developed with other young but growing experimentalists like Bernie Fields and Abner Notkins are the fabric of the tale I will weave and were pivotal in the establishment of viral pathogenesis as a discipline.

  15. Sensitive surface-enhanced Raman scattering activity of triple gold/silver/graphene oxide nanostructures decorated on gold nanowire arrays

    Science.gov (United States)

    Xu, Xiaodi; Ma, Yi; Du, Yuanyuan; Jiang, Tao; Zhou, Jun; Zhao, Ziqi

    2018-01-01

    Triple core–shell gold/silver/graphene oxide (Au/Ag/GO) nanoparticles (NPs) decorated on Au nanowire arrays as sensitive, reproducible, and low-cost platforms for surface-enhanced Raman spectroscopy (SERS) were introduced. An in situ reducing method was used to synthesize core–shell Au/Ag NPs with inbuilt 4-mercaptobenzoic acid, which gave prominent SERS signals. Subsequently, a second ultrathin shell of GO was constructed on the Ag shell to improve the SERS intensity and homogeneity. Details on stability of the Raman enhancement were discussed by mapping of SERS spectra. A composite structure was finally designed by decorating the triple core–shell Au/Ag/GO NPs onto a vertically aligned ultrathin Au nanowire forest to provide additional enhancement of the SERS signals. This hetero structure will provide an alternative choice for the effective SERS substrate.

  16. Prevalence of Germline Mutations in Genes Engaged in DNA Damage Repair by Homologous Recombination in Patients with Triple-Negative and Hereditary Non-Triple-Negative Breast Cancers.

    Directory of Open Access Journals (Sweden)

    Pawel Domagala

    Full Text Available This study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs and to poly(ADP-ribose polymerase (PARP inhibitors.Genetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers.Thirty five (22.2% of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7% of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%, and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%. In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined were identified in the hereditary non-triple-negative group.Identifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs.

  17. Molecular piracy: the viral link to carcinogenesis.

    Science.gov (United States)

    Flaitz, C M; Hicks, M J

    1998-11-01

    The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous

  18. Raw Sewage Harbors Diverse Viral Populations

    Science.gov (United States)

    Cantalupo, Paul G.; Calgua, Byron; Zhao, Guoyan; Hundesa, Ayalkibet; Wier, Adam D.; Katz, Josh P.; Grabe, Michael; Hendrix, Roger W.; Girones, Rosina; Wang, David; Pipas, James M.

    2011-01-01

    ABSTRACT At this time, about 3,000 different viruses are recognized, but metagenomic studies suggest that these viruses are a small fraction of the viruses that exist in nature. We have explored viral diversity by deep sequencing nucleic acids obtained from virion populations enriched from raw sewage. We identified 234 known viruses, including 17 that infect humans. Plant, insect, and algal viruses as well as bacteriophages were also present. These viruses represented 26 taxonomic families and included viruses with single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), positive-sense ssRNA [ssRNA(+)], and dsRNA genomes. Novel viruses that could be placed in specific taxa represented 51 different families, making untreated wastewater the most diverse viral metagenome (genetic material recovered directly from environmental samples) examined thus far. However, the vast majority of sequence reads bore little or no sequence relation to known viruses and thus could not be placed into specific taxa. These results show that the vast majority of the viruses on Earth have not yet been characterized. Untreated wastewater provides a rich matrix for identifying novel viruses and for studying virus diversity. Importance At this time, virology is focused on the study of a relatively small number of viral species. Specific viruses are studied either because they are easily propagated in the laboratory or because they are associated with disease. The lack of knowledge of the size and characteristics of the viral universe and the diversity of viral genomes is a roadblock to understanding important issues, such as the origin of emerging pathogens and the extent of gene exchange among viruses. Untreated wastewater is an ideal system for assessing viral diversity because virion populations from large numbers of individuals are deposited and because raw sewage itself provides a rich environment for the growth of diverse host species and thus their viruses. These studies suggest that

  19. Dicer-2 processes diverse viral RNA species.

    Directory of Open Access Journals (Sweden)

    Leah R Sabin

    Full Text Available RNA silencing pathways play critical roles in gene regulation, virus infection, and transposon control. RNA interference (RNAi is mediated by small interfering RNAs (siRNAs, which are liberated from double-stranded (dsRNA precursors by Dicer and guide the RNA-induced silencing complex (RISC to targets. Although principles governing small RNA sorting into RISC have been uncovered, the spectrum of RNA species that can be targeted by Dicer proteins, particularly the viral RNAs present during an infection, are poorly understood. Dicer-2 potently restricts viral infection in insects by generating virus-derived siRNAs from viral RNA. To better characterize the substrates of Dicer-2, we examined the virus-derived siRNAs produced during the Drosophila antiviral RNAi response to four different viruses using high-throughput sequencing. We found that each virus was uniquely targeted by the RNAi pathway; dicing substrates included dsRNA replication intermediates and intramolecular RNA stem loops. For instance, a putative intergenic RNA hairpin encoded by Rift Valley Fever virus generates abundant small RNAs in both Drosophila and mosquito cells, while repetitive sequences within the genomic termini of Vaccinia virus, which give rise to abundant small RNAs in Drosophila, were found to be transcribed in both insect and mammalian cells. Moreover, we provide evidence that the RNA species targeted by Dicer-2 can be modulated by the presence of a viral suppressor of RNAi. This study uncovered several novel, heavily targeted features within viral genomes, offering insight into viral replication, viral immune evasion strategies, and the mechanism of antiviral RNAi.

  20. Behaviors of tribrachial edge flames and their interactions in a triple-port burner

    KAUST Repository

    Yamamoto, Kazuhiro

    2015-05-01

    In a triple-port burner, various non-premixed flames have been observed previously. Especially for the case with two lifted flames, such configuration could be suitable in studying interaction between two tribrachial flames. In the present study, the flame characteristics have been investigated numerically by adopting a reduced kinetic mechanism in the triple-port burner. Four different types of flame configurations, including two attached flames, inner lifted/outer attached flames, inner attached/outer lifted flames, and twin lifted flames, were successfully simulated depending on the flow conditions. The representative edge propagation speed of a single lifted flame or an upstream lifted flame in the case of twin lifted flames increased as the liftoff height became higher. In the twin lifted flames, the inner lifted flame was affected appreciably when the other flame was located further upstream such that the lifted flame located further downstream encountered the axial velocity acceleration induced by the gas expansion from the lifted flame located upstream, while thermal effects were not observed since the temperature of the incoming flow toward the lifted flame was not affected. A unique flip-flop behavior between the inner and outer flames, observed experimentally previously, was successfully captured in the simulation such that the inner lifted flame became attached to the nozzle as the liftoff height of the outer lifted flame grew higher with an increase in the outer air velocity.

  1. Carnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Yusra Al Dhaheri

    Full Text Available In this study we investigated the in vitro and in vivo anticancer effect of carnosol, a naturally occurring polyphenol, in triple negative breast cancer.We found that carnosol significantly inhibited the viability and colony growth induced G2 arrest in the triple negative MDA-MB-231. Blockade of the cell cycle was associated with increased p21/WAF1 expression and downregulation of p27. Interestingly, carnosol was found to induce beclin1-independent autophagy and apoptosis in MDA-MB-231 cells. The coexistence of both events, autophagy and apoptosis, was confirmed by electron micrography. Induction of autophagy was found to be an early event, detected within 3 h post-treatment, which subsequently led to apoptosis. Carnosol treatment also caused a dose-dependent increase in the levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2. Moreover, we show that carnosol induced DNA damage, reduced the mitochondrial potential and triggered the activation of the intrinsic and extrinsic apoptotic pathway. Furthermore, we found that carnosol induced a dose-dependent generation of reactive oxygen species (ROS and inhibition of ROS by tiron, a ROS scavenger, blocked the induction of autophagy and apoptosis and attenuated DNA damage. To our knowledge, this is the first report to identify the induction of autophagy by carnosol.In conclusion our findings provide strong evidence that carnosol may be an alternative therapeutic candidate against the aggressive form of breast cancer and hence deserves more exploration.

  2. Application of LBIC measurements for characterisation of triple junction solar cells

    International Nuclear Information System (INIS)

    Kwarikunda, N.; Dyk, E.E. van; Vorster, F.J.; Okullo, W.; Munji, M.K.

    2014-01-01

    In this study the Light Beam Induced Current (LBIC) imaging technique was used to characterise InGaP/InGaAs/Ge triple junction solar cells. The study focused on the use of monochromatic and solar light as beam probes to obtain photocurrent response maps from which the presence of any current reducing features on the solar cell were identified. Point illuminated current voltage (I–V) curves were obtained simultaneously while LBIC scanning measurements were being made. Curve fitting using an interval division algorithm based on the single diode model was performed to extract basic point device and performance parameters to give a rough indication of the functioning of the triple junction device. Using red and blue lasers as beam probes, reverse voltage breakdown was observed on the I–V curves which could be attributed to the Ge bottom subcell not being fully activated. The extracted parameters obtained when using monochromatic and solar light beam probes showed a large variation, indicating the dependence of I–V parameters on the spectral content of the beam probe.

  3. Application of LBIC measurements for characterisation of triple junction solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Kwarikunda, N., E-mail: Nicholas.kwarikunda@live.nmmu.ac.za [Nelson Mandela Metropolitan University, P.O. BOX 77000, Port Elizabeth, 6031 (South Africa); Makerere University, P.O. BOX 7062, Kampala (Uganda); Dyk, E.E. van; Vorster, F.J. [Nelson Mandela Metropolitan University, P.O. BOX 77000, Port Elizabeth, 6031 (South Africa); Okullo, W. [Makerere University, P.O. BOX 7062, Kampala (Uganda); Munji, M.K. [Kenyatta University, P.O. BOX 43844-00100, Nairobi (Kenya)

    2014-04-15

    In this study the Light Beam Induced Current (LBIC) imaging technique was used to characterise InGaP/InGaAs/Ge triple junction solar cells. The study focused on the use of monochromatic and solar light as beam probes to obtain photocurrent response maps from which the presence of any current reducing features on the solar cell were identified. Point illuminated current voltage (I–V) curves were obtained simultaneously while LBIC scanning measurements were being made. Curve fitting using an interval division algorithm based on the single diode model was performed to extract basic point device and performance parameters to give a rough indication of the functioning of the triple junction device. Using red and blue lasers as beam probes, reverse voltage breakdown was observed on the I–V curves which could be attributed to the Ge bottom subcell not being fully activated. The extracted parameters obtained when using monochromatic and solar light beam probes showed a large variation, indicating the dependence of I–V parameters on the spectral content of the beam probe.

  4. Reynolds-Stress and Triple-Product Models Applied to a Flow with Rotation and Curvature

    Science.gov (United States)

    Olsen, Michael E.

    2016-01-01

    Turbulence models, with increasing complexity, up to triple product terms, are applied to the flow in a rotating pipe. The rotating pipe is a challenging case for turbulence models as it contains significant rotational and curvature effects. The flow field starts with the classic fully developed pipe flow, with a stationary pipe wall. This well defined condition is then subjected to a section of pipe with a rotating wall. The rotating wall introduces a second velocity scale, and creates Reynolds shear stresses in the radial-circumferential and circumferential-axial planes. Furthermore, the wall rotation introduces a flow stabilization, and actually reduces the turbulent kinetic energy as the flow moves along the rotating wall section. It is shown in the present work that the Reynolds stress models are capable of predicting significant reduction in the turbulent kinetic energy, but triple product improves the predictions of the centerline turbulent kinetic energy, which is governed by convection, dissipation and transport terms, as the production terms vanish on the pipe axis.

  5. Carnosol Induces ROS-Mediated Beclin1-Independent Autophagy and Apoptosis in Triple Negative Breast Cancer

    Science.gov (United States)

    Al Dhaheri, Yusra; Attoub, Samir; Ramadan, Gaber; Arafat, Kholoud; Bajbouj, Khuloud; Karuvantevida, Noushad; AbuQamar, Synan; Eid, Ali; Iratni, Rabah

    2014-01-01

    Background In this study we investigated the in vitro and in vivo anticancer effect of carnosol, a naturally occurring polyphenol, in triple negative breast cancer. Results We found that carnosol significantly inhibited the viability and colony growth induced G2 arrest in the triple negative MDA-MB-231. Blockade of the cell cycle was associated with increased p21/WAF1 expression and downregulation of p27. Interestingly, carnosol was found to induce beclin1-independent autophagy and apoptosis in MDA-MB-231 cells. The coexistence of both events, autophagy and apoptosis, was confirmed by electron micrography. Induction of autophagy was found to be an early event, detected within 3 h post-treatment, which subsequently led to apoptosis. Carnosol treatment also caused a dose-dependent increase in the levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2). Moreover, we show that carnosol induced DNA damage, reduced the mitochondrial potential and triggered the activation of the intrinsic and extrinsic apoptotic pathway. Furthermore, we found that carnosol induced a dose-dependent generation of reactive oxygen species (ROS) and inhibition of ROS by tiron, a ROS scavenger, blocked the induction of autophagy and apoptosis and attenuated DNA damage. To our knowledge, this is the first report to identify the induction of autophagy by carnosol. Conclusion In conclusion our findings provide strong evidence that carnosol may be an alternative therapeutic candidate against the aggressive form of breast cancer and hence deserves more exploration. PMID:25299698

  6. An analytical study on the carrier-phase linear combinations for triple-frequency GNSS

    Science.gov (United States)

    Li, Jinlong; Yang, Yuanxi; He, Haibo; Guo, Hairong

    2017-02-01

    The linear combinations of multi-frequency carrier-phase measurements for Global Navigation Satellite System (GNSS) are greatly beneficial to improving the performance of ambiguity resolution (AR), cycle slip correction as well as precise positioning. In this contribution, the existing definitions of the carrier-phase linear combination are reviewed and the integer property of the resulting ambiguity of the phase linear combinations is examined. The general analytical method for solving the optimal integer linear combinations for all triple-frequency GNSS is presented. Three refined triple-frequency integer combinations solely determined by the frequency values are introduced, which are the ionosphere-free (IF) combination that the Sum of its integer coefficients equal to 0 (IFS0), the geometry-free (GF) combination that the Sum of its integer coefficients equal to 0 (GFS0) and the geometry-free and ionosphere-free (GFIF) combination. Besides, the optimal GF, IF, extra-wide lane and ionosphere-reduced integer combinations for GPS and BDS are solved exhaustively by the presented method. Their potential applications in cycle slip detection, AR as well as precise positioning are discussed. At last, a more straightforward GF and IF AR scheme than the existing method is presented based on the GFIF integer combination.

  7. Cost analysis of residual viremia detected by two real-time PCR assays for response-guided (dual or triple therapy of HCV genotype 1 infection

    Directory of Open Access Journals (Sweden)

    Alessio Aghemo

    2016-12-01

    Full Text Available Cost analysis of residual viremia detected by two real-time PCR assays for response-guided (dual or triple therapy of HCV genotype 1 infectionIntroductionThe duration of interferon-based dual and triple therapies for HCV-G1 is determined by assessment of early viral kinetics. We conducted a cost analysis to determine the mean cost of dual or triple therapy treatment for a patient with HCV-G1, where the therapy duration (24 or 48 weeks is guided by HCV-RNA assay.MethodsHCV-RNA was assessed by two widely used real-time PCR-based assays, Cobas Ampliprep/Cobas TaqMan (CAP-CTM and Real-Time HCV (ART. As far as the dual therapy (PegINFα-2b and RBV is concerned, at week 12 of treatment 16.0% of patients (27/169 were eligible to receive a shorter duration of therapy (24 weeks according to CAP-CTM and 8.9% (15/169 according to ART: 26 patients achieved SVR (15.4% with CAP-CTM and 15 with ART (8.9%. With regard to triple therapy (TPV, PegINFα-2a and RBV, at week 12 of treatment 59.6% of patients (31/52 were eligible to receive a shorter duration of therapy (24 weeks according to CAP-CTM and 28.8% (15/52 according to ART: 30 patients achieved SVR (57.7% with CAP-CTM and 13 with ART (25.0%. The cost analysis was conducted from the perspective of the Italian National Health Service (NHS. Only drug (TPV, PegINFα-2a, PegINFα-2b and RBV and test (CAP-CTM and ART costs were taken into account. Ex-factory prices (included all discounts and national tariffs were used to calculate drug consumptions and tests, respectively. Costs were assessed in Euros 2015.ResultsWith regard to dual therapy, the overall mean treatment cost per patient with CAP-CTM (€9,572.77 was lower than with ART (€9,876.19. With regard to triple therapy, the overall mean treatment cost per patient was lower with CAP-CTM (€31,354.40 than with ART (€33,155.26.ConclusionsCAP-CTM HCV-RNA assay was cost-saving from the Italian NHS perspective compared with ART HCV-RNA assay in the dual

  8. A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients.

    Science.gov (United States)

    Braun, Dominique L; Rauch, Andri; Aouri, Manel; Durisch, Nina; Eberhard, Nadia; Anagnostopoulos, Alexia; Ledergerber, Bruno; Müllhaupt, Beat; Metzner, Karin J; Decosterd, Laurent; Böni, Jürg; Weber, Rainer; Fehr, Jan

    2015-01-01

    The efficacy of first-generation protease inhibitor based triple-therapy against hepatitis C virus (HCV) infection is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and non-response to previous peginterferon-ribavirin. These patients have a low chance of achieving a sustained virologic response (SVR) using first generation triple-therapy, with a success rate of only 20%. We investigated the efficacy and safety of lead-in therapy with intravenous silibinin followed by triple-therapy in this difficult-to-treat patient group. Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented previous treatment failure on peginterferon-ribavirin. The intervention was a lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days, followed by triple-therapy (peginterferon-ribavirin and telaprevir) for 12 weeks, and peginterferon-ribavirin alone for 36 weeks. Outcome measurements were HCV-RNA after silibinin lead-in and during triple-therapy, SVR data at week 12, and safety and tolerability of silibinin. We examined sixteen HIV/HCV-coinfected patients with previous peginterferon-ribavirin failure, of whom 14 had a fibrosis grade METAVIR ≥F3. All were on successful antiretroviral therapy. Median (IQR) HCV-RNA decline after silibinin therapy was 2.65 (2.1-2.8) log10 copies/mL. Fifteen of sixteen patients (94%) had undetectable HCV RNA at weeks 4 and 12, eleven patients (69%) showed end-of-treatment response (i.e., undetectable HCV-RNA at week 48), and ten patients (63%) reached SVR at week 12 (SVR 12). Six of the sixteen patients (37%) did not reach SVR 12: One patient had rapid virologic response (RVR) (i.e., undetectable HCV-RNA at week 4) but stopped treatment at week 8 due to major depression. Five patients had RVR, but experienced viral breakthroughs at week 21, 22, 25, or 32, or a relapse at week 52. The HIV RNA remained below the limit of detection in all patients during the complete treatment period. No serious

  9. Evaluation of the prognostic value of liver stiffness in patients with hepatitis C virus treated with triple or dual antiviral therapy: A prospective pilot study.

    Science.gov (United States)

    Stasi, Cristina; Piluso, Alessia; Arena, Umberto; Salomoni, Elena; Montalto, Paolo; Monti, Monica; Boldrini, Barbara; Corti, Giampaolo; Marra, Fabio; Laffi, Giacomo; Milani, Stefano; Zignego, Anna Linda

    2015-03-14

    To evaluate the association between liver stiffness (LS) prior to the initiation of dual/triple therapy and viral response. LS was measured in all patients before treatment was administered. The therapeutic approach was based on hepatic, virological, and immunological evaluations and considered the fact that patients with severe fibrosis (F3) or compensated cirrhosis (F4) in Child-Pugh class A are the primary candidates for triple therapy. In total, 65 hepatitis C virus (HCV) patients were treated with Peg-interferon/ribavirin (Peg-IFN/RBV); 24 patients were classified as genotypes 1/4 (36.92%), and 41 patients were classified as genotypes 2/3 (63.08%) (dual therapy). In addition, 20 HCV treatment-experienced genotype 1 patients were treated with PegIFN-RBV and boceprevir (triple therapy). Wilcoxon rank-sum tests were used to compare the groups. LS significantly differed between dual therapy and triple therapy (P = 0.002). The mean LS value before dual therapy treatment was 8.61 ± 5.79 kPa and was significantly different between patients achieving a sustained virologic response (SVR) 24 weeks after therapy and those who did not (7.23 ± 5.18 kPa vs 11.72 ± 5.99 kPa, respectively, P = 0.0003). The relative risk of non-response to therapy was 4.45 (95%CI: 2.32-8.55). The attributable risk of non-response to therapy was 49%. The mean LS value before triple therapy treatment was 13.29 ± 8.57 kPa and was significantly different between patients achieving and not achieving SVR24 (9.41 ± 5.05 vs 19.11 ± 9.74, respectively; P = 0.008). The relative risk of non-response to therapy was 5.57% (95%CI: 1.50-20.65). The attributable risk of non-response to therapy (70%) was increased compared with dual therapy patients. Pre-treatment stiffness > 12 kPa was significantly associated with non-SVR (P < 0.025) in both groups. Pre-treatment liver stiffness may be useful for predicting the response to treatment in patients treated with either dual or triple anti-HCV therapy.

  10. Triple pelvic osteotomy in Legg-Calve-Perthes disease using a single anterolateral incision: a 4-year review.

    LENUS (Irish Health Repository)

    Conroy, Eimear

    2010-07-01

    from 9 to 24 whereas postoperative scores ranged from 25 to 46. Triple osteotomy has been advocated in Legg-Calve-Perthes\\' disease after the closure of the triradiate cartilage. Using a single incision is a safer alternative to the traditional two-incision approach. We believe that the single incision approach reduces operative time and potential morbidity associated with the steel triple osteotomy with comparable clinical and radiographic outcomes.

  11. Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions

    DEFF Research Database (Denmark)

    Zibert, John Robert; Wallbrecht, Katrin; Schön, Margarete

    2011-01-01

    with epidermal expression of human TGF-ß1, we have demonstrated that antiangiogenic non-viral somatic gene therapy reduces the cutaneous microvasculature and alleviates chronic inflammatory skin disorders. Transient muscular expression of the recombinant disintegrin domain (RDD) of metargidin (also known as ADAM...... in all models. Thus, non-viral antiangiogenic gene therapy can alleviate psoriasis and may do so in other angiogenesis-related inflammatory skin disorders.......-15) by in vivo electroporation reduced cutaneous angiogenesis and vascularization in all 3 models. As demonstrated using red fluorescent protein-coupled RDD, the treatment resulted in muscular expression of the gene product and its deposition within the cutaneous hyperangiogenic connective tissue...

  12. The anti-obesity drug orlistat reveals anti-viral activity.

    Science.gov (United States)

    Ammer, Elisabeth; Nietzsche, Sandor; Rien, Christian; Kühnl, Alexander; Mader, Theresa; Heller, Regine; Sauerbrei, Andreas; Henke, Andreas

    2015-12-01

    The administration of drugs to inhibit metabolic pathways not only reduces the risk of obesity-induced diseases in humans but may also hamper the replication of different viral pathogens. In order to investigate the value of the US Food and Drug Administration-approved anti-obesity drug orlistat in view of its anti-viral activity against different human-pathogenic viruses, several anti-viral studies, electron microscopy analyses as well as fatty acid uptake experiments were performed. The results indicate that administrations of non-cytotoxic concentrations of orlistat reduced the replication of coxsackievirus B3 (CVB3) in different cell types significantly. Moreover, orlistat revealed cell protective effects and modified the formation of multi-layered structures in CVB3-infected cells, which are necessary for viral replication. Lowering fatty acid uptake from the extracellular environment by phloretin administrations had only marginal impact on CVB3 replication. Finally, orlistat reduced also the replication of varicella-zoster virus moderately but had no significant influence on the replication of influenza A viruses. The data support further experiments into the value of orlistat as an inhibitor of the fatty acid synthase to develop new anti-viral compounds, which are based on the modulation of cellular metabolic pathways.

  13. Grain boundary and triple junction diffusion in nanocrystalline copper

    Energy Technology Data Exchange (ETDEWEB)

    Wegner, M., E-mail: m.wegner@uni-muenster.de; Leuthold, J.; Peterlechner, M.; Divinski, S. V., E-mail: divin@uni-muenster.de [Institut für Materialphysik, Universität Münster, Wilhelm-Klemm-Straße 10, D-48149, Münster (Germany); Song, X., E-mail: xysong@bjut.edu.cn [College of Materials Science and Engineering, Beijing University of Technology, 100124 Beijing (China); Wilde, G. [Institut für Materialphysik, Universität Münster, Wilhelm-Klemm-Straße 10, D-48149, Münster (Germany); Institute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai University, 200444 Shanghai (China)

    2014-09-07

    Grain boundary and triple junction diffusion in nanocrystalline Cu samples with grain sizes, 〈d〉, of ∼35 and ∼44 nm produced by spark plasma sintering were investigated by the radiotracer method using the {sup 63}Ni isotope. The measured diffusivities, D{sub eff}, are comparable with those determined previously for Ni grain boundary diffusion in well-annealed, high purity, coarse grained, polycrystalline copper, substantiating the absence of a grain size effect on the kinetic properties of grain boundaries in a nanocrystalline material at grain sizes d ≥ 35 nm. Simultaneously, the analysis predicts that if triple junction diffusion of Ni in Cu is enhanced with respect to the corresponding grain boundary diffusion rate, it is still less than 500⋅D{sub gb} within the temperature interval from 420 K to 470 K.

  14. Triple and quartic gauge boson couplings at the LHC

    CERN Document Server

    Kupco, Alexander; The ATLAS collaboration

    2017-01-01

    This report at the conference Physics in Collision 2017 reviews recent results from the ATLAS and CMS experiments on production of gauge boson pairs, triples, and vector boson scattering (VBS) processes. Large datasets from LHC proton-proton collisions at $\\sqrt{s}=8$ and $13\\,\\mathrm{TeV}$ allowed the first observations of rare processes: triboson production in channel $Z\\gamma\\gamma$ at $\\sqrt{s}=8\\,\\mathrm{TeV}$ and VBS of same signed WW at $\\sqrt{s}=13\\,\\mathrm{TeV}$. Both experiments observe good agreement with the Standard model (SM) predictions. The data were used to set new limits on anomalous triple and quartic gauge couplings not present in the SM.

  15. Assembly of Liposomes Controlled by Triple Helix Formation

    DEFF Research Database (Denmark)

    Vogel, Stefan; Jakobsen, Ulla

    2013-01-01

    Attachment of DNA to the surface of different solid nanoparticles (e.g. gold- and silica nanoparticles) is well established and a number of DNA-modified solid nanoparticle systems have been applied to thermal denaturation analysis of oligonucleotides. We report herein the non...... sequences (G or C-rich) to explore the applicability of the method for different triple helical assembly modes. We demonstrate advantages and limitations of the approach and proof the reversible and reproducible formation of liposome aggregates during thermal denaturation cycles. Nanoparticle tracking......-covalent immobilization of oligonucleotides on the surface of soft nanoparticles (e.g. liposomes) and the subsequent controlled assembly by DNA triple helix formation. The non-covalent approach avoids tedious surface chemistry and necessary purification procedures and can simplify and extend the available methodology...

  16. EXTREME AO OBSERVATIONS OF TWO TRIPLE ASTEROID SYSTEMS WITH SPHERE

    Energy Technology Data Exchange (ETDEWEB)

    Yang, B.; Wahhaj, Z.; Dumas, C.; Marsset, M. [European Southern Observatory, Santiago (Chile); Beauvalet, L. [National Observatory, Rio de Janeiro (Brazil); Marchis, F.; Nielsen, E. L. [Carl Sagan Center at the SETI Institute, Mountain View, CA (United States); Vachier, F., E-mail: byang@eso.org [Institut de Mécanique Céleste et de Calcul des Éphémérides, Paris (France)

    2016-04-01

    We present the discovery of a new satellite of asteroid (130) Elektra—S/2014 (130) 1—in differential imaging and in integral field spectroscopy data over multiple epochs obtained with Spectro-Polarimetric High-contrast Exoplanet Research/Very Large Telescope. This new (second) moonlet of Elektra is about 2 km across, on an eccentric orbit, and about 500 km away from the primary. For a comparative study, we also observed another triple asteroid system, (93) Minerva. For both systems, component-resolved reflectance spectra of the satellites and primary were obtained simultaneously. No significant spectral difference was observed between the satellites and the primary for either triple system. We find that the moonlets in both systems are more likely to have been created by sub-disruptive impacts as opposed to having been captured.

  17. Synchronizing a Triple Dragline Stripping System in Thick Overburden

    Directory of Open Access Journals (Sweden)

    Erdem Bülent

    2017-06-01

    Full Text Available This study addresses the use of combined stripping systems to investigate the technical feasibility of extracting thick coal seams underlying deep overburden strata. The possibility of using multiple draglines in tandem with bucket wheel excavator systems is explored. Pit geometry design alternatives incorporating a triple dragline excavation fleet with bucket wheel excavator-cross pit spreader subsystems (BWE+XPS are examined. A production simulation algorithm, which emphasizes synchronizing excavator units in the triple dragline system, is developed. The combined methodology is evaluated in Sector-D of the Afşin-Elbistan lignite basin, one of the most important resources for electricity production in Turkey. The results reveal that a combined stripping fleet may successfully perform overburden stripping at the predetermined rate and uncover coal seams.

  18. S-matrix calculation of the triple-alpha reaction

    Science.gov (United States)

    Fushiki, Ikko; Lamb, D. Q.

    1987-01-01

    An S-matrix formalism is developed which can be applied to reactions in which electron screening is important, including three-body reactions and reactions involving weak interactions. The various regimes of the triple-alpha reactions are systematically discussed, and a new nonresonant regime at high densities is identified. Using the S-matrix formalism, an analytic expression is obtained for the screened triple-alpha reactions which is accurate for all temperatures and densities. The results are compared with those of Cameron (1959) and Nomoto et al. (1985), and the latter's expression for the unscreened reaction rate is verified. However, it is shown that the reaction rate in the pycnonuclear regime cannot be obtained from the unscreened rate using a screening factor, and that the results of Nomoto et al. therefore cannot be used in this regime.

  19. Development of triple axis neutron spectrometer (Paper No. 24)

    International Nuclear Information System (INIS)

    Pal, B.C.; Wadhwa, N.R.; Goveas, S.H.

    1987-02-01

    The triple axis neutron spectrometers are the basic instruments intended for use with neutron beams from reactors. Various types of spectrometers, each devoted to different kinds of measurement can be designed and manufactured, once a prototype having all the attributes of a versatile instrument is designed and developed. With the view to achieving self reliance in this field, Central Workshops of Bhabha Atomic Research Centre (BARC), Bombay designed and developed a prototype of triple axis spectrometer meeting the specifications prepared by Nuclear Physics Division of BARC . This spectrometer, with a moving wedge system was successfully manufactured and installed at 'DHRUVA'. Another version of this spectrometer, called the 'Polarised Neutron Spectrometer' was also built and exported to South Korea and installed at Korea Advanced Energy Research Institute, Seoul. This paper deals with basic concept, development of design, engineering of mechanical assemblies, the manufacturing approach and problems encountered during manufacture. (author). 3 figs

  20. Ionospheric Cycle Slip Processing in Triple-frequency GNSS

    Directory of Open Access Journals (Sweden)

    HUANG Lingyong

    2015-07-01

    Full Text Available A new method based on three linear independence geometry-free and ionosphere-free (GIF combinations to detect and repair cycle-slip is advanced to finishing the cycle slip processing under the higher ionospheric activity. In order to ensure that the cycle slip correction is accurate, the repair value is validated by a second-order, time-difference phase ionospheric residual (STPIR combination. And then, this method is validated and analyzed by using the triple-frequency data with higher ionospheric error. The experiment results show that this method can nearly detect and repair all the cycle slip except several insensitive cycle slip under high ionospheric activity. So this method can be used to cycle slip procession in triple-frequency precise point position and other un-differenced dynamic navigation and position.

  1. Immune Responses against Conserved and Variable Viral Epitopes

    OpenAIRE

    Bittner, B.; Wahl, L. M.

    2000-01-01

    We extend well-known mathematical models of viral infection to examine the response of cytotoxic T lymphocytes (CTL) to both conserved and variable viral epitopes. Because most viruses are subject to error-prone reproduction, CTL recognition may be faced with highly variable epitopes, while other CTL epitopes may remain conserved across viral strains. In this paper we examine the steady state conditions for a simple model of viral-immune system dynamics in which the viral strain can be limite...

  2. Intracellular Detection of Viral Transcription and Replication Using RNA FISH

    Science.gov (United States)

    2016-05-26

    Chapter 14. Intracellular detection of viral transcription and replication using RNA FISH i. Summary/Abstract Many hemorrhagic fever viruses...resolution. However, viral RNA tends to cluster in specific subcellular sites (e.g. viral replication factories). Thus while true single-molecule...assays [4]. Detection of viral RNA allows for in depth interrogation of the subcellular sites of viral replication and such experiments will help further

  3. View and review on viral oncology research

    Directory of Open Access Journals (Sweden)

    Parolin Cristina

    2010-05-01

    Full Text Available Abstract To date, almost one and a half million cases of cancer are diagnosed every year in the US and nearly 560,000 Americans are expected to die of cancer in the current year, more than 1,500 people a day (data from the American Cancer Society at http://www.cancer.org/. According to the World Health Organization (WHO, roughly 20% of all cancers worldwide results from chronic infections; in particular, up to 15% of human cancers is characterized by a viral aetiology with higher incidence in Developing Countries. The link between viruses and cancer was one of the pivotal discoveries in cancer research during the past Century. Indeed, the infectious nature of specific tumors has important implications in terms of their prevention, diagnosis, and therapy. In the 21st Century, the research on viral oncology field continues to be vigorous, with new significant and original studies on viral oncogenesis and translational research from basic virology to treatment of cancer. This review will cover different viral oncology aspects, starting from the history of viral oncology and moving to the peculiar features of oncogenic RNA and DNA viruses, with a special focus on human pathogens.

  4. Viral Dynamics of Acute HIV-1 Infection

    Science.gov (United States)

    Little, Susan J.; McLean, Angela R.; Spina, Celsa A.; Richman, Douglas D.; Havlir, Diane V.

    1999-01-01

    Viral dynamics were intensively investigated in eight patients with acute HIV infection to define the earliest rates of change in plasma HIV RNA before and after the start of antiretroviral therapy. We report the first estimates of the basic reproductive number (R 0), the number of cells infected by the progeny of an infected cell during its lifetime when target cells are not depleted. The mean initial viral doubling time was 10 h, and the peak of viremia occurred 21 d after reported HIV exposure. The spontaneous rate of decline (α) was highly variable among individuals. The phase 1 viral decay rate (δI = 0.3/day) in subjects initiating potent antiretroviral therapy during acute HIV infection was similar to estimates from treated subjects with chronic HIV infection. The doubling time in two subjects who discontinued antiretroviral therapy was almost five times slower than during acute infection. The mean basic reproductive number (R 0) of 19.3 during the logarithmic growth phase of primary HIV infection suggested that a vaccine or postexposure prophylaxis of at least 95% efficacy would be needed to extinguish productive viral infection in the absence of drug resistance or viral latency. These measurements provide a basis for comparison of vaccine and other strategies and support the validity of the simian immunodeficiency virus macaque model of acute HIV infection. PMID:10499922

  5. Recombination-dependent concatemeric viral DNA replication.

    Science.gov (United States)

    Lo Piano, Ambra; Martínez-Jiménez, María I; Zecchi, Lisa; Ayora, Silvia

    2011-09-01

    The initiation of viral double stranded (ds) DNA replication involves proteins that recruit and load the replisome at the replication origin (ori). Any block in replication fork progression or a programmed barrier may act as a factor for ori-independent remodelling and assembly of a new replisome at the stalled fork. Then replication initiation becomes dependent on recombination proteins, a process called recombination-dependent replication (RDR). RDR, which is recognized as being important for replication restart and stability in all living organisms, plays an essential role in the replication cycle of many dsDNA viruses. The SPP1 virus, which infects Bacillus subtilis cells, serves as a paradigm to understand the links between replication and recombination in circular dsDNA viruses. SPP1-encoded initiator and replisome assembly proteins control the onset of viral replication and direct the recruitment of host-encoded replisomal components at viral oriL. SPP1 uses replication fork reactivation to switch from ori-dependent θ-type (circle-to-circle) replication to σ-type RDR. Replication fork arrest leads to a double strand break that is processed by viral-encoded factors to generate a D-loop into which a new replisome is assembled, leading to σ-type viral replication. SPP1 RDR proteins are compared with similar proteins encoded by other viruses and their possible in vivo roles are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Viral miRNAs and immune evasion.

    Science.gov (United States)

    Boss, Isaac W; Renne, Rolf

    2011-01-01

    Viral miRNAs, ~22nt RNA molecules which post-transcriptionally regulate gene expression, are emerging as important tools in immune evasion. Viral infection is a complex process that requires immune evasion in order to establish persistent life-long infection of the host. During this process viruses express both protein-coding and non-coding genes, which help to modulate the cellular environment making it more favorable for infection. In the last decade, it was uncovered that DNA viruses express a diverse and abundant pool of small non-coding RNA molecules, called microRNAs (miRNAs). These virally encoded miRNAs are non-immunogenic and therefore are important tools used to evade both innate and adaptive immune responses. This review aims to summarize our current knowledge of herpesvirus- and polyomavirus-encoded miRNAs, and how they contribute to immune evasion by targeting viral and/or host cellular genes. This article is part of a Special Issue entitled: MicroRNAs in viral gene regulation. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Tidal breakup of triple stars in the Galactic Centre

    Science.gov (United States)

    Fragione, Giacomo; Gualandris, Alessia

    2018-04-01

    The last decade has seen the detection of fast moving stars in the Galactic halo, the so-called hypervelocity stars (HVSs). While the bulk of this population is likely the result of a close encounter between a stellar binary and the supermassive black hole (MBH) in the Galactic Centre (GC), other mechanims may contribute fast stars to the sample. Few observed HVSs show apparent ages, which are shorter than the flight time from the GC, thereby making the binary disruption scenario unlikely. These stars may be the result of the breakup of a stellar triple in the GC, which led to the ejection of a hypervelocity binary (HVB). If such binary evolves into a blue straggler star due to internal processes after ejection, a rejuvenation is possible that make the star appear younger once detected in the halo. A triple disruption may also be responsible for the presence of HVBs, of which one candidate has now been observed. We present a numerical study of triple disruptions by the MBH in the GC and find that the most likely outcomes are the production of single HVSs and single/binary stars bound to the MBH, while the production of HVBs has a probability ≲ 1 per cent regardless of the initial parameters. Assuming a triple fraction of ≈ 10 per cent results in an ejection rate of ≲ 1 Gyr - 1, insufficient to explain the sample of HVSs with lifetimes shorter than their flight time. We conclude that alternative mechanisms are responsible for the origin of such objects and HVBs in general.

  8. Lifestyle Triple P: a parenting intervention for childhood obesity

    Directory of Open Access Journals (Sweden)

    Gerards Sanne MPL

    2012-04-01

    Full Text Available Abstract Background Reversing the obesity epidemic requires the development and evaluation of childhood obesity intervention programs. Lifestyle Triple P is a parent-focused group program that addresses three topics: nutrition, physical activity, and positive parenting. Australian research has established the efficacy of Lifestyle Triple P, which aims to prevent excessive weight gain in overweight and obese children. The aim of the current randomized controlled trial is to assess the effectiveness of the Lifestyle Triple P intervention when applied to Dutch parents of overweight and obese children aged 4–8 years. This effectiveness study is called GO4fit. Methods/Design Parents of overweight and obese children are being randomized to either the intervention or the control group. Those assigned to the intervention condition receive the 14-week Lifestyle Triple P intervention, in which they learn a range of nutritional, physical activity and positive parenting strategies. Parents in the control group receive two brochures, web-based tailored advice, and suggestions for exercises to increase active playing at home. Measurements are taken at baseline, directly after the intervention, and at one year follow-up. Primary outcome measure is the children’s body composition, operationalized as BMI z-score, waist circumference, and fat mass (biceps and triceps skinfolds. Secondary outcome measures are children’s dietary behavior and physical activity level, parenting practices, parental feeding style, parenting style, parental self-efficacy, and body composition of family members (parents and siblings. Discussion Our intervention is characterized by a focus on changing general parenting styles, in addition to focusing on changing specific parenting practices, as obesity interventions typically do. Strengths of the current study are the randomized design, the long-term follow-up, and the broad range of both self-reported and objectively measured

  9. Epigenetic Subtypes of Triple-Negative Breast Cancer

    Science.gov (United States)

    2015-10-01

    breast cancer phenotypes and their inheritance pattern, the Polyak lab has generated somatic cell fusions and performed...Determine the contribution of genetic heterogeneity to metastasis in breast cancer ; 2) Develop strategies to assess genomic heterogeneity in human tumors...Dissecting the heterogeneity of triple-negative breast cancer . J Clin Oncol 30, 1879-1887, (2012). 5 Su, Y. et al. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast

  10. Trilayered Morphology of an ABC Triple Crystalline Triblock Terpolymer

    KAUST Repository

    Palacios, Jordana K.

    2017-09-07

    Triple crystalline triblock terpolymers are materials with remarkable semicrystalline superstructures. In this work, we report for first time the alternating triple lamellar morphology that self-assembles inside spherulites of a triblock terpolymer composed of poly(ethylene oxide) (PEO), poly(ε-caprolactone) (PCL), and poly(l-lactide) (PLLA). The morphology of the PEO-b-PCL-b-PLLA triblock terpolymer is compared to an analogous PCL-b-PLLA diblock copolymer. Both diblock and triblock form a single phase in the melt. Two crystallization protocols were employed to create particular crystalline morphologies. In both cases, the isothermal crystallization of the PLA block is induced first (at 81 °C, a temperature above the melting points of both PCL and PEO blocks) and PLLA spherulites form a template, whereupon cooling the other two blocks can crystallize within the PLLA interlamellar spaces. WAXS analysis demonstrated the double crystalline and triple crystalline nature of the materials. The lamellar structure was evaluated by AFM observations and SAXS measurements. Moreover, theoretical SAXS curves of one-dimensional structural models were calculated. AFM micrographs of the triblock terpolymer evidenced the three different lamellae of PLLA, PCL and PEO that coexist together within the same spherulite. Three different lamellar thickness were determined, and their dimensions suggested that all blocks crystallized in chain-folded conformations. The evolution of the triple lamellar morphology during heating of tricrystalline samples was followed by in situ synchrotron SAXS measurements. The theoretical analysis of the SAXS curves of the triblock terpolymer allowed us to propose a stacking morphological model, in which a particular trilayer structure exists, where one lamella of PCL or one lamella of PEO is inserted randomly between two adjacent PLLA lamellae.

  11. Ensemble of Neural Classifiers for Scoring Knowledge Base Triples

    OpenAIRE

    Yamada, Ikuya; Sato, Motoki; Shindo, Hiroyuki

    2017-01-01

    This paper describes our approach for the triple scoring task at the WSDM Cup 2017. The task required participants to assign a relevance score for each pair of entities and their types in a knowledge base in order to enhance the ranking results in entity retrieval tasks. We propose an approach wherein the outputs of multiple neural network classifiers are combined using a supervised machine learning model. The experimental results showed that our proposed method achieved the best performance ...

  12. Kramers Turnover Theory for a Triple Well Potential

    International Nuclear Information System (INIS)

    Pollak, E.; Talkner, P.

    2001-01-01

    Kramers turnover theory is solved for a particle in a symmetric triple well potential for temperatures above the crossover temperature between tunneling and activated barrier crossing. Comparison with the turnover theory for a double well potential shows that the presence of the intermediate well always leads to a decrease of the reaction rate. At most though, the rate is a factor of two smaller than in the case of a double well potential. (author)

  13. Approximate Homomorphisms and Derivations on Normed Lie Triple Systems

    Directory of Open Access Journals (Sweden)

    Hark-Mahn Kim

    2014-01-01

    Full Text Available We investigate the generalized Hyers-Ulam stability of homomorphisms and derivations on normed Lie triple systems for the following generalized Cauchy-Jensen additive equation r0f((s∑j=1pxj+t∑j=1dyj/r0=s∑j=1p‍f(xj+t∑j=1d‍f(yj, where r0,s, and  t are nonzero real numbers. As a results, we generalize some stability results concerning this equation.

  14. Optimization of the triple-pressure combined cycle power plant

    OpenAIRE

    Alus Muammer; Petrović Milan V.

    2012-01-01

    The aim of this work was to develop a new system for optimization of parameters for combined cycle power plants (CCGTs) with triple-pressure heat recovery steam generator (HRSG). Thermodynamic and thermoeconomic optimizations were carried out. The objective of the thermodynamic optimization is to enhance the efficiency of the CCGTs and to maximize the power production in the steam cycle (steam turbine gross power). Improvement of the efficiency of the CCGT plants is achieved through opt...

  15. Triple molybdates one-, one - and three(twovalence metals

    Directory of Open Access Journals (Sweden)

    G. E. Khaikina

    2015-12-01

    Full Text Available The review summarizes experimental data on the phase formation, structure and properties of new complex oxide compounds group – triple molybdates containing tetrahedral molybdate ion, two different singly charged cation, together with tri- or divalent cation. The several structural families of these compounds were distinguished and it shown that many of them are of interest as luminescent, laser, ion-conducting or nonlinear optical materials.

  16. Triple templating of graphitic carbon nitride to enhance photocatalytic properties

    Directory of Open Access Journals (Sweden)

    Z. Yang

    2016-01-01

    Full Text Available Graphitic carbon nitride materials show some promising properties for applications such as photocatalytic water splitting. However, the conversion efficiency is still low due to factors such as a low surface area and limited light absorption. In this paper, we describe a “triple templating” approach to generating porous graphitic carbon nitride. The introduction of pores on several length-scales results in enhanced photocatalytic properties.

  17. Triple templating of graphitic carbon nitride to enhance photocatalytic properties

    OpenAIRE

    Z. Yang; A. E. Danks; J. Wang; Y. Zhang; Z. Schnepp

    2016-01-01

    Graphitic carbon nitride materials show some promising properties for applications such as photocatalytic water splitting. However, the conversion efficiency is still low due to factors such as a low surface area and limited light absorption. In this paper, we describe a “triple templating” approach to generating porous graphitic carbon nitride. The introduction of pores on several length-scales results in enhanced photocatalytic properties.

  18. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    International Nuclear Information System (INIS)

    Kohio, Hinissan P.; Adamson, Amy L.

    2013-01-01

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells

  19. Silver nanoparticles inhibit vaccinia virus infection by preventing viral entry through a macropinocytosis-dependent mechanism.

    Science.gov (United States)

    Trefry, John C; Wooley, Dawn P

    2013-09-01

    Silver nanoparticles have been shown to inhibit viruses. However, very little is known about the mechanism of antiviral activity. This study tested the hypothesis that 25-nm silver nanoparticles inhibited Vaccinia virus replication by preventing viral entry. Plaque reduction, confocal microscopy, and beta-galactosidase reporter gene assays were used to examine viral attachment and entry in the presence and absence of silver nanoparticles. To explore the mechanism of inhibition, viral entry experiments were conducted with silver nanoparticles and small interfering RNAs designed to silence the gene coding for p21-activated kinase 1, a key mediator of macropinocytosis. The silver nanoparticles caused a 4- to 5-log reduction in viral titer at concentrations that were not toxic to cells. Virus was capable of adsorbing to cells but could not enter cells in the presence of silver nanoparticles. Virus particles that had adsorbed to cells in the presence of silver nanoparticles were found to be infectious upon removal from the cells, indicating lack of direct virucidal effect. The half maximal inhibitory concentration for viral entry in the presence of silver nanoparticles was 27.4+/-3.3 microg/ml. When macropinocytosis was blocked, this inhibition was significantly reduced. Thus, macropinocytosis was required for the full antiviral effect. For the first time, this study points to the novel result that a cellular process involved in viral entry is responsible for the antiviral effects of silver nanoparticles.

  20. Design of triple-band polarization controlled terahertz metamaterial absorber

    Science.gov (United States)

    Wang, Ben-Xin; Xie, Qin; Dong, Guangxi; Huang, Wei-Qing

    2018-02-01

    A kind of triple-band polarization tunable terahertz absorber based on a metallic mirror and a metallic patch structure with two indentations spaced by an insulating medium layer is presented. Results prove that three near-perfect absorption peaks with average absorption coefficients of 98.25% are achieved when the polarization angle is equal to zero, and their absorptivities gradually decrease (and even disappear) by increasing the angle of polarization. When the polarization angle is increased to 90°, three new resonance modes with average absorption rates of 96.59% can be obtained. The field distributions are given to reveal the mechanisms of the triple-band absorption and the polarization tunable characteristics. Moreover, by introducing photosensitive silicon materials (its conductivity can be changed by the pump beam) in the indentations of the patch structure, the number of resonance peaks of the device can be actively tuned from triple-band to dual-band. The presented absorbers have potential applications, such as controlling thermal emissivity, and detection of polarization direction of the incident waves.

  1. Prenatal diagnosis and prognosis of triple X syndrome: 47, XXX.

    Science.gov (United States)

    Ben Hamouda, H; Mkacher, N; Elghezal, H; Bannour, H; Kamoun, M; Soua, H; Saad, A; Souissi, M M; Sfar, M T

    2009-11-01

    Triple X syndrome is a relatively common sex chromosomal abnormality occurring in 0,1% of live-born female infants. Most of these infants have a normal phenotype and only a few cases with 47, XXX karyotype have congenital malformations. We report three cases of triple X syndrome that were diagnosed prenatally by genetic amniocentesis for advanced maternal age and have been observed from birth to age of 3 to 12 years. A description of their growth and development is presented. The birth weight was normal in all patients and one of them had facial dysmorphism with right microphtalmia and auricular septal defect. During the first 2 years of life, the neuromotor development of these infants was not distinguishable from chromosomally normal children. By 3 years of age, two patients have a moderate developmental delay in speech and language. One girl 12-year-old had normal schooling. The diagnosis of the triple X syndrome can be never made because clinical demonstrations are not rather important to arouse the demand of a karyotype. Prenatal diagnosis is often made in front of the advanced maternal age. Expectant parents must be counseled as to the significance of this 47, XXX karyotype and prognostic information must be given.

  2. Second Law Of Thermodynamics Analysis Of Triple Cycle Power Plant

    Directory of Open Access Journals (Sweden)

    Matheus M. Dwinanto

    2012-11-01

    Full Text Available Triple cycle power plant with methane as a fuel has been analyzed on the basis of second law of thermodynamics.In this model, ideal Brayton cycle is selected as a topping cycle as it gives higher efficiency at lower pressure ratio comparedintercooler and reheat cycle. In trilple cycle the bottoming cycles are steam Rankine and organic Rankine cycle. Ammoniahas suitable working properties like critical temperature, boiling temperature, etc. Steam cycle consists of a deaerator andreheater. The bottoming ammonia cycle is a ideal Rankine cycle. Single pressure heat recovery steam and ammoniagenerators are selected for simplification of the analysis. The effects of pressure ratio and maximum temperature which aretaken as important parameters regarding the triple cycle are discussed on performance and exergetic losses. On the otherhand, the efficiency of the triple cycle can be raised, especially in the application of recovering low enthalpy content wasteheat. Therefore, by properly combining with a steam Rankine cycle, the ammonia Rankine cycle is expected to efficientlyutilize residual yet available energy to an optimal extent. The arrangement of multiple cycles is compared with combinedcycle having the same sink conditions. The parallel type of arrangement of bottoming cycle is selected due to increasedperformance.

  3. High-rate particle triggering with triple-GEM detector

    CERN Document Server

    Alfonsi, M; De Simone, P; Murtas, F; Poli-Lener, M; Bonivento, W; Cardini, A; Deplano, C; Raspino, D; Pinci, D

    2004-01-01

    We report the results of a systematic study of the time performance of triple-GEM detectors operated with Ar/CO//2/CF//4 and Ar/CF//4 /iso-C//4H//1//0 gas mixtures. This study and the detector development has been performed in the framework of an R&D activity on detectors for the innermost part (region R1) of the first muon station (M1) of the LHCb experiment. The use of fast gas mixtures allows to achieve a time resolution better than 5 ns (r.m.s.) and a single detector efficiency up to similar to 99% in a 20 ns time window. Discharge studies have been performed at the piM1 hadron beam facility of the Paul Scherrer Institute. Local aging properties were investigated exposing the detector to a collimated 5.9 keV X-rays beam. The whole R&D activity with different gas mixtures has been performed with small 10 multiplied by 10 cm**2 triple-GEM detector prototypes. A full size prototype (module-0) constituted by two 20 multiplied by 24 cm**2 triple-GEM detectors, equipped with front-end electronics based ...

  4. Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies.

    Directory of Open Access Journals (Sweden)

    Brian J Willett

    Full Text Available Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV, a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1 or diverse (Group 2 challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development.

  5. Norovirus Polymerase Fidelity Contributes to Viral TransmissionIn Vivo.

    Science.gov (United States)

    Arias, Armando; Thorne, Lucy; Ghurburrun, Elsa; Bailey, Dalan; Goodfellow, Ian

    2016-01-01

    Intrahost genetic diversity and replication error rates are intricately linked to RNA virus pathogenesis, with alterations in viral polymerase fidelity typically leading to attenuation during infections in vivo . We have previously shown that norovirus intrahost genetic diversity also influences viral pathogenesis using the murine norovirus model, as increasing viral mutation frequency using a mutagenic nucleoside resulted in clearance of a persistent infection in mice. Given the role of replication fidelity and genetic diversity in pathogenesis, we have now investigated whether polymerase fidelity can also impact virus transmission between susceptible hosts. We have identified a high-fidelity norovirus RNA-dependent RNA polymerase mutant (I391L) which displays delayed replication kinetics in vivo but not in cell culture. The I391L polymerase mutant also exhibited lower transmission rates between susceptible hosts than the wild-type virus and, most notably, another replication defective mutant that has wild-type levels of polymerase fidelity. These results provide the first experimental evidence that norovirus polymerase fidelity contributes to virus transmission between hosts and that maintaining diversity is important for the establishment of infection. This work supports the hypothesis that the reduced polymerase fidelity of the pandemic GII.4 human norovirus isolates may contribute to their global dominance. IMPORTANCE Virus replication fidelity and hence the intrahost genetic diversity of viral populations are known to be intricately linked to viral pathogenesis and tropism as well as to immune and antiviral escape during infection. In this study, we investigated whether changes in replication fidelity can impact the ability of a virus to transmit between susceptible hosts by the use of a mouse model for norovirus. We show that a variant encoding a high-fidelity polymerase is transmitted less efficiently between mice than the wild-type strain. This constitutes

  6. Viral vector-based influenza vaccines

    Science.gov (United States)

    de Vries, Rory D.; Rimmelzwaan, Guus F.

    2016-01-01

    ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

  7. Viral vector-based influenza vaccines.

    Science.gov (United States)

    de Vries, Rory D; Rimmelzwaan, Guus F

    2016-11-01

    Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors.

  8. Vertebral artery dissection associated with viral meningitis

    Directory of Open Access Journals (Sweden)

    Pan Xudong

    2012-08-01

    Full Text Available Abstract Background Vertebral artery dissection (VAD is often associated with trauma or occurs spontaneously, inevitably causing some neurological deficits. Even though acute infection can be related to the development of spontaneous VAD (sVAD, VAD associated with viral meningitis has never been reported in the literature. Case presentation A 42-year-old man with fever, sore throat, and runny nose developed sudden onset of occipital headache, vertigo, transient confusion, diplopia, and ataxia. Brain stem encephalitis was diagnosed initially because the cerebrospinal fluid (CSF study showed inflammatory changes. However, subsequent diffusion-weighted (DWI magnetic resonance imaging of his brain demonstrated left lateral medullary infarction, and the digital subtraction angiography (DSA confirmed VAD involving left V4 segment of the artery. Consequently, the patient was diagnosed as VAD accompanied by viral meningitis. Conclusion This case suggests that viral meningitis might lead to inflammatory injury of the vertebral arterial wall, even sVAD with multiple neurological symptoms.

  9. V-GAP: Viral genome assembly pipeline

    KAUST Repository

    Nakamura, Yoji

    2015-10-22

    Next-generation sequencing technologies have allowed the rapid determination of the complete genomes of many organisms. Although shotgun sequences from large genome organisms are still difficult to reconstruct perfect contigs each of which represents a full chromosome, those from small genomes have been assembled successfully into a very small number of contigs. In this study, we show that shotgun reads from phage genomes can be reconstructed into a single contig by controlling the number of read sequences used in de novo assembly. We have developed a pipeline to assemble small viral genomes with good reliability using a resampling method from shotgun data. This pipeline, named V-GAP (Viral Genome Assembly Pipeline), will contribute to the rapid genome typing of viruses, which are highly divergent, and thus will meet the increasing need for viral genome comparisons in metagenomic studies.

  10. CT images of infantile viral encephalitis

    International Nuclear Information System (INIS)

    Sugimoto, Tateo; Okazaki, Hitoshi; Woo, Man

    1985-01-01

    Cranial CT scanning was undertaken in 40 patients with infantile viral encephalitis seen from 1977 to 1983. According to the pathogenic viruses, abnormal CT findings were detected most frequently in cases of herpes simplex encephalitis (HSE), followed by non-eruptive viral encephalitis, measles encephalitis, and rubella encephalitis in that order, which coincided well with neurological prognosis. Although CT findings lay within a normal range in cases of measles encephalitis, except a case in which cerebral ventricle was slightly dilated, the degree of consciousness disturbance was unfavorable and it persisted long. This revealed that there is no distinct correlation between the degree of consciousness disturbance and CT findings. Normal CT findings were detected in 13% of patients aged less than 5 years and 76.5% of patients aged 5 years or more. In many patients who had an attack of viral encephalitis at the age of 5 years or more, epileptic seizures occurred frequently, even though CT findings were normal. (Namekawa, K.)

  11. Mechanisms Controlling Virulence Thresholds of Mixed Viral Populations ▿

    Science.gov (United States)

    Lancaster, Karen Z.; Pfeiffer, Julie K.

    2011-01-01

    The propensity of RNA viruses to revert attenuating mutations contributes to disease and complicates vaccine development. Despite the presence of virulent revertant viruses in some live-attenuated vaccines, disease from vaccination is rare. This suggests that in mixed viral populations, attenuated viruses may limit the pathogenesis of virulent viruses, thus establishing a virulence threshold. Here we examined virulence thresholds using mixtures of virulent and attenuated viruses in a transgenic mouse model of poliovirus infection. We determined that a 1,000-fold excess of the attenuated Sabin strain of poliovirus was protective against disease induced by the virulent Mahoney strain. Protection was induced locally, and inactivated virus conferred protection. Treatment with a poliovirus receptor-blocking antibody phenocopied the protective effect of inactivated viruses in vitro and in vivo, suggesting that one mechanism controlling virulence thresholds may be competition for a viral receptor. Additionally, the type I interferon response reduces poliovirus pathogenesis; therefore, we examined virulence thresholds in mice lacking the alpha/beta interferon receptor. We found that the attenuated virus was virulent in immunodeficient mice due to the enhanced replication and reversion of attenuating mutations. Therefore, while the type I interferon response limits the virulence of the attenuated strain by reducing replication, protection from disease conferred by the attenuated strain in immunocompetent mice can occur independently of replication. Our results identified mechanisms controlling the virulence of mixed viral populations and indicate that live-attenuated vaccines containing virulent virus may be safe, as long as virulent viruses are present at levels below a critical threshold. PMID:21795346

  12. Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment.

    Science.gov (United States)

    Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

    2017-02-28

    Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

  13. Fluid flow and thin-film evolution near the triple line during droplet evaporation of self-rewetting fluids.

    Science.gov (United States)

    Yang, Yang; Zhou, Leping; Du, Xiao-Ze; Yang, Yongping

    2018-03-07

    The microscopic region near the triple line plays an important role in the heat and mass transfer of droplets, while the mechanisms of evaporation and internal flow remain unclear. This paper describes an experimental study of fluid flow and thin-film evolution near the triple line in sessile droplets of self-rewetting fluids, aqueous solutions of alcohols with number of carbon atoms varies from 1 to 7, to analyze the influence of various factors on the mesoscale flows. The mechanism of internal flow for self-rewetting fluid droplets was different from that of conventional fluids, and hence a novel expression of in-plane average velocity was fitted for them. The temporal and spatial evolution of thin-film thickness near the triple line during droplet evaporation was obtained by using a proposed sub-region method, which was developed from an evanescent wave based multilayer nanoparticle image velocimetry technique. The self-rewetting fluids are conducive to increase the microscopic critical contact angle and the energy barrier of contact line, which reduces the rate of thin-film thickness variation. The inhibited impact of self-rewetting fluids on the evaporation increases gradually with increasing number of carbon atoms.

  14. A priori tests of combustion models based on a CH{sub 4}/H{sub 2} Triple Flame

    Energy Technology Data Exchange (ETDEWEB)

    Dombard, J.; Naud, B.; Jimenez Sanchez, C.

    2008-07-01

    This document reproduces the final project of Jerome Dombard, presented on June 25, 2008, for the obtention of the Master degree MIMSE (Master Ingenierie Mathematique, Statistique et Economique) of Bordeaux University (Universite Bordeaux 1). We make an a priori study of FPI/FGM-type turbulent combustion models using a 2D DNS of a triple flame. A reduced chemical scheme of 16 species and 12 reactions is used (ARM1, proposed by J.-Y. Chen at Berkeley University). The fuel (CH4/H2 mixture) and oxidizer (air) correspond to the inlet composition of the Sydney bluff-body stabilised flame experiments (flames HM1-3). First, we compute 1D laminar premixed flames. The purpose of those calculations is twofold: 1. check the differences between different computer programs and different treatments of molecular diffusion, and 2. calibrate the 2D-DNS of the laminar triple flame (mainly decide on the grid resolution). Then, the solution of the 2D laminar triple flame is used to test a priori FPI/FGM tables. Finally, preliminary considerations on sub-grid scale modelling in the context of Large Eddy Simulation are made. (Author) 14 refs.

  15. Effect of PAS triple therapy on nerve injury, oxidative stress and inflammatory response in patients with cerebral infarction

    Directory of Open Access Journals (Sweden)

    Li-Jun Deng

    2017-10-01

    Full Text Available Objective: To study the effect of probucol + aspirin + atorvastatin (PAS triple therapy on nerve injury, oxidative stress and inflammatory response in patients with cerebral infarction. Methods: Patients with acute cerebral infarction who were treated in Affiliated Hospital of Jianghan University between February 2015 and January 2015 were selected and randomly divided into the PAS group who received probucol + aspirin + atorvastatin triple therapy and the control group who received aspirin + atorvastatin double therapy. The markers of nerve injury, oxidative stress and inflammatory response were determined before treatment and 15 d after treatment. Results: 15 d after treatment, peripheral blood Keap-1 expression and serum GPX1 contents of both groups of patients were significantly higher than those before treatment while peripheral blood Nrf-2 and ARE expression as well as serum S100B, NSE, sTRAIL, FKN, HMGB-1, sICAM-1, Chemerin and 8-iso-PGF2α contents were significantly lower than those before treatment, and peripheral blood Keap-1 expression and serum GPX1 content of PAS group were significantly higher than those of control group while peripheral blood Nrf-2 and ARE expression as well as serum S100B, NSE, sTRAIL, FKN, HMGB-1, sICAM-1, Chemerin and 8-iso-PGF2α contents were significantly lower than those of control group. Conclusion: PAS triple therapy can reduce the nerve injury as well as oxidative stress response and inflammatory response in patients with cerebral infarction.

  16. Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Antonio Barbieri

    2017-02-01

    Full Text Available Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

  17. Acute Viral Hepatitis in Pediatric Age Groups

    Directory of Open Access Journals (Sweden)

    Sudhamshu KC

    2014-03-01

    Full Text Available Introduction: Our clinical experience showed that there has been no decrease in pediatric cases of acute viral hepatitis in Kathmandu. The objective of the study was to analyze the etiology, clinical features, laboratory parameters, sonological findings and other to determine the probable prognostic factors of Acute Viral Hepatitis in pediatric population. Methods: Consecutive patients of suspected Acute Viral Hepatitis, below the age of 15 years, attending the liver clinic between January 2006 and December2010were studied. After clinical examination they were subjected to blood tests and ultrasound examination of abdomen. The patients were divided in 3 age groups; 0–5, 5–10 and 5–15 years. Clinical features, laboratory parameters, ultrasound findings were compared in three age groups. Results: Etiology of Acute Viral Hepatitis was Hepatitis A virus 266 (85%, Hepatitis E virus in 24 (8%, Hepatitis B virus in 15 (5%. In 7(2% patients etiology was unknown. Three patients went to acute liver failure but improved with conservative treatment. There was no statistical difference in most of the parameters studied in different age groups. Ascites was more common in 5-10 years age group. Patients with secondary bacterial infection, ultrasound evidence of prominent biliary tree and ascites were associated with increased duration of illness. Patients with history of herbal medications had prolonged cholestasis. Conclusions: Hepatitis A is most common cause of Acute Viral Hepatitis in pediatric population. Improper use of herbal medications, secondary bacterial infection and faulty dietary intake was associated with prolonged illness. Patients with prominent biliary radicals should be treated with antibiotics even with normal blood counts for earlier recovery. Keywords: Acute viral hepatitis; hepatitis A; hepatitis E; herbal medications.

  18. The fecal viral flora of wild rodents.

    Directory of Open Access Journals (Sweden)

    Tung G Phan

    2011-09-01

    Full Text Available The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in

  19. [Relevant pathogenesis of heat and phlegm in infantile viral pneumonia: an analysis by association rules].

    Science.gov (United States)

    Al, Jun; Wang, Shou-chuan; Dai, Ming; Chen, Sheng; Yi, Zhan-xiang; Dai, Qi-gang; Xu, Shan

    2013-11-01

    To study the application of association rules in Chinese medical pathogeneses and pathologies of heat and phlegm in infantile viral pneumonia. Association rules were applied to analyze dynamic changes of heat and phlegm correlated symptoms and signs in 297 infants with respiratory syncytial virus (RSV) pneumonia, thus understanding its evolution or pathogenesis. Heat and phlegm co-exist in infantile viral pneumonia. In their relationship, heat was more likely to affect phlegm, but phlegm was less likely to affect heat. Under the intervention of drugs, the possibility of heat induced by phlegm was gradually reduced. But the possibility of phlegm induced by heat was not obvious as time went by. Heat and phlegm have a close relationship in the pathogenesis of infantile viral pneumonia. The intervention of drugs could reduce the pathologic evolution of phlegm causing heat. However, it has little effect on the pathologic evolution of heat causing phlegm.

  20. Clinical Outcomes of SMILE With a Triple Centration Technique and Corneal Wavefront-Guided Transepithelial PRK in High Astigmatism.

    Science.gov (United States)

    Jun, Ikhyun; Kang, David Sung Yong; Reinstein, Dan Z; Arba-Mosquera, Samuel; Archer, Timothy J; Seo, Kyoung Yul; Kim, Tae-Im

    2018-03-01

    To comparatively investigate the clinical outcomes, vector parameters, and corneal aberrations of small incision lenticule extraction (SMILE) with a triple centration technique and corneal wavefront-guided transepithelial photorefractive keratectomy (PRK) for the correction of high astigmatism. This retrospective, comparative case series study included 89 eyes (89 patients) that received treatment for myopia with high astigmatism (≥ 2.50 diopters) using SMILE with a triple centration technique (SMILE group; 45 eyes) and corneal wavefront-guided transepithelial PRK (transepithelial PRK group; 44 eyes). Visual acuity measurement, manifest refraction, slit-lamp examination, autokeratometry, corneal topography, and evaluation of corneal wavefront aberration were performed preoperatively and at 1, 3, and 6 months after surgery. The safety, efficacy, vector parameters, and corneal aberrations at 6 months after surgery were compared between the two groups. At 6 months after surgery, the transepithelial PRK and SMILE groups exhibited comparable mean uncorrected distance visual acuities (-0.06 ± 0.07 and -0.05 ± 0.07 logMAR, respectively), safety, efficacy, and predictability of refractive and visual outcomes. There was a slight but statistically significant difference in the correction index between the transepithelial PRK and SMILE groups (0.96 ± 0.11 and 0.91 ± 0.10, respectively). Whereas the transepithelial PRK group exhibited increased corneal spherical aberration and significantly reduced corneal coma and trefoil, no changes in aberrometric values were noted in the SMILE group. Both SMILE with a triple centration technique and corneal wavefront-guided transepithelial PRK are effective and provide predictable outcomes for the correction of high myopic astigmatism, although slight undercorrection was observed in the SMILE group. The triple centration technique was helpful in astigmatism correction by SMILE. [J Refract Surg. 2018;34(3):156-163.]. Copyright 2018

  1. CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Xiang, Jingyu; Hurchla, Michelle A; Fontana, Francesca; Su, Xinming; Amend, Sarah R; Esser, Alison K; Douglas, Garry J; Mudalagiriyappa, Chidananda; Luker, Kathryn E; Pluard, Timothy; Ademuyiwa, Foluso O; Romagnoli, Barbara; Tuffin, Gérald; Chevalier, Eric; Luker, Gary D; Bauer, Michael; Zimmermann, Johann; Aft, Rebecca L; Dembowsky, Klaus; Weilbaecher, Katherine N

    2015-11-01

    The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow-disseminated tumor cells (DTC)-negative patients at high risk for metastasis and death. The protein epitope mimetic (PEM) POL5551, a novel CXCR4 antagonist, inhibited binding of SDF-1 to CXCR4, had no direct effects on tumor cell viability, but reduced migration of breast cancer cells in vitro. In two orthotopic models of triple-negative breast cancer, POL5551 had little inhibitory effect on primary tumor growth, but significantly reduced distant metastasis. When combined with eribulin, a chemotherapeutic microtubule inhibitor, POL5551 additively reduced metastasis and prolonged survival in mice after resection of the primary tumor compared with single-agent eribulin. Hypothesizing that POL5551 may mobilize tumor cells from their microenvironment and sensitize them to chemotherapy, we used a "chemotherapy framing" dosing strategy. When administered shortly before and after eribulin treatment, three doses of POL5551 with eribulin reduced bone and liver tumor burden more effectively than chemotherapy alone. These data suggest that sequenced administration of CXCR4 antagonists with cytotoxic chemotherapy synergize to reduce distant metastases. ©2015 American Association for Cancer Research.

  2. Evasion of Antiviral Immunity through Sequestering of TBK1/IKKε/IRF3 into Viral Inclusion Bodies

    Science.gov (United States)

    Wu, Xiaodong; Qi, Xian; Qu, Bingqian; Zhang, Zerui; Liang, Mifang; Li, Chuan; Cardona, Carol J.; Li, Dexin

    2014-01-01

    Cells are equipped with pattern recognition receptors (PRRs) such as the Toll-like and RIG-I-like receptors that mount innate defenses against viruses. However, viruses have evolved multiple strategies to evade or thwart host antiviral responses. Viral inclusion bodies (IBs), which are accumulated aggregates of viral proteins, are commonly formed during the replication of some viruses in infected cells, but their role in viral immune evasion has rarely been explored. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging febrile illness caused by a novel phlebovirus in the Bunyaviridae. The SFTS viral nonstructural protein NSs can suppress host beta interferon (IFN-β) responses. NSs can form IBs in infected and transfected cells. Through interaction with tank-binding kinase 1 (TBK1), viral NSs was able to sequester the IKK complex, including IKKε and IRF3, into IBs, although NSs did not interact with IKKε or IRF3 directly. When cells were infected with influenza A virus, IRF3 was phosphorylated and active phosphorylated IRF3 (p-IRF3) was translocated into the nucleus. In the presence of NSs, IRF3 could still be phosphorylated, but p-IRF3 was trapped in cytoplasmic IBs, resulting in reduced IFN-β induction and enhanced viral replication. Sequestration of the IKK complex and active IRF3 into viral IBs through the interaction of NSs and TBK1 is a novel mechanism for viral evasion of innate immunity. PMID:24335286

  3. Viral pneumonias: Typical and atypical findings

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff-Bleck, M.; Bleck, J.S.; Schirg, E.

    1987-10-01

    The clinical and radiological features of viral pneumonias are summarized and discussed. Although viral infections of the lung belong to atypical pneumonias they demonstrate not always the radiographic pattern of an interstitial pneumonia. Characteristic radiographic findings are quite rare. In most cases the microbial etiology cannot be predicted from chest radiographs. The appearance varies depending on the virulence of the organism and the resistence of the host. In this regard knowledge of epidemiological data as well as patients condition and underlying disease is of utmost importance. Differentiation between community- and hospital-acquired infection may be very helpful.

  4. Broad-Spectrum Drugs Against Viral Agents

    Directory of Open Access Journals (Sweden)

    Jonathan P. Wong

    2008-09-01

    Full Text Available Development of antivirals has focused primarily on vaccines and on treatments for specific viral agents. Although effective, these approaches may be limited in situations where the etiologic agent is unknown or when the target virus has undergone mutation, recombination or reassortment. Augmentation of the innate immune response may be an effective alternative for disease amelioration. Nonspecific, broad-spectrum immune responses can be induced by double-stranded (dsRNAs such as poly (ICLC, or oligonucleotides (ODNs containing unmethylated deocycytidyl-deoxyguanosinyl (CpG motifs. These may offer protection against various bacterial and viral pathogens regardless of their genetic makeup, zoonotic origin or drug resistance.

  5. Viral diseases in honey bee queens

    DEFF Research Database (Denmark)

    Francis, Roy Mathew

    Honey bees are important insects for human welfare, due to pollination as well as honey production. Viral diseases strongly impact honey bee health, especially since the spread of varroa mites. This dissertation deals with the interactions between honey bees, viruses and varroa mites. A new tool...... was developed to diagnose three viruses in honey bees. Quantitative PCR was used to investigate the distribution of two popular viruses in five different tissues of 86 honey bee queens. Seasonal variation of viral infection in honey bee workers and varroa mites were determined by sampling 23 colonies under...

  6. Viral pneumonias: Typical and atypical findings

    International Nuclear Information System (INIS)

    Westhoff-Bleck, M.; Bleck, J.S.; Schirg, E.

    1987-01-01

    The clinical and radiological features of viral pneumonias are summarized and discussed. Although viral infections of the lung belong to atypical pneumonias they demonstrate not always the radiographic pattern of an interstitial pneumonia. Characteristic radiographic findings are quite rare. In most cases the microbial etiology cannot be predicted from chest radiographs. The appearance varies depending on the virulence of the organism and the resistence of the host. In this regard knowledge of epidemiological data as well as patients condition and underlying disease is of utmost importance. Differentiation between community- and hospital-acquired infection may be very helpful. (orig.) [de

  7. Structure of viral hepatitis in infants

    Directory of Open Access Journals (Sweden)

    T.V. Sorokman

    2017-03-01

    Full Text Available Background. Many current studies are devoted to the study of hepatitis caused by viral infections, which are qualified as TORCH-infection. In infants TORCH-induced lesions prevail in the structure of viral hepatitis, the largest proportion is hepatitis of cytomegalovirus etiology. The purpose was to study the structure of viral hepatitis in infants. Materials and methods. The study included sixty-two children (mean age 1.8 ± 0.9 years born in 2007–2016 treated in Chernivtsi Regional Children’s Clinical Hospital. The comparison group consisted of 36 healthy children of the same age. The pathogens of viral hepatitis B, C, TORCH infections were verified by enzyme immunoassay and polymerase chain reaction. The results of the research were analyzed using computer package Statistica StatSoft Inc. and Excel XP for Windows for a personal computer. Results. The results of the analysis of the liver diseases structure in 62 young children, according to hospital statistics, determined that the overwhelming majority (38 children; 61.3 % had viral hepatitis (VH, the other 24 (38.7 % patients were divided by the etiological structure of liver damage as follows: 8 (12.9 % patients had prolonged conjunctive jaundice, 7 (11.3 % patients had congenital metabolic disorders, 9 (14.5 % patients had congenital hepatobiliary abnomalities. 16.6 % of young children had hepatitis B and C viruses. In 5.8 % of cases VH was caused by viruses of the TORCH group of infections. Conclusions. In the structure of hepatobiliary diseases in infants, viral hepatitis (68.4 % is on the first ranked place. Among the viral hepatitis in children in the first year of life, CMV-hepatitis (68.4 % is most common, in children over 1 year old chronic hepatitis B and C. Severe obstetrical anamnesis, violations of pregnancy, placental infection are rather significant in the group of children with viral hepatitis. The main clinical signs of CMV-hepatitis are prolonged jaundice, cholestasis

  8. Importance of viral diseases in irradiated persons

    International Nuclear Information System (INIS)

    Blaha, M.; Jebavy, L.; Merka, V.; Horacek, J.

    1988-01-01

    A preliminary study was performed aimed at establishing the incidence of some viral diseases in radiation syndrome patients and the significance of the diseases for prognosis. In the study, 77 patients with syndromologically identical acute hematological forms of radiation sickness, mainly leukemic patients suffering from severe blood formation suppression and/or hematoblastosis were examined for concurrent herpes simplex virus and cytomegalovirus infections. Active viruses were isolated in almost 30% of the patients; nearly 90% of the patients were serologically positive, shedding antibodies. The findings thus confirmed the view that viral disease, especially in immunocompromised patients, has a critical effect on the survival of radiation sickness sufferers. (L.O.). 12 refs

  9. Non-random patterns in viral diversity

    DEFF Research Database (Denmark)

    Anthony, Simon J.; Islam, Ariful; Johnson, Christine

    2015-01-01

    ) or stochastic (not predictable) processes. We sample macaque faeces across nine sites in Bangladesh and use consensus PCR and sequencing to discover 184 viruses from 14 viral families. We then use network modelling and statistical null-hypothesis testing to show the presence of non-random deterministic patterns...... at different scales, between sites and within individuals. We show that the effects of determinism are not absolute however, as stochastic patterns are also observed. In showing that determinism is an important process in viral community assembly we conclude that it should be possible to forecast changes...

  10. Tissue interactions of avian viral attachment proteins

    OpenAIRE

    Ambepitiya Wickramasinghe, I.N.

    2015-01-01

    Viruses can infect a wide range of hosts; varying from bacteria and plants to animals and humans. While many viral infections may pass unnoticed, some are of major importance due to their implications on health and welfare of plants, animals and/or humans. In particular, viruses that can infect avian hosts have been studied intensively due the occurrence of the pandemics of highly pathogenic influenza A virus infection or “bird flu’’. Viral infections in domesticated birds can result in huge ...

  11. Viral miRNAs and immune evasion

    OpenAIRE

    Boss, Isaac W.; Renne, Rolf

    2011-01-01

    Viral miRNAs, ∼22nt RNA molecules which post-transcriptionally regulate gene expression, are emerging as important tools in immune evasion. Viral infection is a complex process that requires immune evasion in order to establish persistent life-long infection of the host. During this process viruses express both protein-coding and non-coding genes, which help to modulate the cellular environment making it more favorable for infection. In the last decade, it was uncovered that DNA viruses expre...

  12. HIV-1 viral diversity and its implications for viral load testing: review of current platforms.

    Science.gov (United States)

    Luft, LeeAnne M; Gill, M John; Church, Deirdre L

    2011-10-01

    The 2008 Recommendations for care of the International AIDS Society reaffirmed the importance of both accurate and sensitive viral load assessment, and by necessity, access to viral load assays. HIV-1 viral load testing is considered essential when initiating antiretroviral therapy (ART), when monitoring ART response, and when considering switching ART regimens. The demand for accurate, reproducible, and cost-effective viral load assays is therefore a global issue. Although the North American and Western European experience has historically been with HIV-1 group M subtype B virus, this paradigm is changing rapidly as migrants and refugees from developing countries with non-B subtype infections often now present for care in the developed world, and travelers to developing countries acquire non-B subtype infection abroad and present for care at home. Awareness of any clinical or laboratory differences between the common HIV-1 group M subtype B and the newer HIV-1 strains being seen in practice is therefore increasingly important. This review of current HIV-1 viral load testing is focused on the potential value of a standardized genotype assignment for HIV-1 viral subtypes, regular monitoring of the performance of available commercial HIV viral load assays on emerging non-B HIV subtypes, circulating recombinant forms (CRFs) and unique recombinant forms (URFs), and a discussion of the implications for resource-limited settings. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  13. ViralORFeome: an integrated database to generate a versatile collection of viral ORFs.

    Science.gov (United States)

    Pellet, J; Tafforeau, L; Lucas-Hourani, M; Navratil, V; Meyniel, L; Achaz, G; Guironnet-Paquet, A; Aublin-Gex, A; Caignard, G; Cassonnet, P; Chaboud, A; Chantier, T; Deloire, A; Demeret, C; Le Breton, M; Neveu, G; Jacotot, L; Vaglio, P; Delmotte, S; Gautier, C; Combet, C; Deleage, G; Favre, M; Tangy, F; Jacob, Y; Andre, P; Lotteau, V; Rabourdin-Combe, C; Vidalain, P O

    2010-01-01

    Large collections of protein-encoding open reading frames (ORFs) established in a versatile recombination-based cloning system have been instrumental to study protein functions in high-throughput assays. Such 'ORFeome' resources have been developed for several organisms but in virology, plasmid collections covering a significant fraction of the virosphere are still needed. In this perspective, we present ViralORFeome 1.0 (http://www.viralorfeome.com), an open-access database and management system that provides an integrated set of bioinformatic tools to clone viral ORFs in the Gateway(R) system. ViralORFeome provides a convenient interface to navigate through virus genome sequences, to design ORF-specific cloning primers, to validate the sequence of generated constructs and to browse established collections of virus ORFs. Most importantly, ViralORFeome has been designed to manage all possible variants or mutants of a given ORF so that the cloning procedure can be applied to any emerging virus strain. A subset of plasmid constructs generated with ViralORFeome platform has been tested with success for heterologous protein expression in different expression systems at proteome scale. ViralORFeome should provide our community with a framework to establish a large collection of virus ORF clones, an instrumental resource to determine functions, activities and binding partners of viral proteins.

  14. UGGT1 enhances enterovirus 71 pathogenicity by promoting viral RNA synthesis and viral replication.

    Directory of Open Access Journals (Sweden)

    Peng-Nien Huang

    2017-05-01

    Full Text Available Positive-strand RNA virus infections can induce the stress-related unfolded protein response (UPR in host cells. This study found that enterovirus A71 (EVA71 utilizes host UDP-glucose glycoprotein glucosyltransferase 1 (UGGT1, a key endoplasmic reticulum protein (ER involved in UPR, to enhance viral replication and virulence. EVA71 forms replication complexes (RCs on cellular membranes that contain a mix of host and viral proteins to facilitate viral replication, but the components and processes involved in the assembly and function of RCs are not fully understood. Using EVA71 as a model, this study found that host UGGT1 and viral 3D polymerase co-precipitate along with other factors on membranous replication complexes to enhance viral replication. Increased UGGT1 levels elevated viral growth rates, while viral pathogenicity was observed to be lower in heterozygous knockout mice (Uggt1 +/- mice. These findings provide important insight on the role of UPR and host UGGT1 in regulating RNA virus replication and pathogenicity.

  15. A proteomics perspective on viral DNA sensors in host defense and viral immune evasion mechanisms.

    Science.gov (United States)

    Crow, Marni S; Javitt, Aaron; Cristea, Ileana M

    2015-06-05

    The sensing of viral DNA is an essential step of cellular immune response to infections with DNA viruses. These human pathogens are spread worldwide, triggering a wide range of virus-induced diseases, and are associated with high levels of morbidity and mortality. Despite similarities between DNA molecules, mammalian cells have the remarkable ability to distinguish viral DNA from their own DNA. This detection is carried out by specialized antiviral proteins, called DNA sensors. These sensors bind to foreign DNA to activate downstream immune signaling pathways and alert neighboring cells by eliciting the expression of antiviral cytokines. The sensing of viral DNA was shown to occur both in the cytoplasm and in the nucleus of infected cells, disproving the notion that sensing occurred by simple spatial separation of viral and host DNA. A number of omic approaches, in particular, mass-spectrometry-based proteomic methods, have significantly contributed to the constantly evolving field of viral DNA sensing. Here, we review the impact of omic methods on the identification of viral DNA sensors, as well as on the characterization of mechanisms involved in host defense or viral immune evasion. Copyright © 2015. Published by Elsevier Ltd.

  16. Geographic health information systems: a platform to support the 'triple aim'.

    Science.gov (United States)

    Miranda, Marie Lynn; Ferranti, Jeffrey; Strauss, Benjamin; Neelon, Brian; Califf, Robert M

    2013-09-01

    Despite the rapid growth of electronic health data, most data systems do not connect individual patient records to data sets from outside the health care delivery system. These isolated data systems cannot support efforts to recognize or address how the physical and environmental context of each patient influences health choices and health outcomes. In this article we describe how a geographic health information system in Durham, North Carolina, links health system and social and environmental data via shared geography to provide a multidimensional understanding of individual and community health status and vulnerabilities. Geographic health information systems can be useful in supporting the Institute for Healthcare Improvement's Triple Aim Initiative to improve the experience of care, improve the health of populations, and reduce per capita costs of health care. A geographic health information system can also provide a comprehensive information base for community health assessment and intervention for accountable care that includes the entire population of a geographic area.

  17. Further triple integral approach to mixed-delay-dependent stability of time-delay neutral systems.

    Science.gov (United States)

    Wang, Ting; Li, Tao; Zhang, Guobao; Fei, Shumin

    2017-09-01

    This paper studies the asymptotic stability for a class of neutral systems with mixed time-varying delays. Through utilizing some Wirtinger-based integral inequalities and extending the convex combination technique, the upper bound on derivative of Lyapunov-Krasovskii (L-K) functional can be estimated more tightly and three mixed-delay-dependent criteria are proposed in terms of linear matrix inequalities (LMIs), in which the nonlinearity and parameter uncertainties are also involved, respectively. Different from those existent works, based on the interconnected relationship between neutral delay and state one, some novel triple integral functional terms are constructed and the conservatism can be effectively reduced. Finally, two numerical examples are given to show the benefits of the proposed criteria. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  18. Using triple isotopes of dissolved oxygen to evaluate global marine productivity.

    Science.gov (United States)

    Juranek, L W; Quay, P D

    2013-01-01

    Since the triple isotopic composition of dissolved O(2) ((17)Δ) was introduced as a natural tracer of photosynthetic gross O(2) production (GOP) over 10 years ago, observations of (17)Δ have been used to constrain marine productivity throughout the global ocean. This incubation-independent approach has several advantages: It allows the determination of production free from containment artifacts and reduces logistical hurdles that can make obtaining productivity with traditional incubation-dependent methods difficult. As such, GOP estimates derived from (17)Δ have been used to give insight into potential biases in incubation-based approaches and to evaluate satellite-based estimates of production at the regional scale. With increased use, we have also learned more about the potential biases and uncertainties of this approach, some of which have been addressed by recent method improvements. We recap the major advances the (17)Δ method has brought to improved understanding of biological carbon cycling, from incubation bottles to ocean basins.

  19. A Liposome Encapsulated Ruthenium Polypyridine Complex as a Theranostic Platform for Triple-Negative Breast Cancer.

    Science.gov (United States)

    Shen, Jianliang; Kim, Han-Cheon; Wolfram, Joy; Mu, Chaofeng; Zhang, Wei; Liu, Haoran; Xie, Yan; Mai, Junhua; Zhang, Hang; Li, Zhi; Guevara, Maria; Mao, Zong-Wan; Shen, Haifa

    2017-05-10

    Ruthenium coordination complexes have the potential to serve as novel theranostic agents for cancer. However, a major limitation in their clinical implementation is effective tumor accumulation. In this study, we have developed a liposome-based theranostic nanodelivery system for [Ru(phen) 2 dppz](ClO 4 ) 2 (Lipo-Ru). This ruthenium polypyridine complex emits a strong fluorescent signal when incorporated in the hydrophobic lipid bilayer of the delivery vehicle or in the DNA helix, enabling visualization of the therapeutic agent in tumor tissues. Incubation of MDA-MB-231 breast cancer cells with Lipo-Ru induced double-strand DNA breaks and triggers apoptosis. In a mouse model of triple-negative breast cancer, treatment with Lipo-Ru dramatically reduced tumor growth. Biodistribution studies of Lipo-Ru revealed that more than 20% of the injected dose accumulated in the tumor. These results suggest that Lipo-Ru could serve as a promising theranostic platform for cancer.

  20. Triple –E Vessels: Tonnage Measurement and Suez Canal Dues Assessment

    Directory of Open Access Journals (Sweden)

    Elsayed Hussein Galall

    2015-08-01

    Full Text Available Container is growing faster than GDP, Shipping lines always attempt to augment efficiencyby reducing cost and by attracting larger volumes of containers. As a result rising containerfreight rates the lines have been driven to increase economic of scale, by building mega shipsand fewer mere efficient port calls. In 2011 Maersk line ordered up to 20 new “Triple- E “Class of container vessels deliversbetween 2013- 2015. These class of mega container vessels have its way through Suez Canal,other companies CMA, CGM also ordered this type of mega container vessels, in order toreach higher profits due to the achieved economics of scale It is believed that 20000 TEUcould be the next target size. Present mega container fleet and any future feasible potential vessel capacity expansionmore than 18000 TEU put Suez Canal route in strong competitive position. MeanwhilePanama Canal will not be able to handle vessels larger than 12600 TEU even after itsexpansion in 2015.

  1. Study of the key factors affecting the triple grid lifetime of the LIPS-300 ion thruster

    Science.gov (United States)

    Mingming, SUN; Liang, WANG; Juntai, YANG; Xiaodong, WEN; Yongjie, HUANG; Meng, WANG

    2018-04-01

    In order to ascertain the key factors affecting the lifetime of the triple grids in the LIPS-300 ion thruster, the thermal deformation, upstream ion density and component lifetime of the grids are simulated with finite element analysis, fluid simulation and charged-particle tracing simulation methods on the basis of a 1500 h short lifetime test. The key factor affecting the lifetime of the triple grids in the LIPS-300 ion thruster is obtained and analyzed through the test results. The results show that ion sputtering erosion of the grids in 5 kW operation mode is greater than in the case of 3 kW. In 5 kW mode, the decelerator grid shows the most serious corrosion, the accelerator grid shows moderate corrosion, and the screen grid shows the least amount of corrosion. With the serious corrosion of the grids in 5 kW operation mode, the intercept current of the acceleration and deceleration grids increases substantially. Meanwhile, the cold gap between the accelerator grid and the screen grid decreases from 1 mm to 0.7 mm, while the cold gap between the accelerator grid and the decelerator grid increases from 1 mm to 1.25 mm after 1500 h of thruster operation. At equilibrium temperature with 5 kW power, the finite element method (FEM) simulation results show that the hot gap between the screen grid and the accelerator grid reduces to 0.2 mm. Accordingly, the hot gap between the accelerator grid and the decelerator grid increases to 1.5 mm. According to the fluid method, the plasma density simulated in most regions of the discharge chamber is 1 × 1018‑8 × 1018 m‑3. The upstream plasma density of the screen grid is in the range 6 × 1017‑6 × 1018 m‑3 and displays a parabolic characteristic. The charged particle tracing simulation method results show that the ion beam current without the thermal deformation of triple grids has optimal perveance status. The ion sputtering rates of the accelerator grid hole and the decelerator hole are 5.5 × 10‑14 kg s‑1 and

  2. Geriatrics and the triple aim: defining preventable hospitalizations in the long-term care population.

    Science.gov (United States)

    Ouslander, Joseph G; Maslow, Katie

    2012-12-01

    Reducing preventable hospitalizations is fundamental to the "triple aim" of improving care, improving health, and reducing costs. New federal government initiatives that create strong pressure to reduce such hospitalizations are being or will soon be implemented. These initiatives use quality measures to define which hospitalizations are preventable. Reducing hospitalizations could greatly benefit frail and chronically ill adults and older people who receive long-term care (LTC) because they often experience negative effects of hospitalization, including hospital-acquired conditions, morbidity, and loss of functional abilities. Conversely, reducing hospitalizations could mean that some people will not receive hospital care they need, especially if the selected measures do not adequately define hospitalizations that can be prevented without jeopardizing the person's health and safety. An extensive literature search identified 250 measures of preventable hospitalizations, but the measures have not been validated in the LTC population and generally do not account for comorbidity or the capacity of various LTC settings to provide the required care without hospitalization. Additional efforts are needed to develop measures that accurately differentiate preventable from necessary hospitalizations for the LTC population, are transparent and fair to providers, and minimize the potential for gaming and unintended consequences. As the new initiatives take effect, it is critical to monitor their effect and to develop and disseminate training and resources to support the many community- and institution-based healthcare professionals and emergency department staff involved in decisions about hospitalization for this population. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  3. Probiotics improve the efficacy of standard triple therapy in the eradication of Helicobacter pylori: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Lau CSM

    2016-12-01

    interval [CI], 1.091–1.153; P<0.001 APP and 14.1% (RR =1.141; 95% CI, 1.106–1.175; P<0.001 ITT. Probiotics were beneficial among children and adults, as well as Asians and non-Asians. No significant difference was observed in efficacy between the various types of probiotics. The risk of diarrhea, nausea, vomiting, and epigastric pain was also reduced. Conclusion: The addition of probiotics is associated with improved H. pylori eradication rates in both children and adults, as well as Asians and non-Asians. Lactobacillus, Bifidobacterium, Saccharomyces, and mixtures of probiotics appear beneficial in H. pylori eradication. Furthermore, the reduction in antibiotic-associated side effects such as nausea, vomiting, diarrhea, and epigastric pain improves medication tolerance and patient compliance. Given the consequences associated with chronic H. pylori infection, the addition of probiotics to the concurrent triple therapy regimen should be considered in all patients with H. pylori infection. However, further studies are required to identify the optimal probiotic species and dose. Keywords: probiotics, Helicobacter pylori, triple therapy, meta-analysis

  4. Meta-analyses on viral hepatitis

    DEFF Research Database (Denmark)

    Gluud, Lise L; Gluud, Christian

    2009-01-01

    This article summarizes the meta-analyses of interventions for viral hepatitis A, B, and C. Some of the interventions assessed are described in small trials with unclear bias control. Other interventions are supported by large, high-quality trials. Although attempts have been made to adjust...

  5. Content Recommendation for Viral Social Influence

    DEFF Research Database (Denmark)

    Ivanov, Sergei; Theocharidis, Konstantinos; Terrovitis, Manolis

    2017-01-01

    How do we create content that will become viral in a whole network after we share it with friends or followers? Significant research activity has been dedicated to the problem of strategically selecting a seed set of initial adopters so as to maximize a meme’s spread in a network. This line of wo...

  6. Sanitation of viral haemorrhagic septicaemia (VHS)

    DEFF Research Database (Denmark)

    Olesen, Niels Jørgen

    1998-01-01

    A sanitation programme for stamping-out viral haemorrhagic septicaemia (VHS) was implemented in Denmark in 1965. The programme has resulted in a dramatic reduction in the number of infected rainbow trout farms, from approximate to 400 to 26. The programme is carried out on a voluntary basis...

  7. Neurons under viral attack: victims or warriors?

    Science.gov (United States)

    Chakraborty, Swarupa; Nazmi, Arshed; Dutta, Kallol; Basu, Anirban

    2010-01-01

    When the central nervous system (CNS) is under viral attack, defensive antiviral responses must necessarily arise from the CNS itself to rapidly and efficiently curb infections with minimal collateral damage to the sensitive, specialized and non-regenerating neural tissue. This presents a unique challenge because an intact blood-brain barrier (BBB) and lack of proper lymphatic drainage keeps the CNS virtually outside the radar of circulating immune cells that are at constant vigilance for antigens in peripheral tissues. Limited antigen presentation skills of CNS cells in comparison to peripheral tissues is because of a total lack of dendritic cells and feeble expression of major histocompatibility complex (MHC) proteins in neurons and glia. However, research over the past two decades has identified immune effector mechanisms intrinsic to the CNS for immediate tackling, attenuating and clearing of viral infections, with assistance pouring in from peripheral circulation in the form of neutralizing antibodies and cytotoxic T cells at a later stage. Specialized CNS cells, microglia and astrocytes, were regarded as sole sentinels of the brain for containing a viral onslaught but neurons held little recognition as a potential candidate for protecting itself from the proliferation and pathogenesis of neurotropic viruses. Accumulating evidence however indicates that extracellular insult causes neurons to express immune factors characteristic of lymphoid tissues. This article aims to comprehensively analyze current research on this conditional alteration in the protein expression repertoire of neurons and the role it plays in CNS innate immune response to counter viral infections. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. Viral mimicry of the complement system

    Indian Academy of Sciences (India)

    The complement system is a potent innate immune mechanism consisting of cascades of proteins which are designed to fight against and annul intrusion of all the ... of cell-free viruses, phagocytosis of C3b-coated viral particles, lysis of virus-infected cells, and generation of inflammatory and specific immune responses.

  9. Bovine viral diarrhea virus: biosecurity and control

    Science.gov (United States)

    This paper discusses the recommended procedures involved in setting up biosecurity and control programs designed to limit bovine viral diarrhea virus infections in beef cattle operations. For the purpose of these discussions, a working definition of a biosecurity plan was considered to be an organiz...

  10. Recombinant viruses as vaccines against viral diseases

    Directory of Open Access Journals (Sweden)

    A.P.D. Souza

    2005-04-01

    Full Text Available Vaccine approaches to infectious diseases are widely applied and appreciated. Amongst them, vectors based on recombinant viruses have shown great promise and play an important role in the development of new vaccines. Many viruses have been investigated for their ability to express proteins from foreign pathogens and induce specific immunological responses against these antigens in vivo. Generally, gene-based vaccines can stimulate potent humoral and cellular immune responses and viral vectors might be an effective strategy for both the delivery of antigen-encoding genes and the facilitation and enhancement of antigen presentation. In order to be utilized as a vaccine carrier, the ideal viral vector should be safe and enable efficient presentation of required pathogen-specific antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its production on a large-scale basis. Several viral vaccine vectors have thus emerged to date, all of them having relative advantages and limits depending on the proposed application, and thus far none of them have proven to be ideal vaccine carriers. In this review we describe the potential, as well as some of the foreseeable obstacles associated with viral vaccine vectors and their use in preventive medicine.

  11. Viral Hepatitis and Thrombosis: A Narrative Review

    NARCIS (Netherlands)

    Squizzato, Alessandro; Gerdes, Victor E. A.

    2012-01-01

    Venous thromboembolism (VTE) is a multicausal disease. Among minor risk factors, acute infections in general are associated with a transient increased risk of VTE. However, acute hepatitis is usually not reported as a potential risk factor for VTE. Recent studies suggest a possible role of viral

  12. Microbial oceanography: Viral strategies at sea

    Science.gov (United States)

    Thingstad, T. Frede; Bratbak, Gunnar

    2016-03-01

    The finding that marine environments with high levels of host microbes have fewer viruses per host than when host abundance is low challenges a theory on the relative roles of lysogenic and lytic viral-survival strategies. See Article p.466

  13. Vaccination of cattle against bovine viral diarrhoea

    NARCIS (Netherlands)

    Oirschot, van J.T.; Bruschke, C.J.M.; Rijn, van P.A.

    1999-01-01

    This brief review describes types and quality (efficacy and safety) of bovine viral diarrhoea virus (BVDV) vaccines that are in the market or under development. Both conventional live and killed vaccines are available. The primary aim of vaccination is to prevent congenital infection, but the few

  14. Viral hepatitis among prisoners in Norway.

    Science.gov (United States)

    Hurlen, B; Siebke, J C; Stensland, A

    1980-12-01

    The present survey reveals high frequencies of hepatitis B surface antigen and antibody in criminals committed to prison in Norway compared to the general population. The high rate of antigen carriers and the intramural supply of illicit drugs constitute a threat to fellow prisoners regarding viral hepatitis as well as drug addiction.

  15. Viral immune evasion: a masterpiece of evolution

    NARCIS (Netherlands)

    Vossen, Mireille T. M.; Westerhout, Ellen M.; Söderberg-Nauclér, Cécilia; Wiertz, Emmanuel J. H. J.

    2002-01-01

    Coexistence of viruses and their hosts imposes an evolutionary pressure on both the virus and the host immune system. On the one hand, the host has developed an immune system able to attack viruses and virally infected cells, whereas on the other hand, viruses have developed an array of immune

  16. Tissue interactions of avian viral attachment proteins

    NARCIS (Netherlands)

    Ambepitiya Wickramasinghe, I.N.

    2015-01-01

    Viruses can infect a wide range of hosts; varying from bacteria and plants to animals and humans. While many viral infections may pass unnoticed, some are of major importance due to their implications on health and welfare of plants, animals and/or humans. In particular, viruses that can infect

  17. Viral mimicry of the complement system

    Indian Academy of Sciences (India)

    Unknown

    et al 1978) and gp41 (Ebenbichler et al 1991) and gp120. (Susal et al 1994) of human immunodeficiency virus. (HIV-1) .... Blocks binding of properdin and C5 to C3b. Friedman et al 1984; Fries et al. 1986; Kostavasil .... respective viral genomes (Zezulak and Spear 1984;. Swain et al 1985). It is important to note that none of.

  18. The proteasomal Rpn11 metalloprotease suppresses tombusvirus RNA recombination and promotes viral replication via facilitating assembly of the viral replicase complex.

    Science.gov (United States)

    Prasanth, K Reddisiva; Barajas, Daniel; Nagy, Peter D

    2015-03-01

    RNA viruses co-opt a large number of cellular proteins that affect virus replication and, in some cases, viral genetic recombination. RNA recombination helps viruses in an evolutionary arms race with the host's antiviral responses and adaptation of viruses to new hosts. Tombusviruses and a yeast model host are used to identify cellular factors affecting RNA virus replication and RNA recombination. In this study, we have examined the role of the conserved Rpn11p metalloprotease subunit of the proteasome, which couples deubiquitination and degradation of proteasome substrates, in tombusvirus replication and recombination in Saccharomyces cerevisiae and plants. Depletion or mutations of Rpn11p lead to the rapid formation of viral RNA recombinants in combination with reduced levels of viral RNA replication in yeast or in vitro based on cell extracts. Rpn11p interacts with the viral replication proteins and is recruited to the viral replicase complex (VRC). Analysis of the multifunctional Rpn11p has revealed that the primary role of Rpn11p is to act as a "matchmaker" that brings the viral p92(pol) replication protein and the DDX3-like Ded1p/RH20 DEAD box helicases into VRCs. Overexpression of Ded1p can complement the defect observed in rpn11 mutant yeast by reducing TBSV recombination. This suggests that Rpn11p can suppress tombusvirus recombination via facilitating the recruitment of the cellular Ded1p helicase, which is a strong suppressor of viral recombination, into VRCs. Overall, this work demonstrates that the co-opted Rpn11p, which is involved in the assembly of the functional proteasome, also functions in the proper assembly of the tombusvirus VRCs. RNA viruses evolve rapidly due to genetic changes based on mutations and RNA recombination. Viral genetic recombination helps viruses in an evolutionary arms race with the host's antiviral responses and facilitates adaptation of viruses to new hosts. Cellular factors affect viral RNA recombination, although the role

  19. Acute Viral Hepatitis in Pediatric Age Groups.

    Science.gov (United States)

    Kc, Sudhamshu; Sharma, Dilip; Poudyal, Nandu; Basnet, Bhupendra Kumar

    2014-01-01

    Our clinical experience showed that there has been no decrease in pediatric cases of acute viral hepatitis in Kathmandu. The objective of the study was to analyze the etiology, clinical features, laboratory parameters, sonological findings and other to determine the probable prognostic factors of Acute Viral Hepatitis in pediatric population. Consecutive patients of suspected Acute Viral Hepatitis, below the age of 15 years, attending the liver clinic between January 2006 and December 2010 were studied. After clinical examination they were subjected to blood tests and ultrasound examination of abdomen. The patients were divided in 3 age groups; 0-5, 5-10 and 5-15 years. Clinical features, laboratory parameters, ultrasound findings were compared in three age groups. Etiology of Acute Viral Hepatitis was Hepatitis A virus 266 (85%), Hepatitis E virus in 24 (8%), Hepatitis B virus in 15 (5%). In 7(2%) patients etiology was unknown. Three patients went to acute liver failure but improved with conservative treatment. There was no statistical difference in most of the parameters studied in different age groups. Ascites was more common in 5-10 years age group. Patients with secondary bacterial infection, ultrasound evidence of prominent biliary tree and ascites were associated with increased duration of illness. Patients with history of herbal medications had prolonged cholestasis. Hepatitis A is most common cause of Acute Viral Hepatitis in pediatric population. Improper use of herbal medications, secondary bacterial infection and faulty dietary intake was associated with prolonged illness. Patients with prominent biliary radicals should be treated with antibiotics even with normal blood counts for earlier recovery.

  20. Plant viral vectors for delivery by Agrobacterium.

    Science.gov (United States)

    Gleba, Yuri Y; Tusé, Daniel; Giritch, Anatoli

    2014-01-01

    Plant viral vectors delivered by Agrobacterium are the basis of several manufacturing processes that are currently in use for producing a wide range of proteins for multiple applications, including vaccine antigens, antibodies, protein nanoparticles such as virus-like particles (VLPs), and other protein and protein-RNA scaffolds. Viral vectors delivered by agrobacterial T-DNA transfer (magnifection) have also become important tools in research. In recent years, essential advances have been made both in the development of second-generation vectors designed using the 'deconstructed virus' approach, as well as in the development of upstream manufacturing processes that are robust and fully scalable. The strategy relies on Agrobacterium as a vector to deliver DNA copies of one or more viral RNA/DNA replicons; the bacteria are delivered into leaves by vacuum infiltration, and the viral machinery takes over from the point of T-DNA transfer to the plant cell nucleus, driving massive RNA and protein production and, if required, cell-to-cell spread of the replicons. Among the most often used viral backbones are those of the RNA viruses Tobacco mosaic virus (TMV), Potato virus X (PVX) and Cowpea mosaic virus (CPMV), and the DNA geminivirus Bean yellow dwarf virus. Prototypes of industrial processes that provide for high yield, rapid scale up and fast manufacturing cycles have been designed, and several GMP-compliant and GMP-certified manufacturing facilities are in place. These efforts have been successful as evidenced by the fact that several antibodies and vaccine antigens produced by magnifection are currently in clinical development.

  1. Viral interference with antigen presentation: trapping TAP.

    Science.gov (United States)

    Ressing, Maaike E; Luteijn, Rutger D; Horst, Daniëlle; Wiertz, Emmanuel J

    2013-09-01

    Following primary infection, herpesviruses persist for life in their hosts, even when vigorous anti-viral immunity has been induced. Failure of the host immune system to eliminate infected cells is facilitated by highly effective immune evasion strategies acquired by these herpesviruses during millions of years of co-evolution with their hosts. Here, we review the mechanisms of action of viral gene products that lead to cytotoxic T cell evasion through interference with the function of the transporter associated with antigen processing, TAP. The viral TAP inhibitors impede transport of peptides from the cytosol into the ER lumen, thereby preventing peptide loading onto MHC class I complexes. Recent insights have revealed a pattern of functional convergent evolution. In every herpesvirus subfamily, inhibitors of TAP function have been identified that are, surprisingly, unrelated in genome location, structure, and mechanism of action. Recently, cowpox virus has also been found to encode a TAP inhibitor. Expanding our knowledge on how viruses perturb antigen presentation, in particular by targeting TAP, not only provides information on viral pathogenesis, but also reveals novel aspects of the cellular processes corrupted by these viruses, notably the translocation of peptides by the ATP-binding cassette (ABC) transporter TAP. As the various TAP inhibitors are anticipated to impede discrete conformational transitions it is expected that crystal structures of TAP-inhibitor complexes will reveal valuable structural information on the actual mechanism of peptide translocation by TAP. Viral TAP inhibitors are also used for various (clinical) applications, for example, as effective tools in antigen presentation studies and as immunomodulators in immunotherapy for cancer, heterologous vaccination, and transplant protection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. The Spectrum of Triple-Negative Breast Disease: High- and Low-Grade Lesions.

    Science.gov (United States)

    Geyer, Felipe C; Pareja, Fresia; Weigelt, Britta; Rakha, Emad; Ellis, Ian O; Schnitt, Stuart J; Reis-Filho, Jorge S

    2017-10-01

    Triple-negative breast cancer is viewed clinically as an aggressive subgroup of breast cancer. In fact, most triple-negative breast cancers are poor-prognosis tumors with a complex genomic landscape. However, triple-negative disease is vastly heterogeneous, encompassing multiple entities with marked genetic, transcriptional, histologic, and clinical differences, with neoplasms in this group ranging from low to high grade. Among the less common low-grade triple-negative lesions, two large subgroups, both with a rather indolent behavior, can be distinguished: a low-grade triple-negative breast neoplasia family, which includes nonobligate precursors of triple-negative breast cancer, and, despite being low-grade, harbors the complex genomic landscape of usual triple-negative breast cancer, and the salivary gland-like tumors of the breast, lacking all the cardinal molecular features of conventional triple-negative breast cancer and underpinned by specific fusion genes or hotspot mutations, which may be of diagnostic and possibly therapeutic utility. Progression to high-grade triple-negative breast cancer likely occurs in both subgroups but at different rates. In this review, we describe the heterogeneity of triple-negative disease, focusing on the histologic and molecular features of the low-grade lesions. Recognition that triple-negative breast cancer is an operational term and that triple-negative disease is heterogeneous and includes low-grade forms driven by distinct sets of genetic alterations is germane to the successful implementation of precision medicine. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Compositional limits and analogs of monoclinic triple-chain silicates

    Science.gov (United States)

    Jenkins, David M.; Gilleaudeau, Geoffrey J.; Kawa, Cynthia; Dibiase, Jaclyn M.; Fokin, Maria

    2012-08-01

    Growing recognition of triple-chain silicates in nature has prompted experimental research into the conditions under which they can form and the extent of solid solution that is feasible for some key chemical substitutions. Experiments were done primarily in the range of 0.1-0.5 GPa and 200-850 °C for durations of 18-1,034 h. A wide range of bulk compositions were explored in this study that can be classified broadly into two groups: those that are Na free and involve various possible chemical substitutions into jimthompsonite (Mg10Si12O32(OH)4), and those that are Na bearing and involve chemical substitutions into the ideal end-member Na4Mg8Si12O32(OH)4. Numerous attempts to synthesize jimthompsonite or clinojimthompsonite were unsuccessful despite the type of starting material used (reagent oxides, magnesite + SiO2, talc + enstatite, or anthophyllite). Similarly, the chemical substitutions of F- for OH-, Mn2+, Ca2+, or Fe2+ for Mg2+, and 2Li+ for Mg2+ and a vacancy were unsuccessful at nucleating triple-chain silicates. Conversely, nearly pure yields of monoclinic triple-chain silicate could be made at temperatures of 440-630 °C and 0.2 GPa from the composition Na4Mg8Si12O32(OH)4, as found in previous studies, though its composition is most likely depleted in Na as evidenced by electron microprobe and FTIR analysis. Pure yields of triple-chain silicate were also obtained for the F-analog composition Na4Mg8Si12O32F4 at 550-750 °C and 0.2-0.5 GPa if a flux consisting of Na-halide salt and water in a 2:1 ratio by weight was used. In addition, limited chemical substitution could be documented for the substitutions of 2 Na+ for Na+ + H+ and of Mg2+ + vacancy for 2Na+. For the former, the Na content appears to be limited to 2.5 cations giving the ideal composition of Na2.5Mg8Si12O30.5(OH)5.5, while for the latter substitution the Na content may go as low as 1.1 cations giving the composition Na1.1Mg9.4Si12O31.9(OH)4.1 based on a fixed number of Si cations. Further

  4. The 21-Nucleotide, but Not 22-Nucleotide, Viral Secondary Small Interfering RNAs Direct Potent Antiviral Defense by Two Cooperative Argonautes in Arabidopsis thaliana[W][OA

    Science.gov (United States)

    Wang, Xian-Bing; Jovel, Juan; Udomporn, Petchthai; Wang, Ying; Wu, Qingfa; Li, Wan-Xiang; Gasciolli, Virginie; Vaucheret, Herve; Ding, Shou-Wei

    2011-01-01

    Arabidopsis thaliana defense against distinct positive-strand RNA viruses requires production of virus-derived secondary small interfering RNAs (siRNAs) by multiple RNA-dependent RNA polymerases. However, little is known about the biogenesis pathway and effector mechanism of viral secondary siRNAs. Here, we describe a mutant of Cucumber mosaic virus (CMV-Δ2b) that is silenced predominantly by the RNA-DEPENDENT RNA POLYMERASE6 (RDR6)-dependent viral secondary siRNA pathway. We show that production of the viral secondary siRNAs targeting CMV-Δ2b requires SUPPRESSOR OF GENE SILENCING3 and DICER-LIKE4 (DCL4) in addition to RDR6. Examination of 25 single, double, and triple mutants impaired in nine ARGONAUTE (AGO) genes combined with coimmunoprecipitation and deep sequencing identifies an essential function for AGO1 and AGO2 in defense against CMV-Δ2b, which act downstream the biogenesis of viral secondary siRNAs in a nonredundant and cooperative manner. Our findings also illustrate that dicing of the viral RNA precursors of primary and secondary siRNA is insufficient to confer virus resistance. Notably, although DCL2 is able to produce abundant viral secondary siRNAs in the absence of DCL4, the resultant 22-nucleotide viral siRNAs alone do not guide efficient silencing of CMV-Δ2b. Possible mechanisms for the observed qualitative difference in RNA silencing between 21- and 22-nucleotide secondary siRNAs are discussed. PMID:21467580

  5. Filovirus Entry: A Novelty in the Viral Fusion World

    Directory of Open Access Journals (Sweden)

    Wendy Maury

    2012-02-01

    Full Text Available Ebolavirus (EBOV and Marburgvirus (MARV that compose the filovirus family of negative strand RNA viruses infect a broad range of mammalian cells. Recent studies indicate that cellular entry of this family of viruses requires a series of cellular protein interactions and molecular mechanisms, some of which are unique to filoviruses and others are commonly used by all viral glycoproteins. Details of this entry pathway are highlighted here. Virus entry into cells is initiated by the interaction of the viral glycoprotein1 subunit (GP1 with both adherence factors and one or more receptors on the surface of host cells. On epithelial cells, we recently demonstrated that TIM-1 serves as a receptor for this family of viruses, but the cell surface receptors in other cell types remain unidentified. Upon receptor binding, the virus is internalized into endosomes primarily via macropinocytosis, but perhaps by other mechanisms as well. Within the acidified endosome, the heavily glycosylated GP1 is cleaved to a smaller form by the low pH-dependent cellular proteases Cathepsin L and B, exposing residues in the receptor binding site (RBS. Details of the molecular events following cathepsin-dependent trimming of GP1 are currently incomplete; however, the processed GP1 specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1 protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. Additional events such as further GP1 processing and/or reducing events may also be required to generate a fusion-ready form of the glycoprotein. Once this has been achieved, sequences in the filovirus GP2 subunit mediate viral/cellular membrane fusion via mechanisms similar to those previously described for other enveloped viruses. This multi-step entry pathway highlights the complex and highly orchestrated path of internalization and fusion that

  6. Assembly of viral metagenomes from yellowstone hot springs.

    Science.gov (United States)

    Schoenfeld, Thomas; Patterson, Melodee; Richardson, Paul M; Wommack, K Eric; Young, Mark; Mead, David

    2008-07-01

    Thermophilic viruses were reported decades ago; however, knowledge of their diversity, biology, and ecological impact is limited. Previous research on thermophilic viruses focused on cultivated strains. This study examined metagenomic profiles of viruses directly isolated from two mildly alkaline hot springs, Bear Paw (74 degrees C) and Octopus (93 degrees C). Using a new method for constructing libraries from picograms of DNA, nearly 30 Mb of viral DNA sequence was determined. In contrast to previous studies, sequences were assembled at 50% and 95% identity, creating composite contigs up to 35 kb and facilitating analysis of the inherent heterogeneity in the populations. Lowering the assembly identity reduced the estimated number of viral types from 1,440 and 1,310 to 548 and 283, respectively. Surprisingly, the diversity of viral species in these springs approaches that in moderate-temperature environments. While most known thermophilic viruses have a chronic, nonlytic infection lifestyle, analysis of coding sequences suggests lytic viruses are more common in geothermal environments than previously thought. The 50% assembly included one contig with high similarity and perfect synteny to nine genes from Pyrobaculum spherical virus (PSV). In fact, nearly all the genes of the 28-kb genome of PSV have apparent homologs in the metagenomes. Similarities to thermoacidophilic viruses isolated on other continents were limited to specific open reading frames but were equally strong. Nearly 25% of the reads showed significant similarity between the hot springs, suggesting a common subterranean source. To our knowledge, this is the first application of metagenomics to viruses of geothermal origin.

  7. Contagious Content: Viral Video Ads Identification of Content Characteristics that Help Online Video Advertisements Go Viral

    Directory of Open Access Journals (Sweden)

    Yentl Knossenburg

    2016-12-01

    Full Text Available Why do some online video advertisements go viral while others remain unnoticed? What kind of video content keeps the viewer interested and motivated to share? Many companies have realized the need to innovate their marketing strategies and have embraced the newest ways of using technology, as the Internet, to their advantage as in the example of virality. Yet few marketers actually understand how, and academic literature on this topic is still in development. This study investigated which content characteristics distinguish successful from non-successful online viral video advertisements by analyzing 641 cases using Structural Equation Modeling. Results show that Engagement and Surprise are two main content characteristics that significantly increase the chance of online video advertisements to go viral.  

  8. Triple oxygen isotope systematics of structurally bonded water in gypsum

    Science.gov (United States)

    Herwartz, Daniel; Surma, Jakub; Voigt, Claudia; Assonov, Sergey; Staubwasser, Michael

    2017-07-01

    The triple oxygen isotopic composition of gypsum mother water (gmw) is recorded in structurally bonded water in gypsum (gsbw). Respective fractionation factors have been determined experimentally for 18O/16O and 17O/16O. By taking previous experiments into account we suggest using 18αgsbw-gmw = 1.0037; 17αgsbw-gmw = 1.00195 and θgsbw-gmw = 0.5285 as fractionation factors in triple oxygen isotope space. Recent gypsum was sampled from a series of 10 ponds located in the Salar de Llamara in the Atacama Desert, Chile. Total dissolved solids (TDS) in these ponds show a gradual increase from 23 g/l to 182 g/l that is accompanied by an increase in pond water 18O/16O. Gsbw falls on a parallel curve to the ambient water from the saline ponds. The offset is mainly due to the equilibrium fractionation between gsbw and gmw. However, gsbw represents a time integrated signal biased towards times of strong evaporation, hence the estimated gmw comprises elevated 18O/16O compositions when compared to pond water samples taken on site. Gypsum precipitation is associated with algae mats in the ponds with lower salinity. No evidence for respective vital effects on the triple oxygen isotopic composition of gypsum hydration water is observed, nor are such effects expected. In principle, the array of δ18Ogsbw vs. 17Oexcess can be used to: (1) provide information on the degree of evaporation during gypsum formation; (2) estimate pristine meteoric water compositions; and (3) estimate local relative humidity which is the controlling parameter of the slope of the array for simple hydrological situations. In our case study, local mining activities may have decreased deep groundwater recharge, causing a recent change of the local hydrology.

  9. efficacy of highly active triple antiretroviral therapy in preventing ...

    African Journals Online (AJOL)

    were assessed by CD4 count, viral load, liver enzymes level, fasting blood sugar level, blood urea and haemoglobin concentration level before and after treatment and the .... occupation, marital status, religion and regional origin were collected. ... Caesarean section was performed only for obstetric indications or when ...

  10. Contagious Content: Viral Video Ads Identification of Content Characteristics that Help Online Video Advertisements Go Viral

    OpenAIRE

    Yentl Knossenburg; Roberto Nogueira; Paula Chimenti

    2016-01-01

    Why do some online video advertisements go viral while others remain unnoticed? What kind of video content keeps the viewer interested and motivated to share? Many companies have realized the need to innovate their marketing strategies and have embraced the newest ways of using technology, as the Internet, to their advantage as in the example of virality. Yet few marketers actually understand how, and academic literature on this topic is still in development. This study investigated which con...

  11. Triple-root jump in spacecraft potential due to electron beam emission or impact

    International Nuclear Information System (INIS)

    Lai, S.T.

    1992-01-01

    Triple-root jump in spacecraft potential is well understood in the double Maxwellian model of the natural space environment. In this paper, however, the author points out that triple-root jumps in spacecraft potential may also occur during photoemission or electron beam emission from a spacecraft. Impact of an incoming electron beam on a spacecraft may also cause triple-root jumps provided that the beam, ambient plasma, and surface parameters satisfy certain inequality conditions. The parametric conditions under which such beam induced triple-root jumps may occur are presented

  12. Pembrolizumab and Ruxolitinib Phosphate in Treating Patients With Metastatic Stage IV Triple Negative Breast Cancer

    Science.gov (United States)

    2018-03-05

    Breast Carcinoma Metastatic in the Bone; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  13. Management Options in Triple-Negative Breast Cancer

    Science.gov (United States)

    Minami, Christina A.; Chung, Debra U.; Chang, Helena R.

    2011-01-01

    Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease’s nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date. PMID:21863131

  14. Wnt signaling in triple-negative breast cancer

    Science.gov (United States)

    Pohl, SÖ-G; Brook, N; Agostino, M; Arfuso, F; Kumar, A P; Dharmarajan, A

    2017-01-01

    Wnt signaling regulates a variety of cellular processes, including cell fate, differentiation, proliferation and stem cell pluripotency. Aberrant Wnt signaling is a hallmark of many cancers. An aggressive subtype of breast cancer, known as triple-negative breast cancer (TNBC), demonstrates dysregulation in canonical and non-canonical Wnt signaling. In this review, we summarize regulators of canonical and non-canonical Wnt signaling, as well as Wnt signaling dysfunction that mediates the progression of TNBC. We review the complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease. PMID:28368389

  15. Compact Size UWB Monopole Antenna with Triple Band-Notches

    OpenAIRE

    Ali, W.; Ibrahim, A. A.; Machac, J.

    2017-01-01

    This paper presents triple band notched ultra wide band (UWB) monopole antenna with overall size of 36 × 32 mm2 fed by microstrip transmission line. In order to achieve a good impedance matching from 2.7 GHz to 13.4 GHz, a tapered transition between the rectangular patch and the feeding line is utilized. The three notched frequency bands are accomplished by a defected microstrip structure (DMS) which is inserted in the microstrip feeding line and by an open loop slot etched in the radiating p...

  16. Triple M-brane configurations and preserved supersymmetries

    International Nuclear Information System (INIS)

    Golubtsova, A.A.; Ivashchuk, V.D.

    2013-01-01

    We investigate all standard triple composite M-brane intersections defined on products of Ricci-flat manifolds for preserving supersymmetries in eleven-dimensional N=1 supergravity. The explicit formulae for computing the numbers of preserved supersymmetries are obtained, which generalize the relations for topologically trivial flat factor spaces presented in the classification by Bergshoeff et al. We obtain certain examples of configurations preserving some fractions of supersymmetries, e.g. containing such factor spaces as K3, C ⁎ 2 /Z 2 , a four-dimensional pp-wave manifold and the two-dimensional pseudo-Euclidean manifold R ⁎ 1,1 /Z 2

  17. Controllable optomechanical coupling in serially-coupled triple resonators

    Directory of Open Access Journals (Sweden)

    Chenguang Huang

    2014-12-01

    Full Text Available Radiation pressure can efficiently couple mechanical modes with optical modes in an optical cavity. The coupling efficiency is quite dependent on the interaction between the optical mode and mechanical mode. In this report, we investigate a serially-coupled triple resonator system, where a freestanding beam is placed in the vicinity of the middle resonator. In this coupled system, we demonstrate that the mechanical mode of the free-standing beam can be selectively coupled to different resonance supermodes through the near field interaction.

  18. Triple-phase bone image abnormalities in Lyme arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Brown, S.J.; Dadparvar, S.; Slizofski, W.J.; Glab, L.B.; Burger, M. (Hahnemann Univ. Hospital, Philadelphia, PA (USA))

    1989-10-01

    Arthritis is a frequent manifestation of Lyme disease. Limited triple-phase Tc-99m MDP bone imaging of the wrists and hands with delayed whole-body images was performed in a patient with Lyme arthritis. This demonstrated abnormal joint uptake in the wrists and hands in all three phases, with increased activity seen in other affected joints on delayed whole-body images. These findings are nonspecific and have been previously described in a variety of rheumatologic conditions, but not in Lyme disease. Lyme disease should be considered in the differential diagnosis of articular and periarticular bone scan abnormalities.

  19. Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

    DEFF Research Database (Denmark)

    Szallasi, Zoltan Imre; Eklund, Aron Charles; Li, Qiyuan

    2010-01-01

    PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer...... share features suggesting common pathogenesis, we conducted a neoadjuvant trial of cisplatin in TNBC and explored specific biomarkers to identify predictors of response. PATIENTS AND METHODS Twenty-eight women with stage II or III breast cancers lacking estrogen and progesterone receptors and HER2/Neu...

  20. A triple-GEM telescope for the TOTEM experiment

    CERN Document Server

    Lami, S; Oliveri, E; Ropelewski, Leszek; Turini, N

    2007-01-01

    The TOTEM experiment at LHC has chosen the triple Gas Electron Multiplier (GEM) technology for its T2 telescope which will provide charged track reconstruction in the rapidity range 5.3<|eta|<6.5 and a fully inclusive trigger for diffractive events. GEMs are gas-filled detectors that have the advantageous decoupling of the charge amplification structure from the charge collection and readout structure. Furthermore, they combine good spatial resolution with very high rate capability and a good resistance to radiation. Results from a detailed T2 GEM simulation and from laboratory tests on a final design detector performed at CERN are presented.

  1. Synchrotron X-ray diffraction using triple-axis spectrometry

    International Nuclear Information System (INIS)

    Als-Nielsen, J.

    1980-12-01

    High resolution X-ray diffraction studies of (i) monolayers of the noble gases Kr and Ar physiosorbed on graphite (ii) smectic A fluctuations in the nematic and the smectic A phases of liquid crystals are described. The apparatus used is a triple axis spectrometer situated at the storage ring DORIS at Hasylab, DESY, Hamburg. A monochromatic, well collimated beam is extracted from the synchrotron radiation spectrum by Bragg reflection from perfect Si or Ge crystals. The direction of the beam scattered from the sample is determined by Bragg reflection from a perfect Si or Ge crystal. High intensities even with resolution extending beyond the wavelength of visible light can be obtained. (Auth.)

  2. Ionospheric Cycle Slip Processing in Triple-frequency GNSS

    OpenAIRE

    HUANG Lingyong; ZHAI Guojun; OUYANG Yongzhong; XU Guangxiu; LI Kaifeng; HUANG Xianyuan; FAN Long

    2015-01-01

    A new method based on three linear independence geometry-free and ionosphere-free (GIF) combinations to detect and repair cycle-slip is advanced to finishing the cycle slip processing under the higher ionospheric activity. In order to ensure that the cycle slip correction is accurate, the repair value is validated by a second-order, time-difference phase ionospheric residual (STPIR) combination. And then, this method is validated and analyzed by using the triple-frequency data with higher ion...

  3. Kinetics of viral shedding provide insights into the epidemiology of viral hemorrhagic septicemia in Pacific herring

    Science.gov (United States)

    Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Courtney; Collins, Rachael

    2010-01-01

    Losses from infectious diseases are an important component of natural mortality among marine fish species, but factors controlling the ecology of these diseases and their potential responses to anthropogenic changes are poorly understood. We used viral hemorrhagic septicemia virus (VHSV) and a laboratory stock of Pacific herring Clupea pallasii to investigate the kinetics of viral shedding and its effect on disease transmission and host mortality. Outbreaks of acute disease, accompanied by mortality and viral shedding, were initiated after waterborne exposure of herring to concentrations of VHSV as low as 101 plaque-forming units (pfu) ml–1. Shed virus in flow-through tanks was first detected 4 to 5 d post-exposure, peaked after 6 to 10 d, and was no longer detected after 16 d. Shedding rates, calculated from density, flow and waterborne virus titer reached 1.8 to 5.0 × 108 pfu fish–1 d–1. Onset of viral shedding was dose-dependent and preceded initial mortality by 2 d. At 21 d, cumulative mortality in treatment groups ranged from 81 to 100% and was dependent not on challenge dose, but on the kinetics and level of viral shedding by infected fish in the tank. Possible consequences of the viral shedding and disease kinetics are discussed in the context of epizootic initiation and perpetuation among populations of wild Pacific herring.

  4. Application of the Intuitionistic Fuzzy InterCriteria Analysis Method with Triples to a Neural Network Preprocessing Procedure.

    Science.gov (United States)

    Sotirov, Sotir; Atanassova, Vassia; Sotirova, Evdokia; Doukovska, Lyubka; Bureva, Veselina; Mavrov, Deyan; Tomov, Jivko

    2017-01-01

    The approach of InterCriteria Analysis (ICA) was applied for the aim of reducing the set of variables on the input of a neural network, taking into account the fact that their large number increases the number of neurons in the network, thus making them unusable for hardware implementation. Here, for the first time, with the help of the ICA method, correlations between triples of the input parameters for training of the neural networks were obtained. In this case, we use the approach of ICA for data preprocessing, which may yield reduction of the total time for training the neural networks, hence, the time for the network's processing of data and images.

  5. Vitamin D compounds inhibit cancer stem-like cells and induce differentiation in triple negative breast cancer.

    Science.gov (United States)

    Shan, Naing Lin; Wahler, Joseph; Lee, Hong Jin; Bak, Min Ji; Gupta, Soumyasri Das; Maehr, Hubert; Suh, Nanjoo

    2017-10-01

    Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures. In the present study, the effects of vitamin D compounds in regulating breast cancer stem-like cells and differentiation in triple-negative breast cancer were assessed. Mammosphere cultures, which enriches for breast cancer cells with stem-like properties, were used to assess the effects of 1α,25(OH) 2 D 3 and BXL0124 on cancer stem cell markers in the triple-negative breast cancer cell line, SUM159. Vitamin D compounds significantly reduced the mammosphere forming efficiency in primary, secondary and tertiary passages of mammospheres compared to control groups. Key markers of cancer stem-like phenotype and pluripotency were analyzed in mammospheres treated with 1α,25(OH) 2 D 3 and BXL0124. As a result, OCT4, CD44 and LAMA5 levels were decreased. The vitamin D compounds also down-regulated the Notch signaling molecules, Notch1, Notch2, Notch3, JAG1, JAG2, HES1 and NFκB, which are involved in breast cancer stem cell maintenance. In addition, the vitamin D compounds up-regulated myoepithelial differentiating markers, cytokeratin 14 and smooth muscle actin, and down-regulated the luminal marker, cytokeratin 18. Cytokeratin 5, a biomarker associated with basal-like breast cancer, was found to be significantly down-regulated by the vitamin D compounds. These results suggest

  6. Viral Hepatitis: Retrospective Review in a Canadian Pediatric Hospital

    OpenAIRE

    Cybulska, Paulina; Ni, Andy; Jimenez-Rivera, Carolina

    2011-01-01

    Introduction. Clinical presentation of viral hepatitis ranges from mild symptoms to fulminant hepatitis. Our aim is to describe clinical presentation and outcomes of children with viral hepatitis from the Eastern Ontario/Western Quebec regions of Canada. Methods. Retrospective chart review of children diagnosed with viral hepatitis at our institution from January 1, 1998, to December 31, 2007. Results. There were 261 charts reviewed, only 64 had a confirmed viral etiology: 34 (53%) hepatitis ...

  7. ViPTree: the viral proteomic tree server

    OpenAIRE

    Nishimura, Yosuke; Yoshida, Takashi; Kuronishi, Megumi; Uehara, Hideya; Ogata, Hiroyuki; Goto, Susumu

    2017-01-01

    ViPTree is a web server provided through GenomeNet to generate viral proteomic trees for classification of viruses based on genome-wide similarities. Users can upload viral genomes sequenced either by genomics or metagenomics. ViPTree generates proteomic trees for the uploaded genomes together with flexibly selected reference viral genomes. ViPTree also serves as a platform to visually investigate genomic alignments and automatically annotated gene functions for the uploaded viral genomes, th...

  8. Adenovirus-Mediated Gene Therapy Against Viral Biothreat Agents

    Science.gov (United States)

    2016-04-12

    economy. Vaccine development is an important strategy to thwart the threat of these viral biothreat agents. There is an urgent need to improve...Alberta, Tl A 8K6. Canada E-mail: josh. wu@drdc-rddc.gc.ca .• 78 JoshQ.H. Wu existing vaccines against these agents and to develop new ones. Gene...of vaccines against viral biothreat agents. Genes encoding protective antigens of viral biothreat agents can be carried by these viral vectors and

  9. Toward Information Diffusion Model for Viral Marketing in Business

    OpenAIRE

    Lulwah AlSuwaidan; Mourad Ykhlef

    2016-01-01

    Current obstacles in the study of social media marketing include dealing with massive data and real-time updates have motivated to contribute solutions that can be adopted for viral marketing. Since information diffusion and social networks are the core of viral marketing, this article aims to investigate the constellation of diffusion methods for viral marketing. Studies on diffusion methods for viral marketing have applied different computational methods, but a systematic investigation of t...

  10. Viral Genetic Linkage Analysis in the Presence of Missing Data.

    Directory of Open Access Journals (Sweden)

    Shelley H Liu

    Full Text Available Analyses of viral genetic linkage can provide insight into HIV transmission dynamics and the impact of prevention interventions. For example, such analyses have the potential to determine whether recently-infected individuals have acquired viruses circulating within or outside a given community. In addition, they have the potential to identify characteristics of chronically infected individuals that make their viruses likely to cluster with others circulating within a community. Such clustering can be related to the potential of such individuals to contribute to the spread of the virus, either directly through transmission to their partners or indirectly through further spread of HIV from those partners. Assessment of the extent to which individual (incident or prevalent viruses are clustered within a community will be biased if only a subset of subjects are observed, especially if that subset is not representative of the entire HIV infected population. To address this concern, we develop a multiple imputation framework in which missing sequences are imputed based on a model for the diversification of viral genomes. The imputation method decreases the bias in clustering that arises from informative missingness. Data from a household survey conducted in a village in Botswana are used to illustrate these methods. We demonstrate that the multiple imputation approach reduces bias in the overall proportion of clustering due to the presence of missing observations.

  11. Novel viral vectored vaccines for the prevention of influenza.

    Science.gov (United States)

    Lambe, Teresa

    2012-10-24

    Influenza represents a substantial global healthcare burden, with annual epidemics resulting in 3-5 million cases of severe illness with a significant associated mortality. In addition, the risk of a virulent and lethal influenza pandemic has generated widespread and warranted concern. Currently licensed influenza vaccines are limited in their ability to induce efficacious and long-lasting herd immunity. In addition, and as evidenced by the H1N1 pandemic in 2009, there can be a significant delay between the emergence of a pandemic influenza and an effective, antibody-inducing vaccine. There is, therefore, a continued need for new, efficacious vaccines conferring cross-clade protection-obviating the need for biannual reformulation of seasonal influenza vaccines. Development of such a vaccine would yield enormous health benefits to society and also greatly reduce the associated global healthcare burden. There are a number of alternative influenza vaccine technologies being assessed both preclinically and clinically. In this review we discuss viral vectored vaccines, either recombinant live-attenuated or replication-deficient viruses, which are current lead candidates for inducing efficacious and long-lasting immunity toward influenza viruses. These alternate influenza vaccines offer real promise to deliver viable alternatives to currently deployed vaccines and more importantly may confer long-lasting and universal protection against influenza viral infection.

  12. Therapy of respiratory viral infections with intranasal siRNAs.

    Science.gov (United States)

    Barik, Sailen; Lu, Patrick

    2015-01-01

    Chemically synthesized short interfering RNA (siRNA) has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) (two Paramyxoviruses), and influenza virus (an Orthomyxovirus). As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of single intranasal siRNA against RSV, we now offer two new strategies: (1) second-generation siRNAs, used against the paramyxoviral RNA polymerase large subunit (L), (2) siRNA cocktail with a novel transfection reagent, used against influenza virus. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (a) modified 19-27 nt-long double-stranded siRNAs are functional in the lung, (b) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, (c) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent, (d) cocktail of multiple siRNAs can be highly effective against multiple viral strains and subtypes.

  13. Virale commercials: de consument als marketeer. Onderzoek naar de redenen waarom consumenten virale commercials doorsturen: hun motieven, de inhoudskenmerken van viral commercials en de mediumcontext waarin virale commercials verschijnen

    NARCIS (Netherlands)

    Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

    2010-01-01

    Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers,

  14. Respiratory viral infections in children with asthma: do they matter and can we prevent them?

    Directory of Open Access Journals (Sweden)

    Ahanchian Hamid

    2012-09-01

    Full Text Available Abstract Background Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. Discussion While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use. Summary Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children.

  15. A Novel Tunable Triple-Band Left-Handed Metamaterial

    Directory of Open Access Journals (Sweden)

    Si Li

    2017-01-01

    Full Text Available A novel tunable triple-band left-handed metamaterial (LHM composed of a single-loop resonator (SLR and a variable capacitor-loaded short wire pair (CL-SWP printed on both sides of a substrate is presented in this paper. The CL-SWP-based metamaterial (MTM is a novel single-sided LHM. It is theoretically analyzed capable of extracting tunable negative permeability and a wide-band negative permittivity. We ran simulations for the CL-SWP-based MTM, the SLR-based MTM, and the proposed LHM. Together with the measured results, it is identified that this novel LHM exhibits a tunable triple-band left-handed (LH property. With the increase of the loaded capacitance, one LH band is relatively stable, while the other two are moving towards lower frequencies with their bandwidth getting wider and narrower, respectively. The surface current density distributions indicate that the first LH band is mainly decided by the SLR, one of the rest 2 LH bands is mainly decided by the CL-SWP, and the other one is decided by the SLR and CL-SWP together.

  16. "Triple-bottom-line" assessment of urban stormwater projects.

    Science.gov (United States)

    Taylor, A C; Fletcher, T D

    2006-01-01

    New guidelines have been developed and trialled in Australia to assist urban stormwater managers to assess options for projects that aim to improve urban waterway health. These guidelines help users to examine the financial, ecological and social dimensions of projects (i.e., the so-called "triple-bottom-line"). Features of the assessment process described in the guidelines include use of multi criteria analysis, input from technical experts as well as non-technical stakeholders, and provision of three alternative levels of assessment to suit stormwater managers with differing needs and resources. This paper firstly provides a background to the new guidelines and triple-bottom-line assessment. The assessment methodology promoted in the new guidelines is then briefly summarised. This methodology is compared and contrasted with European guidelines from the "SWARD" project that have been primarily developed for assessing the relative sustainability of options involving urban water supply and sewerage assets. Finally, the paper discusses how assessment methodologies that evaluate the financial, ecological and social dimensions of projects can, under some circumstances, be used to evaluate the relative progress of options for urban water management on a journey towards the widely pursued, but vaguely defined goal of "sustainable development".

  17. Overlay metrology solutions in a triple patterning scheme

    Science.gov (United States)

    Leray, Philippe; Mao, Ming; Baudemprez, Bart; Amir, Nuriel

    2015-03-01

    Overlay metrology tool suppliers are offering today several options to their customers: Different hardware (Image Based Overlay or Diffraction Based Overlay), different target designs (with or without segmentation) or different target sizes (from 5 um to 30 um). All these variations are proposed to resolve issues like robustness of the target towards process variations, be more representative of the design or increase the density of measurements. In the frame of the development of a triple patterning BEOL scheme of 10 nm node layer, we compare IBO targets (standard AIM, AIMid and multilayer AIMid). The metrology tools used for the study are KLA-Tencor's nextgeneration Archer 500 system (scatterometry- and imaging-based measurement technologies on the same tool). The overlay response and fingerprint of these targets will be compared using a very dense sampling (up to 51 pts per field). The benefit of indie measurements compared to the traditional scribes is discussed. The contribution of process effects to overlay values are compared to the contribution of the performance of the target. Different targets are combined in one measurement set to benefit from their different strengths (performance vs size). The results are summarized and possible strategies for a triple patterning schemes are proposed.

  18. Shifting to triple value healthcare: Reflections from England.

    Science.gov (United States)

    Jani, Anant; Jungmann, Sven; Gray, Muir

    2018-02-01

    Increasing need and demand because of growing and aging populations combined with stagnant or decreasing resources being invested into healthcare globally mean that a radical shift is needed to ensure that healthcare systems can meet current and future challenges. Quality-, safety- and efficiency-improvement approaches have been used as means to address many problems in healthcare and while they are essential and necessary, they are not sufficient to meet our current challenges. To build resilient and sustainable healthcare systems, we need a shift to focus on triple value healthcare, which will help healthcare professionals improve outcomes at the process, patient and population levels while also optimising resource utilisation. Here we present a brief history of the Quality and Evidence-based Healthcare model and then describe how value emerged as a predominant theme in England. We then highlight the four solutions that we, as part of the RightCare programme, designed and refined in the English NHS to turn theory into practice: We end with a description of how triple value is being introduced into Germany and steps that can be taken to facilitate its adoption. Copyright © 2018. Published by Elsevier GmbH.

  19. Triple Difference Approach to Low Earth Orbiter Precision Orbit Determination

    Science.gov (United States)

    Kwon, Jay-Hyoun; Grejner-Brzezinska, Dorota A.; Yom, Jae-Hong; Cheon, Lee-Dong

    2003-03-01

    A precise kinematic orbit determination (P-KOD) procedure for Low Earth Orbiter(LEO) using the GPS ion-free triple differenced carrier phases is presented. Because the triple differenced observables provide only relative information, the first epoch's positions of the orbit should be held fixed. Then, both forward and backward filtering was executed to mitigate the effect of biases of the first epoch's position. P-KOD utilizes the precise GPS orbits and ground stations data from International GPS Service (IGS) so that the only unknown parameters to be solved are positions of the satellite at each epoch. Currently, the 3-D accuracy of P-KOD applied to CHAMP (CHAllenging Minisatellite Payload) shows better than 35 cm compared to the published rapid scientific orbit (RSO) solution from GFZ (GeoForschungsZentrum Potsdam). The data screening for cycle slips is a particularly challenging procedure for LEO, which moves very fast in the middle of the ionospheric layer. It was found that data screening using SNR (signal to noise ratio) generates best results based on the residual analysis using RSO. It is expected that much better accuracy are achievable with refined prescreening procedure and optimized geometry of the satellites and ground stations.

  20. Measuring the "triple aim" in transition care: a systematic review.

    Science.gov (United States)

    Prior, Megan; McManus, Margaret; White, Patience; Davidson, Laurie

    2014-12-01

    Without adequate support, adolescents transitioning from the pediatric to the adult health care system are at increased risk for poor health outcomes. Numerous interventions attempt to improve this transition, yet few comprehensively evaluate efficacy. To advance evaluation methods and ultimately the quality of transition services, it is necessary to understand the current state of health care transition measurement. This study examines and categorizes transition measures by using the "Triple Aim" framework of experience of care, population health, and cost of care. Ovid Medline and the Cumulative Index to Nursing and Allied Health Literature were searched for articles published between 1995 and 2013. Two reviewers independently screened studies and included those that evaluated the impact of a health care transition intervention. Measures were subsequently classified according to population health, experience of care, and costs of care. Of the 2282 studies initially identified, 33 met inclusion criteria. Population health measures were used in 27 studies, with disease-specific measures collected most frequently. Fifteen studies measured cost, most often service utilization. Eight studies measured experience of care, with satisfaction assessed most commonly. Only 3 studies examined all 3 domains of the "Triple Aim." Transition interventions described in the gray literature were not reviewed. Transition programs are inconsistently evaluated in terms of their impact on population health, patient experience, and cost. To demonstrate improvement in the transition from pediatric to adult health care, a more robust and consistent set of measures is needed. Copyright © 2014 by the American Academy of Pediatrics.

  1. Use of locking plate and screws for triple pelvic osteotomy.

    Science.gov (United States)

    Rose, Scott A; Bruecker, Ken A; Petersen, Steve W; Uddin, Nizam

    2012-01-01

    To evaluate the efficacy and complication rate associated with use of a purpose-specific locking triple pelvic osteotomy (LTPO) plate. Prospective study. Dogs (n = 9; 15 hips). Physical examination, plain film radiography, computed tomography (CT) of the pelvis, and coxofemoral arthroscopy were performed before unilateral triple pelvic osteotomy (TPO) or staged bilateral TPO. Radiographs were taken after each procedure and 3-5, 6-8, and ≥12 weeks postoperatively. Pelvic width was measured at 3 locations to evaluate pelvic canal narrowing. No screw loosening occurred. Complications occurred in only 1 hip (7%) where pullout of the locking plate-screw construct from the caudal iliac segment occurred because of a fracture of the cis-cortex; the dog made a full recovery after a salvage procedure. There was no significant reduction in the cranial pelvic width but a small reduction at the level of the acetabuli and ischiatic tuberosities was noted 3-5 weeks after the 2nd TPO. The LTPO plate was associated with a lower complication rate than previously reported for TPOs using Slocum canine pelvic osteotomy plates (CPOP) and warrants further investigation. Pullout of the caudal plate-screw construct is a complication specific to LTPO implants. Bicortical screw purchase is recommended to prevent fracture of the cis-cortex and implant pullout. © Copyright 2011 by The American College of Veterinary Surgeons.

  2. Seroprevalence of viral and bacterial diseases among the bovines in Himachal Pradesh, India

    Directory of Open Access Journals (Sweden)

    Shailja Katoch

    2017-12-01

    Full Text Available Aim: The study was designed to measure the seroprevalence of viral and bacterial diseases: Infectious bovine rhinotracheitis, bovine viral diarrhea, bovine leukemia, bovine parainfluenza, bovine respiratory syncytial disease, brucellosis, and paratuberculosis among bovine of Himachal Pradesh during the year 2013-2015. Materials and Methods: The serum samples were collected from seven districts of state, namely, Bilaspur, Kangra, Kinnaur, Lahul and Spiti, Mandi, Sirmour, and Solan. The samples were screened using indirect ELISA kits to measure the seroprevalence of viral and bacterial diseases. Results: The overall seroprevalence of infectious bovine rhinotracheitis was 24.24%, bovine viral diarrhea 1.52%, bovine leukemia 9.09%, bovine parainfluenza 57.58%, bovine respiratory syncytial disease 50%, brucellosis 19.69%, and paratuberculosis 9.09% in Himachal Pradesh. The seroprevalence of bovine rhinotracheitis, bovine leukemia, bovine parainfluenza, bovine respiratory syncytial disease, and paratuberculosis in the state varied significantly (p0.01. Multiple seropositivity has been observed in this study. Bovine parainfluenza virus 3 was observed commonly in mixed infection with almost all viruses and bacteria under study. Conclusion: The viral and bacterial diseases are prevalent in the seven districts of Himachal Pradesh investigated in the study. Therefore, appropriate management practices and routine vaccination programs should be adopted to reduce the prevalence of these diseases.

  3. Seasonality of Acute Otitis Media and the Role of Respiratory Viral Activity in Children

    Science.gov (United States)

    Stockmann, Chris; Ampofo, Krow; Hersh, Adam L.; Carleton, Scott T.; Korgenski, Kent; Sheng, Xiaoming; Pavia, Andrew T.; Byington, Carrie L.

    2012-01-01

    Background Acute otitis media (AOM) occurs as a complication of viral upper respiratory tract infections in young children. AOM and respiratory viruses both display seasonal variation. Our objective was to examine the temporal association between circulating respiratory viruses and the occurrence of pediatric ambulatory care visits for AOM. Methods This retrospective study included 9 seasons of respiratory viral activity (2002-2010) in Utah. We used Intermountain Healthcare's electronic medical records to assess community respiratory viral activity via laboratory-based active surveillance and to identify children <18 years with outpatient visits and ICD-9 codes for AOM. We assessed the strength of the association between AOM and individual respiratory viruses using interrupted time series analyses. Results During the study period, 96,418 respiratory viral tests were performed; 46,460 (48%) were positive. The most commonly identified viruses were: RSV (22%), rhinovirus (8%), influenza (8%), parainfluenza (4%), human metapneumovirus (3%), and adenovirus (3%). AOM was diagnosed during 271,268 ambulatory visits. There were significant associations between peak activity of RSV, human metapneumovirus, influenza A, and office visits for AOM. Adenovirus, parainfluenza, and rhinovirus were not associated with visits for AOM. Conclusions Seasonal RSV, human metapneumovirus, and influenza activity were temporally associated with increased diagnoses of AOM among children. These findings support the role of individual respiratory viruses in the development AOM. These data also underscore the potential for respiratory viral vaccines to reduce the burden of AOM. PMID:23249910

  4. Phosphorylation of human respiratory syncytial virus P protein at serine 54 regulates viral uncoating

    International Nuclear Information System (INIS)

    Asenjo, Ana; Gonzalez-Armas, Juan C.; Villanueva, Nieves

    2008-01-01

    The human respiratory syncytial virus (HRSV) structural P protein, phosphorylated at serine (S) and threonine (T) residues, is a co-factor of viral RNA polymerase. The phosphorylation of S54 is controlled by the coordinated action of two cellular enzymes: a lithium-sensitive kinase, probably glycogen synthetase kinase (GSK-3) β and protein phosphatase 2A (PP2A). Inhibition of lithium-sensitive kinase, soon after infection, blocks the viral growth cycle by inhibiting synthesis and/or accumulation of viral RNAs, proteins and extracellular particles. P protein phosphorylation at S54 is required to liberate viral ribonucleoproteins (RNPs) from M protein, during the uncoating process. Kinase inhibition, late in infection, produces a decrease in genomic RNA and infectious viral particles. LiCl, intranasally applied to mice infected with HRSV A2 strain, reduces the number of mice with virus in their lungs and the virus titre. Administration of LiCl to humans via aerosol should prevent HRSV infection, without secondary effects

  5. A method for quantifying mechanical properties of tissue following viral infection.

    Directory of Open Access Journals (Sweden)

    Vy Lam

    Full Text Available Viral infection and replication involves the reorganization of the actin network within the host cell. Actin plays a central role in the mechanical properties of cells. We have demonstrated a method to quantify changes in mechanical properties of fabricated model three-dimensional (3D connective tissue following viral infection. Using this method, we have characterized the impact of infection by the human herpesvirus, cytomegalovirus (HCMV. HCMV is a member of the herpesvirus family and infects a variety of cell types including fibroblasts. In the body, fibroblasts are necessary for maintaining connective tissue and function by creating mechanical force. Using this 3D connective tissue model, we observed that infection disrupted the cell's ability to generate force and reduced the cumulative contractile force of the tissue. The addition of HCMV viral particles in the absence of both viral gene expression and DNA replication was sufficient to disrupt tissue function. We observed that alterations of the mechanical properties are, in part, due to a disruption of the underlying complex actin microfilament network established by the embedded fibroblasts. Finally, we were able to prevent HCMV-mediated disruption of tissue function by the addition of human immune globulin against HCMV. This study demonstrates a method to quantify the impact of viral infection on mechanical properties which are not evident using conventional cell culture systems.

  6. Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus.

    Science.gov (United States)

    Soto-Acosta, Rubén; Bautista-Carbajal, Patricia; Syed, Gulam H; Siddiqui, Aleem; Del Angel, Rosa M

    2014-09-01

    Dengue is the most common mosquito borne viral disease in humans. The infection with any of the 4 dengue virus serotypes (DENV) can either be asymptomatic or manifest in two clinical forms, the mild dengue fever or the more severe dengue hemorrhagic fever that may progress into dengue shock syndrome. A DENV replicative cycle relies on host lipid metabolism; specifically, DENV infection modulates cholesterol and fatty acid synthesis, generating a lipid-enriched cellular environment necessary for viral replication. Thus, the aim of this work was to evaluate the anti-DENV effect of the Nordihydroguaiaretic acid (NDGA), a hypolipidemic agent with antioxidant and anti-inflammatory properties. A dose-dependent inhibition in viral yield and NS1 secretion was observed in supernatants of infected cells treated for 24 and 48 h with different concentrations of NDGA. To evaluate the effect of NDGA in DENV replication, a DENV4 replicon transfected Vero cells were treated with different concentrations of NDGA. NDGA treatment significantly reduced DENV replication, reiterating the importance of lipids in viral replication. NDGA treatment also led to reduction in number of lipid droplets (LDs), the neutral lipid storage organelles involved in DENV morphogenesis that are known to increase in number during DENV infection. Furthermore, NDGA treatment resulted in dissociation of the C protein from LDs. Overall our results suggest that NDGA inhibits DENV infection by targeting genome replication and viral assembly. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Trehalose-mediated autophagy impairs the anti-viral function of human primary airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Qun Wu

    Full Text Available Human rhinovirus (HRV is the most common cause of acute exacerbations of chronic lung diseases including asthma. Impaired anti-viral IFN-λ1 production and increased HRV replication in human asthmatic airway epithelial cells may be one of the underlying mechanisms leading to asthma exacerbations. Increased autophagy has been shown in asthmatic airway epithelium, but the role of autophagy in anti-HRV response remains uncertain. Trehalose, a natural glucose disaccharide, has been recognized as an effective autophagy inducer in mammalian cells. In the current study, we used trehalose to induce autophagy in normal human primary airway epithelial cells in order to determine if autophagy directly regulates the anti-viral response against HRV. We found that trehalose-induced autophagy significantly impaired IFN-λ1 expression and increased HRV-16 load. Inhibition of autophagy via knockdown of autophagy-related gene 5 (ATG5 effectively rescued the impaired IFN-λ1 expression by trehalose and subsequently reduced HRV-16 load. Mechanistically, ATG5 protein interacted with retinoic acid-inducible gene I (RIG-I and IFN-β promoter stimulator 1 (IPS-1, two critical molecules involved in the expression of anti-viral interferons. Our results suggest that induction of autophagy in human primary airway epithelial cells inhibits the anti-viral IFN-λ1 expression and facilitates HRV infection. Intervention of excessive autophagy in chronic lung diseases may provide a novel approach to attenuate viral infections and associated disease exacerbations.

  8. IL-9 inhibits viral replication in Coxsackievirus B3-induced myocarditis

    Directory of Open Access Journals (Sweden)

    Miao Yu

    2016-10-01

    Full Text Available Myocardial injuries in viral myocarditis (VMC are caused by viral infection and related autoimmune disorders. Recent studies suggest that IL-9 mediated both antimicrobial immune and autoimmune responses in addition to allergic diseases. However, the role of IL-9 in viral infection and VMC remains controversial and uncertain. In this study, we infected Balb/c mice with Coxsackievirus B3 (CVB3, and found that IL-9 was enriched in the blood and hearts of VMC mice on days 5 and 7 after virus infection. Most of IL-9 was secreted by CD8+ T cells on day 5 and CD4+ T cells on day 7 in the myocardium. Further, IL-9 knockout exacerbated cardiac damage following CVB3 infection, along with a sharp increase in viral replication and IL-17a expression, as well as a decrease in TGF-β. In contrast, repletion of IL-9 in Balb/c mice with CVB infection induced the opposite effect. Studies in vitro further revealed that IL-9 directly inhibited viral replication in cardiomyocytes by reducing coxsackie and adenovirus receptor expression, which might be associated with up-regulation of TGF-β autocrine effect in these cells. However, IL-9 had no direct effect on apoptosis in cardiomyocytes. Our data indicated that IL-9 played a protective role in disease progression by inhibiting CVB3 replication in the early stages of VMC.

  9. US findings in acute viral hepatitis

    International Nuclear Information System (INIS)

    Corsi, M.; Lorenzon, G.; Mesaglio, S.

    1988-01-01

    Reports on colecystic alterations during acute viral hepatitis are more and more frequent; the pathogenesis and clinical meaning of these alterations are still debated. Consensual periportal lymphnode enlargment has been not yet reported. The authors describe four cases of acute viral hepatites in whichUS showed alterations of colecystic walls and/or contents; in two cases enlarged periportal lymphnodes were demonstrated too. Later US exams showed a complete regression of both colecystic and lymphnodal lesions. Clinical findings and laboratory out-comes are evaluated; the connection of US results with hepatitis and its meaning are discussed. The causes of colecystic alterations are still questionable; they might be related to blood disorders or to an increased portal pressure, or else they might be considered as phlogistic lesions. The authors conclude that both colecystic and lymphnodal alterations have a phlogistic nature; moreover, they are not related to a particulary evolution of hepatitis. The importance of distinguishing colecystic alterations from different pathology is stressed

  10. Viral subversion of the immune system

    International Nuclear Information System (INIS)

    Gillet, L.; Vanderplasschen, A.

    2005-01-01

    The continuous interactions between host and viruses during their co-evolution have shaped not only the immune system but also the countermeasures used by viruses. Studies in the last decade have described the diverse arrays of pathways and molecular targets that are used by viruses to elude immune detection or destruction, or both. These include targeting of pathways for major histocompatibility complex class I and class II antigen presentation, natural killer cell recognition, apoptosis, cytokine signalling, and complement activation. This paper provides an overview of the viral immune-evasion mechanisms described to date. It highlights the contribution of this field to our understanding of the immune system, and the importance of understanding this aspect of the biology of viral infection to develop efficacious and safe vaccines. (author)

  11. Multiplexing Short Primers for Viral Family PCR

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, S N; Hiddessen, A L; Hara, C A; Williams, P L; Wagner, M; Colston, B W

    2008-06-26

    We describe a Multiplex Primer Prediction (MPP) algorithm to build multiplex compatible primer sets for large, diverse, and unalignable sets of target sequences. The MPP algorithm is scalable to larger target sets than other available software, and it does not require a multiple sequence alignment. We applied it to questions in viral detection, and demonstrated that there are no universally conserved priming sequences among viruses and that it could require an unfeasibly large number of primers ({approx}3700 18-mers or {approx}2000 10-mers) to generate amplicons from all sequenced viruses. We then designed primer sets separately for each viral family, and for several diverse species such as foot-and-mouth disease virus, hemagglutinin and neuraminidase segments of influenza A virus, Norwalk virus, and HIV-1.

  12. Beclin-1 Targeting for Viral Immune Escape

    Directory of Open Access Journals (Sweden)

    Christian Münz

    2011-07-01

    Full Text Available Macroautophagy is a catabolic pathway in eukaryotic cells that has recently been shown to facilitate pathogen detection, pathogen restriction and pathogen-derived antigen presentation to CD4+ T cells. Due to these protective functions during immune responses, several pathogens, including RNA and DNA viruses, have developed strategies to inhibit autophagosome generation or maturation. Interestingly, most of the respective viral proteins exert these functions via binding to Beclin-1, an essential macroautophagy protein that constitutes part of the phosphatidylinositol-3 kinase complexes that mark membranes for autophagosome generation and facilitate autophagosome fusion with lyososomes. The viruses that inhibit macroautophagy by this pathway include herpesviruses, HIV and influenza A virus. Inhibition either before or after autophagosome formation seems to benefit their viral replication by different mechanisms, which are discussed here.

  13. Beclin-1 targeting for viral immune escape.

    Science.gov (United States)

    Münz, Christian

    2011-07-01

    Macroautophagy is a catabolic pathway in eukaryotic cells that has recently been shown to facilitate pathogen detection, pathogen restriction and pathogen-derived antigen presentation to CD4(+) T cells. Due to these protective functions during immune responses, several pathogens, including RNA and DNA viruses, have developed strategies to inhibit autophagosome generation or maturation. Interestingly, most of the respective viral proteins exert these functions via binding to Beclin-1, an essential macroautophagy protein that constitutes part of the phosphatidylinositol-3 kinase complexes that mark membranes for autophagosome generation and facilitate autophagosome fusion with lyososomes. The viruses that inhibit macroautophagy by this pathway include herpesviruses, HIV and influenza A virus. Inhibition either before or after autophagosome formation seems to benefit their viral replication by different mechanisms, which are discussed here.

  14. Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer.

    Science.gov (United States)

    Grob, Tobias J; Heilenkötter, Uwe; Geist, Stefan; Paluchowski, Peter; Wilke, Christian; Jaenicke, Fritz; Quaas, Alexander; Wilczak, Waldemar; Choschzick, Matthias; Sauter, Guido; Lebeau, Annette

    2012-07-01

    Women with triple-negative breast cancer (TNBC) do not benefit from endocrine therapy or trastuzumab. Chemotherapy is the only systemic therapy currently available. To reduce the elevated risk of disease progression in these patients, better treatment options are needed, which are less toxic and more targeted to this patient population. We performed a comprehensive analysis of potential targetable genetic aberrations affecting the receptor tyrosine kinase/RAS/MAPK pathway, which are observed at higher frequencies in adenocarcinomas of other organs. Sixty-five individual TNBCs were studied by sequence analysis for HER2 (exon 18-23), EGFR (exon 18-21), KRAS (exon 2), and BRAF (exon 15) mutations. In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. Triple-negative status was confirmed by immunohistochemistry and FISH on tissue microarray sections. EGFR and CK5/6 immunohistochemical analyses were performed for identification of the basal-like phenotype. In addition, mutation analysis of TP53 (exon 5-8) was included. Sequence analysis revealed HER2 gene mutation in only one patient (heterozygous missense mutation in exon 19: p.L755S). No mutations were found in EGFR, KRAS, and BRAF. High polysomy of EGFR was detected in 5 of the 62 informative cases by FISH. True EGFR gene amplification accompanied by strong membranous EGFR protein expression was observed in only one case. No rearrangement of the ALK gene was detected. Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5 %). TP53 gene mutation was found in 36/63 (57.1 %) tumors. We conclude that targetable genetic aberrations in the receptor tyrosine kinase/RAS/MAPK pathway occur rarely in TNBC.

  15. Sequential crystallization and morphology of triple crystalline biodegradable PEO-b-PCL-b-PLLA triblock terpolymers

    KAUST Repository

    Palacios, Jordana

    2016-01-05

    The sequential crystallization of poly(ethylene oxide)-b-poly(e-caprolactone)-b-poly(L-lactide) (PEO-b-PCL-b-PLLA) triblock terpolymers, in which the three blocks are able to crystallize separately and sequentially from the melt, is presented. Two terpolymers with identical PEO and PCL block lengths and two different PLLA block lengths were prepared, thus the effect of increasing PLLA content on the crystallization behavior and morphology was evaluated. Wide angle X-Ray scattering (WAXS) experiments performed on cooling from the melt confirmed the triple crystalline nature of these terpolymers and revealed that they crystallize in sequence: the PLLA block crystallizes first, then the PCL block, and finally the PEO block. Differential scanning calorimetry (DSC) analysis further demonstrated that the three blocks can crystallize from the melt when a low cooling rate is employed. The crystallization process takes place from a homogenous melt as indicated by small angle X-Ray scattering (SAXS) experiments. The crystallization and melting enthalpies and temperatures of both PEO and PCL blocks decrease as PLLA content in the terpolymer increases. Polarized light optical microscopy (PLOM) demonstrated that the PLLA block templates the morphology of the terpolymer, as it forms spherulites upon cooling from the melt. The subsequent crystallization of PCL and PEO blocks occurs inside the interlamellar regions of the previously formed PLLA block spherulites. In this way, unique triple crystalline mixed spherulitic superstructures have been observed for the first time. As the PLLA content in the terpolymer is reduced the superstructural morphology changes from spherulites to a more axialitic-like structure.

  16. Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Rajeshwari Mehta

    Full Text Available Treatment of breast cancer patients with antiestrogens and aromatase inhibitor(s or Herceptin have shown significant success in steroid receptor positive or Her-2+ breast cancers respectively. However, choice of treatments for breast cancer patients with negative status for estrogen, progesterone receptors and HER2/neu is limited. As a result, search for appropriate therapy regimen for these triple negative breast cancers (TNBC has become a major focus of investigations for many laboratories. Recently, Deguelin, a natural product isolated from African plant Mundulea sericea (Leguminossae has shown both antiproliferative actions in various cancers including breast as well as chemoprenventive activity against carcinogen induced experimental cancers. In this report we evaluated efficacy and mechanism of action of Deguelin in triple negative breast cancer cell lines.In vitro, Deguelin in a dose and time dependent manner inhibited the growth of MDA-MB-231, MDA-MB-468, BT-549 and BT-20 cells. Deguelin (2 or 4 mg/kg body weight, when injected intraperitoneally, reduced the in vivo tumor growth of MDA-MB-231 cells transplanted subcutaneously in athymic mice. Moreover it was nontoxic as evident from daily observations on mobility, food and water consumption and comparison of bodyweight and other visceral organ weights with those in control animals at the termination of the study. The western blot analyses and immunostaining studies indicated that the deguelin effects may be mediated through EGFR-PAKT/c-Met p-ERK and NF-κB by down regulating their downstream targets such as p-STAT3, c-Myc, Survivin.These results suggest that Deguelin may have a significant therapeutic value for the treatment of TNBC patients.

  17. Performance of triple bagging hermetic technology for postharvest storage of cowpea grain in Niger

    KAUST Repository

    Baoua, Ibrahim B.

    2012-10-01

    Triple bagging technology for protecting postharvest cowpea grain from losses to the bruchid, Callosobruchus maculatus Fabricius (Coleoptera: Chrysomelidae: Bruchinae) is currently being adopted on a fairly large scale in ten West and Central African countries, including Niger. The triple bag consists of two inner high-density polyethylene bags acting as oxygen barriers, which in turn are encased in an outer woven polypropylene bag that serves primarily for mechanical strength. These hermetic bags, available in either 50 or 100 kg capacity, are called Purdue Improved Cowpea Storage (PICS) bags. Adoption of PICS technology in West and Central Africa has been driven by its effectiveness, simplicity, low cost, durability, and manufacture within the region. From surveys on adoption we discovered that farmers have begun to re-use bags they had used the previous year or even the previous two years. In the present study, we compared the performance of three different types of PICS bags: (1) new 50 kg (2) new 100 kg bags and (3) once-used 50 kg bags, all filled with naturally infested untreated cowpeas. In these PICS bags the O 2 levels within the bags initially fell to about 3 percent (v/v) while the CO 2 rose to nearly 5 percent (v/v). After five months of storage, new and used 50 kg bags and new 100 kg bags preserved the grain equally well. There were greatly reduced numbers of adults and larvae in the PICS bags versus the controls, which consisted of grain stored in single layer woven bags. The proportion of grain having C. maculatus emergence holes after five months of storage in PICS bags was little changed from that found when the grain was first put into the bags. The PICS technology is practical and useful in Sahelian conditions and can contribute to improved farmers\\' incomes as well as increase availability of high quality, insecticide-free cowpea grain as food. © 2012 Elsevier Ltd.

  18. Undiagnosed Acute Viral Febrile Illnesses, Sierra Leone

    Science.gov (United States)

    2014-07-01

    dengue , West Nile, yellow fever , Rift Valley fever , chikungunya, Ebola, and Marburg viruses but not to Crimean-Congo hemorrhagic ...patients have acute diseases of unknown origin. To investigate what other ar- thropod-borne and hemorrhagic fever viral diseases might cause serious...ELISAs, we evaluated samples for antibodies to arthropod-borne and other hemorrhagic fever viruses. Approximately 25% of LASV-negative

  19. The epidemiology of viral hepatitis in Qatar

    Directory of Open Access Journals (Sweden)

    Bener Abdulbari

    2009-01-01

    Full Text Available Viral hepatitis is a major public health problem in many countries all over the world and especially in Middle East, Asia, East-Europe, and Africa. The aim of our study was to assess the incidence of viral hepatitis A, B and C in Qatar and compare it with other countries. This is a retrospective cohort study, which was conducted at Hamad General Hospital, State of Qatar from 2002-2006. Patients who were screened and diagnosed with viral hepatitis were included in this study. The diagnostic classification of definite viral hepatitis was made in accordance with criteria based on the International Classification of Disease tenth revision (ICD-10. A total of 527 cases of hepatitis C, 396 cases of hepatitis B, 162 cases of hepatitis A and 108 cases of unspecified were reported during the year 2006. Reported incidence rate per 10,000 populations during the year 2006 for hepatitis A was 1.9, hepatitis B 4.7, and Hepatitis C 6.3. The proportion of hepatitis B and C was significantly higher in male population than females across the years (2002-2006. Hepatitis A was more prevalent in children below 15 years (72.3%, hepatitis B in adults aged above 15 years, and hepatitis C in the population above 35 years of age. The incidence of hepatitis A has been declining in Qataris and increasing in expatriates. There was a significant relationship in gender and age group of the patients with hepatitis A, B and C. We conclude that hepatitis has become a national health issue in Qatar. The incidence rate of hepatitis in Qatar is comparable to its neighboring countries, United Arab Emirates and Saudi Arabia. There is a need for further research on hepatitis and the associated risk factors.

  20. Effects of Infrastructure on Ebola Viral Disease

    Science.gov (United States)

    2016-06-10

    to effectively building additional healthcare infrastructure, such as clinics and hospitals , to meet the long term needs of Liberia and Sierra...and Schubert 2014, 2). USAID conducted a cost-benefit analysis of which improvements would have the most long term benefit for Liberia, and... EFFECTS OF INFRASTRUCTURE ON EBOLA VIRAL DISEASE A thesis presented to the Faculty of the U.S. Army Command and General Staff College