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Sample records for hsv-2 genome inherent

  1. Identification of restriction endonuclease with potential ability to cleave the HSV-2 genome: Inherent potential for biosynthetic versus live recombinant microbicides

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    Wayengera Misaki

    2008-08-01

    Full Text Available Abstract Background Herpes Simplex virus types 1 and 2 are enveloped viruses with a linear dsDNA genome of ~120–200 kb. Genital infection with HSV-2 has been denoted as a major risk factor for acquisition and transmission of HIV-1. Developing biomedical strategies for HSV-2 prevention is thus a central strategy in reducing global HIV-1 prevalence. This paper details the protocol for the isolation of restriction endunucleases (REases with potent activity against the HSV-2 genome and models two biomedical interventions for preventing HSV-2. Methods and Results Using the whole genome of HSV-2, 289 REases and the bioinformatics software Webcutter2; we searched for potential recognition sites by way of genome wide palindromics. REase application in HSV-2 biomedical therapy was modeled concomitantly. Of the 289 enzymes analyzed; 77(26.6% had potential to cleave the HSV-2 genome in > 100 but 400 but Conclusion Viral genome slicing by way of these bacterially- derived R-M enzymatic peptides may have therapeutic potential in HSV-2 infection; a cofactor for HIV-1 acquisition and transmission.

  2. Characterization of Inherent Particles and Mechanism of Thermal Stress Induced Particle Formation in HSV-2 Viral Vaccine Candidate.

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    Li, Lillian; Kirkitadze, Marina; Bhandal, Kamaljit; Roque, Cristopher; Yang, Eric; Carpick, Bruce; Rahman, Nausheen

    2017-11-10

    Vaccine formulations may contain visible and/or subvisible particles, which can vary in both size and morphology. Extrinsic particles, which are particles not part of the product such as foreign contaminants, are generally considered undesirable and should be eliminated or controlled in injectable products. However, biological products, in particular vaccines, may also contain particles that are inherent to the product. Here we focus on the characterization of visible and subvisible particles in a live, replication-deficient viral vaccine candidate against HSV genital herpes in an early developmental stage. HSV-2 viral vaccine was characterized using a panel of analytical methods, including Fourier transform infrared spectroscopy (FTIR), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, liquid chromatography-mass spectrometry (LC-MS), light microscopy, transmission electron microscopy (TEM), micro-flow imaging (MFI), dynamic light scattering (DLS), right angle light scattering (RALS), and intrinsic fluorescence. Particles in HSV-2 vaccine typically ranged from hundreds of nanometers to hundreds of micrometers in size and were determined to be inherent to the product. The infectious titer did not correlate with any trend in subvisible particle concentration and size distribution as shown by DLS, MFI, and TEM under stressed conditions. This suggested that particle changes in the submicron range were related to HSV-2 virion structure and had direct impact on biological activity. It was also observed that subvisible and visible particles could induce aggregation in the viral product. The temperature induced aggregation was observed by RALS, intrinsic fluorescence, and DLS. The increase of subvisible particle size with temperature could be fitted to a two-step thermokinetic model. Visible and subvisible particles were found to be inherent to the HSV-2 viral vaccine product. The mechanism of protein aggregation was discussed and a two

  3. Identity of zinc finger nucleases with specificity to herpes simplex virus type II genomic DNA: novel HSV-2 vaccine/therapy precursors

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    Wayengera Misaki

    2011-06-01

    Full Text Available Abstract Background Herpes simplex type II (HSV-2 is a member of the family herpesviridae. Human infection with this double stranded linear DNA virus causes genital ulcerative disease and existing treatment options only serve to resolve the symptomatology (ulcers associated with active HSV-2 infection but do not eliminate latent virus. As a result, infection with HSV-2 follows a life-long relapsing (active versus latent course. On the basis of a primitive bacterium anti-phage DNA defense, the restriction modification (R-M system, we previously identified the Escherichia coli restriction enzyme (REase EcoRII as a novel peptide to excise or irreversibly disrupt latent HSV-2 DNA from infected cells. However, sequences of the site specificity palindrome of EcoRII 5'-CCWGG-3' (W = A or T are equally present within the human genome and are a potential source of host-genome toxicity. This feature has limited previous HSV-2 EcoRII based therapeutic models to microbicides only, and highlights the need to engineer artificial REases (zinc finger nucleases-ZFNs with specificity to HSV-2 genomic-DNA only. Herein, the therapeutic-potential of zinc finger arrays (ZFAs and ZFNs is identified and modeled, with unique specificity to the HSV-2 genome. Methods and results Using the whole genome of HSV-2 strain HG52 (Dolan A et al.,, and with the ZFN-consortium's CoDA-ZiFiT software pre-set at default, more than 28,000 ZFAs with specificity to HSV-2 DNA were identified. Using computational assembly (through in-silico linkage to the Flavobacterium okeanokoites endonuclease Fok I of the type IIS class, 684 ZFNs with specificity to the HSV-2 genome, were constructed. Graphic-analysis of the HSV-2 genome-cleavage pattern using the afore-identified ZFNs revealed that the highest cleavage-incidence occurred within the 30,950 base-pairs (~between the genomic context coordinates 0.80 and 1.00 at the 3' end of the HSV-2 genome. At approximately 3,095 bp before and after the

  4. Highly conserved intragenic HSV-2 sequences: Results from next-generation sequencing of HSV-2 UL and US regions from genital swabs collected from 3 continents.

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    Johnston, Christine; Magaret, Amalia; Roychoudhury, Pavitra; Greninger, Alexander L; Cheng, Anqi; Diem, Kurt; Fitzgibbon, Matthew P; Huang, Meei-Li; Selke, Stacy; Lingappa, Jairam R; Celum, Connie; Jerome, Keith R; Wald, Anna; Koelle, David M

    2017-10-01

    Understanding the variability in circulating herpes simplex virus type 2 (HSV-2) genomic sequences is critical to the development of HSV-2 vaccines. Genital lesion swabs containing ≥ 10 7 log 10 copies HSV DNA collected from Africa, the USA, and South America underwent next-generation sequencing, followed by K-mer based filtering and de novo genomic assembly. Sites of heterogeneity within coding regions in unique long and unique short (U L _U S ) regions were identified. Phylogenetic trees were created using maximum likelihood reconstruction. Among 46 samples from 38 persons, 1468 intragenic base-pair substitutions were identified. The maximum nucleotide distance between strains for concatenated U L_ U S segments was 0.4%. Phylogeny did not reveal geographic clustering. The most variable proteins had non-synonymous mutations in < 3% of amino acids. Unenriched HSV-2 DNA can undergo next-generation sequencing to identify intragenic variability. The use of clinical swabs for sequencing expands the information that can be gathered directly from these specimens. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Strong Country Level Correlation between Syphilis and HSV-2 Prevalence

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    Kenyon, Chris Richard; Tsoumanis, Achilleas

    2016-01-01

    Background. Syphilis is curable but Herpes Simplex Virus-2 (HSV-2) is not. As a result, the prevalence of syphilis but not HSV-2 may be influenced by the efficacy of national STI screening and treatment capacity. If the prevalence of syphilis and HSV-2 is found to be correlated, then this makes it more likely that something other than differential STI treatment is responsible for variations in the prevalence of both HSV-2 and syphilis. Methods. Simple linear regression was used to evaluate the relationship between national antenatal syphilis prevalence and HSV-2 prevalence in women in two time periods: 1990–1999 and 2008. Adjustments were performed for the laboratory syphilis testing algorithm used and the prevalence of circumcision. Results. The prevalence of syphilis was positively correlated with that of HSV-2 for both time periods (adjusted correlations, 20–24-year-olds: 1990–99: R 2 = 0.54, P < 0.001; 2008: R 2 = 0.41, P < 0.001 and 40–44-year-olds: 1990–99: R 2 = 0.42, P < 0.001; 2008: R 2 = 0.49, P < 0.001). Conclusion. The prevalence of syphilis and HSV-2 is positively correlated. This could be due to a common set of risk factors underpinning both STIs. PMID:27069710

  6. Incident HSV-2 Infections Are Common Among HIV-1-discordant Couples

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    Muiru, Anthony N.; Guthrie, Brandon L.; Bosire, Rose; Merkel, Michele; Liu, Amy Y.; Choi, Robert Y.; Lohman-Payne, Barbara; Gatuguta, Ann; Mackelprang, Romel D.; Kiarie, James N.; Farquhar, Carey

    2013-01-01

    Background. The synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) is well known, but lack of knowledge about the epidemiology of HSV-2 acquisition in HIV-1-discordant couples hampers development of HSV-2 prevention interventions that could reduce HIV-1 transmission. Methods. HIV-1-discordant couples were enrolled in Nairobi, Kenya, and followed for up to 2 years. HSV-2 status was determined using HerpeSelect HSV-2 ELISA. Correlates of prevalence and incidence were assessed. Results. Of 469 HIV-1-discordant couples, at baseline, 353 (75.3%) were affected by HSV-2, of which 189 (53.5%) were concordantly HSV-2 seropositive and 164 (46.5%) were HSV-2-discordant. Prevalence was lowest among HIV-1-uninfected men (39.9%) compared to HIV-1-infected women (64.8%), HIV-1-infected men (66.7%), and HIV-1-uninfected women (68.5%). During follow-up, HSV-2 seroincidence was 14.9 per 100 person-years. Incidence was 1.6-fold higher among females compared to males (95% confidence interval [CI], 1.00–2.48) and 2.5-fold higher in HIV-1-infected compared to uninfected women (95% CI, 1.12–5.74). At least 30% of incident HSV-2 infections originated from an outside partner. Conclusions. The high HSV-2 prevalence and incidence in HIV-1-discordant couples in sub-Saharan Africa suggest HSV-2 treatment and prevention could be an effective targeted strategy to reduce HSV-2 and HIV-1 transmission in this high-risk population. PMID:23840044

  7. Herpes simplex virus type 2 (HSV-2) genital shedding in HSV-2-/HIV-1-co-infected women receiving effective combination antiretroviral therapy.

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    Péré, Héléne; Rascanu, Aida; LeGoff, Jérome; Matta, Mathieu; Bois, Frédéric; Lortholary, Olivier; Leroy, Valériane; Launay, Odile; Bélec, Laurent

    2016-03-01

    The dynamics of genital shedding of HSV-2 DNA was assessed in HIV-1-infected women taking combination antiretroviral therapy (cART). HIV-1 RNA, HIV-1 DNA and HSV DNA loads were measured during 12-18 months using frozen plasma, PBMC and cervicovaginal lavage samples from 22 HIV-1-infected women, including 17 women naive for antiretroviral therapy initiating cART and 5 women with virological failure switching to a new regimen. Nineteen (86%) women were HSV-2-seropositive. Among HSV-2-/HIV-1-co-infected women, HIV-1 RNA loads showed a rapid fall from baseline after one month of cART, in parallel in paired plasma and cervicovaginal secretions. In contrast, HIV-1 DNA loads did not show significant variations from baseline up to 18 months of treatment in both systemic and genital compartments. HSV DNA was detected at least once in 12 (63%) of 19 women during follow up: HSV-2 shedding in the genital compartment was observed in 11% of cervicovaginal samples at baseline and in 16% after initiating or switching cART. Cervicovaginal HIV-1 RNA loads were strongly associated with plasma HIV-1 RNA loads over time, but not with cervicovaginal HSV DNA loads. Reactivation of genital HSV-2 replication frequently occurred despite effective cART in HSV-2-/HIV-1-co-infected women. Genital HSV-2 replication under cART does not influence cervicovaginal HIV-1 RNA or DNA shedding. © The Author(s) 2015.

  8. Gene network inherent in genomic big data improves the accuracy of prognostic prediction for cancer patients.

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    Kim, Yun Hak; Jeong, Dae Cheon; Pak, Kyoungjune; Goh, Tae Sik; Lee, Chi-Seung; Han, Myoung-Eun; Kim, Ji-Young; Liangwen, Liu; Kim, Chi Dae; Jang, Jeon Yeob; Cha, Wonjae; Oh, Sae-Ock

    2017-09-29

    Accurate prediction of prognosis is critical for therapeutic decisions regarding cancer patients. Many previously developed prognostic scoring systems have limitations in reflecting recent progress in the field of cancer biology such as microarray, next-generation sequencing, and signaling pathways. To develop a new prognostic scoring system for cancer patients, we used mRNA expression and clinical data in various independent breast cancer cohorts (n=1214) from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO). A new prognostic score that reflects gene network inherent in genomic big data was calculated using Network-Regularized high-dimensional Cox-regression (Net-score). We compared its discriminatory power with those of two previously used statistical methods: stepwise variable selection via univariate Cox regression (Uni-score) and Cox regression via Elastic net (Enet-score). The Net scoring system showed better discriminatory power in prediction of disease-specific survival (DSS) than other statistical methods (p=0 in METABRIC training cohort, p=0.000331, 4.58e-06 in two METABRIC validation cohorts) when accuracy was examined by log-rank test. Notably, comparison of C-index and AUC values in receiver operating characteristic analysis at 5 years showed fewer differences between training and validation cohorts with the Net scoring system than other statistical methods, suggesting minimal overfitting. The Net-based scoring system also successfully predicted prognosis in various independent GEO cohorts with high discriminatory power. In conclusion, the Net-based scoring system showed better discriminative power than previous statistical methods in prognostic prediction for breast cancer patients. This new system will mark a new era in prognosis prediction for cancer patients.

  9. Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development.

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    Schiffer, Joshua T; Gottlieb, Sami L

    2017-09-25

    Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa. These cells are targets for HIV entry and replication. Prophylactic HSV-2 vaccines (to prevent infection) and therapeutic vaccines (to modify or treat existing infections) are currently under development. By preventing or modifying infection, an effective HSV-2 vaccine could limit HSV-associated genital mucosal inflammation and thus HIV risk. However, a vaccine might have competing effects on HIV risk depending on its mechanism of action and cell populations generated in the genital mucosa. In this article, we review biologic interactions between HSV-2 and HIV-1, consider HSV-2 vaccine development in the context of HIV risk, and discuss implications and research needs for future HSV vaccine development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Detection of herpes simplex virus type 2 (HSV-2) -specific cell-mediated immune responses in guinea pigs during latent HSV-2 genital infection.

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    Perry, Clarice L; Banasik, Brianne N; Gorder, Summer R; Xia, Jingya; Auclair, Sarah; Bourne, Nigel; Milligan, Gregg N

    2016-12-01

    Genital infections with herpes simplex virus type 2 (HSV-2) are a source of considerable morbidity and are a health concern for newborns exposed to virus during vaginal delivery. Additionally, HSV-2 infection diminishes the integrity of the vaginal epithelium resulting in increased susceptibility of individuals to infection with other sexually transmitted pathogens. Understanding immune protection against HSV-2 primary infection and immune modulation of virus shedding events following reactivation of the virus from latency is important for the development of effective prophylactic and therapeutic vaccines. Although the murine model of HSV-2 infection is useful for understanding immunity following immunization, it is limited by the lack of spontaneous reactivation of HSV-2 from latency. Genital infection of guinea pigs with HSV-2 accurately models the disease of humans including the spontaneous reactivation of HSV-2 from latency and provides a unique opportunity to examine virus-host interactions during latency. Although the guinea pig represents an accurate model of many human infections, relatively few reagents are available to study the immunological response to infection. To analyze the cell-mediated immune response of guinea pigs at extended periods of time after establishment of HSV-2 latency, we have modified flow-cytometry based proliferation assays and IFN-γ ELISPOT assays to detect and quantify HSV-specific cell-mediated responses during latent infection of guinea pigs. Here we demonstrate that a combination of proliferation and ELISPOT assays can be used to quantify and characterize effecter function of virus-specific immune memory responses during HSV-latency. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Serological profile of HSV-2 in patients attending STI clinic: Evaluation of diagnostic utility of HSV-2 IgM detection

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    Choudhry Shilpee

    2009-07-01

    Full Text Available Objective: The present study was done to evaluate the serological profile of herpes simplex virus-2 (HSV-2 among patients attending sexually transmitted infections (STI clinic and to determine the utility of detecting HSV-2 IgM antibodies in such patients. A correlation of HSV-2 infection with other STI including HIV has also been attempted. Materials and Methods: Hundred consecutive patients who attended STI clinic, with one or more of the complaints as enunciated by WHO in syndromic approach for the diagnosis of STI, were included as subjects. All subjects were screened for common STI by standard laboratory procedures/ commercially available kits. HSV-1 and HSV-2 IgM antibody was detected by commercially available enzyme immuno assay kit in all patient′s sera. Sera were also tested for other STI, namely HIV, Hepatitis B virus, Hepatitis C virus and Treponema pallidum. Antigen detection for Chlamydia trachomatis was done in genital swabs of all patients by Bio-Rad Chlamydia Microplate EIA 31189 (United States kit. Results: Thirty patients were found to have genital herpes. In 17/30 (56.6% patients, HSV-2 serology was found to correlate with the clinical diagnosis. The coexistence of other infection in HSV-2 seropositive patients was detected in 8/30 patients. None of the patients having concomitant infections were clinically diagnosed accurately. Sensitivity, specificity, positive predictive value and negative predictive value of IgM antibodies for the diagnosis of genital herpes was 73.91%, 90.91%, 70.83% and 92.91% respectively. Conclusion: HSV-2 IgM detection could only be used as a supportive test for the diagnosis of genital herpes . It needs to be emphasized that the sensitivity and positive predictive value scores are pointers for further improvement in the commercial assay systems and a large sample size may determine the broader utility of such systems.

  12. In Situ Detection of Regulatory T Cells in Human Genital Herpes Simplex Virus Type 2 (HSV-2) Reactivation and Their Influence on Spontaneous HSV-2 Reactivation.

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    Milman, Neta; Zhu, Jia; Johnston, Christine; Cheng, Anqi; Magaret, Amalia; Koelle, David M; Huang, Meei-Li; Jin, Lei; Klock, Alexis; Layton, Erik D; Corey, Lawrence

    2016-07-01

    Herpes simplex virus type 2 (HSV-2) reactivation is accompanied by a sustained influx of CD4(+) and CD8(+) T cells that persist in genital tissue for extended periods. While CD4(+) T cells have long been recognized as being present in herpetic ulcerations, their role in subclinical reactivation and persistence is less well known, especially the role of CD4(+) regulatory T cells (Tregs). We characterized the Treg (CD4(+)Foxp3(+)) population during human HSV-2 reactivation in situ in sequential genital skin biopsy specimens obtained from HSV-2-seropositive subjects at the time of lesion onset up to 8 weeks after healing. High numbers of Tregs infiltrated to the site of viral reactivation and persisted in proximity to conventional CD4(+) T cells (Tconvs) and CD8(+) T cells. Treg density peaked during the lesion stage of the reactivation. The number of Tregs from all time points (lesion, healed, 2 weeks after healing, 4 weeks after healing, and 8 weeks after healing) was significantly higher than in control biopsy specimens from unaffected skin. There was a direct correlation between HSV-2 titer and Treg density. The association of a high Treg to Tconv ratio with high viral shedding suggests that the balance between regulatory and effector T cells influences human HSV-2 disease. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  13. Low acceptance of HSV-2 testing among high-risk women.

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    Roth, A M; Dodge, B M; Van Der Pol, B; Reece, M; Zimet, G D

    2011-06-01

    We evaluated the acceptability of a community-based herpes simplex virus type 2 (HSV-2) screening programme for at-risk women and assessed factors related to uptake of point of care HSV-2 testing. One hundred recently arrested women (median age 34 years) were recruited from a community court handling lower-level misdemeanour cases in Indianapolis, Indiana. Individuals completed a survey assessing factors related to HSV-2 screening intentions and were offered point of care HSV-2 testing. Rates of HSV-2 infection in this population are high; 61.1% of women tested were positive. The majority (81%) accepted a prescription for suppressive therapy. Women in this sample indicated that HSV-2 screening is an important component of health care but were unwilling to pay the US$10 it cost to be tested. To encourage this and other high-risk populations to be screened for HSV-2, public health resources will be needed to help individuals overcome cost-related barriers to care.

  14. Avidity of Antibodies against HSV-2 and Risk to Neonatal Transmission among Mexican Pregnant Women

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    Antonia Herrera-Ortiz

    2013-01-01

    Full Text Available Objective. To determine HSV-2 seroprevalence, risk factors, and antibody avidity among a sample of Mexican pregnant women. Material and Methods. The avidity test was standardized with different urea concentrations and incubation times; the cut-off point was calculated to determine the low avidity (early infection. IgG antibodies against HSV-2 were detected from pregnant and postpartum women from Morelos, Mexico, and the avidity test was performed to positive samples. Multivariate regression logistic analysis was employed to evaluate demographic and sexual behavior characteristics associated with HSV-2 infection. Results. HSV-2 seroprevalence among Mexican women analyzed was 14.5% (333/2300, demographic factors (location of General Hospital, age, education level, and civil status, and risky sexual behaviors (STI self-report and number of sexual partners during last year were associated with HSV-2 infection. Seventeen women were detected with low avidity antibodies (early infection with a cut-off point of 66.1%. Conclusions. HSV-2 infection was common among this group of women from Mexico; the avidity test detected women with recent infections, and these women were more likely to transmit HSV-2 to their neonates. Neonatal herpes has no epidemiological surveillance, the disease could be overlooked, and so more studies are needed to estimate the magnitude of neonatal infection.

  15. Nucleocytoplasmic shuttling of the HSV-2 serine/threonine kinase Us3

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    Finnen, Renee L.; Johnston, Susan M.; Neron, Casey E.; Banfield, Bruce W.

    2011-01-01

    The alphaherpesvirus serine/threonine kinase Us3 plays diverse roles in virus multiplication and modifies both nuclear and cytoplasmic substrates. We recently reported that treatment of HSV-2 Us3-transfected and HSV-2-infected cells with leptomycin B, an inhibitor of nuclear export mediated by interaction of chromosomal regional maintenance protein (CRM1) with leucine rich nuclear export signals (NESs), resulted in nuclear trapping of Us3. Here, we utilized fluorescence loss in photobleaching to monitor nuclear export of HSV-2 Us3 and confirm that this process proceeds solely via a CRM1-mediated mechanism. Analysis of deletion derivatives of HSV-2 Us3 fused to a nuclear export reporter protein implicated the involvement of NES-like sequences in nuclear export. However, nuclear trapping of HSV-2 Us3 proteins carrying mutations in these potential NESs was not observed, indicating that these sequences are not functional in the context of full-length protein. Our analyses also revealed previously unidentified regions of HSV-2 Us3 that contribute to its kinase activity.

  16. Population-level effect of potential HSV2 prophylactic vaccines on HIV incidence in sub-Saharan Africa

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    Freeman, Esther E.; White, Richard G.; Bakker, Roel; Orroth, Kate K.; Weiss, Helen A.; Buvé, Anne; Hayes, Richard J.; Glynn, Judith R.

    2009-01-01

    Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30–40% after 20 years (range 4–66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine. PMID:19071187

  17. Genital Shedding of Herpes Simplex Virus Among Symptomatic and Asymptomatic Persons with HSV-2 Infection

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    Tronstein, Elizabeth; Johnston, Christine; Huang, Meei-Li; Selke, Stacy; Magaret, Amalia; Warren, Terri; Corey, Lawrence; Wald, Anna

    2011-01-01

    Context Since HSV-2 antibody tests have become commercially available, an increasing number of persons learn that they have genital herpes through serologic testing. The course of natural history of HSV-2 in asymptomatic, seropositive persons is uncertain. Objective To evaluate the virologic and clinical course of HSV genital shedding among participants with symptomatic and asymptomatic HSV-2 infection. Design, Setting and Participants Cohort of 498 immunocompetent HSV-2 seropositive persons enrolled in prospective studies of genital HSV shedding at the University of Washington Virology Research Clinic, Seattle, Washington, and Westover Heights Clinic in Portland, Oregon, between 1992 and 2008. Each participant obtained daily self-collected swabs of genital secretions for ≥ 30 days. Main Outcome Measurement The rate of viral shedding measured by quantitative real-time fluorescence polymerase chain reaction (PCR) for HSV DNA from genital swabs. Results HSV was detected on 4,753 of 23,683 days (20.1%; 95% CI, 18.3 to 22.0) in persons with symptomatic genital HSV-2 infection compared with 519 of 5,070 days (10.2%; 95% CI, 7.7 to 13.6) in persons with asymptomatic infection, pgenital viral shedding among persons with symptomatic genital HSV-2 infection compared with 85 of 519 days (16.4%; 95% CI, 11.2 to 23.9) among persons with asymptomatic infection, pgenital tract less frequently than persons with symptomatic infection, but much of the difference is attributable to less frequent genital lesions, as lesions are accompanied by frequent viral shedding. PMID:21486977

  18. Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2

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    Celum, Connie; Wald, Anna; Lingappa, Jairam R.; Magaret, Amalia S.; Wang, Richard S.; Mugo, Nelly; Mujugira, Andrew; Baeten, Jared M.; Mullins, James I.; Hughes, James P.; Bukusi, Elizabeth A.; Cohen, Craig R.; Katabira, Elly; Ronald, Allan; Kiarie, James; Farquhar, Carey; Stewart, Grace John; Makhema, Joseph; Essex, Myron; Were, Edwin; Fife, Kenneth H.; de Bruyn, Guy; Gray, Glenda E.; McIntyre, James A.; Manongi, Rachel; Kapiga, Saidi; Coetzee, David; Allen, Susan; Inambao, Mubiana; Kayitenkore, Kayitesi; Karita, Etienne; Kanweka, William; Delany, Sinead; Rees, Helen; Vwalika, Bellington; Stevens, Wendy; Campbell, Mary S.; Thomas, Katherine K.; Coombs, Robert W.; Morrow, Rhoda; Whittington, William L.H.; McElrath, M. Juliana; Barnes, Linda; Ridzon, Renee; Corey, Lawrence

    2010-01-01

    BACKGROUND Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, ≥250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P = 0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log10 copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2–positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir

  19. Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract.

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    Posavad, C M; Zhao, L; Dong, L; Jin, L; Stevens, C E; Magaret, A S; Johnston, C; Wald, A; Zhu, J; Corey, L; Koelle, D M

    2017-09-01

    Local mucosal cellular immunity is critical in providing protection from HSV-2. To characterize and quantify HSV-2-reactive mucosal T cells, lymphocytes were isolated from endocervical cytobrush and biopsy specimens from 17 HSV-2-infected women and examined ex vivo for the expression of markers associated with maturation and tissue residency and for functional T-cell responses to HSV-2. Compared with their circulating counterparts, cervix-derived CD4+ and CD8+ T cells were predominantly effector memory T cells (CCR7-/CD45RA-) and the majority expressed CD69, a marker of tissue residency. Co-expression of CD103, another marker of tissue residency, was highest on cervix-derived CD8+ T cells. Functional HSV-2 reactive CD4+ and CD8+ T-cell responses were detected in cervical samples and a median of 17% co-expressed CD103. HSV-2-reactive CD4+ T cells co-expressed IL-2 and were significantly enriched in the cervix compared with blood. This first direct ex vivo documentation of local enrichment of HSV-2-reactive T cells in the human female genital mucosa is consistent with the presence of antigen-specific tissue-resident memory T cells. Ex vivo analysis of these T cells may uncover tissue-specific mechanisms of local control of HSV-2 to assist the development of vaccine strategies that target protective T cells to sites of HSV-2 infection.

  20. Hexagonal-shaped chondroitin sulfate self-assemblies have exalted anti-HSV-2 activity.

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    Galus, Aurélia; Mallet, Jean-Maurice; Lembo, David; Cagno, Valeria; Djabourov, Madeleine; Lortat-Jacob, Hugues; Bouchemal, Kawthar

    2016-01-20

    The initial step in mucosal infection by the herpes simplex virus type 2 (HSV-2) requires its binding to certain glycosaminoglycans naturally present on host cell membranes. We took advantage of this interaction to design biomimetic supramolecular hexagonal-shaped nanoassemblies composed of chondroitin sulfate having exalted anti-HSV-2 activity in comparison with native chondroitin sulfate. Nanoassemblies were formed by mixing hydrophobically-modified chondroitin sulfate with α-cyclodextrin in water. Optimization of alkyl chain length grafted on chondroitin sulfate and the ratio between hydrophobically-modified chondroitin sulfate and α-cyclodextrin showed that more cohesive and well-structured nanoassemblies were obtained using higher α-cyclodextrin concentration and longer alkyl chain lengths. A structure-activity relationship was found between anti-HSV-2 activity and the amphiphilic nature of hydrophobically-modified chondroitin sulfate. Also, antiviral activity of hexagonal nanoassemblies against HSV-2 was further improved in comparison with hydrophobically-modified chondroitin sulfate. This work suggests a new biomimetic formulation approach that can be extended to other heparan-sulfate-dependent viruses. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Spatial modeling of HIV and HSV-2 among women in Kenya with spatially varying coefficients

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    Elphas Okango

    2016-04-01

    Full Text Available Abstract Background Disease mapping has become popular in the field of statistics as a method to explain the spatial distribution of disease outcomes and as a tool to help design targeted intervention strategies. Most of these models however have been implemented with assumptions that may be limiting or altogether lead to less meaningful results and hence interpretations. Some of these assumptions include the linearity, stationarity and normality assumptions. Studies have shown that the linearity assumption is not necessarily true for all covariates. Age for example has been found to have a non-linear relationship with HIV and HSV-2 prevalence. Other studies have made stationarity assumption in that one stimulus e.g. education, provokes the same response in all the regions under study and this is also quite restrictive. Responses to stimuli may vary from region to region due to aspects like culture, preferences and attitudes. Methods We perform a spatial modeling of HIV and HSV-2 among women in Kenya, while relaxing these assumptions i.e. the linearity assumption by allowing the covariate age to have a non-linear effect on HIV and HSV-2 prevalence using the random walk model of order 2 and the stationarity assumption by allowing the rest of the covariates to vary spatially using the conditional autoregressive model. The women data used in this study were derived from the 2007 Kenya AIDS indicator survey where women aged 15–49 years were surveyed. A full Bayesian approach was used and the models were implemented in R-INLA software. Results Age was found to have a non-linear relationship with both HIV and HSV-2 prevalence, and the spatially varying coefficient model provided a significantly better fit for HSV-2. Age-at first sex also had a greater effect on HSV-2 prevalence in the Coastal and some parts of North Eastern regions suggesting either early marriages or child prostitution. The effect of education on HIV prevalence among women was more

  2. Efficacy of the Herpes Simplex Virus 2 (HSV-2) Glycoprotein D/AS04 Vaccine against Genital HSV-2 and HSV-1 Infection and Disease in the Cotton Rat Sigmodon hispidus Model.

    Science.gov (United States)

    Boukhvalova, Marina; McKay, Jamall; Mbaye, Aissatou; Sanford-Crane, Hannah; Blanco, Jorge C G; Huber, Ashley; Herold, Betsy C

    2015-10-01

    Subunit vaccines based on the herpes simplex virus 2 (HSV-2) glycoprotein D (gD-2) have been the major focus of HSV-2 vaccine development for the past 2 decades. Based on the promising data generated in the guinea pig model, a formulation containing truncated gD-2, aluminum salt, and MPL (gD/AS04) advanced to clinical trials. The results of these trials, however, were unexpected, as the vaccine protected against HSV-1 infection but not against HSV-2. To address this discrepancy, we developed a Depot medroxyprogesterone acetate (DMPA)-treated cotton rat Sigmodon hispidus model of HSV-2 and HSV-1 genital infection. The severity of HSV-1 genital herpes was less than that of HSV-2 genital herpes in cotton rats, and yet the model allowed for comparative evaluation of gD/AS04 immunogenicity and efficacy. Cotton rats were intramuscularly vaccinated using a prime boost strategy with gD/AS04 (Simplirix vaccine) or control vaccine formulation (hepatitis B vaccine FENDrix) and subsequently challenged intravaginally with HSV-2 or HSV-1. The gD/AS04 vaccine was immunogenic in cotton rats and induced serum IgG directed against gD-2 and serum HSV-2 neutralizing antibodies but failed to efficiently protect against HSV-2 disease or to decrease the HSV-2 viral load. However, gD/AS04 significantly reduced vaginal titers of HSV-1 and better protected animals against HSV-1 compared to HSV-2 genital disease. The latter finding is generally consistent with the clinical outcome of the Herpevac trial of Simplirix. Passive transfer of serum from gD/AS04-immunized cotton rats conferred stronger protection against HSV-1 genital disease. These findings suggest the need for alternative vaccine strategies and the identification of new correlates of protection. In spite of the high health burden of genital herpes, there is still no effective intervention against the disease. The significant gap in knowledge on genital herpes pathogenesis has been further highlighted by the recent failure of GSK

  3. Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.

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    Sine K Kratholm

    Full Text Available Interleukin (IL -21 is produced by Natural Killer T (NKT cells and CD4(+ T cells and is produced in response to virus infections, where IL-21 has been shown to be essential in adaptive immune responses. Cells from the innate immune system such as Natural Killer (NK cells and macrophages are also important in immune protection against virus. These cells express the IL-21 receptor (IL-21R and respond to IL-21 with increased cytotoxicity and cytokine production. Currently, however it is not known whether IL-21 plays a significant role in innate immune responses to virus infections. The purpose of this study was to investigate the role of IL-21 and IL-21R in the innate immune response to a virus infection. We used C57BL/6 wild type (WT and IL-21R knock out (KO mice in a murine vaginal Herpes Simplex Virus type 2 (HSV-2 infection model to show that IL-21 - IL-21R signalling is indeed important in innate immune responses against HSV-2. We found that the IL-21R was expressed in the vaginal epithelium in uninfected (u.i WT mice, and expression increased early after HSV-2 infection. IL-21R KO mice exhibited increased vaginal viral titers on day 2 and 3 post infection (p.i. and subsequently developed significantly higher disease scores and a lower survival rate compared to WT mice. In addition, WT mice infected with HSV-2 receiving intra-vaginal pre-treatment with murine recombinant IL-21 (mIL-21 had decreased vaginal viral titers on day 2 p.i., significantly lower disease scores, and a higher survival rate compared to infected untreated WT controls. Collectively our data demonstrate the novel finding that the IL-21R plays a critical role in regulating innate immune responses against HSV-2 infection.

  4. A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy.

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    Ugaonkar, Shweta R; Wesenberg, Asa; Wilk, Jolanta; Seidor, Samantha; Mizenina, Olga; Kizima, Larisa; Rodriguez, Aixa; Zhang, Shimin; Levendosky, Keith; Kenney, Jessica; Aravantinou, Meropi; Derby, Nina; Grasperge, Brooke; Gettie, Agegnehu; Blanchard, James; Kumar, Narender; Roberts, Kevin; Robbiani, Melissa; Fernández-Romero, José A; Zydowsky, Thomas M

    2015-09-10

    Women urgently need a self-initiated, multipurpose prevention technology (MPT) that simultaneously reduces their risk of acquiring HIV-1, HSV-2, and HPV (latter two associated with increased risk of HIV-1 acquisition) and prevents unintended pregnancy. Here, we describe a novel core-matrix intravaginal ring (IVR), the MZCL IVR, which effectively delivered the MZC combination microbicide and a contraceptive. The MZCL IVR contains four active pharmaceutical ingredients (APIs): MIV-150 (targets HIV-1), zinc acetate (ZA; targets HIV-1 and HSV-2), carrageenan (CG; targets HPV and HSV-2), and levonorgestrel (LNG; targets unintended pregnancy). The elastomeric IVR body (matrix) was produced by hot melt extrusion of the non-water swellable elastomer, ethylene vinyl acetate (EVA-28), containing the hydrophobic small molecules, MIV-150 and LNG. The solid hydrophilic core, embedded within the IVR by compression, contained the small molecule ZA and the macromolecule CG. Hydrated ZA/CG from the core was released by diffusion via a pore on the IVR while the MIV-150/LNG diffused from the matrix continuously for 94 days (d) in vitro and up to 28 d (study period) in macaques. The APIs released in vitro and in vivo were active against HIV-1ADA-M, HSV-2, and HPV16 PsV in cell-based assays. Serum LNG was at levels associated with local contraceptive effects. The results demonstrate proof-of-concept of a novel core-matrix IVR for sustained and simultaneous delivery of diverse molecules for the prevention of HIV, HSV-2 and HPV acquisition, as well as unintended pregnancy. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Prevalence and Determinants of Herpes Simplex Virus Type 2 (HSV-2)/Syphilis Co-Infection and HSV-2 Mono-Infection among Human Immunodeficiency Virus Positive Men Who Have Sex with Men: a Cross-Sectional Study in Northeast China.

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    Hu, Qing-Hai; Xu, Jun-Jie; Chu, Zhen-Xing; Zhang, Jing; Yu, Yan-Qiu; Yu, Huan; Ding, Hai-Bo; Jiang, Yong-Jun; Geng, Wen-Qing; Wang, Ning; Shang, Hong

    2017-05-24

    This study assessed the prevalence and determinants of herpes simplex virus type 2 (HSV-2)/syphilis co-infection and HSV-2 mono-infection in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) in China. A cross-sectional study was conducted of 545 HIV-positive MSM in Shenyang between February 2009 and October 2014. Participants underwent physical examinations and serological tests for HSV-2 and syphilis. A multinomial logistic regression was used to identify the risk factors associated with HSV-2/syphilis co-infection and HSV-2 mono-infection. The prevalence of HSV-2 mono-infection, syphilis mono-infection, and HSV-2/syphilis co-infection (95% confidence interval) was 48.6% (44.4-52.8%), 34.3% (30.3-38.3%), and 22.9% (19.4-26.5%), respectively. After controlling within HSV-2/syphilis-seropositive cases, regression analysis revealed that the related factors for HSV-2/syphilis co-infection included age (25-50 vs. ≤ 24 years: adjusted odds ratio [aOR], 4.55; > 50 vs. ≤ 24 years: aOR, 43.02), having regular female sexual partner(s) in the past 6 months (aOR, 0.43), and age at first MSM experience (≤ 18 vs. > 18 years: aOR, 2.59) (all P syphilis co-infection in HIV-positive MSM indicates a high secondary HIV transmission risk. A campaign for detection and treatment of HSV-2 and syphilis is urgently required for HIV-positive MSM in China.

  6. HSV-2 Infection as a Cause of Female/Male and Racial/Ethnic Disparities in HIV Infection.

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    Don C Des Jarlais

    Full Text Available To examine the potential contribution of herpes simplex virus 2 (HSV-2 infection to female/male and racial/ethnic disparities in HIV among non-injecting heroin and cocaine drug users. HSV-2 infection increases susceptibility to HIV infection by a factor of two to three.Subjects were recruited from entrants to the Beth Israel drug detoxification program in New York City 2005-11. All subjects reported current use of heroin and/or cocaine and no lifetime injection drug use. A structured questionnaire was administered and serum samples collected for HIV and HSV-2 testing. Population-attributable risk percentages (PAR%s were calculated for associations between HSV-2 infection and increased susceptibility to HIV.1745 subjects were recruited from 2005-11. Overall HIV prevalence was 14%. Females had higher prevalence than males (22% vs. 12% (p<0.001, African-Americans had the highest prevalence (15%, Hispanics an intermediate prevalence (12%, and Whites the lowest prevalence (3% (p<.001. There were parallel variations in HSV-2 prevalence (females 86%, males 51%, African-Americans 66%, Hispanics 47%, Whites 36%, HSV-2 prevalence was strongly associated with HIV prevalence (OR  =  3.12 95% CI 2.24 to 4.32. PAR%s for HSV-2 as a cause of HIV ranged from 21% for Whites to 50% for females. Adjusting for the effect of increased susceptibility to HIV due to HSV-2 infection greatly reduced all disparities (adjusted prevalence  =  males 8%, females 11%; Whites 3%, African-Americans 10%, Hispanics 9%.Female/male and racial/ethnic variations in HSV-2 infection provide a biological mechanism that may generate female/male and racial/ethnic disparities in HIV infection among non-injecting heroin and cocaine users in New York City. HSV-2 infection should be assessed as a potential contributing factor to disparities in sexually transmitted HIV throughout the US.

  7. Virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (HSV-2 infection in guinea pigs.

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    Jingya Xia

    Full Text Available Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4+ and CD8+ resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the

  8. Virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (HSV-2) infection in guinea pigs.

    Science.gov (United States)

    Xia, Jingya; Veselenak, Ronald L; Gorder, Summer R; Bourne, Nigel; Milligan, Gregg N

    2014-01-01

    Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4+ and CD8+ resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency

  9. Modelling the effects of sexting on the transmission dynamics of HSV-2 amongst adolescents

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    A. Mhlanga

    2015-12-01

    Full Text Available Prior studies have indicated that adolescents who are into sexting are likely to engage in risky sexual behaviours. In this paper, a mathematical model to assess the impact of sexting and peer influence on the spread of HSV-2 amongst adolescents is developed. The threshold parameters of the model are determined and stabilities are analysed. The impact of filtering and awareness campaigns is explored. Results from the study suggest that HSV-2 prevalence is high amongst adolescents who are into sexting as compared to those who do not. Further, we applied optimal control theory to the proposed model. The controls represent filtering and awareness campaigns. The objective is based on minimising the susceptible sexting adolescents, infected non-sexting adolescents and the infected sexting adolescents. The optimal control is characterised and numerically solved. Overall, the application of optimal control theory suggests that more effort should be devoted to both controls, filtering and awareness campaigns.

  10. Effect of genital herpes on cervicovaginal HIV shedding in women co-infected with HIV AND HSV-2 in Tanzania.

    Science.gov (United States)

    Todd, Jim; Riedner, Gabriele; Maboko, Leonard; Hoelscher, Michael; Weiss, Helen A; Lyamuya, Eligius; Mabey, David; Rusizoka, Mary; Belec, Laurent; Hayes, Richard

    2013-01-01

    To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV. Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1) 57 women at 70 clinic visits with clinical genital herpes; (2) 39 of the same women at 46 clinic visits when asymptomatic; (3) 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4) 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL), herpetic lesions, HSV shedding and other factors were examined. Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03). In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL) was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41-0.60, pgenital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.

  11. Cervical HSV-2 infection causes cervical remodeling and increases risk for ascending infection and preterm birth

    Science.gov (United States)

    McGee, Devin; Poncil, Sharra; Patterson, Amanda

    2017-01-01

    Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of neonatal mortality worldwide. Cervical viral infections have been established as risk factors for PTB in women, although the mechanism leading to increased risk is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal HSV2 infection caused increased rates of preterm birth following an intra-vaginal bacterial infection. HSV2 infection resulted in histological changes in the cervix mimicking cervical ripening, including significant collagen remodeling and increased hyaluronic acid synthesis. Viral infection also caused aberrant expression of estrogen and progesterone receptor in the cervical epithelium. Further analysis using human ectocervical cells demonstrated a role for Src kinase in virus-mediated changes in estrogen receptor and hyaluronic acid expression. In conclusion, HSV2 affects proteins involved in tissue hormone responsiveness, causes significant changes reminiscent of premature cervical ripening, and increases risk of preterm birth. Studies such as this improve our chances of identifying clinical interventions in the future. PMID:29190738

  12. An age-structured model for the coupled dynamics of HIV and HSV-2.

    Science.gov (United States)

    Kapitanov, Georgi; Alvey, Christina; Vogt-Geisse, Katia; Feng, Zhilan

    2015-08-01

    Evidence suggests a strong correlation between the prevalence of HSV-2 (genital herpes) and the perseverance of the HIV epidemic. HSV-2 is an incurable viral infection, characterized by periodic reactivation. We construct a model of the co-infection dynamics between the two diseases by incorporating a time-since-infection variable to track the alternating periods of infectiousness of HSV-2. The model considers only heterosexual relationships and distinguishes three population groups: males, general population females, and female sex workers. We calculate the basic reproduction numbers for each disease that provide threshold conditions, which determine whether a disease dies out or becomes endemic in the absence of the other disease. We also derive the invasion reproduction numbers that determine whether or not a disease can invade into a population in which the other disease is endemic. The calculations of the invasion reproduction numbers suggest a new aspect in their interpretation - the class from which the initial disease carrier arises is important for understanding the invasion dynamics and biological interpretation of the expressions of the reproduction numbers. Sensitivity analysis is conducted to examine the role of model parameters in influencing the model outcomes. The results are discussed in the last section.

  13. Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVΔnef Vaccination.

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    Natalia Guerra-Pérez

    Full Text Available Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Δnef (SIVΔnef vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt infection even in SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques, while 1 out of 3 animals co-infected with SIVΔnef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings.

  14. Effect of HSV-2 infection on subsequent HIV acquisition: an updated systematic review and meta-analysis.

    Science.gov (United States)

    Looker, Katharine J; Elmes, Jocelyn A R; Gottlieb, Sami L; Schiffer, Joshua T; Vickerman, Peter; Turner, Katherine M E; Boily, Marie-Claude

    2017-12-01

    HIV and herpes simplex virus type 2 (HSV-2) infections cause a substantial global disease burden and are epidemiologically correlated. Two previous systematic reviews of the association between HSV-2 and HIV found evidence that HSV-2 infection increases the risk of HIV acquisition, but these reviews are now more than a decade old. For this systematic review and meta-analysis, we searched PubMed, MEDLINE, and Embase (from Jan 1, 2003, to May 25, 2017) to identify studies investigating the risk of HIV acquisition after exposure to HSV-2 infection, either at baseline (prevalent HSV-2 infection) or during follow-up (incident HSV-2 infection). Studies were included if they were a cohort study, controlled trial, or case-control study (including case-control studies nested within a cohort study or clinical trial); if they assessed the effect of pre-existing HSV-2 infection on HIV acquisition; and if they determined the HSV-2 infection status of study participants with a type-specific assay. We calculated pooled random-effect estimates of the association between prevalent or incident HSV-2 infection and HIV seroconversion. We also extended previous investigations through detailed meta-regression and subgroup analyses. In particular, we investigated the effect of sex and risk group (general population vs higher-risk populations) on the relative risk (RR) of HIV acquisition after prevalent or incident HSV-2 infection. Higher-risk populations included female sex workers and their clients, men who have sex with men, serodiscordant couples, and attendees of sexually transmitted infection clinics. We identified 57 longitudinal studies exploring the association between HSV-2 and HIV. HIV acquisition was almost tripled in the presence of prevalent HSV-2 infection among general populations (adjusted RR 2·7, 95% CI 2·2-3·4; number of estimates [N e ]=22) and was roughly doubled among higher-risk populations (1·7, 1·4-2·1; N e =25). Incident HSV-2 infection in general

  15. 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

  16. Correlates of Bacterial Ulcers and Acute HSV-2 Infection among Men with Genital Ulcer Disease in South Africa: Age, Recent Sexual Behaviors, and HIV

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    Leichliter, Jami S.; Lewis, David A.; Paz-Bailey, Gabriela

    2016-01-01

    Data from baseline surveys and STI/HIV laboratory tests (n=615 men) were used to examine correlates of bacterial ulcers (Treponema pallidum, Haemophilus ducreyi, or Chlamydia trachomatis L1–L3 detected in ulcer) and acute HSV-2 ulcers (HSV-2 positive ulcer specimen, HSV-2 sero-negative, and negative for bacterial pathogens) vs. recurrent HSV-2 ulcers (sero-positive), separately. Compared to men with recurrent HSV-2 ulcers, men with bacterial ulcers had larger ulcers but were less likely to be...

  17. Validity of genito-urinary discharges, genital ulcers and genital rashes as indicators of seroincident HSV-2 infection

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    Eziyi Iche Kalu

    2015-06-01

    Full Text Available Objective: To evaluate the validity of vaginal discharges, urethral discharges, genital rashes, and painful genital ulcers as indicators of early detection of incident herpes simplex virus type 2 (HSV-2 infection among pregnant women in Benin metropolis. Methods: Participants were antenatal clinic attendees of University of Benin Teaching Hospital and Central Hospital, Benin. Baseline sociodemographic, obstetric and HSV-2 serological data were collected. The HSV-2-seronegative returned for a repeat HSV-2 antibody assay before delivery date. Data on incidence of genital rashes, abnormal vaginal discharges, painful genital ulcers and urethral discharges were collected. Results: The sensitivities of abnormal vaginal discharges, genital rashes, urethral discharges and painful genital ulcers were 82.3%, 70.6%, 41.2% and 28.6% respectively; while their positive-predictive values were 53.8%, 60.0%, 58.3% and 66.7% respective. All the symptoms had >95% specificities and 95% negative-predictive values for seroincident HSV-2 infection. Conclusions: Abnormal vaginal discharge, genital rashes, urethral discharges and genital ulcers are valid indicators of seroincident HSV-2 infection and could be useful in formulation of screening tools in resource-limited settings.

  18. Correlates of Bacterial Ulcers and Acute HSV-2 Infection among Men with Genital Ulcer Disease in South Africa: Age, Recent Sexual Behaviors, and HIV.

    Science.gov (United States)

    Leichliter, Jami S; Lewis, David A; Paz-Bailey, Gabriela

    2016-01-01

    Data from baseline surveys and STI/HIV laboratory tests (n=615 men) were used to examine correlates of bacterial ulcers ( Treponema pallidum , Haemophilus ducreyi , or Chlamydia trachomatis L1-L3 detected in ulcer) and acute HSV-2 ulcers (HSV-2 positive ulcer specimen, HSV-2 sero-negative, and negative for bacterial pathogens) vs. recurrent HSV-2 ulcers (sero-positive), separately. Compared to men with recurrent HSV-2 ulcers, men with bacterial ulcers had larger ulcers but were less likely to be HIV-positive whereas men with acute HSV-2 ulcers were younger with fewer partners. Acute HIV was higher among men with bacterial and acute HSV-2 ulcers; the difference was not statistically significant.

  19. Effect of genital herpes on cervicovaginal HIV shedding in women co-infected with HIV AND HSV-2 in Tanzania.

    Directory of Open Access Journals (Sweden)

    Jim Todd

    Full Text Available To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV.Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1 57 women at 70 clinic visits with clinical genital herpes; (2 39 of the same women at 46 clinic visits when asymptomatic; (3 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL, herpetic lesions, HSV shedding and other factors were examined.Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03. In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41-0.60, p<0.001 and HSV shedding (β = 0.24 per log10 copies/ml increase, 95% CI:0.16-0.32, p<0.001 but not the presence of herpetic lesions (β = -0.10, 95%CI:-0.28-0.08, p = 0.27.HIV PVL and HSV shedding were more important determinants of genital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.

  20. NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

    DEFF Research Database (Denmark)

    Iversen, Marie Beck; Jensen, Simon Kok; Hansen, Anne Louise

    2015-01-01

    . The marine sponge derived lipid αGalCer has recently been demonstrated as a specific agonist for activation of human and murine NKT cells. In the present study we investigated the applicability of αGalCer pre-treatment for immune protection against intra-vaginal HSV-2 infection. We found that C57BL/6 WT mice...... that received local pre-treatment with αGalCer prior to intra-vaginal HSV-2 infection had a lower mean disease score, mortality and viral load in the vagina following infection, compared to mice that did not receive αGalCer pre-treatment. Further, we found increased numbers of CD45 and NK1.1 positive cells...... in vaginal tissue and elevated levels of IFN-γ in the vaginal tissue and in vaginal fluids 24h after αGalCer pre-treatment. Collectively our data demonstrate a protective effect of αGalCer induced activation of NKT cells in the innate immune protection against viral infection....

  1. The "enemies within": regions of the genome that are inherently difficult to replicate [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Rahul Bhowmick

    2017-05-01

    Full Text Available An unusual feature of many eukaryotic genomes is the presence of regions that appear intrinsically difficult to copy during the process of DNA replication. Curiously, the location of these difficult-to-replicate regions is often conserved between species, implying a valuable role in some aspect of genome organization or maintenance. The most prominent class of these regions in mammalian cells is defined as chromosome fragile sites, which acquired their name because of a propensity to form visible gaps/breaks on otherwise-condensed chromosomes in mitosis. This fragility is particularly apparent following perturbation of DNA replication—a phenomenon often referred to as “replication stress”. Here, we review recent data on the molecular basis for chromosome fragility and the role of fragile sites in the etiology of cancer. In particular, we highlight how studies on fragile sites have provided unexpected insights into how the DNA repair machinery assists in the completion of DNA replication.

  2. A live-attenuated HSV-2 ICP0 virus elicits 10 to 100 times greater protection against genital herpes than a glycoprotein D subunit vaccine.

    Directory of Open Access Journals (Sweden)

    William P Halford

    2011-03-01

    Full Text Available Glycoprotein D (gD-2 is the entry receptor of herpes simplex virus 2 (HSV-2, and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0⁻ virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain. In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0⁻ virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein.

  3. Seroprevalence of Herpes Simplex Virus type-2 (HSV-2) among pregnant women who participated in a national HIV surveillance activity in Haiti.

    Science.gov (United States)

    Domercant, Jean Wysler; Jean Louis, Frantz; Hulland, Erin; Griswold, Mark; Andre-Alboth, Jocelyne; Ye, Tun; Marston, Barbara J

    2017-08-18

    Herpes simplex virus type 2 (HSV-2), one the most common causes of genital ulcers, appears to increase both the risk of HIV acquisition and HIV transmission. HSV-2/HIV co-infection among pregnant women may increase the risk of perinatal transmission of HIV. This study describes rates of HSV-2 among pregnant women in Haiti and HSV-2 test performance in this population. Unlinked residual serum specimens from the 2012 National HIV and Syphilis Sentinel Surveillance Survey among pregnant women in Haiti were tested using two commercial kits (Focus HerpeSelect, Kalon) for HSV-2 antibodies. We evaluated rates of HSV-2 seropositivity and HSV-2/HIV co-infection, associations between HSV-2 and demographic characteristics using multivariable Cox proportional hazards modeling, and HSV-2 test performance in this population. Serum samples from 1000 pregnant women (all 164 HIV positive and 836 random HIV negative) were selected. The overall weighted prevalence of HSV-2 was 31.4% (95% CI: 27.7-35.4) and the prevalence of HIV-positivity among HSV-2 positive pregnant women was five times higher than the prevalence among HSV-2 negative women (4.8% [95% CI: 3.9-6.0] vs. 0.9% [95% CI: 0.6-1.3], respectively). Factors significantly associated with HSV-2 positivity were HIV-positivity (PR: 2.27 [95% CI: 1.94-2.65]) and older age (PRs: 1.41 [95% CI: 1.05-1.91] for 20-24 years, 1.71 [95% CI:1.13-2.60] for 30-34 years, and 1.55 [95% CI: 1.10-2.19] for 35 years or greater]), while rural residence was negatively associated with HSV-2 positivity (PR 0.83 [95% CI: 0.69-1.00]), after controlling for other covariables. For this study a conservative Focus index cutoff of 3.5 was used, but among samples with a Focus index value ≥2.5, 98.4% had positive Kalon tests. The prevalence of HSV-2 is relatively high among pregnant women in Haiti. Public health interventions to increase access to HSV-2 screening in antenatal services are warranted.

  4. Application of shRNA-containing herpes simplex virus type 1 (HSV-1)-based gene therapy for HSV-2-induced genital herpes.

    Science.gov (United States)

    Liu, Zhihong; Xiang, Yang; Wei, Zhun; Yu, Bo; Shao, Yong; Zhang, Jie; Yang, Hong; Li, Manmei; Guan, Ming; Wan, Jun; Zhang, Wei

    2013-11-01

    HSV-1-based vectors have been widely used to achieve targeted delivery of genes into the nervous system. In the current study, we aim to use shRNA-containing HSV-1-based gene delivery system for the therapy of HSV-2 infection. Guinea pigs were infected intravaginally with HSV-2 and scored daily for 100 days for the severity of vaginal disease. HSV-2 shRNA-containing HSV-1 was applied intravaginally daily between 8 and 14 days after HSV-2 challenge. Delivery of HSV-2 shRNA-containing HSV-1 had no effect on the onset of disease and acute virus shedding in animals, but resulted in a significant reduction in both the cumulative recurrent lesion days and the number of days with recurrent disease. Around half of the animals in the HSV-2 shRNA group did not develop recurrent disease 100 days post HSV-2 infection. In conclusion, HSV-2 shRNA-containing HSV-1 particles are effective in reducing the recurrence of genital herpes caused by HSV-2. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Contribution of N-linked glycans on HSV-2 gB to cell–cell fusion and viral entry

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Sukun [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Hu, Kai [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); He, Siyi; Wang, Ping; Zhang, Mudan; Huang, Xin [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Du, Tao [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); Zheng, Chunfu [Soochow University, Institutes of Biology and Medical Sciences, Suzhou 215123 (China); Liu, Yalan [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); Hu, Qinxue, E-mail: qhu@wh.iov.cn [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); Institute for Infection and Immunity, St George' s University of London, London SW17 0RE (United Kingdom)

    2015-09-15

    HSV-2 is the major cause of genital herpes and its infection increases the risk of HIV-1 acquisition and transmission. HSV-2 glycoprotein B together with glycoproteins D, H and L are indispensable for viral entry, of which gB, as a class III fusogen, plays an essential role. HSV-2 gB has seven potential N-linked glycosylation (N-CHO) sites, but their significance has yet to be determined. For the first time, we systematically analyzed the contributions of N-linked glycans on gB to cell–cell fusion and viral entry. Our results demonstrated that, of the seven potential N-CHO sites on gB, mutation at N390, N483 or N668 decreased cell–cell fusion and viral entry, while mutation at N133 mainly affected protein expression and the production of infectious virus particles by blocking the transport of gB from the endoplasmic reticulum to Golgi. Our findings highlight the significance of N-linked glycans on HSV-2 gB expression and function. - Highlights: • N-linked glycan at N133 is important for gB intracellular trafficking and maturation. • N-linked glycans at N390, N483 and N668 on gB are necessary for optimal cell–cell fusion. • N-linked glycans at N390, N483 and N668 on gB are necessary for optimal viral entry.

  6. Contribution of N-linked glycans on HSV-2 gB to cell–cell fusion and viral entry

    International Nuclear Information System (INIS)

    Luo, Sukun; Hu, Kai; He, Siyi; Wang, Ping; Zhang, Mudan; Huang, Xin; Du, Tao; Zheng, Chunfu; Liu, Yalan; Hu, Qinxue

    2015-01-01

    HSV-2 is the major cause of genital herpes and its infection increases the risk of HIV-1 acquisition and transmission. HSV-2 glycoprotein B together with glycoproteins D, H and L are indispensable for viral entry, of which gB, as a class III fusogen, plays an essential role. HSV-2 gB has seven potential N-linked glycosylation (N-CHO) sites, but their significance has yet to be determined. For the first time, we systematically analyzed the contributions of N-linked glycans on gB to cell–cell fusion and viral entry. Our results demonstrated that, of the seven potential N-CHO sites on gB, mutation at N390, N483 or N668 decreased cell–cell fusion and viral entry, while mutation at N133 mainly affected protein expression and the production of infectious virus particles by blocking the transport of gB from the endoplasmic reticulum to Golgi. Our findings highlight the significance of N-linked glycans on HSV-2 gB expression and function. - Highlights: • N-linked glycan at N133 is important for gB intracellular trafficking and maturation. • N-linked glycans at N390, N483 and N668 on gB are necessary for optimal cell–cell fusion. • N-linked glycans at N390, N483 and N668 on gB are necessary for optimal viral entry

  7. The epidemiology of HIV and HSV-2 infections among women participating in microbicide and vaccine feasibility studies in Northern Tanzania.

    Directory of Open Access Journals (Sweden)

    Saidi H Kapiga

    Full Text Available To prepare for future HIV prevention trials, we conducted prospective cohort studies among women working in food and recreational facilities in northern Tanzania. We examined the prevalence and incidence of HIV and HSV-2, and associated risk factors.Women aged 18-44 years working in food and recreational facilities were screened to determine their eligibility for the studies. Between 2008-2010, HIV-negative women were enrolled and followed for 12 months. At enrolment and 3-monthly, we collected socio-demographic and behavioural data, and performed clinical examinations for collection of biological specimens that were tested for reproductive tract infections. Risk factors for HIV and HSV-2 incidence were investigated using Poisson regression models.We screened 2,229 and enrolled 1,378 women. The median age was 27 years (interquartile range, IQR 22, 33, and median duration working at current facility was 2 years. The prevalences of HIV at screening and HSV-2 at enrolment were 16% and 67%, respectively. Attendance at the 12-month visit was 86%. HIV and HSV-2 incidence rates were 3.7 (95% confidence interval, CI: 2.8,5.1 and 28.6 (95% CI: 23.5,35.0/100 person-years, respectively. Women who were separated, divorced, or widowed were at increased risk of HIV (adjusted incidence rate ratio, aRR = 6.63; 95% CI: 1.97,22.2 and HSV-2 (aRR = 2.00; 95% CI: 1.15,3.47 compared with married women. Women reporting ≥3 partners in the past 3 months were at higher HIV risk compared with women with 0-1 partner (aRR = 4.75; 95% CI: 2.10,10.8, while those who had reached secondary education or above were at lower risk of HSV-2 compared with women with incomplete primary education (aRR = 0.42; 95% CI: 0.22,0.82.HIV and HSV-2 rates remain substantially higher in this cohort than in the general population, indicating urgent need for effective interventions. These studies demonstrate the feasibility of conducting trials to test new interventions in this

  8. Ex vivo 2D and 3D HSV-2 infection model using human normal vaginal epithelial cells.

    Science.gov (United States)

    Zhu, Yaqi; Yang, Yan; Guo, Juanjuan; Dai, Ying; Ye, Lina; Qiu, Jianbin; Zeng, Zhihong; Wu, Xiaoting; Xing, Yanmei; Long, Xiang; Wu, Xufeng; Ye, Lin; Wang, Shubin; Li, Hui

    2017-02-28

    Herpes simplex virus type 2 (HSV-2) infects human genital mucosa and establishes life-long latent infection. It is unmet need to establish a human cell-based microphysiological system for virus biology and anti-viral drug discovery. One of barriers is lacking of culture system of normal epithelial cells in vitro over decades. In this study, we established human normal vaginal epithelial cell (HNVEC) culture using co-culture system. HNVEC cells were then propagated rapidly and stably in a defined culture condition. HNVEC cells exhibited a normal diploid karyotype and formed the well-defined and polarized spheres in matrigel three-dimension (3D) culture, while malignant cells (HeLa) formed disorganized and nonpolar solid spheres. HNVEC cells had a normal cellular response to DNA damage and had no transforming property using soft agar assays. HNVEC expressed epithelial marker cytokeratin 14 (CK14) and p63, but not cytokeratin 18 (CK18). Next, we reconstructed HNVEC-derived 3D vaginal epithelium using air-liquid interface (ALI) culture. This 3D vaginal epithelium has the basal and apical layers with expression of epithelial markers as its originated human vaginal tissue. Finally, we established an HSV-2 infection model based on the reconstructed 3D vaginal epithelium. After inoculation of HSV-2 (G strain) at apical layer of the reconstructed 3D vaginal epithelium, we observed obvious pathological effects gradually spreading from the apical layer to basal layer with expression of a viral protein. Thus, we established an ex vivo 2D and 3D HSV-2 infection model that can be used for HSV-2 virology and anti-viral drug discovery.

  9. Prospective cohort study showing persistent HSV-2 shedding in women with genital herpes 2 years after acquisition.

    Science.gov (United States)

    Ramchandani, Meena; Selke, Stacy; Magaret, Amalia; Barnum, Gail; Huang, Meei-Li Wu; Corey, Lawrence; Wald, Anna

    2017-11-25

    Herpes simplex virus type 2 (HSV-2) is a prevalent infection with great variability in clinical and virological manifestations among individuals. This prospective cohort study aims to evaluate the natural history of HSV-2 reactivation in the genital area in the same group of women over time. Eighteen immunocompetent HSV-2 seropositive women were evaluated for viral shedding for 70 consecutive days within a median of 8 months (range 1-24 months) of HSV-2 acquisition and again approximately 2.5 years later from the original study. Participants obtained daily swabs of genital secretions for HSV PCR and recorded genital symptoms. The viral shedding rate was 29% during the initial study and 19% in the follow-up study (32% reduction, P=0.019). Subclinical shedding rate also decreased from 24% to 13% (37% reduction, P=0.032), as did the rate of days with genital lesions from 22% to 15% (33% reduction, P=0.24). The mean copy number during viral shedding remained unchanged over time at 4.8 log 10 c/mL (SD=2.0 and 1.6 during each study, respectively, P=0.33). Women with high viral shedding rates in the past were likely to continue to have high shedding rates (r=0.63, P=0.005). Despite some reduction, high viral shedding rates persist in women with genital HSV-2 greater than 2 years after acquisition. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Inactivated HSV-2 in MPL/alum adjuvant provides nearly complete protection against genital infection and shedding following long term challenge and rechallenge.

    Science.gov (United States)

    Morello, Christopher S; Kraynyak, Kimberly A; Levinson, Michael S; Chen, Zhijiang; Lee, Kuo-Fen; Spector, Deborah H

    2012-10-12

    Herpes Simplex Virus Type 2 (HSV-2) infection can result in life-long recurrent genital disease, asymptomatic virus shedding, and transmission. No vaccine to date has shown significant protection clinically. Here, we used a mouse model of genital HSV-2 infection to test the efficacy of a vaccine consisting of whole, formalin-inactivated HSV-2 (FI-HSV2) formulated with monophosphoryl lipid A (MPL) and alum adjuvants. Vaccine components were administered alone or as a prime-boost immunization together with DNA vaccines encoding a truncated glycoprotein D2 (gD2t) and two conserved HSV-2 genes necessary for virus replication, UL5 (DNA helicase) and UL30 (DNA polymerase). Our results show: (1) compared with mock immunized controls, mice immunized with FI-HSV2 plus MPL/alum consistently showed protection against disease burden and total viral shedding while the mice immunized with gD2t protein with MPL/alum did not; (2) protection against genital disease and viral replication correlated with the type of boost in a prime-boost immunization with little advantage afforded by a DNA prime; (3) intramuscular (i.m.) immunization with FI-HSV2 in MPL/Alhydrogel adjuvant provided nearly complete protection against vaginal HSV-2 shedding after a lethal intravaginal (i.vag.) short-term challenge and long-term rechallenge; (4) single formulation immunization with DNA vaccines, FI-HSV2, and MPL in an aluminum phosphate (Adju-Phos) adjuvant did not increase protection relative to FI-HSV2/MPL/Adju-Phos alone; and (5) addition of MPL/alum to the FI-HSV2 was required for optimal protection against disease, viral replication, and latent virus load in the dorsal root ganglia (DRG). Most notably, an optimized vaccine formulation of FI-HSV2 MPL/Alhydrogel given i.m. completely protected against detectable vaginal HSV-2 shedding in the majority of animals and HSV-2 latent DNA in the DRG of all animals. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. 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

  12. HSV-2-Driven Increase in the Expression of α4β7 Correlates with Increased Susceptibility to Vaginal SHIVSF162P3 Infection

    Science.gov (United States)

    Goode, Diana; Truong, Rosaline; Villegas, Guillermo; Calenda, Giulia; Guerra-Perez, Natalia; Piatak, Michael; Lifson, Jeffrey D.; Blanchard, James; Gettie, Agegnehu; Robbiani, Melissa; Martinelli, Elena

    2014-01-01

    The availability of highly susceptible HIV target cells that can rapidly reach the mucosal lymphoid tissues may increase the chances of an otherwise rare transmission event to occur. Expression of α4β7 is required for trafficking of immune cells to gut inductive sites where HIV can expand and it is expressed at high level on cells particularly susceptible to HIV infection. We hypothesized that HSV-2 modulates the expression of α4β7 and other homing receptors in the vaginal tissue and that this correlates with the increased risk of HIV acquisition in HSV-2 positive individuals. To test this hypothesis we used an in vivo rhesus macaque (RM) model of HSV-2 vaginal infection and a new ex vivo model of macaque vaginal explants. In vivo we found that HSV-2 latently infected RMs appeared to be more susceptible to vaginal SHIVSF162P3 infection, had higher frequency of α4β7 high CD4+ T cells in the vaginal tissue and higher expression of α4β7 and CD11c on vaginal DCs. Similarly, ex vivo HSV-2 infection increased the susceptibility of the vaginal tissue to SHIVSF162P3. HSV-2 infection increased the frequencies of α4β7 high CD4+ T cells and this directly correlated with HSV-2 replication. A higher amount of inflammatory cytokines in vaginal fluids of the HSV-2 infected animals was similar to those found in the supernatants of the infected explants. Remarkably, the HSV-2-driven increase in the frequency of α4β7 high CD4+ T cells directly correlated with SHIV replication in the HSV-2 infected tissues. Our results suggest that the HSV-2-driven increase in availability of CD4+ T cells and DCs that express high levels of α4β7 is associated with the increase in susceptibility to SHIV due to HSV-2. This may persists in absence of HSV-2 shedding. Hence, higher availability of α4β7 positive HIV target cells in the vaginal tissue may constitute a risk factor for HIV transmission. PMID:25521298

  13. HSV-2-driven increase in the expression of α4β7 correlates with increased susceptibility to vaginal SHIV(SF162P3) infection.

    Science.gov (United States)

    Goode, Diana; Truong, Rosaline; Villegas, Guillermo; Calenda, Giulia; Guerra-Perez, Natalia; Piatak, Michael; Lifson, Jeffrey D; Blanchard, James; Gettie, Agegnehu; Robbiani, Melissa; Martinelli, Elena

    2014-12-01

    The availability of highly susceptible HIV target cells that can rapidly reach the mucosal lymphoid tissues may increase the chances of an otherwise rare transmission event to occur. Expression of α4β7 is required for trafficking of immune cells to gut inductive sites where HIV can expand and it is expressed at high level on cells particularly susceptible to HIV infection. We hypothesized that HSV-2 modulates the expression of α4β7 and other homing receptors in the vaginal tissue and that this correlates with the increased risk of HIV acquisition in HSV-2 positive individuals. To test this hypothesis we used an in vivo rhesus macaque (RM) model of HSV-2 vaginal infection and a new ex vivo model of macaque vaginal explants. In vivo we found that HSV-2 latently infected RMs appeared to be more susceptible to vaginal SHIVSF162P3 infection, had higher frequency of α4β7high CD4+ T cells in the vaginal tissue and higher expression of α4β7 and CD11c on vaginal DCs. Similarly, ex vivo HSV-2 infection increased the susceptibility of the vaginal tissue to SHIVSF162P3. HSV-2 infection increased the frequencies of α4β7high CD4+ T cells and this directly correlated with HSV-2 replication. A higher amount of inflammatory cytokines in vaginal fluids of the HSV-2 infected animals was similar to those found in the supernatants of the infected explants. Remarkably, the HSV-2-driven increase in the frequency of α4β7high CD4+ T cells directly correlated with SHIV replication in the HSV-2 infected tissues. Our results suggest that the HSV-2-driven increase in availability of CD4+ T cells and DCs that express high levels of α4β7 is associated with the increase in susceptibility to SHIV due to HSV-2. This may persists in absence of HSV-2 shedding. Hence, higher availability of α4β7 positive HIV target cells in the vaginal tissue may constitute a risk factor for HIV transmission.

  14. HSV-2-driven increase in the expression of α4β7 correlates with increased susceptibility to vaginal SHIV(SF162P3 infection.

    Directory of Open Access Journals (Sweden)

    Diana Goode

    2014-12-01

    Full Text Available The availability of highly susceptible HIV target cells that can rapidly reach the mucosal lymphoid tissues may increase the chances of an otherwise rare transmission event to occur. Expression of α4β7 is required for trafficking of immune cells to gut inductive sites where HIV can expand and it is expressed at high level on cells particularly susceptible to HIV infection. We hypothesized that HSV-2 modulates the expression of α4β7 and other homing receptors in the vaginal tissue and that this correlates with the increased risk of HIV acquisition in HSV-2 positive individuals. To test this hypothesis we used an in vivo rhesus macaque (RM model of HSV-2 vaginal infection and a new ex vivo model of macaque vaginal explants. In vivo we found that HSV-2 latently infected RMs appeared to be more susceptible to vaginal SHIVSF162P3 infection, had higher frequency of α4β7high CD4+ T cells in the vaginal tissue and higher expression of α4β7 and CD11c on vaginal DCs. Similarly, ex vivo HSV-2 infection increased the susceptibility of the vaginal tissue to SHIVSF162P3. HSV-2 infection increased the frequencies of α4β7high CD4+ T cells and this directly correlated with HSV-2 replication. A higher amount of inflammatory cytokines in vaginal fluids of the HSV-2 infected animals was similar to those found in the supernatants of the infected explants. Remarkably, the HSV-2-driven increase in the frequency of α4β7high CD4+ T cells directly correlated with SHIV replication in the HSV-2 infected tissues. Our results suggest that the HSV-2-driven increase in availability of CD4+ T cells and DCs that express high levels of α4β7 is associated with the increase in susceptibility to SHIV due to HSV-2. This may persists in absence of HSV-2 shedding. Hence, higher availability of α4β7 positive HIV target cells in the vaginal tissue may constitute a risk factor for HIV transmission.

  15. Effects of Female Sex Hormones on Susceptibility to HSV-2 in Vaginal Cells Grown in Air-Liquid Interface.

    Science.gov (United States)

    Lee, Yung; Dizzell, Sara E; Leung, Vivian; Nazli, Aisha; Zahoor, Muhammad A; Fichorova, Raina N; Kaushic, Charu

    2016-08-30

    The lower female reproductive tract (FRT) is comprised of the cervix and vagina, surfaces that are continuously exposed to a variety of commensal and pathogenic organisms. Sexually transmitted viruses, such as herpes simplex virus type 2 (HSV-2), have to traverse the mucosal epithelial lining of the FRT to establish infection. The majority of current culture systems that model the host-pathogen interactions in the mucosal epithelium have limitations in simulating physiological conditions as they employ a liquid-liquid interface (LLI), in which both apical and basolateral surfaces are submerged in growth medium. We designed the current study to simulate in vivo conditions by growing an immortalized vaginal epithelial cell line (Vk2/E6E7) in culture with an air-liquid interface (ALI) and examined the effects of female sex hormones on their growth, differentiation, and susceptibility to HSV-2 under these conditions, in comparison to LLI cultures. ALI conditions induced Vk2/E6E7 cells to grow into multi-layered cultures compared to the monolayers present in LLI conditions. Vk2 cells in ALI showed higher production of cytokeratin in the presence of estradiol (E2), compared to cells grown in progesterone (P4). Cells grown under ALI conditions were exposed to HSV-2-green fluorescent protein (GFP) and the highest infection and replication was observed in the presence of P4. Altogether, this study suggests that ALI cultures more closely simulate the in vivo conditions of the FRT compared to the conventional LLI cultures. Furthermore, under these conditions P4 was found to confer higher susceptibility to HSV-2 infection in vaginal cells. The vaginal ALI culture system offers a better alternative to study host-pathogen interactions.

  16. Purification and characterization of a novel anti-HSV-2 protein with antiproliferative and peroxidase activities from Stellaria media

    Institute of Scientific and Technical Information of China (English)

    Yu Shan; Yuhong Zheng; Fuqin Guan; Jianjian Zhou; Haiguang Zhao; Bing Xia; Xu Feng

    2013-01-01

    A novel antiviral protein,designated as Stellarmedin A,was purified from Stellaria media (L.) Vill.(Caryophyllaceae) by using ammonium sulfate precipitation,cation-exchange chromatography system.Gel electrophoresis analysis showed that Stellarmedin A is a highly basic glycoprotein with a molecular weight of 35.1 kDa and an isoelectric point of ~8.7.The Nterminal 14-amino acid sequence,MGNTGVLTGERNDR,is similar to those of other plant peroxidases.This protein inhibited herpes simplex virus type 2 (HSV-2) replication in vitro with an ICso of 13.18 μg/ml and a therapeutic index exceeding 75.9.It was demonstrated that Stellarmedin A affects the initial stage of HSV-2 infection and is able to inhibit the proliferation of promyelocytic leukemia HL-60 and colon carcinoma LoVo cells with an ICso of 9.09 and 12.32 μM,respectively.Moreover,Stellarmedin A has a peroxidase activity of 36.6 μmol/min/mg protein,when gualacol was used as substrate.To our knowledge,this is the first report about an anti-HSV-2 protein with antiproliferative and peroxidase activities from S.media.

  17. HIV-1, HSV-2 and syphilis among pregnant women in a rural area of Tanzania: Prevalence and risk factors

    Directory of Open Access Journals (Sweden)

    Evjen-Olsen Bjørg

    2008-06-01

    Full Text Available Abstract Background Evidence suggests that a substantial proportion of new HIV infections in African countries are associated with herpes simplex virus type 2 (HSV-2. Thus, the magnitude of HSV-2 infection in an area may suggest the expected course of the HIV epidemic. We determined prevalence of genital herpes, syphilis and associated factors among pregnant women from a remote rural Tanzanian community that has a low but increasing HIV prevalence. Methods We analysed 1296 sera and responses to a standard structured questionnaire collected from pregnant women aged between 15–49 years, attending six different antenatal clinics within rural Manyara and Singida regions in Tanzania. Linked anonymous testing (with informed consent of the serum for specific antibodies against HSV-2 was done using a non-commercial peptide- 55 ELISA. Antibodies against syphilis were screened by using rapid plasma reagin (RPR and reactive samples confirmed by Treponema pallidum haemagglutination assay (TPHA. Results Previous analysis of the collected sera had shown the prevalence of HIV antibodies to be 2%. In the present study the prevalence of genital herpes and syphilis was 20.7% (95% CI: 18.53–23.00 and 1.6% (95% CI: 1.03–2.51, respectively. The presence of HSV-2 antibodies was associated with polygamy (OR 2.2, 95% CI: 1.62 – 3.01 and the use of contraceptives other than condoms (OR 1.7, 95% CI: 1.21 – 2.41. Syphilis was associated with reporting more than one lifetime sexual partner (OR 5.4, 95% CI: 1.88 – 15.76 and previous spontaneous abortion (OR 4.3, 95% CI: 1.52–12.02. Conclusion The low prevalence of HIV infection offers a unique opportunity for strengthening HIV prevention in a cost-effective manner. The identification and control of other prevalent curable STIs other than syphilis and specific intervention of HSV-2 in specific populations like pregnant women would be one among approaches towards preventing incident HIV infections.

  18. Seroprevalence of HSV-1 and HSV-2 antibodies in Canadian women screened for enrolment in a herpes simplex virus vaccine trial.

    Science.gov (United States)

    Gorfinkel, I S; Aoki, F; McNeil, S; Dionne, M; Shafran, S D; Zickler, P; Halperin, S; Langley, J; Bellamy, A; Schulte, J; Heineman, T; Belshe, R

    2013-05-01

    Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) infections continue to be among the most common and unrecognized sexually transmitted infections in the world. Although treatable, HSV-1 and HSV-2 infections remain incurable. Hence, there is interest in the development of a vaccine to prevent genital herpes. As part of a multicentre, randomized, placebo-controlled trial to test such a vaccine, healthy women 18-30 years were enrolled as volunteers in several Canadian centres between 2005 and 2007. This study reports the seroprevalence of HSV-1 and HSV-2 antibodies in this group. A total of 2694 adult female volunteers in Canada with no known history of herpes simplex were screened for HSV antibodies using Western blot assay (the gold standard for diagnosis of HSV) for potential participation in a randomized, double-blind efficacy field trial of a herpes simplex vaccine. This trial provides a unique opportunity to examine the prevalence of antibodies to HSV-1 and of antibodies to HSV-2 in women with no known history of herpes simplex infection. The prevalence of antibodies to HSV-1 and to HSV-2 is compared with that found in previous Canadian studies that focused on a more general population. The overall seroprevalence of antibody to HSV-1 was 43%; that of HSV-2 was 2.5% and seropositivity to both was 2%. The prevalence of antibody to both HSV-1 and to HSV-2 increased with age. Seronegativity to both HSV-1 and HSV-2 was 56% in participating centres with populations under 250,000 and 46% in participating centres with populations over 250,000. Significant racial differences in seropositivity to HSV-1 and to HSV-2 were noted. The likelihood of participants being seropositive to HSV-1 and to HSV-2 was found to increase with age and to positively correlate with the population of the city in which they resided. Hypotheses are proposed to account for differences in racial seropositivity to HSV-1 and to HSV-2.

  19. Evaluation of poly(lactic-co-glycolic acid) and poly(DL-lactide-co-ε-caprolactone) electrospun fibers for the treatment of HSV-2 infection

    Energy Technology Data Exchange (ETDEWEB)

    Aniagyei, Stella E.; Sims, Lee B. [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Malik, Danial A. [Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202 (United States); Tyo, Kevin M. [Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202 (United States); Center for Predictive Medicine, University of Louisville, Louisville, KY 40202 (United States); Curry, Keegan C. [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Kim, Woihwan [Department of Medicine, University of Louisville, Louisville, KY 40202 (United States); Hodge, Daniel A. [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Duan, Jinghua [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Center for Predictive Medicine, University of Louisville, Louisville, KY 40202 (United States); Steinbach-Rankins, Jill M., E-mail: jill.steinbach@louisville.edu [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202 (United States); Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202 (United States); Center for Predictive Medicine, University of Louisville, Louisville, KY 40202 (United States)

    2017-03-01

    More diverse multipurpose prevention technologies are urgently needed to provide localized, topical pre-exposure prophylaxis against sexually transmitted infections (STIs). In this work, we established the foundation for a multipurpose platform, in the form of polymeric electrospun fibers (EFs), to physicochemically treat herpes simplex virus 2 (HSV-2) infection. To initiate this study, we fabricated different formulations of poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL) EFs that encapsulate Acyclovir (ACV), to treat HSV-2 infection in vitro. Our goals were to assess the release and efficacy differences provided by these two different biodegradable polymers, and to determine how differing concentrations of ACV affected fiber efficacy against HSV-2 infection and the safety of each platform in vitro. Each formulation of PLGA and PLCL EFs exhibited high encapsulation efficiency of ACV, sustained-delivery of ACV through one month, and in vitro biocompatibility at the highest doses of EFs tested. Additionally, all EF formulations provided complete and efficacious protection against HSV-2 infection in vitro, regardless of the timeframe of collected fiber eluates tested. This work demonstrates the potential for PLGA and PLCL EFs as delivery platforms against HSV-2, and indicates that these delivery vehicles may be expanded upon to provide protection against other sexually transmitted infections. - Highlights: • PLGA and PLCL EFs exhibit sustained-delivery of ACV through one month. • EFs exhibit high ACV encapsulation efficiency and in vitro biocompatibility. • EFs serve as both physical and chemical barriers to HSV-2 infection. • Potent in vitro efficacy is provided against HSV-2 infection for all formulations. • HSV-2 protection is independent of administration times within one month.

  20. Vaccination with a HSV-2 UL24 mutant induces a protective immune response in murine and guinea pig vaginal infection models.

    Science.gov (United States)

    Visalli, Robert J; Natuk, Robert J; Kowalski, Jacek; Guo, Min; Blakeney, Susan; Gangolli, Seema; Cooper, David

    2014-03-10

    The rational design and development of genetically attenuated HSV-2 mutant viruses represent an attractive approach for developing both prophylactic and therapeutic vaccines for genital herpes. Previously, HSV-2 UL24 was shown to be a virulence determinant in both murine and guinea pig vaginal infection models. An UL24-βgluc insertion mutant produced syncytial plaques and replicated to nearly wild type levels in tissue culture, but induced little or no pathological effects in recipient mice or guinea pigs following vaginal infection. Here we report that immunization of mice or guinea pigs with high or low doses of UL24-βgluc elicited a highly protective immune response. UL24-βgluc immunization via the vaginal or intramuscular routes was demonstrated to protect mice from a lethal vaginal challenge with wild type HSV-2. Moreover, antigen re-stimulated splenic lymphocytes harvested from immunized mice exhibited both HSV-2 specific CTL activity and IFN-γ expression. Humoral anti-HSV-2 responses in serum were Th1-polarized (IgG2a>IgG1) and contained high-titer anti-HSV-2 neutralizing activity. Guinea pigs vaccinated subcutaneously with UL24-βgluc or the more virulent parental strain (186) were challenged with a heterologous HSV-2 strain (MS). Acute disease scores were nearly indistinguishable in guinea pigs immunized with either virus. Recurrent disease scores were reduced in UL24-βgluc immunized animals but not to the same extent as those immunized with strain 186. In addition, challenge virus was not detected in 75% of guinea pigs subcutaneously immunized with UL24-βgluc. In conclusion, disruption of the UL24 gene is a prime target for the development of a genetically attenuated live HSV-2 vaccine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Evaluation of poly(lactic-co-glycolic acid) and poly(DL-lactide-co-ε-caprolactone) electrospun fibers for the treatment of HSV-2 infection

    International Nuclear Information System (INIS)

    Aniagyei, Stella E.; Sims, Lee B.; Malik, Danial A.; Tyo, Kevin M.; Curry, Keegan C.; Kim, Woihwan; Hodge, Daniel A.; Duan, Jinghua; Steinbach-Rankins, Jill M.

    2017-01-01

    More diverse multipurpose prevention technologies are urgently needed to provide localized, topical pre-exposure prophylaxis against sexually transmitted infections (STIs). In this work, we established the foundation for a multipurpose platform, in the form of polymeric electrospun fibers (EFs), to physicochemically treat herpes simplex virus 2 (HSV-2) infection. To initiate this study, we fabricated different formulations of poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL) EFs that encapsulate Acyclovir (ACV), to treat HSV-2 infection in vitro. Our goals were to assess the release and efficacy differences provided by these two different biodegradable polymers, and to determine how differing concentrations of ACV affected fiber efficacy against HSV-2 infection and the safety of each platform in vitro. Each formulation of PLGA and PLCL EFs exhibited high encapsulation efficiency of ACV, sustained-delivery of ACV through one month, and in vitro biocompatibility at the highest doses of EFs tested. Additionally, all EF formulations provided complete and efficacious protection against HSV-2 infection in vitro, regardless of the timeframe of collected fiber eluates tested. This work demonstrates the potential for PLGA and PLCL EFs as delivery platforms against HSV-2, and indicates that these delivery vehicles may be expanded upon to provide protection against other sexually transmitted infections. - Highlights: • PLGA and PLCL EFs exhibit sustained-delivery of ACV through one month. • EFs exhibit high ACV encapsulation efficiency and in vitro biocompatibility. • EFs serve as both physical and chemical barriers to HSV-2 infection. • Potent in vitro efficacy is provided against HSV-2 infection for all formulations. • HSV-2 protection is independent of administration times within one month.

  2. Study on antiviral activities, drug-likeness and molecular docking of bioactive compounds of Punica granatum L. to Herpes simplex virus - 2 (HSV-2).

    Science.gov (United States)

    Arunkumar, Jagadeesan; Rajarajan, Swaminathan

    2018-03-28

    Herpes simplex virus - 2 (HSV-2) causes lifelong persisting infection in the immunocompromised host and intermittent in healthy individuals with high morbidity in neonatals and also increase the transmission of HIV. Acyclovir is widely used drug to treat HSV-2 infection but it unable to control viral latency and recurrent infection and prolonged usage lead to drug resistance. Plant-based bioactive compounds are the lead structural bio-molecules play an inevitable role as a potential antiviral agent with reduced toxicity. Therefore, there is an urgent need to develop anti-HSV-2 bioactive molecules to prevent viral resistance and control of latent infection. Punica granatum fruit is rich in major bioactive compounds with potential antimicrobial properties. Hence, we evaluated the anti-HSV-2 efficacy of lyophilized extracts and bioactive compounds isolated from fruit peel of P. granatum. As a result, ethanolic peel extract showed significant inhibition at 62.5 μg/ml. Hence, the fruit peel ethanolic extract was subjected for the isolation of bioactive compounds isolation by bioactivity-guided fractionation. Among isolated bioactive compounds, punicalagin showed 100% anti-HSV-2 activity at 31.25 μg/ml with supportive evidence of desirable in silico ADMET properties and strong interactions to selected protein targets of HSV-2 by docking analysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. The impact of brief messages on HSV-2 screening uptake among female defendants in a court setting: a randomized controlled trial utilizing prospect theory.

    Science.gov (United States)

    Roth, Alexis M; Van Der Pol, Barbara; Fortenberry, J Dennis; Dodge, Brian; Reece, Michael; Certo, David; Zimet, Gregory D

    2015-01-01

    Epidemiologic data demonstrate that women involved with the criminal justice system in the United States are at high risk for sexually transmitted infections, including herpes simplex virus type 2 (HSV-2). Female defendants were recruited from a misdemeanor court to assess whether brief framed messages utilizing prospect theory could encourage testing for HSV-2. Participants were randomly assigned to a message condition (gain, loss, or control), completed an interviewer-administered survey assessing factors associated with antibody test uptake/refusal and were offered free point-of-care HSV-2 serologic testing. Although individuals in the loss-frame group accepted testing at the highest rate, an overall statistical difference in HSV-2 testing behavior by group (p ≤ .43) was not detected. The majority of the sample (74.6%) characterized receiving a serological test for HSV-2 as health affirming. However, this did not moderate the effect of the intervention nor was it significantly associated with test acceptance (p ≤ .82). Although the effects of message framing are subtle, the findings have important theoretical implications given the participants' characterization of HSV-2 screening as health affirming despite being a detection behavior. Implications of study results for health care providers interested in brief, low cost interventions are also explored.

  4. Discordance of HIV and HSV-2 biomarkers and self-reported sexual behaviour among orphan adolescents in Western Kenya.

    Science.gov (United States)

    Cho, Hyunsan; Luseno, Winnie; Halpern, Carolyn; Zhang, Lei; Mbai, Isabella; Milimo, Benson; Hallfors, Denise Dion

    2015-06-01

    This paper examines the discordance between biological data of HIV and herpes simplex virus type 2 (HSV-2) infections and self-reported questionnaire responses among orphan adolescents in Western Kenya. In 2011, 837 orphan adolescents from 26 primary schools were enrolled in an HIV prevention trial. At baseline, blood samples were drawn for HIV and HSV-2 infection biomarker testing, and participants completed an audio computer-assisted self-interviewing survey. Comparing biological data with self-reported responses indicated that 70% of HIV-positive (7 out of 10) and 64% of HSV-2-positive (18 out of 28 positive) participants reported never having had sex. Among ever-married adolescents, 65% (57 out of 88) reported never having had sex. Overall, 10% of study participants appeared to have inconsistently reported their sexual behaviour. Logistic regression analyses indicated that lower educational level and exam scores were significant predictors of inconsistent reporting. Our study demonstrates the discordance between infections measured by biomarkers and self-reports of having had sex among orphan adolescents in Kenya. In order to detect programme effects accurately in prevention research, it is necessary to collect both baseline and endline biological data. Furthermore, it is recommended to triangulate multiple data sources about adolescent participants' self-reported information about marriage and pregnancies from school records and parent/guardians to verify the information. Researchers should recognise potential threats to validity in data and design surveys to consider cognitive factors and/or cultural context to obtain more accurate and reliable information from adolescents regarding HIV/sexually transmitted infection risk behaviours. NCT01501864. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Anti-HSV-1 and HSV-2 Flavonoids and a New Kaempferol Triglycoside from the Medicinal Plant Kalanchoe daigremontiana.

    Science.gov (United States)

    Ürményi, Fernanda Gouvêa Gomes; Saraiva, Georgia do Nascimento; Casanova, Livia Marques; Matos, Amanda Dos Santos; de Magalhães Camargo, Luiza Maria; Romanos, Maria Teresa Villela; Costa, Sônia Soares

    2016-12-01

    Kalanchoe daigremontiana (Crassulaceae) is a medicinal plant native to Madagascar. The aim of this study was to investigate the flavonoid content of an aqueous leaf extract from K. daigremontiana (Kd), and assess its antiherpetic potential. The major flavonoid, kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside (1), was isolated from the AcOEt fraction (Kd-AC). The BuOH-soluble fraction afforded quercetin 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside (2) and the new kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside-7-O-β-d-glucopyranoside (3), named daigremontrioside. The crude extract, Kd-AC fraction, flavonoids 1 and 2 were evaluated using acyclovir-sensitive strains of HSV-1 and HSV-2. Kd-AC was highly active against HSV-1 (EC 50  = 0.97 μg/ml, SI > 206.1) and HSV-2 (EC 50  = 0.72 μg/ml, SI > 277.7). Flavonoids 1 and 2 showed anti-HSV-1 (EC 50  = 7.4 μg/ml; SI > 27 and EC 50  = 5.8 μg/ml; SI > 8.6, respectively) and anti-HSV-2 (EC 50  = 9.0 μg/ml; SI > 22.2 and EC 50  = 36.2 μg/ml; SI > 5.5, respectively) activities, suggesting the contribution of additional substances to the antiviral activity. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

  6. MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa.

    Science.gov (United States)

    Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick; Litterst, Claudia; Levendosky, Keith; Gettie, Agegnehu; Cooney, Michael L; Blanchard, James; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia

    2017-03-01

    The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.

  7. Inherently safe reactors

    International Nuclear Information System (INIS)

    Maartensson, Anders

    1992-01-01

    A rethinking of nuclear reactor safety has created proposals for new designs based on inherent and passive safety principles. Diverging interpretations of these concepts can be found. This article reviews the key features of proposed advanced power reactors. An evaluation is made of the degree of inherent safety for four different designs: the AP-600, the PIUS, the MHTGR and the PRISM. The inherent hazards of today's most common reactor principles are used as reference for the evaluation. It is concluded that claims for the new designs being inherently, naturally or passively safe are not substantiated by experience. (author)

  8. Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2 suppression to reduce HIV-1 transmission: the partners study.

    Directory of Open Access Journals (Sweden)

    Jairam R Lingappa

    Full Text Available The Partners HSV-2/HIV-1 Transmission Study (Partners Study is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2 suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort.HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed.Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9 with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (500 relative to <350, respectively, p<0.001.The Partners Study successfully enrolled a cohort of 3408 heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1 transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir for HSV-2 suppression in preventing HIV-1 transmission and provide insights into biological and behavioral factors determining heterosexual HIV-1 transmission.ClinicalTrials.gov NCT00194519.

  9. [Co-infections of HIV, syphilis and HSV-2 among men who have sex with men at the voluntary HIV counseling and testing clinics in Shanghai].

    Science.gov (United States)

    Liu, Y; Tang, H F; Ning, Z; Zheng, H; He, N; Zhang, Y Y

    2017-10-10

    Objective: To understand the prevalence rates of HIV-syphilis and HIV-herpes simplex virus 2 (HSV-2) co-infections and related factors among men having sex with men (MSM) who had visited the voluntary HIV counseling and testing (VCT) clinics in Shanghai, China. Methods: 756 eligible MSM who attended the VCT clinics of Shanghai Municipality and Putuo district during March to August, 2015 were recruited to participate in a cross-sectional survey with questionnaire interview and blood testing for HIV, syphilis and HSV-2. Results: A total of 732 participants completed a valid questionnaire survey. The prevalence rates were 3.3 % (24/732) for HIV/Syphilis co-infection, 1.9 % (14/732) for HIV/HSV-2 co-infection, and 0.7 % (5/732) for HIV/Syphilis/HSV-2 co-infection, respectively. HIV prevalence appeared significantly higher among syphilis-infected participants (45.3 % , 24/53) than those without Syphilis (7.2 % , 61/679) (χ(2)=63.11, P Syphilis co-infection. Those participants who had high middle school or lower levels of education ( OR =6.87, 95 %CI : 1.86-25.42; OR =9.82, 95 %CI : 2.25-42.85) were under risk on HIV and HSV-2 co-infection. Conclusion: HIV/Syphilis and HIV/HSV-2 co-infection were seen among MSM who attended the VCT clinics in Shanghai that called for special attention, especially on migrants, those with low education or illicit drug users.

  10. False-negative type-specific glycoprotein G antibody responses in STI clinic patients with recurrent HSV-1 or HSV-2 DNA positive genital herpes, The Netherlands.

    Science.gov (United States)

    van Rooijen, Martijn S; Roest, Wim; Hansen, Gino; Kwa, David; de Vries, Henry J C

    2016-06-01

    Herpes simplex virus (HSV) type-discriminating antibody tests (glycoprotein G (gG) directed) are used to identify naïve persons and differentiate acute infections from recurrences. We studied test characteristics of three commercially available antibody tests in patients with recurrent (established by viral PCR tests) herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) genital herpes episodes. Serum samples (at minimum 3 months after t=0) were examined for the presence of gG-1-specific or gG-2-specific antibodies using the HerpeSelect 1 and 2 Immunoblot IgG, the HerpeSelect 1 and 2 enzyme linked immunoassays IgG and the LIAISON HSV-1 and HSV-2 IgG indirect chemiluminescence immunoassays. The immunoblot was HSV-1 positive in 70.6% (95% CI 44.0% to 89.7%), the LIAISON in 88.2% (95% CI 63.5% to 98.5%) and the ELISA in 82.4% (95% CI 56.6% to 96.2%) of the 17 patients with a recurrent HSV-1 episode. From 33 patients with a recurrent HSV-2 episode, the immunoblot was HSV-2 positive in 84.8% (95% CI 68.1% to 94.9%), the LIAISON in 69.7% (95% CI 51.3% to 84.4%) and the ELISA in 84.8% (95% CI 68.1% to 94.9%). Among 15/17 (88.2%; 95% CI 63.5% to 98.5%) patients with HSV-1 and 30/33 (90.1%; 95% CI 75.7% to 98.1%) patients with HSV-2, HSV-1 or HSV-2 antibodies, respectively, were detected in at least one of the three antibody tests. Commercial type-specific gG HSV-1 or HSV-2 antibody assays were false negative in 12-30% of patients with recurrent HSV-1 or HSV-2 DNA positive genital lesions. The clinical and epidemiological use of type-specific HSV serology can be hampered by false-negative results, especially if based on a single test. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  11. FSL-1, a bacterial-derived toll-like receptor 2/6 agonist, enhances resistance to experimental HSV-2 infection

    Directory of Open Access Journals (Sweden)

    Pyles Richard B

    2009-11-01

    Full Text Available Abstract Background Herpes simplex virus type 2 (HSV-2 is a leading cause of genital ulceration that can predispose individuals to an increased risk of acquiring other sexually transmitted infections. There are no approved HSV-2 vaccines and current suppressive therapies require daily compound administration that does not prevent all recurrences. A promising experimental strategy is the use of toll-like receptor (TLR agonists to induce an innate immune response that provides resistance to HSV-2 infection. Previous studies showed that anti-herpetic activity varied based on origin of the agonists and activation of different TLR indicating that activity likely occurs through elaboration of a specific innate immune response. To test the hypothesis, we evaluated the ability of a bacterial-derived TLR2/6 agonist (FSL-1 to increase resistance to experimental genital HSV-2 infection. Methods Vaginal application of FSL-1 at selected doses and times was evaluated to identify potential increased resistance to genital HSV-2 infection in the mouse model. The FSL-1 induced cytokine profile was quantified using kinetically collected vaginal lavages. Additionally, cytokine elaboration and organ weights were evaluated after single or multiple FSL-1 doses to establish a preliminary safety profile. Human vaginal EC cultures were used to confirm the mouse model outcomes. Results The results showed that vaginally-applied FSL-1 created an environment resistant to a 25-fold higher HSV-2 challenge dose. Mechanistically, vaginal FSL-1 application led to transient elaboration of cytokines linked to anti-herpetic innate immune responses. No gross local or peripheral immunotoxicity was observed even after multiple dosing. FSL-1 also created an anti-herpetic environment in cultures of human vaginal epithelial cells (EC. Conclusion The results showed, for the first time, that the bacterial-derived TLR2/6 agonist FSL-1 induced significant resistance to HSV-2 infection when

  12. In vitro inactivation of Chlamydia trachomatis and of a panel of DNA (HSV-2, CMV, adenovirus, BK virus) and RNA (RSV, enterovirus) viruses by the spermicide benzalkonium chloride.

    Science.gov (United States)

    Bélec, L; Tevi-Benissan, C; Bianchi, A; Cotigny, S; Beumont-Mauviel, M; Si-Mohamed, A; Malkin, J E

    2000-11-01

    Kinetics of inactivation by the detergent spermicide benzalkonium chloride (BZK) of Chlamydia trachomatis and of a panel of DNA viruses [herpes simplex virus hominis type 2 (HSV-2), cytomegalovirus (CMV), adenovirus (ADV) and BK virus (BKV)] and RNA [respiratory syncytial virus (RSV) and enterovirus (ENV)] were established in accordance with a standardized in vitro protocol. After a 5 min incubation, inactivation of >95% of HSV-2 and CMV was obtained at a concentration of 0.0025% (w/v) (25 Ig/L); concentrations as low as 0.0005%, 0.0050% and 0.0125%, induced a 3.0 log10 reduction in infectivity of HSV-2 and CMV, RSV and ADV, respectively. After a 60 min incubation, concentrations of 0.0125% and 0.050% provided a 3.0 log10 reduction in infectivity of ENV and BKV, respectively. These features indicate that sensitivity to BZK was very high (HSV-2 and CMV) or high (RSV) for enveloped viruses, intermediate (ADV) or low (ENV and BKV) for non-enveloped viruses. Furthermore, BZK had marked antichlamydial activity, showing >99% killing after only a 1 min incubation at a concentration of 0.00125%. BZK demonstrates potent in vitro activity against the majority of microorganisms causing sexually transmitted infectious diseases, including those acting as major genital cofactors of human immunodeficiency virus transmission. These attributes qualify BZK as a particularly attractive candidate for microbicide development.

  13. Assessment of IgG Antibodies Against HSV1, HSV2, CMV and EBV in Patients with Pemphigus Vulgaris versus Healthy People

    Directory of Open Access Journals (Sweden)

    Parichehr Ghalayani

    2016-08-01

    Full Text Available Objectives: Regarding the implication of viruses particularly herpes in pemphigus vulgaris, we sought to assess and compare the level of immunoglobulin G (IgG antibodies against herpes simplex virus types 1 and 2 (HSV1 and HSV2, cytomegalovirus (CMV and Epstein-Barr virus (EBV in patients with pemphigus vulgaris and healthy people.    Materials and Methods: In this cross-sectional study, 25 patients with pemphigus vulgaris and 27 healthy individuals comprised the experimental and control groups, respectively. Serum samples were taken from both groups; the levels of IgG antibodies against HSV1, HSV2, CMV and EBV were measured using ELISA.  Results: Immunoglobulin G titer was higher for all four viruses in the patient group in comparison to the control group. This difference was significant for anti-EBV (P= 0.005, anti-CMV (P=0.0001 and anti-HSV2 (P=0.001 but not significant for anti-HSV1 (P= 0.36.Conclusion: Viruses including EBV, CMV, and HSV2 probably play a role in the pathogenesis of pemphigus in addition to the effects of genetics, toxins and other predisposing factors. In this study, no statistically significant relationship was observed between HSV1 and pemphigus vulgaris, which was probably due to the high titer of anti-HSV1 IgG in healthy individuals in the community. More studies must be done in this regard.

  14. Immunization with a dominant-negative recombinant Herpes Simplex Virus (HSV type 1 protects against HSV-2 genital disease in guinea pigs

    Directory of Open Access Journals (Sweden)

    Brans Richard

    2010-06-01

    Full Text Available Abstract Background CJ9-gD is a novel dominant-negative recombinant herpes simplex virus type 1 (HSV-1 that is completely replication-defective, cannot establish detectable latent infection in vivo, and expresses high levels of the major HSV-1 antigen glycoprotein D immediately following infection. In the present study, CJ9-gD was evaluated as a vaccine against HSV-2 genital infection in guinea pigs. Results Animals immunized with CJ9-gD developed at least 700-fold higher titers of HSV-2-specific neutralization antibodies than mock-immunized controls. After challenge with wild-type HSV-2, all 10 control guinea pigs developed multiple genital lesions with an average of 21 lesions per animal. In contrast, only 2 minor lesions were found in 2 of 8 CJ9-gD-immunized animals, representing a 40-fold reduction on the incidence of primary genital lesions in immunized animals (p Conclusions Collectively, we demonstrate that vaccination with the HSV-1 recombinant CJ9-gD elicits strong and protective immune responses against primary and recurrent HSV-2 genital disease and significantly reduces the extent of latent infection.

  15. Mathematical Modeling Predicts that Increased HSV-2 Shedding in HIV-1 Infected Persons Is Due to Poor Immunologic Control in Ganglia and Genital Mucosa.

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    Joshua T Schiffer

    Full Text Available A signature feature of HIV infection is poor control of herpes virus infections, which reactivate from latency and cause opportunistic infections. While the general mechanism underlying this observation is deficient CD4+T-cell function, it is unknown whether increased severity of herpes virus infections is due primarily to poor immune control in latent or lytic sites of infection, or whether CD4+ immunodeficiency leads to more critical downstream deficits in humoral or cell-mediated immunologic responses. Here we compare genital shedding patterns of herpes simplex virus-2 (HSV-2 in 98 HIV infected and 98 HIV uninfected men matched on length of infection, HSV-1 serostatus and nationality. We demonstrate that high copy HSV-2 shedding is more frequent in HIV positive men, particularly in participants with CD4+ T-cell count <200/μL. Genital shedding is more frequent due to higher rate of shedding episodes, as well as a higher proportion of prolonged shedding episodes. Peak episode viral load was not found to differ between HIV infected and uninfected participants regardless of CD4+ T-cell count. We simulate a mathematical model which recapitulates these findings and identifies that rate of HSV-2 release from neural tissue increases, duration of mucosal cytolytic immune protection decreases, and cell-free viral lifespan increases in HIV infected participants. These results suggest that increased HSV-2 shedding in HIV infected persons may be caused by impaired immune function in both latent and lytic tissue compartments, with deficits in clearance of HSV-2 infected cells and extracellular virus.

  16. Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.

    Science.gov (United States)

    Bernard, Marie-Clotilde; Barban, Véronique; Pradezynski, Fabrine; de Montfort, Aymeric; Ryall, Robert; Caillet, Catherine; Londono-Hayes, Patricia

    2015-01-01

    HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529) derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige) mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a prophylactic vaccine.

  17. Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.

    Directory of Open Access Journals (Sweden)

    Marie-Clotilde Bernard

    Full Text Available HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29 has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529 derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a

  18. Nasal and skin delivery of IC31(®)-adjuvanted recombinant HSV-2 gD protein confers protection against genital herpes.

    Science.gov (United States)

    Wizel, Benjamin; Persson, Josefine; Thörn, Karolina; Nagy, Eszter; Harandi, Ali M

    2012-06-19

    Genital herpes caused by herpes simplex virus type 2 (HSV-2) remains the leading cause of genital ulcers worldwide. Given the disappointing results of the recent genital herpes vaccine trials in humans, development of novel vaccine strategies capable of eliciting protective mucosal and systemic immune responses to HSV-2 is urgently required. Here we tested the ability of the adjuvant IC31(®) in combination with HSV-2 glycoprotein D (gD) used through intranasal (i.n.), intradermal (i.d.), or subcutaneous (s.c.) immunization routes for induction of protective immunity against genital herpes infection in C57BL/6 mice. Immunization with gD plus IC31(®) through all three routes of immunization developed elevated gD-specific serum antibody responses with HSV-2 neutralizing activity. Whereas the skin routes promoted the induction of a mixed IgG2c/IgG1 isotype profile, the i.n. route only elicited IgG1 antibodies. All immunization routes were able to induce gD-specific IgG antibody responses in the vaginas of mice immunized with IC31(®)-adjuvanted gD. Although specific lymphoproliferative responses were observed in splenocytes from mice of most groups vaccinated with IC31(®)-adjuvanted gD, only i.d. immunization resulted in a significant splenic IFN-γ response. Further, immunization with gD plus IC31(®) conferred 80-100% protection against an otherwise lethal vaginal HSV-2 challenge with amelioration of viral replication and disease severity in the vagina. These results warrant further exploration of IC31(®) for induction of protective immunity against genital herpes and other sexually transmitted infections. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Operation: Inherent Resolve

    DEFF Research Database (Denmark)

    Cramer-Larsen, Lars

    2015-01-01

    Kapitlet giver læseren indsigt i den internationale koalitions engagement mod IS igennem Operaton Inherent Resolve; herunder koalitionens strategi i forhold til IS strategi, ligesom det belyser kampagnens legalitet og folkeretlige grundlag, ligesom det giver et bud på overvejelser om kampagnens...

  20. An indole alkaloid from a tribal folklore inhibits immediate early event in HSV-2 infected cells with therapeutic efficacy in vaginally infected mice.

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    Paromita Bag

    Full Text Available Herpes genitalis, caused by HSV-2, is an incurable genital ulcerative disease transmitted by sexual intercourse. The virus establishes life-long latency in sacral root ganglia and reported to have synergistic relationship with HIV-1 transmission. Till date no effective vaccine is available, while the existing therapy frequently yielded drug resistance, toxicity and treatment failure. Thus, there is a pressing need for non-nucleotide antiviral agent from traditional source. Based on ethnomedicinal use we have isolated a compound 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole (HM from the traditional herb Ophiorrhiza nicobarica Balkr, and evaluated its efficacy on isolates of HSV-2 in vitro and in vivo. The cytotoxicity (CC50, effective concentrations (EC50 and the mode of action of HM was determined by MTT, plaque reduction, time-of-addition, immunofluorescence (IFA, Western blot, qRT-PCR, EMSA, supershift and co-immunoprecipitation assays; while the in vivo toxicity and efficacy was evaluated in BALB/c mice. The results revealed that HM possesses significant anti-HSV-2 activity with EC50 of 1.1-2.8 µg/ml, and selectivity index of >20. The time kinetics and IFA demonstrated that HM dose dependently inhibited 50-99% of HSV-2 infection at 1.5-5.0 µg/ml at 2-4 h post-infection. Further, HM was unable to inhibit viral attachment or penetration and had no synergistic interaction with acyclovir. Moreover, Western blot and qRT-PCR assays demonstrated that HM suppressed viral IE gene expression, while the EMSA and co-immunoprecipitation studies showed that HM interfered with the recruitment of LSD-1 by HCF-1. The in vivo studies revealed that HM at its virucidal concentration was nontoxic and reduced virus yield in the brain of HSV-2 infected mice in a concentration dependent manner, compared to vaginal tissues. Thus, our results suggest that HM can serve as a prototype to develop non-nucleotide antiviral lead targeting the viral IE

  1. An indole alkaloid from a tribal folklore inhibits immediate early event in HSV-2 infected cells with therapeutic efficacy in vaginally infected mice.

    Science.gov (United States)

    Bag, Paromita; Ojha, Durbadal; Mukherjee, Hemanta; Halder, Umesh Chandra; Mondal, Supriya; Chandra, Nidhi S; Nandi, Suman; Sharon, Ashoke; Sarkar, Mamta Chawla; Chakrabarti, Sekhar; Chattopadhyay, Debprasad

    2013-01-01

    Herpes genitalis, caused by HSV-2, is an incurable genital ulcerative disease transmitted by sexual intercourse. The virus establishes life-long latency in sacral root ganglia and reported to have synergistic relationship with HIV-1 transmission. Till date no effective vaccine is available, while the existing therapy frequently yielded drug resistance, toxicity and treatment failure. Thus, there is a pressing need for non-nucleotide antiviral agent from traditional source. Based on ethnomedicinal use we have isolated a compound 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole (HM) from the traditional herb Ophiorrhiza nicobarica Balkr, and evaluated its efficacy on isolates of HSV-2 in vitro and in vivo. The cytotoxicity (CC50), effective concentrations (EC50) and the mode of action of HM was determined by MTT, plaque reduction, time-of-addition, immunofluorescence (IFA), Western blot, qRT-PCR, EMSA, supershift and co-immunoprecipitation assays; while the in vivo toxicity and efficacy was evaluated in BALB/c mice. The results revealed that HM possesses significant anti-HSV-2 activity with EC50 of 1.1-2.8 µg/ml, and selectivity index of >20. The time kinetics and IFA demonstrated that HM dose dependently inhibited 50-99% of HSV-2 infection at 1.5-5.0 µg/ml at 2-4 h post-infection. Further, HM was unable to inhibit viral attachment or penetration and had no synergistic interaction with acyclovir. Moreover, Western blot and qRT-PCR assays demonstrated that HM suppressed viral IE gene expression, while the EMSA and co-immunoprecipitation studies showed that HM interfered with the recruitment of LSD-1 by HCF-1. The in vivo studies revealed that HM at its virucidal concentration was nontoxic and reduced virus yield in the brain of HSV-2 infected mice in a concentration dependent manner, compared to vaginal tissues. Thus, our results suggest that HM can serve as a prototype to develop non-nucleotide antiviral lead targeting the viral IE transcription for the

  2. Vowel Inherent Spectral Change

    CERN Document Server

    Assmann, Peter

    2013-01-01

    It has been traditional in phonetic research to characterize monophthongs using a set of static formant frequencies, i.e., formant frequencies taken from a single time-point in the vowel or averaged over the time-course of the vowel. However, over the last twenty years a growing body of research has demonstrated that, at least for a number of dialects of North American English, vowels which are traditionally described as monophthongs often have substantial spectral change. Vowel Inherent Spectral Change has been observed in speakers’ productions, and has also been found to have a substantial effect on listeners’ perception. In terms of acoustics, the traditional categorical distinction between monophthongs and diphthongs can be replaced by a gradient description of dynamic spectral patterns. This book includes chapters addressing various aspects of vowel inherent spectral change (VISC), including theoretical and experimental studies of the perceptually relevant aspects of VISC, the relationship between ar...

  3. Mucosal HSV-2 specific CD8+ T-cells represent containment of prior viral shedding rather than a correlate of future protection

    Directory of Open Access Journals (Sweden)

    Joshua Tisdell Schiffer

    2013-07-01

    Full Text Available It is largely unknown why certain infected hosts shed Herpes Simplex Virus-2 (HSV-2 more frequently and have more severe disease manifestations than others. One idea is that different density or functional capacity of tissue resident effector memory CD8+ T-cells between infected persons may explain phenotypic variability. To generate hypotheses for contrasting shedding patterns in different infected hosts, a spatial mathematical model was employed to evaluate the effects of variability in tissue resident effector memory CD8+ T-cell response, and HSV-2 replication and spread, on viral shedding rate. Model simulations suggest that high levels of CD8+ T-cells in the mucosa do not necessarily indicate a protective phenotype but rather an effective response to recent shedding. Moreover, higher CD8+ T-cell expansion rate and lower viral replication rate, which correlate with better short-term control, may have only a minor impact on long term shedding rates. Breakthrough shedding occurs under all sets of model parameter assumptions, because CD8+ T-cell levels only surpass a protective threshold in a minority of genital tract mucosal micro-regions. If CD8+ T-cell levels are artificially increased using an immunotherapeutic approach, better control of shedding is predicted to occur for at least a year. These results highlight the complex co-dependent relationship between HSV-2 and tissue resident CD8+ lymphocytes during the course of natural infection.

  4. Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay

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    Sherif T. S. Hassan

    2017-04-01

    Full Text Available For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS and its bioactive constituent protocatechuic acid (PCA, have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC50 values of 0.92 and 1.43 µg∙mL−1, respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC50 value of 82.4 µg∙mL−1. This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

  5. Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay.

    Science.gov (United States)

    Hassan, Sherif T S; Švajdlenka, Emil; Berchová-Bímová, Kateřina

    2017-04-30

    For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC 50 values of 0.92 and 1.43 µg∙mL -1 , respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC 50 value of 82.4 µg∙mL -1 . This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

  6. Efficacy of the anti-VZV (anti-HSV3 vaccine in HSV1 and HSV2 recurrent herpes simplex disease: a prospective study

    Directory of Open Access Journals (Sweden)

    Le Goaster J

    2012-07-01

    Full Text Available Jacqueline Le Goaster,1 Sylvie Gonzalo,2 Patrice Bourée,1 Frederic Tangy,3 Anne-Lise Haenni41Department of Tropical Diseases, Centre Hospitalo-Universitaire (CHU, University of Paris XI, Le Kremlin Bicêtre, 2Biomnis Laboratory, Ivry-sur-Seine, 3Retro-Virology, Centre National de Recherche Scientifique (CNRS, Pasteur Institute, Paris; 4Jacques Monod Institute, Centre National de Recherche Scientifique (CNRS, University of Paris VII, Paris, FranceBackground: The aim of this study was to evaluate the possibility of using the anti-varicella zoster virus (anti-VZV, also known as anti-HSV3 vaccine against orobuccal herpes simplex virus type 1 (HSV1 and genital herpes simplex virus type 2 (HSV2. This was suggested by study of the phylogenetic tree of members of the herpes virus family, which showed a close relationship between VZV (HSV3 and the HSV1 and HSV2 herpes viruses.Methods: The present prospective study was conducted from January 2005 through January 2011. Twenty-four patients afflicted with HSV1 and HSV2 herpes recurrences over a period of years, numbering 6–8 and more recurrences per year, agreed to receive the anti-VZV vaccine. They were compared with 26 nonvaccinated patients presenting with herpes simplex diseases 2–5 times a year. All 50 patients were documented with anti-HSV1, anti-HSV2, and anti-VZV antibody serological testing.Results: From 2005 through 2011, for the 24 anti-VZV vaccinated patients, the average number of herpes relapses decreased to 0, correlated with an increased anti-VZV antibody level and clinical recovery of all patients, whereas no improvement was observed for the 26 nonvaccinated herpes patients.Conclusion: Data for the anti-VZV serological antibody levels tested before and after anti-VZV vaccination showed a significant (P < 0.001 increase among vaccinated patients. This suggests defective anti-VZV immune power in these patients. After 6 years of positive results for anti-VZV vaccine, this is a logical and

  7. Genital herpes evaluation by quantitative TaqMan PCR: correlating single detection and quantity of HSV-2 DNA in cervicovaginal lavage fluids with cross-sectional and longitudinal clinical data

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    Cox Christopher

    2010-11-01

    Full Text Available Abstract Objective To evaluate the utility of a single quantitative PCR (qPCR measurement of HSV (HSV-1&2 DNA in cervicovaginal lavage (CVL specimens collected from women with predominantly chronic HSV-2 infection in assessing genital HSV shedding and the clinical course of genital herpes (GH within a cohort with semiannual schedule of follow up and collection of specimens. Methods Two previously described methods used for detection of HSV DNA in mucocutaneous swab samples were adapted for quantification of HSV DNA in CVLs. Single CVL specimens from 509 women were tested. Presence and quantity of CVL HSV DNA were explored in relation to observed cross-sectional and longitudinal clinical data. Results The PCR assay was sensitive and reproducible with a limit of quantification of ~50 copies per milliliter of CVL. Overall, 7% of the samples were positive for HSV-2 DNA with median log10 HSV-2 DNA copy number of 3.9 (IQR: 2.6-5.7. No HSV-1 was detected. Presence and quantity of HSV-2 DNA in CVL directly correlated with the clinical signs and symptoms of presence of active symptomatic disease with frequent recurrences. Conclusion Single qPCR measurement of HSV DNA in CVL fluids of women with chronic HSV-2 infection provided useful information for assessing GH in the setting of infrequent sampling of specimens. Observed positive correlation of the presence and quantity of HSV-2 DNA with the presence of active and more severe course of HSV-2 infection may have clinical significance in the evaluation and management of HSV-2 infected patients.

  8. Prevalence of HIV, HSV-2 and pregnancy among high school students in rural KwaZulu-Natal, South Africa: a bio-behavioural cross-sectional survey.

    Science.gov (United States)

    Abdool Karim, Quarraisha; Kharsany, Ayesha B M; Leask, Kerry; Ntombela, Fanelisibonge; Humphries, Hilton; Frohlich, Janet A; Samsunder, Natasha; Grobler, Anneke; Dellar, Rachael; Abdool Karim, Salim S

    2014-12-01

    Adolescents in southern African high schools are a key population for HIV prevention interventions. We report on the prevalence of HIV, HSV-2 and pregnancy as indicators of high-risk sexual behaviour among high school students in rural KwaZulu-Natal. Bio-behavioural cross-sectional survey. Students completed a self-administered structured, standardised demographic and sexual behavioural questionnaire. Dried blood spot specimens were collected for HIV and HSV-2 testing. Urine specimens were used for pregnancy testing in female students. A total of 2675 (1423 females, 1252 males) consenting students were enrolled from 14 high schools between September and November 2010. The median age of students was 16 years (IQR 15-18). HIV prevalence was 1.4% (95% CI 0.9 to 1.9) in males and 6.4% (95% CI 4.6 to 8.3) in females (pPregnancy prevalence was 3.6% (95% CI 2.6 to 4.5). Risk factors for prevalent HIV infection in female students included being over 18 years of age (adjusted OR (aOR)=2.67, 95% CI 1.67 to 4.27; ppregnancy (aOR=1.66, 95% CI 1.10 to 2.51; p=0.016) and experience of two or more deaths in the household in the previous year (aOR=1.97, 95% CI 1.13 to 3.44; p=0.016). The high prevalence of HIV, HSV-2 and pregnancy underscore the need for school-based sexual and reproductive health services, and provide further impetus for the inclusion of adolescents in behavioural and biomedical trials with HIV incidence endpoints. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Clinical evaluation of a helicase-dependant amplification (HDA)-based commercial assay for the simultaneous detection of HSV-1 and HSV-2.

    Science.gov (United States)

    Teo, Jeanette W P; Chiang, Donald; Jureen, Roland; Lin, Raymond T P

    2015-11-01

    In this study, we evaluate the performance of a commercial assay, the AmpliVue HSV 1+2 Assay (Quidel), which employs HDA for the detection of both HSV-1 and HSV-2. The assay was tested on 307 clinical specimens (genital, oral, and dermal). When compared to shell vial virus culture and immunofluorescence typing of HSV, the positive percent agreement and negative percent agreement values were 98.2% and 90.9%, respectively. Excellent assay performance was demonstrated. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Herpes simplex virus type 2 (HSV-2) as a coronary atherosclerosis risk factor in HIV-infected men: multicenter AIDS cohort study.

    Science.gov (United States)

    Hechter, Rulin C; Budoff, Matthew; Hodis, Howard N; Rinaldo, Charles R; Jenkins, Frank J; Jacobson, Lisa P; Kingsley, Lawrence A; Taiwo, Babafemi; Post, Wendy S; Margolick, Joseph B; Detels, Roger

    2012-08-01

    We assessed associations of herpes simplex virus types 1 and 2 (HSV-1 and -2), cytomegalovirus (CMV), and human herpesvirus 8 (HHV-8) infection with subclinical coronary atherosclerosis in 291 HIV-infected men in the Multicenter AIDS Cohort Study. Coronary artery calcium (CAC) was measured by non-contrast coronary CT imaging. Markers for herpesviruses infection were measured in frozen specimens collected 10-12 years prior to case identification. Multivariable logistic regression models and ordinal logistic regression models were performed. HSV-2 seropositivity was associated with coronary atherosclerosis (adjusted odds ratio [AOR]=4.12, 95% confidence interval [CI]=1.58-10.85) after adjustment for age, race/ethnicity, cardiovascular risk factors, and HIV infection related factors. Infection with a greater number of herpesviruses was associated with elevated CAC levels (AOR=1.58, 95% CI=1.06-2.36). Our findings suggest HSV-2 may be a risk factor for subclinical coronary atherosclerosis in HIV-infected men. Infection with multiple herpesviruses may contribute to the increased burden of atherosclerosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. A high resolution melting (HRM) technology-based assay for cost-efficient clinical detection and genotyping of herpes simplex virus (HSV)-1 and HSV-2.

    Science.gov (United States)

    Lieveld, M; Carregosa, A; Benoy, I; Redzic, N; Berth, M; Vanden Broeck, D

    2017-10-01

    Genital herpes can be caused by two very similar viruses, herpes simplex virus (HSV)-1 or HSV-2. These two HSV types cannot be distinguished clinically, but genotyping is recommended in the first-episodes of genital herpes to guide counselling and management. Quantitative polymerase chain reaction (qPCR) is the preferred diagnostic method for HSV typing. However, commercial qPCR methods use expensive fluorescent labeled probes for detection. Furthermore, most low-cost methods are not able to differentiate between HSV-1 and -2. The aim of this study was to develop a high resolution melting (HRM) technology-based assay for sensitive HSV-1 and HSV-2 detection and genotyping. Using a panel of 46 clinical specimens, the performance of the HRM assay was compared to two commercial HSV tests: the HRM assay detected HSV in all 23 positive samples, with no false positive results (100% concordance with HSV I/II Real-TM assay). Additionally, the HRM assay correctly genotyped both HSV types in a subset of these clinical samples, as determined by the Realstar HSV PCR Kit. The HSV HRM assay provides a cost-effective alternative method to conventional more expensive assays and can be used in routine clinical specimens, in cases where it is particularly necessary to detect and distinguish HSV-1 from -2. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The Prevalence of HIV by Ethnic Group Is Correlated with HSV-2 and Syphilis Prevalence in Kenya, South Africa, the United Kingdom, and the United States

    Directory of Open Access Journals (Sweden)

    Chris Richard Kenyon

    2014-01-01

    Full Text Available Background. This paper investigates two issues: do ethnic/racial groups with high HIV prevalences also have higher prevalences of other STIs? and is HIV prevalence by ethnic group correlated with the prevalence of circumcision, concurrency, or having more than one partner in the preceding year? Methods. We used Spearman’s correlation to estimate the association between the prevalence of HIV per ethnic/racial group and HSV-2, syphilis, symptoms of an STI, having more than one partner in the past year, concurrency, and circumcision in Kenya, South Africa, the United Kingdom, and the United States. Results. We found that in each country HSV-2, syphilis, and symptomatic STIs were positively correlated with HIV prevalence (HSV-2: Kenya rho = 0.50, P = 0.207; South Africa rho-1, P = 0.000; USA rho-1, P = 0.000, Syphilis: Kenya rho = 0.33, P = 0.420; South Africa rho-1, P = 0.000; USA rho-1, P = 0.000, and STI symptoms: Kenya rho = 0.92, P = 0.001; South Africa rho-1, P = 0.000; UK rho = 0.87, P = 0.058; USA rho-1, P = 0.000. The prevalence of circumcision was only negatively associated with HIV prevalence in Kenya. Both having more than one partner in the previous year and concurrency were positively associated with HIV prevalence in all countries (concurrency: Kenya rho = 0.79, P = 0.036; South Africa rho-1, P = 0.000; UK 0.87, P = 0.058; USA rho-1, P = 0.000 and multiple partners: Kenya rho = 0.82, P = 0.023; South Africa rho-1, P = 0.000; UK rho = 0.87, P = 0.058; USA rho-1, P = 0.000. Not all associations were statistically significant. Conclusion. Further attention needs to be directed to what determines higher rates of partner change and concurrency in communities with high STI prevalence.

  13. [A study on syphilis and HSV-2 infection and related behaviors among female sex workers who take new types of drugs in Jiaozhou city].

    Science.gov (United States)

    Li, Zheng; Li, Dongmin; Jiang, Zhenxia; Liu, Huixin; Wang, Ning

    2014-10-01

    To explore the prevalence of syphilis and HSV-2 among female sex workers (FSWs) who use new types of drugs in Jiaozhou city. Through convenient sampling, an anonymous questionnaire survey was conducted among female sex workers to collect demographic characteristics, new-type drugs abusing characteristics and related sexual behaviors from October to December, 2013. Blood specimens were drawn for serological tests of syphilis antibody and HSV-2 antibody. Urine specimens of the subjects surveyed were collected to test for methamphetamine. Differences in demographic characteristics, new-type drug abusing characteristics, and sexual behaviours between drug-abusing FSWs and non-drug-abusing FSWs were compared by t-test and χ(2)-test. A total of 460 FSWs were recruited in this study, and 105 FSWs admitted their drug abuse history. Among the 341 urine specimens confirmed to be methamphetamine positive, there were 3 FSWs claimed that they never abuse new-type drugs. The rate of new-type drug abuse was 23.5% (108/460). A total of 71.4% (75/105) of the new drug-abusing FSWs started using drugs under 25 years old. The main reasons for drug abuse were clients request (24, 22.9%), making more money (23, 21.9%) and companion temptations (22, 21.0%). Totally, 41.9% of them (44/105) took drugs with 4-5 persons, 32.4% (34/105) had sex with 2-3 men after taking drugs, and 60.2% of new-type drug-abusing FSWs (65/108) used condoms in the latest commercial intercourse, while only 7.4% FSWs (8/108) used condoms every time during their commercial sex activities in the recent month. Compared with FSWs having no drug abuse behavior, drug-abusing FSWs had higher single proportion (73.2% (79/108) vs 63.6% (224/352), χ(2) = 8.64, P drug-abusing FSWs, the prevalence rates of syphilis and HSV-2 were 12.0% (13/108) and 55.6% (60/108) , respectively. A total of 33 FSWs claimed that they were diagnosed with STDs in the recent year (30.6%) . The rates of syphilis(12.0% (13/108) vs 4.0% (14/352),

  14. Inherently safe light water reactors

    International Nuclear Information System (INIS)

    Ise, Takeharu

    1987-01-01

    Today's large nuclear power reactors of world-wise use have been designed based on the philosophy. It seems that recent less electricity demand rates, higher capital cost and the TMI accident let us acknowledge relative small and simplified nuclear plants with safer features, and that Chernobyl accident in 1983 underlines the needs of intrinsic and passive safety characteristics. In such background, several inherently safe reactor concepts have been presented abroad and domestically. First describing 'Can inherently safe reactors be designed,' then I introduce representative reactor concepts of inherently safe LWRs advocated abroad so far. All of these innovative reactors employ intrinsic and passive features in their design, as follows: (1) PIUS, an acronym for Process Inherent Ultimate Safety, or an integral PWR with passive heat sink and passive shutdown mechanism, advocated by ASEA-ATOM of Sweden. (2) MAP(Minimum Attention Plant), or a self-pressurized, natural circulation integral PWR, promoted by CE Inc. of the U.S. (3) TPS(TRIGA Power System), or a compact PWR with passive heat sink and inherent fuel characteristics of large prompt temperature coefficient, prompted by GA Technologies Inc. of the U.S. (4) PIUS-BWR, or an inherently safe BWR employing passively actuated fluid valves, in competition with PIUS, prompted by ORNL of the U.S. Then, I will describe the domestic trends in Japan and the innovative inherently safe LWRs presented domestically so far. (author)

  15. Dual-strain genital herpes simplex virus type 2 (HSV-2) infection in the US, Peru, and 8 countries in sub-Saharan Africa: A nested cross-sectional viral genotyping study.

    Science.gov (United States)

    Johnston, Christine; Magaret, Amalia; Roychoudhury, Pavitra; Greninger, Alexander L; Reeves, Daniel; Schiffer, Joshua; Jerome, Keith R; Sather, Cassandra; Diem, Kurt; Lingappa, Jairam R; Celum, Connie; Koelle, David M; Wald, Anna

    2017-12-01

    Quantitative estimation of the extent to which the immune system's protective effect against one herpes simplex virus type 2 (HSV-2) infection protects against infection with additional HSV-2 strains is important for understanding the potential for HSV-2 vaccine development. Using viral genotyping, we estimated the prevalence of HSV-2 dual-strain infection and identified risk factors. People with and without HIV infection participating in HSV-2 natural history studies (University of Washington Virology Research Clinic) and HIV prevention trials (HIV Prevention Trials Network 039 and Partners in Prevention HSV/HIV Transmission Study) in the US, Africa, and Peru with 2 genital specimens each containing ≥105 copies herpes simplex virus DNA/ml collected a median of 5 months apart (IQR: 2-11 months) were included. It is unlikely that 2 strains would be detected in the same sample simultaneously; therefore, 2 samples were required to detect dual-strain infection. We identified 85 HSV-2 SNPs that, in aggregate, could determine whether paired HSV-2 strains were the same or different with >90% probability. These SNPs were then used to create a customized high-throughput array-based genotyping assay. Participants were considered to be infected with more than 1 strain of HSV-2 if their samples differed by ≥5 SNPs between the paired samples, and dual-strain infection was confirmed using high-throughput sequencing (HTS). We genotyped pairs of genital specimens from 459 people; 213 (46%) were men, the median age was 34 years (IQR: 27-44), and 130 (28%) were HIV seropositive. Overall, 272 (59%) people were from the US, 59 (13%) were from Peru, and 128 (28%) were from 8 countries in Africa. Of the 459 people, 18 (3.9%) met the criteria for dual-strain infection. HTS and phylogenetic analysis of paired specimens confirmed shedding of 2 distinct HSV-2 strains collected at different times in 17 pairs, giving an estimated dual-strain infection prevalence of 3.7% (95% CI = 2

  16. Dual-strain genital herpes simplex virus type 2 (HSV-2 infection in the US, Peru, and 8 countries in sub-Saharan Africa: A nested cross-sectional viral genotyping study.

    Directory of Open Access Journals (Sweden)

    Christine Johnston

    2017-12-01

    Full Text Available Quantitative estimation of the extent to which the immune system's protective effect against one herpes simplex virus type 2 (HSV-2 infection protects against infection with additional HSV-2 strains is important for understanding the potential for HSV-2 vaccine development. Using viral genotyping, we estimated the prevalence of HSV-2 dual-strain infection and identified risk factors.People with and without HIV infection participating in HSV-2 natural history studies (University of Washington Virology Research Clinic and HIV prevention trials (HIV Prevention Trials Network 039 and Partners in Prevention HSV/HIV Transmission Study in the US, Africa, and Peru with 2 genital specimens each containing ≥105 copies herpes simplex virus DNA/ml collected a median of 5 months apart (IQR: 2-11 months were included. It is unlikely that 2 strains would be detected in the same sample simultaneously; therefore, 2 samples were required to detect dual-strain infection. We identified 85 HSV-2 SNPs that, in aggregate, could determine whether paired HSV-2 strains were the same or different with >90% probability. These SNPs were then used to create a customized high-throughput array-based genotyping assay. Participants were considered to be infected with more than 1 strain of HSV-2 if their samples differed by ≥5 SNPs between the paired samples, and dual-strain infection was confirmed using high-throughput sequencing (HTS. We genotyped pairs of genital specimens from 459 people; 213 (46% were men, the median age was 34 years (IQR: 27-44, and 130 (28% were HIV seropositive. Overall, 272 (59% people were from the US, 59 (13% were from Peru, and 128 (28% were from 8 countries in Africa. Of the 459 people, 18 (3.9% met the criteria for dual-strain infection. HTS and phylogenetic analysis of paired specimens confirmed shedding of 2 distinct HSV-2 strains collected at different times in 17 pairs, giving an estimated dual-strain infection prevalence of 3.7% (95% CI = 2

  17. Dual-strain genital herpes simplex virus type 2 (HSV-2) infection in the US, Peru, and 8 countries in sub-Saharan Africa: A nested cross-sectional viral genotyping study

    Science.gov (United States)

    Schiffer, Joshua; Sather, Cassandra; Diem, Kurt; Celum, Connie

    2017-01-01

    Background Quantitative estimation of the extent to which the immune system’s protective effect against one herpes simplex virus type 2 (HSV-2) infection protects against infection with additional HSV-2 strains is important for understanding the potential for HSV-2 vaccine development. Using viral genotyping, we estimated the prevalence of HSV-2 dual-strain infection and identified risk factors. Methods and findings People with and without HIV infection participating in HSV-2 natural history studies (University of Washington Virology Research Clinic) and HIV prevention trials (HIV Prevention Trials Network 039 and Partners in Prevention HSV/HIV Transmission Study) in the US, Africa, and Peru with 2 genital specimens each containing ≥105 copies herpes simplex virus DNA/ml collected a median of 5 months apart (IQR: 2–11 months) were included. It is unlikely that 2 strains would be detected in the same sample simultaneously; therefore, 2 samples were required to detect dual-strain infection. We identified 85 HSV-2 SNPs that, in aggregate, could determine whether paired HSV-2 strains were the same or different with >90% probability. These SNPs were then used to create a customized high-throughput array-based genotyping assay. Participants were considered to be infected with more than 1 strain of HSV-2 if their samples differed by ≥5 SNPs between the paired samples, and dual-strain infection was confirmed using high-throughput sequencing (HTS). We genotyped pairs of genital specimens from 459 people; 213 (46%) were men, the median age was 34 years (IQR: 27–44), and 130 (28%) were HIV seropositive. Overall, 272 (59%) people were from the US, 59 (13%) were from Peru, and 128 (28%) were from 8 countries in Africa. Of the 459 people, 18 (3.9%) met the criteria for dual-strain infection. HTS and phylogenetic analysis of paired specimens confirmed shedding of 2 distinct HSV-2 strains collected at different times in 17 pairs, giving an estimated dual-strain infection

  18. Prospects for inherently safe reactors

    International Nuclear Information System (INIS)

    Barkenbus, J.N.

    1988-01-01

    Public fears over nuclear safety have led some within the nuclear community to investigate the possibility of producing inherently safe nuclear reactors; that is, reactors that are transparently incapable of producing a core melt. While several promising designs of such reactors have been produced, support for large-scale research and development efforts has not been forthcoming. The prospects for commercialization of inherently safe reactors, therefore, are problematic; possible events such as further nuclear reactor accidents and superpower summits, could alter the present situation significantly. (author)

  19. Fusion blanket inherent safety assessment

    International Nuclear Information System (INIS)

    Sze, D.K.; Jung, J.; Cheng, E.T.

    1986-01-01

    Fusion has significant potential safety advantages. There is a strong incentive for designing fusion plants to ensure that inherent safety will be achieved. Accordingly, both the Tokamak Power Systems Studies and MINIMARS have identified inherent safety as a design goal. A necessary condition is for the blanket to maintain its configuration and integrity under all credible accident conditions. A main problem is caused by afterheat removal in an accident condition. In this regard, it is highly desirable to achieve the required level of protection of the plant capital investment and limitation of radioactivity release by systems that rely only on inherent properties of matter (e.g., thermal conductivity, specific heat, etc.) and without the use of active safety equipment. This paper assesses the conditions under which inherent safety is feasible. Three types of accident conditions are evaluated for two blankets. The blankets evaluated are a self cooled vanadium/lithium blanket and a self-cooled vanadium/Flibe blanket. The accident conditions evaluated are: (1) loss-of-flow accident; (2) loss-of-coolant accident (LOCA); and (3) partial loss-of-coolant accident

  20. The representation of inherent properties.

    Science.gov (United States)

    Prasada, Sandeep

    2014-10-01

    Research on the representation of generic knowledge suggests that inherent properties can have either a principled or a causal connection to a kind. The type of connection determines whether the outcome of the storytelling process will include intuitions of inevitability and a normative dimension and whether it will ground causal explanations.

  1. Frequent detection of HPV before and after initiation of antiretroviral therapy among HIV/HSV-2 co-infected women in Uganda.

    Directory of Open Access Journals (Sweden)

    Anne F Rositch

    Full Text Available Most data on HPV and antiretroviral therapy (ART come from high-resource countries with infrequent sampling for HPV pre- and post-ART initiation. Therefore, we examined the frequency of cervical HPV DNA detection among HIV/HSV-2 co-infected women followed monthly for 6 months both before and after initiation of ART in Rakai, Uganda.Linear Array was used to detect 37 HPV genotypes in self-collected cervicovaginal swabs from 96 women who initiated ART. Random-effects log-binomial regression was used to compare the prevalence of HPV detection in the pre- and post-ART periods and determine other potential risk factors, including CD4 counts and HIV viral load.Nearly all women had detectable HPV in the 6 months preceding ART initiation (92% and the cumulative prevalence remained high following initiation of therapy (90%. We found no effect of ART on monthly HPV DNA detection (prevalence ratio: 1.0; 95% confidence interval: 0.96, 1.08, regardless of immune reconstitution or HIV viral suppression. Older age and higher pre-ART CD4 counts were associated with a significantly lower risk of HPV DNA detection.ART did not impact HPV detection within 6 months of therapy initiation, highlighting the importance of continued and consistent screening, even after ART-initiation and immune reconstitution.

  2. Intravaginal infection with herpes simplex virus type-2 (HSV-2) generates a functional effector memory T cell population that persists in the murine genital tract.

    Science.gov (United States)

    Tang, Vera A; Rosenthal, Kenneth L

    2010-12-01

    Although the female genital tract is the main portal of entry for sexually transmitted infections in women, we still have limited understanding of the generation, maintenance and characteristics of memory T cells in the local tissue. Here, we utilized a mouse model of intravaginal HSV-2 infection and tetramers against the immunodominant HSV glycoprotein B epitope recognized by CD8+ T cells to examine the generation, maintenance and characteristics of anti-HSV memory T cells in the genital tract following acute infection. Our results show that the highest percentage of HSVgB-specific CD8+ T cells was found in the genital tract compared to the spleen or iliac lymphnode. Indeed, although the actual number of CD8+ T cells contracted following viral clearance, approximately one quarter of the CD8+ population that remained in the genital tissue was HSVgB-specific. Memory gB-tetramer+CD8 T cells in the genital tract were positive for CD127 and KLRG1 and negative for CD62L and CCR7, thus confirming that HSV-specific CD8 cells were effector memory T cells that lack the capacity for homing to lymphoid tissues. Functionally, both memory CD8+ and CD4+ HSV-specific populations in the genital tract produced IFNγ when stimulated in vitro and CD4+ cells also produced TNFα. Genital HSVgB-specific memory T cells expressed tissue-homing integrins CD103 (αE integrin) and CD49a (VLA-1 or α1 integrin). Our findings suggest that HSV-specific memory T cells are retained in the genital tract, poised to act as an early line of defense against future virus encounter. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue

    Directory of Open Access Journals (Sweden)

    Seok Joong Yun

    2016-06-01

    Full Text Available Purpose: Previously, we reported the presence of virus-encoded microRNAs (miRNAs in the urine of prostate cancer (CaP patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. Methods: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH, 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR and immunocytochemistry using nanoparticles as molecular beacons. Results: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001. Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9. Conclusions: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.

  4. HSV-1/HSV-2 Infection-Related Cancers in Bantu Populations Driving HIV-1 Prevalence in Africa: Tracking the Origin of AIDS at the Onset of the 20th Century.

    Science.gov (United States)

    Le Goaster, Jacqueline; Bouree, Patrice; El Sissy, Franck N; Phuong Bui, Florence; Pokossy Epee, Johanna; Rollin, Paul; Tangy, Frédéric; Haenni, Anne-Lise

    2016-01-01

    At the onset of the 20th century, ancient clinical observations of cancer epidemics in Bantu populations of Sub-Saharan Africa were discovered. They were reported from 1914 to 1960, but remained unexplained. In 1983, in San Francisco, Calif., USA, cancer epidemics were related to infections by the human immunodeficiency virus type 1 (HIV-1) known as AIDS disease. Yet since 1996, it is known that HIV-1 strains are not the only ones involved. In Sub-Saharan Africa, recurrent orobuccal herpes simplex virus type 1 (HSV-1) and genital recurrent herpes simplex virus type 2 (HSV-2) appeared many times prior to infection by HIV-1. Data on these ancient medical observations regarding African cancer epidemics can today be referred to as the relationship between the unfortunate immune deficiency of herpes in Bantu populations and HIV-1 viral strains. For centuries, the Bantu populations dispersed in forests were living in close proximity to chimpanzees infected by simian immunodeficiency virus (SIV) and were exposed to SIV contamination which became HIV-1 in human beings. Presently, these unexplained Bantu cancer epidemics can be linked to the viral partnership of HSV-1/HSV-2 to HIV-1 strains. The key issue is now to prevent HSV-1/HSV-2 diseases related to HIV-1. An anti-herpes treatment administered early during childhood to Bantu populations will offer a mean of preventing herpes diseases related to HIV-1 infection and hence avoid cancer epidemics.

  5. Protection from genital herpes disease, seroconversion and latent infection in a non-lethal murine genital infection model by immunization with an HSV-2 replication-defective mutant virus.

    Science.gov (United States)

    Diaz, Fernando M; Knipe, David M

    2016-01-15

    Viral vaccines have traditionally protected against disease, but for viruses that establish latent infection, it is desirable for the vaccine to reduce infection to reduce latent infection and reactivation. While seroconversion has been used in clinical trials of herpes simplex virus (HSV) vaccines to measure protection from infection, this has not been modeled in animal infection systems. To measure the ability of a genital herpes vaccine candidate to protect against various aspects of infection, we established a non-lethal murine model of genital HSV-2 infection, an ELISA assay to measure antibodies specific for infected cell protein 8 (ICP8), and a very sensitive qPCR assay. Using these assays, we observed that immunization with HSV-2 dl5-29 virus reduced disease, viral shedding, seroconversion, and latent infection by the HSV-2 challenge virus. Therefore, it may be feasible to obtain protection against genital disease, seroconversion and latent infection by immunization, even if sterilizing immunity is not achieved. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. HSV-1/HSV-2 Infection-Related Cancers in Bantu Populations Driving HIV-1 Prevalence in Africa: Tracking the Origin of AIDS at the Onset of the 20th Century

    Directory of Open Access Journals (Sweden)

    Jacqueline Le Goaster

    2016-11-01

    Full Text Available Introduction: At the onset of the 20th century, ancient clinical observations of cancer epidemics in Bantu populations of Sub-Saharan Africa were discovered. They were reported from 1914 to 1960, but remained unexplained. In 1983, in San Francisco, Calif., USA, cancer epidemics were related to infections by the human immunodeficiency virus type 1 (HIV-1 known as AIDS disease. Yet since 1996, it is known that HIV-1 strains are not the only ones involved. In Sub-Saharan Africa, recurrent orobuccal herpes simplex virus type 1 (HSV-1 and genital recurrent herpes simplex virus type 2 (HSV-2 appeared many times prior to infection by HIV-1. Case Reports: Data on these ancient medical observations regarding African cancer epidemics can today be referred to as the relationship between the unfortunate immune deficiency of herpes in Bantu populations and HIV-1 viral strains. For centuries, the Bantu populations dispersed in forests were living in close proximity to chimpanzees infected by simian immunodeficiency virus (SIV and were exposed to SIV contamination which became HIV-1 in human beings. Presently, these unexplained Bantu cancer epidemics can be linked to the viral partnership of HSV-1/HSV-2 to HIV-1 strains. Conclusion: The key issue is now to prevent HSV-1/HSV-2 diseases related to HIV-1. An anti-herpes treatment administered early during childhood to Bantu populations will offer a mean of preventing herpes diseases related to HIV-1 infection and hence avoid cancer epidemics.

  7. MHTGR inherent heat transfer capability

    International Nuclear Information System (INIS)

    Berkoe, J.M.

    1992-01-01

    This paper reports on the Commercial Modular High Temperature Gas-Cooled Reactor (MHTGR) which achieves improved reactor safety performance and reliability by utilizing a completely passive natural convection cooling system called the RCCS to remove decay heat in the event that all active cooling systems fail to operate. For the highly improbable condition that the RCCS were to become non-functional following a reactor depressurization event, the plant would be forced to rely upon its inherent thermo-physical characteristics to reject decay heat to the surrounding earth and ambient environment. A computational heat transfer model was created to simulate such a scenario. Plant component temperature histories were computed over a period of 20 days into the event. The results clearly demonstrate the capability of the MHTGR to maintain core integrity and provide substantial lead time for taking corrective measures

  8. Inherent/passive safety for fusion

    International Nuclear Information System (INIS)

    Piet, S.J.

    1986-06-01

    The concept of inherent or passive passive safety for fusion energy is explored, defined, and partially quantified. Four levels of safety assurance are defined, which range from true inherent safety to passive safety to protection via active engineered safeguard systems. Fusion has the clear potential for achieving inherent or passive safety, which should be an objective of fusion research and design. Proper material choice might lead to both inherent safety and high mass power density, improving both safety and economics. When inherent safety is accomplished, fusion will be well on the way to achieving its ultimate potential and to be truly different and superior

  9. Cutting Edge: Genetic Association between IFI16 Single Nucleotide Polymorphisms and Resistance to Genital Herpes Correlates with IFI16 Expression Levels and HSV-2-Induced IFN-β Expression.

    Science.gov (United States)

    Eriksson, Kristina; Svensson, Alexandra; Hait, Alon S; Schlüter, Kerstin; Tunbäck, Petra; Nordström, Inger; Padyukov, Leonid; Liljeqvist, Jan-Åke; Mogensen, Trine H; Paludan, Søren R

    2017-10-15

    IFN-γ-inducible protein 16 (IFI16) is an immunological DNA sensor proposed to act in the cyclic GMP-AMP synthase-stimulator of IFN genes pathway. Because mice do not have a clear ortholog of IFI16, this system is not suitable for genetic studies of IFI16. In this study, we have compared the dependency on IFI16, cyclic GMP-AMP synthase, and stimulator of IFN genes for type I IFN induction by a panel of pathogenic bacteria and DNA viruses. The IFN response induced by HSV-2 was particularly dependent on IFI16. In a cohort of patients with genital herpes and healthy controls, the minor G allele of the IFI16 single nucleotide polymorphism rs2276404 was associated with resistance to infection. Furthermore, the combination of this allele with the C allele of rs1417806 was significantly overrepresented in uninfected individuals. Cells from individuals with the protective GC haplotype expressed higher levels of IFI16 and induced more IFN-β upon HSV-2 infection. These data provide genetic evidence for a role for IFI16 in protection against genital herpes. Copyright © 2017 by The American Association of Immunologists, Inc.

  10. ‘It’s not about money, it’s about my health’: determinants of participation and adherence among women in an HIV-HSV2 prevention trial in Johannesburg, South Africa

    Directory of Open Access Journals (Sweden)

    MacPhail C

    2012-08-01

    Full Text Available Catherine MacPhail,1 Sinead Delany-Moretlwe,1 Philippe Mayaud21Wits Reproductive Health and HIV Institute, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, South Africa; 2Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UKAbstract: High levels of adherence in clinical trials are essential for producing accurate intervention efficacy estimates. Adherence to clinical trial products and procedures is dependent on the motivations that drive participants. Data are presented to document reasons for trial participation and adherence to daily aciclovir for HSV-2 and HIV-1 genital shedding suppression among 300 HIV-1/HSV-2 seropositive women in South Africa. In-depth interviews after exit from the trial with 31 randomly selected women stratified by age and time since HIV diagnosis confirmed high levels of adherence measured during the trial. Main reasons for trial participation were related to seeking high-quality health care, which explains high levels of adherence in both study arms. Concerns that women would abuse reimbursements, fabricate data, and share or dump pills were not corroborated. Altruism is not a primary motivator in these settings where access to quality services is an issue. This study provides further evidence that good adherence of daily medication is possible in developing countries, particularly where study activities resonate with participants or fill an unmet need.Keywords: adherence, trial, HIV prevention, South Africa

  11. Genomes

    National Research Council Canada - National Science Library

    Brown, T. A. (Terence A.)

    2002-01-01

    ... of genome expression and replication processes, and transcriptomics and proteomics. This text is richly illustrated with clear, easy-to-follow, full color diagrams, which are downloadable from the book's website...

  12. Does partner selection mediate the relationship between school attendance and HIV/HSV-2 among adolescent girls and young women in South Africa: An analysis of HPTN 068 data.

    Science.gov (United States)

    Stoner, Marie Cd; Edwards, Jessie K; Miller, William C; Aiello, Allison E; Halpern, Carolyn T; Julien, Aimée; Rucinski, Katherine B; Selin, Amanda; Twine, Rhian; Hughes, James P; Wang, Jing; Agyei, Yaw; Gómez-Olivé, F Xavier; Wagner, Ryan G; Laeyendecker, Oliver; Macphail, Catherine; Kahn, Kathleen; Pettifor, Audrey

    2018-05-22

    Similar prior publications by the first author using the same data source include: Stoner M.C.D, Edwards J, Miller W, Aiello A, Halpern C, Selin A, Hughes J, Wang J, Laeyendecker O, Agyei Y, McPhail C, Kahn K, Pettifor A.(2017) The effect of schooling on incident HIV and HSV-2 infection in young South African women enrolled in HPTN 068. AIDS. 24;31(15):2127-213. PMC5599334. Stoner M.C.D, Edwards J, Miller W, Aiello A, Halpern C, Julien Suarez, Selin A, Hughes J, Wang J, McPhail C, Kahn K, Pettifor A. (2017) The effect of schooling on age-disparate relationships and number of sexual partners among young women in rural South Africa enrolled in HPTN 068. J Acquir Immune Defic Syndr. 76 (5):e107-e114. PMC56801112This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.Abstract OBJECTIVE:: School attendance prevents HIV and HSV-2 in adolescent girls and young women (AGYW) but the mechanisms to explain this relationship remain unclear. Our study assesses the extent to which characteristics of sex partners, partner age and number, mediate the relationship between attendance and risk of infection in AGYW in South Africa. We use longitudinal data from the HPTN 068 randomized controlled trial in rural South Africa where girls were enrolled in early adolescence and followed in the main trial for over three years. We examined older partners and number of partners as possible mediators. We use the parametric g-formula to estimate 4-year risk differences for the effect of school attendance on cumulative incidence of HIV/HSV-2 overall and the controlled direct effect (CDE) for mediation. We examined mediation separately and jointly for the mediators of interest. We found that young women with high attendance in school had

  13. Can the inherence heuristic explain vitalistic reasoning?

    Science.gov (United States)

    Bastian, Brock

    2014-10-01

    Inherence is an important component of psychological essentialism. By drawing on vitalism as a way in which to explain this link, however, the authors appear to conflate causal explanations based on fixed features with those based on general causal forces. The disjuncture between these two types of explanatory principles highlights potential new avenues for the inherence heuristic.

  14. Inherently safe characteristics of nuclear reactors

    International Nuclear Information System (INIS)

    1989-01-01

    This report is based on a detailed study which was carried out by Colenco (a company of the Motor-Columbus Group) on behalf of the Commission of the European Communities (CEC). It presents a summary of this study and concentrates more on the generic issues involved in the subject of inherent safety in nuclear power plants. It is assumed that the reader is reasonably familiar with the design outline of the systems included in the report. The report examines the role of inherent design features in achieving the safety of nuclear power plants as an alternative to the practice, which is largely followed in current reactors, of achieving safety by the addition of engineered safety features. The report examines current reactor systems to identify the extent to which their characteristics are either already inherently safe or, on the other hand, have inherent characteristics that require protective action to be taken. It then considers the advantages of introducing design changes to improve their inherent safety characteristics. Next, it looks at some new reactor types for which claims of inherent safety are made to see to what extent these claims are justified. The general question is then considered whether adoption of the inherently safe reactors would give advantages (by reducing risk in real terms or by improving the public acceptability of nuclear power) which are sufficient to offset the expected high costs and the technical risks associated with any new technology

  15. Licensing issues for inherently safe fast reactors

    International Nuclear Information System (INIS)

    Kastenberg, W.E.; Lee, S.; Okrent, D.

    1986-01-01

    There has been considerable interest recently in a new generation of liquid metal reactor (LMR) concepts in the US. Some significant changes in regulatory philosophy will be required if the anticipated cost advantages of inherently safe designs are to be achieved. The defense in depth philosophy will need to be significantly re-evaluated in the context of inherently safe reactors. It is the purpose of this paper to begin such a re-evaluation of this regulatory philosophy

  16. Implications of inherent safe nuclear power system

    International Nuclear Information System (INIS)

    Song, Yo-Taik

    1987-01-01

    The safety of present day nuclear power reactors and research reactors depends on a combination of design features of passive and active systems, and the alert judgement of their operators. A few inherently safe designs of nuclear reactors for power plants are currently under development. In these designs, the passive systems are emphasized, and the active systems are minimized. Also efforts are made to eliminate the potential for human failures that initiate the series of accidents. If a major system fails in these designs, the core is flooded automatically with coolants that flow by gravity, not by mechanical pumps or electromagnetic actuators. Depending on the choice of the coolants--water, liquid metal and helium gas--there are three principal types of inherently safe reactors. In this paper, these inherently safe reactor designs are reviewed and their implications are discussed. Further, future perspectives of their acceptance by nuclear industries are discussed. (author)

  17. Informing patients of risks inherent in treatment.

    Science.gov (United States)

    Griffith, Richard; Tengnah, Cassam

    2009-11-01

    Consent to treatment lies at the heart of autonomous decision making by patients who are entitled to make a free choice about whether to accept or refuse treatment. To help patients arrive at their decision district nurses must ensure that they give sufficient information about the nature and risks inherent in the treatment to allow an informed choice to be made. This article considers how much information regarding risks needs to be disclosed. It discusses how the law requires a different level of disclosure for patients who ask no questions about risks, those who make general enquiries about risks and those who ask specific questions about the risks inherent in treatment.

  18. Students' Perception of Live Lectures' Inherent Disadvantages

    Science.gov (United States)

    Petrovic, Juraj; Pale, Predrag

    2015-01-01

    This paper aims to provide insight into various properties of live lectures from the perspective of sophomore engineering students. In an anonymous online survey conducted at the Faculty of Electrical Engineering and Computing, University of Zagreb, we investigated students' opinions regarding lecture attendance, inherent disadvantages of live…

  19. An inherently safe power reactor module

    International Nuclear Information System (INIS)

    Salerno, L.N.

    1985-01-01

    General Electric's long participation in liquid metal reactor technology has led to a Power Reactor Inherently Safe Module (PRISM) concept supported by DOE contract DE-AC06-85NE37937. The reactor module is sized to maximize inherent safety features. The small size allows factory fabrication, reducing field construction and field QA/QC labor, and allows safety to be demonstrated in full scale, to support a pre-licensed standard commercial product. The module is small enough to be placed underground, and can be combined with steam and electrical generating equipment to provide a complete electrical power producing plant in the range of 400-1200 MWe. Initial assessments are that the concept has the potential to be economically competitive with existing methods of power production used by the utility industry

  20. Inherently safe technologies-chemical and nuclear

    International Nuclear Information System (INIS)

    Weinberg, A.M.

    1984-01-01

    Probabilistic risk assessments show an inverse relationship between the likelihood and the consequences of nuclear and chemical plant accidents, but the Bhopal accident has change public complacency about the safety of chemical plants to such an extent that public confidence is now at the same low level as with nuclear plants. The nuclear industry's response was to strengthen its institutions and improve its technologies, but the public may not be convinced. One solution is to develop reactors which do not depend upon the active intervention of humans of electromechanical devices to deal with emergencies, but which have physical properties that limit the possible temperature and power of a reactor. The Process Inherent Ultimately Safe and the modular High-Temperature Gas-Cooled reactors are two possibilities. the chemical industry needs to develop its own inherently safe design precepts that incorporate smallness, safe processes, and hardening against sabotage. 5 references

  1. A general index of inherent risk

    OpenAIRE

    Schnytzer, Adi; Westreich, Sara

    2009-01-01

    We extend the pioneering work of Aumann and Serrano by presenting an index of inherent riskiness of a gamble having the desirable properties of their index, while being applicable to gambles with either positive or negative expectations. As such, our index provides a measure of riskiness which is of use for both risk lovers and risk aversive gamblers, and is defined for all discrete and a large class of continuous gambles. We analyze abstract properties of our index, and present in addition t...

  2. Iser: an international inherently safe reactor concept

    International Nuclear Information System (INIS)

    Wakabayashi, Hiroaki

    1988-01-01

    Iser is a modular standardised 200-300 MWe power reactor based on the PIUS principle. It differs from PIUS in being simpler, and making full use of existing steel-vessel-based LWR technology. Iser is an inherently safe reactor concept under development in Japan. It is a generic concept, not a patented commodity, and it is expected that an international association to develop the concept will be formed. (U.K.)

  3. Integral fast reactor concept inherent safety features

    International Nuclear Information System (INIS)

    Marchaterre, J.F.; Sevy, R.H.; Cahalan, J.E.

    1987-01-01

    The Integral Fast Reactor (IFR) is an innovative liquid-metal-cooled reactor concept being developed at Argonne National Laboratory. The two major goals of the IFT development effort are improved economics and enhanced safety. The design features that together fulfill these goals are: 1) a liquid metal (sodium) coolant, 2) a pool-type reactor primary system configuration, 3) an advanced ternary alloy metallic fuel, and 4) an integral fuel cycle. This paper reviews the design features that contribute to the safety margins inherent to the IFR concept. Special emphasis is placed on the ability of the IFR design to accommodate anticipated transients without scram (ATWS)

  4. Integral Fast Reactor concept inherent safety features

    International Nuclear Information System (INIS)

    Marchaterre, J.F.; Sevy, R.H.; Cahalan, J.E.

    1986-01-01

    The Integral Fast Reactor (IFR) is an innovative liquid-metal-cooled reactor concept being developed at Argonne National Laboratory. The two major goals of the IFR development effort are improved economics and enhanced safety. The design features that together fulfill these goals are: (1) a liquid metal (sodium) coolant, (2) a pool-type reactor primary system configuration, (3) an advanced ternary alloy metallic fuel, and (4) an integral fuel cycle. This paper reviews the design features that contribute to the safety margins inherent to the IFR concept. Special emphasis is placed on the ability of the IFR design to accommodate anticipated transients without scram (ATWS)

  5. Is human fracture hematoma inherently angiogenic?

    LENUS (Irish Health Repository)

    Street, J

    2012-02-03

    This study attempts to explain the cellular events characterizing the changes seen in the medullary callus adjacent to the interfragmentary hematoma during the early stages of fracture healing. It also shows that human fracture hematoma contains the angiogenic cytokine vascular endothelial growth factor and has the inherent capability to induce angiogenesis and thus promote revascularization during bone repair. Patients undergoing emergency surgery for isolated bony injury were studied. Raised circulating levels of vascular endothelial growth factor were seen in all injured patients, whereas the fracture hematoma contained significantly higher levels of vascular endothelial growth factor than did plasma from these injured patients. However, incubation of endothelial cells in fracture hematoma supernatant significantly inhibited the in vitro angiogenic parameters of endothelial cell proliferation and microtubule formation. These phenomena are dependent on a local biochemical milieu that does not support cytokinesis. The hematoma potassium concentration is cytotoxic to endothelial cells and osteoblasts. Subcutaneous transplantation of the fracture hematoma into a murine wound model resulted in new blood vessel formation after hematoma resorption. This angiogenic effect is mediated by the significant concentrations of vascular endothelial growth factor found in the hematoma. This study identifies an angiogenic cytokine involved in human fracture healing and shows that fracture hematoma is inherently angiogenic. The differences between the in vitro and in vivo findings may explain the phenomenon of interfragmentary hematoma organization and resorption that precedes fracture revascularization.

  6. Inherently safe in situ uranium recovery

    International Nuclear Information System (INIS)

    Krumhansl, James Lee; Beauheim, Richard Louis; Brady, Patrick Vane; Arnold, Bill Walter; Kanney, Joseph F.; McKenna, Sean Andrew

    2009-01-01

    Expansion of uranium mining in the United States is a concern to some environmental groups and sovereign Native American Nations. An approach which may alleviate some problems is to develop inherently safe in situ uranium recovery ('ISR') technologies. Current ISR technology relies on chemical extraction of trace levels of uranium from aquifers that, once mined, can still contain dissolved uranium and other trace metals that are a health concern. Existing ISR operations are few in number; however, high uranium prices are driving the industry to consider expanding operations nation-wide. Environmental concerns and enforcement of the new 30 ppb uranium drinking water standard may make opening new mining operations more difficult and costly. Here we propose a technological fix: the development of inherently safe in situ recovery (ISISR) methods. The four central features of an ISISR approach are: (1) New 'green' leachants that break down predictably in the subsurface, leaving uranium, and associated trace metals, in an immobile form; (2) Post-leachant uranium/metals-immobilizing washes that provide a backup decontamination process; (3) An optimized well-field design that increases uranium recovery efficiency and minimizes excursions of contaminated water; and (4) A combined hydrologic/geochemical protocol for designing low-cost post-extraction long-term monitoring. ISISR would bring larger amounts of uranium to the surface, leave fewer toxic metals in the aquifer, and cost less to monitor safely - thus providing a 'win-win-win' solution to all stakeholders.

  7. Sensors and actuators inherent in biological species

    Science.gov (United States)

    Taya, Minoru; Stahlberg, Rainer; Li, Fanghong; Zhao, Ying Joyce

    2007-04-01

    This paper addresses examples of sensing and active mechanisms inherent in some biological species where both plants and animals cases are discussed: mechanosensors and actuators in Venus Fly Trap and cucumber tendrils, chemosensors in insects, two cases of interactions between different kingdoms, (i) cotton plant smart defense system and (ii) bird-of-paradise flower and hamming bird interaction. All these cases lead us to recognize how energy-efficient and flexible the biological sensors and actuators are. This review reveals the importance of integration of sensing and actuation functions into an autonomous system if we make biomimetic design of a set of new autonomous systems which can sense and actuate under a number of different stimuli and threats.

  8. The inherent limits of predicting school violence.

    Science.gov (United States)

    Mulvey, E P; Cauffman, E

    2001-10-01

    The recent media hype over school shootings has led to demands for methods of identifying school shooters before they act. Despite the fact that schools remain one of the safest places for youths to be, schools are beginning to adopt identification systems to determine which students could be future killers. The methods used to accomplish this not only are unproven but are inherently limited in usefulness and often do more harm than good for both the children and the school setting. The authors' goals in the present article are to place school shootings in perspective relative to other risks of violence that children face and to provide a reasonable and scientifically defensible approach to improving the safety of schools.

  9. Inherent Error in Asynchronous Digital Flight Controls.

    Science.gov (United States)

    1980-02-01

    operation will be eliminated. If T* is close to T, the inherent error (eA) is a small value. Then the deficiency of the basic model, which is de... tK2 at m ~VCONTR0RKIPPIL I~+ R tKT 2 TKT 5 ~I G E 1 i V OTN TRIL 2-REDN HNE IjT e UT 3 ~49__I 4.) 4 -4 - 4.-4 U 4.) k-4E-- Iz E-4 P E-44)-4. 4.)l 1s...indicate the channel failure. To reduce this deficiency , the new model computes a tolerance value equal to the maximum steady-state sample covariance of the

  10. Inherently safe in situ uranium recovery

    Science.gov (United States)

    Krumhansl, James L; Brady, Patrick V

    2014-04-29

    An in situ recovery of uranium operation involves circulating reactive fluids through an underground uranium deposit. These fluids contain chemicals that dissolve the uranium ore. Uranium is recovered from the fluids after they are pumped back to the surface. Chemicals used to accomplish this include complexing agents that are organic, readily degradable, and/or have a predictable lifetime in an aquifer. Efficiency is increased through development of organic agents targeted to complexing tetravalent uranium rather than hexavalent uranium. The operation provides for in situ immobilization of some oxy-anion pollutants under oxidizing conditions as well as reducing conditions. The operation also artificially reestablishes reducing conditions on the aquifer after uranium recovery is completed. With the ability to have the impacted aquifer reliably remediated, the uranium recovery operation can be considered inherently safe.

  11. Geometries inherent to N=1 supergravities

    International Nuclear Information System (INIS)

    Galperin, A.S.; Ogievetsky, V.I.; Sokatchev, E.S.

    1981-01-01

    The first part of the talk is devoted to a consideration of linearized N=1 supergravities. The second main part deals with complex geometries inherent to different N=1 supergravities. A special attention is paid to a new version with local symmetry. It is connected to the special nonminimal case (n=0) having a remarkable property of supervolume preservation in Csup(4.4) superspace. Therefore the superdeterminant of change of variables from left to right-handed Rsup(4.4) parametrization is a dimensionless scalar. This geometric invariant has to be constrained to obtain an action. Solving such a constraint on vector and spinor prepotentials in Wess-Zumino gauge one obtains the new supergravity with 12+12 fields and local symmetry. A possible relaxation of this constraint is briefly considered (16+16 fields version) [ru

  12. Magnetic latch trigger for inherent shutdown assembly

    International Nuclear Information System (INIS)

    Sowa, E.S.

    1976-01-01

    An inherent shutdown assembly for a nuclear reactor is provided. A neutron absorber is held ready to be inserted into the reactor core by a magnetic latch. The latch includes a magnet whose lines of force are linked by a yoke of material whose Curie point is at the critical temperature of the reactor at which the neutron absorber is to be inserted into the reactor core. The yoke is in contact with the core coolant or fissionable material so that when the coolant or the fissionable material increase in temperature above the Curie point the yoke loses its magnetic susceptibility and the magnetic link is broken, thereby causing the absorber to be released into the reactor core. 6 claims, 3 figures

  13. Inherent safety characteristics of innovative reactors

    International Nuclear Information System (INIS)

    Heil, J.A.

    1995-11-01

    The added safety value of innovative or third generation reactor designs has been evaluated in order to determine the most suitable candidate for Dutch government funded research and development support. To this end, four innovative reactor concepts, viz. PIUS (Process Inherent Ultimate Safety), PRISM (Power Reactor Innovative Small), HTR-M (High Temperature Reactor Module) and MHTGR (Modular High Temperature Gas-cooled Reactor), have been studied and their passive and inherent safety characteristics have been outlined. Also the outlook for further technological and industrial development has been considered. The results of the study confirm the perspective of the innovative reactors for reduced dependence on active safety provisions and for a further reduced vulnerability to technical failures and human errors. The accident responses to generic accident initiators, viz. reactivity and cooling accidents, and also to reactor specific accidents show that neither active safety systems nor short term operator actions are required for maintaining the reactor core in a controlled and coolable condition. Whether this gives rise to a higher total safety of the innovative reactor designs, compared to evolutionary or advanced reactors, cannot be concluded. Supplementary experimental and analytical analyses of reactor specific accidents are required to be able to assess the safety of these innovative designs in a more quantitative manner. It is believed that the safety case of innovative reactors, which are less dependent on active safety systems, can be communicated with the general public in a more transparent way. Considering the perspective for further technological and industrial development it is not expected that any of the considered innovative reactor concepts will become commercially available within the next one to two decades. However, they could be made available earlier if they would receive sufficient financial backing. Considering the added safety perspectives

  14. Inherent safety, ethics and human error.

    Science.gov (United States)

    Papadaki, Maria

    2008-02-11

    stated. The reason this article is presented here is that I believe that often, complex accidents, similarly to insignificant ones, often demonstrate an attitude which can be characterized as "inherently unsafe". I take the view that the enormous human potential and the human ability to minimize accidents needs to become a focal point towards inherent safety. Restricting ourselves to human limitations and how we could "treat" or prevent humans from not making accidents needs to be re-addressed. The purpose of this presentation is to highlight observations and provoke a discussion on how we could possibly improve the understanding of safety related issues. I do not intent to reject or criticize existing methodologies. (The entire presentation is strongly influenced by Trevor Kletz's work although our views are often different.).

  15. Conceptual design of inherently safe integral reactor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J. I.; Chang, M. H.; Lee, D. J. and others

    1999-03-01

    The design concept of a 300 MWt inherently safe integral reactor(ISIR) for the propulsion of extra large and superhigh speed container ship was developed in this report. The scope and contents of this report are as follows : 1. The state of the art of the technology for ship-mounted reactor 2. Design requirements for ISIR 3. Fuel and core design 4. Conceptual design of fluid system 5. Conceptual design of reactor vessel assembly and primary components 6. Performance analyses and safety analyses. Installation of two ISIRs with total thermal power of 600MWt and efficiency of 21% is capable of generating shaft power of 126,000kW which is sufficient to power a container ship of 8,000TEU with 30knot cruise speed. Larger and speedier ship can be considered by installing 4 ISIRs. Even though the ISIR was developed for ship propulsion, it can be used also for a multi-purpose nuclear power plant for electricity generation, local heating, or seawater desalination by mounting on a movable floating barge. (author)

  16. The Inherent Asymmetry of DNA Replication.

    Science.gov (United States)

    Snedeker, Jonathan; Wooten, Matthew; Chen, Xin

    2017-10-06

    Semiconservative DNA replication has provided an elegant solution to the fundamental problem of how life is able to proliferate in a way that allows cells, organisms, and populations to survive and replicate many times over. Somewhat lost, however, in our admiration for this mechanism is an appreciation for the asymmetries that occur in the process of DNA replication. As we discuss in this review, these asymmetries arise as a consequence of the structure of the DNA molecule and the enzymatic mechanism of DNA synthesis. Increasing evidence suggests that asymmetries in DNA replication are able to play a central role in the processes of adaptation and evolution by shaping the mutagenic landscape of cells. Additionally, in eukaryotes, recent work has demonstrated that the inherent asymmetries in DNA replication may play an important role in the process of chromatin replication. As chromatin plays an essential role in defining cell identity, asymmetries generated during the process of DNA replication may play critical roles in cell fate decisions related to patterning and development.

  17. Improved inherent safety in liquid fuel reactors

    International Nuclear Information System (INIS)

    Taube, M.

    1982-01-01

    The molten salt reactor system divided into core (thermal and fast) and breeding zone (fission breeder reactor, fusion hybrid system, accelerator-spallation system) has some unique inherent safety properties: a) reduced inventory of fission products during normal operation due to on-line chemical reprocessing and in-core gas purging; b) fast removal of freshly bred fissile nuclides and fission products from the breeding zone (the so called suppressed fission system); c) pressureless fuel and primary coolant system; d) elimination of the possibility of a violent exoenergetic chemical reaction with air, water or metals; e) elimination of the possibility of gaseous hydrogen production during an accident; f) provides a non-engineered feature of dumping of fuel from the core and heat exchanger to a safe drain tank; g) presence of a large heat sink in the form of an inactive diluent salt; h) possibility of natural convection heat removal during an accident and even normal operation (by means of gas lifting); i) dissipation of the remaining decayheat by spraying water on the containment from outside, which allows to manage the worst accident; i) Even in the case of the destruction in the war by conventional or nuclear weapon the contaminated land is significantly reduced. The world-wide present activity in the field of molten salt technology is reviewed. (orig.)

  18. Measurement of inherent optical properties in the Arabian Sea

    Digital Repository Service at National Institute of Oceanography (India)

    Suresh, T.; Desa, E.; Kurian, J.; Mascarenhas, A.A.M.Q.

    Inherent optical properties, absorption and began attenuation were measured in situ using a reflective tube absorption meter at nint wavelength, 412, 440, 488, 510, 555, 630, 650, 676 and 715 nm, in the Arabian Sea during March. Since inherent...

  19. Inherent/passive safety in fusion power plants

    International Nuclear Information System (INIS)

    Piet, S.J.; Crocker, J.G.

    1986-01-01

    The concept of inherent or passive safety for fusion energy is explored, defined, and partially quantified. Four levels of safety assurance are defined, which range from true inherent safety to passive safety to protection via active engineered safeguard systems. Fusion has the clear potential for achieving inherent or passive safety, which should be an objective of fusion research and design. Proper material choice might lead to both inherent/passive safety and high mass power density, improving both safety and economics. When inherent or passive safety is accomplished, fusion will be well on the way to achieving its ultimate potential and to be a truly superior energy source for the future

  20. The inherently-safe power reactor DYONISOS (Dynamic Nuclear Inherently-Safe Reactor Operating with Spheres)

    International Nuclear Information System (INIS)

    Taube, M.; Lanfranchi, M.; Weissenfluh, Th. von; Ligou, J.; Yadigaroglu, G.; Taube, P.

    1986-01-01

    A philosophy of inherent safety is formulated and an inherently-safe thermal power reactor is presented. Solid fuel in the form of spheres a few centimetres in diameter is suspended under the hydro-dynamic pressure of molten lead coolant in vertical channels within the graphite moderator. Loss of main pump pressure, or a loss-of-coolant accident (LOCA), results in immediate removal of the fuel to rigid sieves below the core, with consequent subcriticality. Residual and decay heat are carried away by thermal conduction through the coolant or, in the case of a LOCA, by a combination of radiation and natural convection of cover gas or incoming air from the fuel to the reactor vessel and convection of air between the vessel and steel containment wall. All decay heat removal systems are passive, though actively initiated external spray cooling of the containment can be used to reduce wall temperature. This, however, is only necessary in the case of a LOCA and after a period of 24 h. (author)

  1. The genome of herpesvirus papio 2 is closely related to the genomes of human herpes simplex viruses.

    Science.gov (United States)

    Bigger, John E; Martin, David W

    2003-06-01

    Infection of baboons (Papio species) with herpesvirus papio 2 (HVP-2) produces a disease that is clinically similar to herpes simplex virus (HSV-1 and HSV-2) infection of humans. The development of a primate model of simplexvirus infection based on HVP-2 would provide a powerful resource to study virus biology and test vaccine strategies. In order to characterize the molecular biology of HVP-2 and justify further development of this model system we have constructed a physical map of the HVP-2 genome. The results of these studies have identified the presence of 26 reading frames that closely resemble HSV homologues. Furthermore, the HVP-2 genome shares a collinear arrangement with the genome of HSV. These studies further validate the development of the HVP-2 model as a surrogate system to study the biology of HSV infections.

  2. Does the inherence heuristic take us to psychological essentialism?

    Science.gov (United States)

    Marmodoro, Anna; Murphy, Robin A; Baker, A G

    2014-10-01

    We argue that the claim that essence-based causal explanations emerge, hydra-like, from an inherence heuristic is incomplete. No plausible mechanism for the transition from concrete properties, or cues, to essences is provided. Moreover, the fundamental shotgun and storytelling mechanisms of the inherence heuristic are not clearly enough specified to distinguish them, developmentally, from associative or causal networks.

  3. Approaches to achieving inherently safe fusion power plants

    International Nuclear Information System (INIS)

    Piet, S.J.

    1986-01-01

    Achieving inherently safe fusion facilities and conceptual designs is a challenge to the fusion community. Success should provide fusion with important competitive advantages versus other energy technologies. Inherent safety should mean a facility designed with passive safety features such that the public is protected from any acute fatalities under all credible accidental circumstances. A key aspect to inherent safety is demonstrability - the ability to prove that a deign is as safe as claimed. Three complementary approaches to achieving inherent safety are examined: toxin inventory reduction, energy source reduction and design fault tolerance. Four levels of assurance are defined, associated with uncertainty in the words ''credible' and ''demonstrable.'' Sound reasons exist for believing that inherent safety puts a modest upper bound on all accident consequences; it should be considered a part of the collection of safety and environmental issues, which also include lower consequence accidents, waste management, and effluent control

  4. Development of physiotherapy inherent requirement statements - an Australian experience.

    Science.gov (United States)

    Bialocerkowski, Andrea; Johnson, Amanda; Allan, Trevor; Phillips, Kirrilee

    2013-04-16

    The United Nations Convention on the Rights of People with Disabilities promotes equal rights of people with a disability in all aspects of their life including their education. In Australia, Disability Discrimination legislation underpins this Convention. It mandates that higher education providers must demonstrate that no discrimination has occurred and all reasonable accommodations have been considered and implemented, to facilitate access and inclusion for a student with a disability. The first step to meeting legislative requirements is to provide students with information on the inherent requirements of a course. This paper describes the steps which were taken to develop inherent requirement statements for a 4-year entry-level physiotherapy program at one Australian university. Inherent requirement statements were developed using an existing framework, which was endorsed and mandated by the University. Items which described inherencies were extracted from Australian physiotherapy professional standards and statutory regulatory requirements, and units contained in the physiotherapy program. Data were integrated into the 8 prescribed domains: ethical behaviour, behavioural stability, legal, communication, cognition, sensory abilities, strength and mobility, and sustainable performance. Statements for each domain were developed using a 5-level framework (introductory statement, description of the inherent requirement, justification for inherency, characteristics of reasonable adjustments and exemplars) and reviewed by a University Review Panel. Refinement of statements continued until no further changes were required. Fifteen physiotherapy inherent requirement statements were developed. The eight domains identified in the existing framework, developed for Nursing, were relevant to the study of physiotherapy. The inherent requirement statements developed in this study provide a transparent, defensible position on the current requirements of physiotherapy study at

  5. Development of physiotherapy inherent requirement statements – an Australian experience

    Science.gov (United States)

    2013-01-01

    Background The United Nations Convention on the Rights of People with Disabilities promotes equal rights of people with a disability in all aspects of their life including their education. In Australia, Disability Discrimination legislation underpins this Convention. It mandates that higher education providers must demonstrate that no discrimination has occurred and all reasonable accommodations have been considered and implemented, to facilitate access and inclusion for a student with a disability. The first step to meeting legislative requirements is to provide students with information on the inherent requirements of a course. This paper describes the steps which were taken to develop inherent requirement statements for a 4-year entry-level physiotherapy program at one Australian university. Case presentation Inherent requirement statements were developed using an existing framework, which was endorsed and mandated by the University. Items which described inherencies were extracted from Australian physiotherapy professional standards and statutory regulatory requirements, and units contained in the physiotherapy program. Data were integrated into the 8 prescribed domains: ethical behaviour, behavioural stability, legal, communication, cognition, sensory abilities, strength and mobility, and sustainable performance. Statements for each domain were developed using a 5-level framework (introductory statement, description of the inherent requirement, justification for inherency, characteristics of reasonable adjustments and exemplars) and reviewed by a University Review Panel. Refinement of statements continued until no further changes were required. Fifteen physiotherapy inherent requirement statements were developed. The eight domains identified in the existing framework, developed for Nursing, were relevant to the study of physiotherapy. Conclusions The inherent requirement statements developed in this study provide a transparent, defensible position on the

  6. Inherent Anticipation in the Pharmaceutical and Biotechnology Industries.

    Science.gov (United States)

    Goldman, Michael; Evans, Georgia; Zappia, Andrew

    2015-04-15

    Pharmaceutical and biotech research often involves discovering new properties of, or new methods to use, existing compositions. The doctrine of inherent anticipation, however, prevents the issuance and/or validity of a patent for discoveries deemed to have been implicitly disclosed in the prior art. This can be a barrier to patent rights in these technologies. Inherent anticipation therefore creates uncertainty for patent protection in the pharmaceutical and biotech sciences. Despite this uncertainty, Federal Circuit jurisprudence provides guidance on the boundaries of the inherent anticipation doctrine. In view of the case law, certain strategies may be employed to protect inventions that may potentially be viewed as inherent in the prior art. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  7. Inherent-opening-controlled pattern formation in carbon nanotube arrays

    International Nuclear Information System (INIS)

    Huang Xiao; Zhou, Jijie J; Sansom, Elijah; Gharib, Morteza; Haur, Sow Chorng

    2007-01-01

    We have introduced inherent openings into densely packed carbon nanotube arrays to study self-organized pattern formation when the arrays undergo a wetting-dewetting treatment from nanotube tips. These inherent openings, made of circular or elongated hollows in nanotube mats, serve as dewetting centres, from where liquid recedes from. As the dewetting centres initiate dry zones and the dry zones expand, surrounding nanotubes are pulled away from the dewetting centres by liquid surface tension. Among short nanotubes, the self-organized patterns are consistent with the shape of the inherent openings, i.e. slender openings lead to elongated trench-like structures, and circular holes result in relatively round nest-like arrangements. Nanotubes in a relatively high mat are more connected, like in an elastic body, than those in a short mat. Small cracks often initialize themselves in a relatively high mat, along two or more adjacent round openings; each of the cracks evolves into a trench as liquid dries up. Self-organized pattern control with inherent openings needs to initiate the dewetting process above the nanotube tips. If there is no liquid on top, inherent openings barely enlarge themselves after the wetting-dewetting treatment

  8. Cost-competitive, inherently safe LFMBR pool plant

    International Nuclear Information System (INIS)

    McDonald, J.S.; Brunings, J.E.; Chang, Y.I.; Hren, R.R.; Seidensticker, R.W.

    1984-01-01

    The Cost-Competitive, Inherently Safe LMFBR Pool Plant design was prepared in GFY 1983 under a DOE-sponsored program. This plant design was developed as a joint effort by Rockwell International and the Argonne National Laboratory with major contributions from the Bechtel Group, Inc.; Combustion engineering, Inc.; the Chicago Bridge and Iron Company; and the General Electric Company. Using current LMFBR technology, many innovative features were developed and incorporated into the design to meet the ultimate objectives of the Breeder Program, i.e., energy costs competitive with LWRs and inherent safety features to maintain the plant in a safe condition following assumed accidents without requiring operator action. This paper provides a description of the principal features that were incorporated into the design to achieve low cost and inherent safety

  9. The inherent politics of quality in public park management

    DEFF Research Database (Denmark)

    Lindholst, Andrej Christian; Konijnendijk, Cecil Cornelis; Fors, Hanna

    2012-01-01

    In this paper, we highlight and illustrate the inherent politics embedded in “quality” as a concept for managing public parks. Reflecting more generic quality concepts, contemporary quality models in park management include concepts for both operational, strategic and stakeholder management as well...... managing the park organisation itself. However, quality concepts and their application through various management models include as well as exclude the access, values and worldviews of particular interests. In this way, any particular quality concept and model embeds its own politics by inherent...... allocations of ‘who gets what, when and how’. We illustrate the inherent politics by providing a case study of a widely adopted quality model for operational management that has been adopted and implemented in Denmark as part of new public management reforms. In perspective, other quality concepts and models...

  10. "A Fiber Optic Ethernet With Inherent Migration Capability To FDDI"

    Science.gov (United States)

    Ferris, Kenneth D.; Chan, Tammy S.

    1988-12-01

    A Local Area Network (LAN) designed to a standard commercial interface, the Institute of Electrical and Electronics Engineers (IEEE) 802.3 or Ethernet, has been developed using fiber optics as the physical medium. The LAN, WhisperNet, operates in an active ring and thus has an inherent low cost migration path to a Fiber Distributed Data Interface (FDDI) implementation.

  11. The distribution of inherent phosphorus in fifteen water treatment ...

    African Journals Online (AJOL)

    The aim of this investigation was to characterise the chemical properties relevant to P-sorption/desorption processes of 15 South African WTR and to determine the inherent distribution of P within the WTR using a chemical fractionation procedure. The pH, exchangeable Ca and organic carbon content ranged from 4.77 to ...

  12. The application of probabilistic risk assessment to inherently safe reactors

    International Nuclear Information System (INIS)

    Cave, L.; Kastenberg, W.E.

    1987-01-01

    In the development of safety goals and design criteria for 'inherently safe' reactors a question which arises is 'To what extent is PRA relevant.' To answer this question it is necessary to consider both the risk to the public and the investment risk to the utility. In this paper the factors which are likely to determine safety objectives and their allocation are presented. (orig.)

  13. Influence of Inherent Moisture Content on the Deformation ...

    African Journals Online (AJOL)

    Influence of Inherent Moisture Content on the Deformation. Properties of Coconut Tissues During Mechanical Oil. Expression. *J. J. Mpagalile1 and B. Clarke2. 1Department of ... The study confirmed that moisture content has an important role in the deformation of coconut ..... A micro penetration technique for mechanical.

  14. Tactical supply chain planning models with inherent flexibility

    DEFF Research Database (Denmark)

    Esmaeilikia, Masoud; Fahimnia, Behnam; Sarkis, Joeseph

    2016-01-01

    Supply chains (SCs) can be managed at many levels. The use of tactical SC planning models with multiple flexibility options can help manage the usual operations efficiently and effectively, whilst improve the SC resiliency in response to inherent environmental uncertainties. This paper defines ta...

  15. Inherently safe high temperature gas-cooled reactor

    International Nuclear Information System (INIS)

    Yamada, Masao; Hayakawa, Hitoshi

    1987-01-01

    It is recognized in general that High Temperature Gas-cooled Reactors have remarkable characteristics in inherent safety and it is well known that credits of the time margin have been admitted for accident evaluation in the licensing of the currently operating prototype HTGRs (300 MWe class). Recently, more inherently safe HTGRs are being developed in various countries and drawing attention on their possibility for urban siting. The inherent safety characteristics of these HTRs differ each other depending on their design philosophy and on the features of the components/structures which constitute the plant. At first, the specific features/characteristics of the elemental components/structures of the HTRs are explained one by one and then the overall safety features/characteristics of these HTR plants are explained in connection with their design philosophy and combination of the elemental features. Taking the KWU/Interatom Modular Reactor System as an example, the particular design philosophy and safety characteristics of the inherently safe HTR are explained with a result of preliminary evaluation on the possibility of siting close to densely populated area. (author)

  16. Inherent reactor power controller for a metal-fueled ALMR

    International Nuclear Information System (INIS)

    Wood, R.T.; Wilson, T.L. Jr.

    1990-01-01

    Inherent power control for metal-fueled ALMR designs involves using reactivity thermal feedback effects to control reactor power. This paper describes how, using classical control design techniques, a control system for normal load following maneuvers was deigned for a pool-type ALMR. This design provides active control of power removal in the balance of plant, direct control of selected primary and intermediate loop temperatures, and passive control of reactor power. The inherent stability of the strong, fast reactivity feedback effects bring heat production in the core into balance with the heat removal system temperatures, which are controlled to meet power demand. A simulation of the control system successfully responded to a 10% step change in power demand by changing power at an acceptable rate without causing large temperature fluctuations or exceeding thermal limits

  17. Observation and analysis of water inherent optical properties

    Science.gov (United States)

    Sun, Deyong; Li, Yunmei; Le, Chengfeng; Huang, Changchun

    2008-03-01

    Inherent optical property is an important part of water optical properties, and is the foundation of water color analytical model establishment. Through quantity filter technology (QFT) and backscattering meter BB9 (WETlabs Inc), absorption coefficients of CDOM, total suspended minerals and backscattering coefficients of total suspended minerals had been observed in Meiliang Bay of Taihu lake at summer and winter respectively. After analyzing the spectral characteristics of absorption and backscattering coefficients, the differences between two seasons had been illustrated adequately, and the reasons for the phenomena, which are related to the changes of water quality coefficient, had also been explained. So water environment states can be reflected by inherent optical properties. In addition, the relationship models between backscattering coefficients and suspended particle concentrations had been established, which can support coefficients for analytical models.

  18. Posttest analysis of the FFTF inherent safety tests

    International Nuclear Information System (INIS)

    Padilla, A. Jr.; Claybrook, S.W.

    1987-01-01

    Inherent safety tests were performed during 1986 in the 400-MW (thermal) Fast Flux Test Facility (FFTF) reactor to demonstrate the effectiveness of an inherent shutdown device called the gas expansion module (GEM). The GEM device provided a strong negative reactivity feedback during loss-of-flow conditions by increasing the neutron leakage as a result of an expanding gas bubble. The best-estimate pretest calculations for these tests were performed using the IANUS plant analysis code (Westinghouse Electric Corporation proprietary code) and the MELT/SIEX3 core analysis code. These two codes were also used to perform the required operational safety analyses for the FFTF reactor and plant. Although it was intended to also use the SASSYS systems (core and plant) analysis code, the calibration of the SASSYS code for FFTF core and plant analysis was not completed in time to perform pretest analyses. The purpose of this paper is to present the results of the posttest analysis of the 1986 FFTF inherent safety tests using the SASSYS code

  19. On the maximum entropy distributions of inherently positive nuclear data

    Energy Technology Data Exchange (ETDEWEB)

    Taavitsainen, A., E-mail: aapo.taavitsainen@gmail.com; Vanhanen, R.

    2017-05-11

    The multivariate log-normal distribution is used by many authors and statistical uncertainty propagation programs for inherently positive quantities. Sometimes it is claimed that the log-normal distribution results from the maximum entropy principle, if only means, covariances and inherent positiveness of quantities are known or assumed to be known. In this article we show that this is not true. Assuming a constant prior distribution, the maximum entropy distribution is in fact a truncated multivariate normal distribution – whenever it exists. However, its practical application to multidimensional cases is hindered by lack of a method to compute its location and scale parameters from means and covariances. Therefore, regardless of its theoretical disadvantage, use of other distributions seems to be a practical necessity. - Highlights: • Statistical uncertainty propagation requires a sampling distribution. • The objective distribution of inherently positive quantities is determined. • The objectivity is based on the maximum entropy principle. • The maximum entropy distribution is the truncated normal distribution. • Applicability of log-normal or normal distribution approximation is limited.

  20. Identification of multiple sites suitable for insertion of foreign genes in herpes simplex virus genomes.

    Science.gov (United States)

    Morimoto, Tomomi; Arii, Jun; Akashi, Hiroomi; Kawaguchi, Yasushi

    2009-03-01

    Information on sites in HSV genomes at which foreign gene(s) can be inserted without disrupting viral genes or affecting properties of the parental virus are important for basic research on HSV and development of HSV-based vectors for human therapy. The intergenic region between HSV-1 UL3 and UL4 genes has been reported to satisfy the requirements for such an insertion site. The UL3 and UL4 genes are oriented toward the intergenic region and, therefore, insertion of a foreign gene(s) into the region between the UL3 and UL4 polyadenylation signals should not disrupt any viral genes or transcriptional units. HSV-1 and HSV-2 each have more than 10 additional regions structurally similar to the intergenic region between UL3 and UL4. In the studies reported here, it has been demonstrated that insertion of a reporter gene expression cassette into several of the HSV-1 and HSV-2 intergenic regions has no effect on viral growth in cell culture or virulence in mice, suggesting that these multiple intergenic regions may be suitable HSV sites for insertion of foreign genes.

  1. Inherent Conservatism in Deterministic Quasi-Static Structural Analysis

    Science.gov (United States)

    Verderaime, V.

    1997-01-01

    The cause of the long-suspected excessive conservatism in the prevailing structural deterministic safety factor has been identified as an inherent violation of the error propagation laws when reducing statistical data to deterministic values and then combining them algebraically through successive structural computational processes. These errors are restricted to the applied stress computations, and because mean and variations of the tolerance limit format are added, the errors are positive, serially cumulative, and excessively conservative. Reliability methods circumvent these errors and provide more efficient and uniform safe structures. The document is a tutorial on the deficiencies and nature of the current safety factor and of its improvement and transition to absolute reliability.

  2. Inherently safe nuclear-driven internal combustion engines

    International Nuclear Information System (INIS)

    Alesso, P.; Chow, Tze-Show; Condit, R.; Heidrich, J.; Pettibone, J.; Streit, R.

    1991-01-01

    A family of nuclear driven engines is described in which nuclear energy released by fissioning of uranium or plutonium in a prompt critical assembly is used to heat a working gas. Engine performance is modeled using a code that calculates hydrodynamics, fission energy production, and neutron transport self-consistently. Results are given demonstrating a large negative temperature coefficient that produces self-shutoff of energy production. Reduced fission product inventory and the self-shutoff provide inherent nuclear safety. It is expected that nuclear engine reactor units could be scaled from 100 MW on up. 7 refs., 3 figs

  3. Inherent security benefits of underground dry storage of nuclear materials

    International Nuclear Information System (INIS)

    Moore, R.D.; Zahn, T.

    1997-07-01

    This paper, augmented by color slides and handouts, will examine the inherent security benefits of underground dry storage of nuclear materials. Specific items to be presented include: the successful implementation of this type of storage configuration at Argonne National Laboratory - West; facility design concepts with security as a primary consideration; physical barriers achieved by container design; detection, assessment, and monitoring capabilities; and open-quotes self protectionclose quotes strategies. This is a report on the security features of such a facility. The technical operational aspects of the facility are beyond the scope of this paper

  4. Inherent and antigen-induced airway hyperreactivity in NC mice

    OpenAIRE

    Tetsuto Kobayashi; Toru Miura; Tomoko Haba; Miyuki Sato; Masao Takei; Isao Serizawa

    1999-01-01

    In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those st...

  5. Plants status monitor: Modelling techniques and inherent benefits

    International Nuclear Information System (INIS)

    Breeding, R.J.; Lainoff, S.M.; Rees, D.C.; Prather, W.A.; Fickiessen, K.O.E.

    1987-01-01

    The Plant Status Monitor (PSM) is designed to provide plant personnel with information on the operational status of the plant and compliance with the plant technical specifications. The PSM software evaluates system models using a 'distributed processing' technique in which detailed models of individual systems are processed rather than by evaluating a single, plant-level model. In addition, development of the system models for PSM provides inherent benefits to the plant by forcing detailed reviews of the technical specifications, system design and operating procedures, and plant documentation. (orig.)

  6. The minimum attention plant inherent safety through LWR simplification

    International Nuclear Information System (INIS)

    Turk, R.S.; Matzie, R.A.

    1987-01-01

    The Minimum Attention Plant (MAP) is a unique small LWR that achieves greater inherent safety, improved operability, and reduced costs through design simplification. The MAP is a self-pressurized, indirect-cycle light water reactor with full natural circulation primary coolant flow and multiple once-through steam generators located within the reactor vessel. A fundamental tenent of the MAP design is its complete reliance on existing LWR technology. This reliance on conventional technology provides an extensive experience base which gives confidence in judging the safety and performance aspects of the design

  7. Inherent overload protection for the series resonant converter

    Science.gov (United States)

    King, R. J.; Stuart, T. A.

    1983-01-01

    The overload characteristics of the full bridge series resonant power converter are considered. This includes analyses of the two most common control methods presently in use. The first of these uses a current zero crossing detector to synchronize the control signals and is referred to as the alpha controller. The second is driven by a voltage controlled oscillator and is referred to as the gamma controller. It is shown that the gamma controller has certain reliability advantages in that it can be designed with inherent short circuit protection. Experimental results are included for an 86 kHz converter using power metal-oxide-semiconductor field-effect transistors (MOSFETs).

  8. Inherent uncertainties in meteorological parameters for wind turbine design

    Science.gov (United States)

    Doran, J. C.

    1982-01-01

    Major difficulties associated with meteorological measurments such as the inability to duplicate the experimental conditions from one day to the next are discussed. This lack of consistency is compounded by the stochastic nature of many of the meteorological variables of interest. Moreover, simple relationships derived in one location may be significantly altered by topographical or synoptic differences encountered at another. The effect of such factors is a degree of inherent uncertainty if an attempt is made to describe the atmosphere in terms of universal laws. Some of these uncertainties and their causes are examined, examples are presented and some implications for wind turbine design are suggested.

  9. The inherent inefficiency of simultaneously feasible financial transmission rights auctions

    International Nuclear Information System (INIS)

    Deng, Shi-Jie; Oren, Shmuel; Meliopoulos, A.P.

    2010-01-01

    Empirical evidence from the New York ISO shows that the clearing prices for point-to-point congestion revenue rights, also known as financial transmission rights (FTRs), resulting from centralized auctions conducted by Independent System Operators differ significantly and systematically from the realized congestion revenues that determine the accrued payoffs of these rights. The question addressed by this paper is whether such deviations are due to price discovery errors which will eventually vanish or due to inherent inefficiencies in the auction structure. We show that even with perfect foresight of average congestion rents the clearing prices for the FTRs depend on the bid quantity and therefore may not be priced correctly in the financial transmission right (FTR) auction. In particular, we prove that quantity limits on the FTR bids may cause the auction clearing prices to differ from the bid prices. This phenomenon which is inherent in the theoretical properties of the optimization algorithm used to clear the auction, is further illustrated through numerical simulations with test systems. We conclude that price discovery alone would not remedy the discrepancy between the auction prices and the realized values of the FTRs. Secondary markets or frequent reconfiguration auctions are necessary in order to achieve such convergence. (author)

  10. Basis, evidences and consequences of the inherent stellar encocooning

    CERN Document Server

    Celis, L

    2002-01-01

    Based on 7093 observations with photoelectrical photometrical measurements of 191 Mira stars, the following equations (from the papers [1] to [18]) give the basis to establish the Inherent Stellar Encocooning with the spectro-photometric characteristics of the red giant variable stars, especially the Miras, which have large amplitudes (approx 50% of giant variables). The specific basis that justifies a progressive covering with ionized molecules, cold gases, dust and grains are: The relation of the visual amplitudes A sub v =A sub r +E sub A whose real luminosity separate the intrinsic pulsation and amplitude excess effects due to the presence of molecules [145] and an opaque envelope of cool gases; The relation of the visual absolute magnitudes M sub v =M sub v sub r (P)+M sub a (delta sub T sub i sub O V) which is affected by an inherent absorption and/or occultation, and; The relation that defines the probable absolute luminosity and depends on the period and the (Sa) spectral type at maximum M sub v =-2.2...

  11. Drug policy in sport: hidden assumptions and inherent contradictions.

    Science.gov (United States)

    Smith, Aaron C T; Stewart, Bob

    2008-03-01

    This paper considers the assumptions underpinning the current drugs-in-sport policy arrangements. We examine the assumptions and contradictions inherent in the policy approach, paying particular attention to the evidence that supports different policy arrangements. We find that the current anti-doping policy of the World Anti-Doping Agency (WADA) contains inconsistencies and ambiguities. WADA's policy position is predicated upon four fundamental principles; first, the need for sport to set a good example; secondly, the necessity of ensuring a level playing field; thirdly, the responsibility to protect the health of athletes; and fourthly, the importance of preserving the integrity of sport. A review of the evidence, however, suggests that sport is a problematic institution when it comes to setting a good example for the rest of society. Neither is it clear that sport has an inherent or essential integrity that can only be sustained through regulation. Furthermore, it is doubtful that WADA's anti-doping policy is effective in maintaining a level playing field, or is the best means of protecting the health of athletes. The WADA anti-doping policy is based too heavily on principals of minimising drug use, and gives insufficient weight to the minimisation of drug-related harms. As a result drug-related harms are being poorly managed in sport. We argue that anti-doping policy in sport would benefit from placing greater emphasis on a harm minimisation model.

  12. Inherent and antigen-induced airway hyperreactivity in NC mice

    Directory of Open Access Journals (Sweden)

    Tetsuto Kobayashi

    1999-01-01

    Full Text Available In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those strains in vivo. NC mice again showed comparable airway reactivity to that seen in A/J mice and a significantly greater reactivity than that seen in BALB/c and C57BL/6 mice. To investigate the effects of airway inflammation on airway reactivity to acetylcholine in vivo, NC and BALB/c mice were sensitized to and challenged with antigen. Sensitization to and challenge with antigen induced accumulation of inflammatory cells, especially eosinophils, in lung and increased airway reactivity in NC and BALB/c mice. These results indicate that NC mice exhibit inherent and antigen-induced airway hyperreactivity. Therefore, NC mice are a suitable strain to use in investigating the mechanisms underlying airway hyperreactivity and such studies will provide beneficial information for understanding the pathophysiology of asthma.

  13. The inherent catastrophic traps in retrograde CTO PCI.

    Science.gov (United States)

    Wu, Eugene B; Tsuchikane, Etsuo

    2018-05-01

    When we learn to drive, our driving instructor tells us how to check the side mirror and turn your head to check the blind spot before changing lanes. He tells us how to stop at stop signs, how to drive in slippery conditions, the safe stopping distances, and these all make our driving safe. Similarly, when we learn PCI, our mentors teach us to seat the guiding catheter co-axially, to wire the vessel safely, to deliver balloon and stents over the wire, to watch the pressure of the guiding, in order that we perform PCI safely and evade complications. In retrograde CTO PCI, there is no such published teaching. Also many individual mentors have not had the wide experience to see all the possible complications of retrograde CTO PCI and, therefore, may not be able to warn their apprentice. As the number of retrograde procedures increase worldwide, there is a corresponding increase in catastrophic complications, many of which, we as experts, can see are easily avoidable. To breach this gap in knowledge, this article describes 12 commonly met inherent traps in retrograde CTO PCI. They are inherent because by arranging our equipment in the manner to perform retrograde CTO PCI, these complications are either induced directly or happen easily. We hope this work will enhance safety of retrograde CTO PCI and avoid many catastrophic complications for our readers and operators. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Inherent optical properties of the coccolithophore: Emiliania huxleyi.

    Science.gov (United States)

    Zhai, Peng-Wang; Hu, Yongxiang; Trepte, Charles R; Winker, David M; Josset, Damien B; Lucker, Patricia L; Kattawar, George W

    2013-07-29

    A realistic nonspherical model for Emiliania huxleyi (EHUX) is built, based on electron micrographs of coccolithophore cells. The Inherent Optical Properties (IOP) of the EHUX are then calculated numerically by using the discrete dipole approximation. The coccolithophore model includes a near-spherical core with the refractive index of 1.04 + m(i)j, and a carbonate shell formed by smaller coccoliths with refractive index of 1.2 + m(i)j, where m(i) = 0 or 0.01 and j(2) = -1. The reported IOP are the Mueller scattering matrix, backscattering probability, and depolarization ratio. Our calculation shows that the Mueller matrices of coccolithophores show different angular dependence from those of coccoliths.

  15. Project of a binary breeder reactor and its inherent safety

    International Nuclear Information System (INIS)

    Nascimento, J.A. do; Dias, A.F.; Ishiguro, Y.

    1983-01-01

    A core layout for the binary breeder reactor (BBR) is developed based on the results of preliminary burnup calculations. In the U 233 /TH fueled inner core, the apparent breeding ratio is low due to the accumulation of Pa-233 in the first few months of operation. The loss of reactivity during this time is approximatelly 3%. The BBR requires more reactivity control than Pu/U-fueled LMFBRs and the core layout developed has 19 control rod assemblies in the inner core. Three aspects related to the inherent safety of the BBR have been studied: radial distribution of the sodium-void reactivity, zone-wise Doppler reactivity, and the delayed neutron fractions. Results show excellent safety characteristics of the BBR. (Author) [pt

  16. A simple graphical method for measuring inherent safety

    International Nuclear Information System (INIS)

    Gupta, J.P.; Edwards, David W.

    2003-01-01

    Inherently safer design (ISD) concepts have been with us for over two decades since their elaboration by Kletz [Chem. Ind. 9 (1978) 124]. Interest has really taken off globally since the early nineties after several major mishaps occurred during the eighties (Bhopal, Mexico city, Piper-alfa, Philips Petroleum, to name a few). Academic and industrial research personnel have been actively involved into devising inherently safer ways of production. The regulatory bodies have also shown deep interest since ISD makes the production safer and hence their tasks easier. Research funding has also been forthcoming for new developments as well as for demonstration projects. A natural question that arises is as to how to measure ISD characteristics of a process? Several researchers have worked on this [Trans. IChemE, Process Safety Environ. Protect. B 71 (4) (1993) 252; Inherent safety in process plant design, Ph.D. Thesis, VTT Publication Number 384, Helsinki University of Technology, Espoo, Finland, 1999; Proceedings of the Mary Kay O'Connor Process Safety Center Symposium, 2001, p. 509]. Many of the proposed methods are very elegant, yet too involved for easy adoption by the industry which is scared of yet another safety analysis regime. In a recent survey [Trans. IChemE, Process Safety Environ. Prog. B 80 (2002) 115], companies desired a rather simple method to measure ISD. Simplification is also an important characteristic of ISD. It is therefore desirable to have a simple ISD measurement procedure. The ISD measurement procedure proposed in this paper can be used to differentiate between two or more processes for the same end product. The salient steps are: Consider each of the important parameters affecting the safety (e.g., temperature, pressure, toxicity, flammability, etc.) and the range of possible values these parameters can have for all the process routes under consideration for an end product. Plot these values for each step in each process route and compare. No

  17. Transient behaviour and inherent safety research of LMFBR power plants

    International Nuclear Information System (INIS)

    Zhu Jizhou; Wang Ping; Yu Baoan

    1995-06-01

    Fast Breeder Reactor will be the next generation reactor for nuclear electricity production, the development of FBR will give the profits of efficient utilization of nuclear resources. The fast reactor safety analysis is the foundation and key of FBR research work. Therefore, a block-oriented mathematical model for the primary system of LMFBRs was constructed, and the dynamic simulating results which have been carried out on micro-computer are presented for various transients, i.e. TOP, LOFS, LOHS. The results agree well with the corresponding results of the code NATDEMO and experiment results of EBR-II. Based on previous analysis, various methods are discussed to confirm the inherent safety of LMFBR

  18. Inherent calibration of microdosemeters for dose distributions in lineal energy

    Energy Technology Data Exchange (ETDEWEB)

    Crossman, J.S.P.; Watt, D.E. [Saint Andrews Univ. (United Kingdom). Dept. of Physics and Astronomy

    1994-12-31

    A method, utilising the inherent electron event spectra, is described for the absolute calibration of microdosemeters in the presence of a photon field. The method, which avoids the problems and uncertainties present in conventional calibration techniques, involves simple extrapolation of the dose distribution in lineal energy associated with `exact stopper` electrons. Validation of the method is made using the published experimental distributions of Rossi, of Kliauga, and of Dvorak and by direct theoretical calculation of the components of the microdose distributions for gamma rays. Further experimental data from a cylindrical TEPC in a photon field generated by an external source of {sup 137}Cs are obtained for comparison. A `universal` calibration curve for the dose-weighted lineal energy as a function of the simulated mean diameter of the microdosemeter, is presented for use in practical applications. (author).

  19. Inherent calibration of microdosemeters for dose distributions in lineal energy

    International Nuclear Information System (INIS)

    Crossman, J.S.P.; Watt, D.E.

    1994-01-01

    A method, utilising the inherent electron event spectra, is described for the absolute calibration of microdosemeters in the presence of a photon field. The method, which avoids the problems and uncertainties present in conventional calibration techniques, involves simple extrapolation of the dose distribution in lineal energy associated with 'exact stopper' electrons. Validation of the method is made using the published experimental distributions of Rossi, of Kliauga, and of Dvorak and by direct theoretical calculation of the components of the microdose distributions for gamma rays. Further experimental data from a cylindrical TEPC in a photon field generated by an external source of 137 Cs are obtained for comparison. A 'universal' calibration curve for the dose-weighted lineal energy as a function of the simulated mean diameter of the microdosemeter, is presented for use in practical applications. (author)

  20. Design strategy for control of inherently safe reactors

    International Nuclear Information System (INIS)

    Chisholm, G.H.

    1984-01-01

    Reactor power plant safety is assured through a combination of engineered barriers to radiation release (e.g., reactor containment) in combination with active reactor safety systems to shut the reactor down and remove decay heat. While not specifically identified as safety systems, the control systems responsible for continuous operation of plant subsystems are the first line of defense for mitigating radiation releases and for plant protection. Inherently safe reactors take advantage of passive system features for decay-heat removal and reactor shutdown functions normally ascribed to active reactor safety systems. The advent of these reactors may permit restructuring of the present control system design strategy. This restructuring is based on the fact that authority for protection against unlikely accidents is, as much as practical, placed upon the passive features of the system instead of the traditional placement upon the PPS. Consequently, reactor control may be simplified, allowing the reliability of control systems to be improved and more easily defended

  1. Results of the 1986 FFTF inherent safety tests

    International Nuclear Information System (INIS)

    Burke, T.M.; Campbell, L.R.; Franz, G.R.; Knecht, W.L.

    1987-01-01

    A series of tests was recently completed at the 400-MW (thermal) Fast Flux Test Facility (FFTF) to further demonstrate the passive safety characteristics of liquid-metal-cooled fast reactors. Earlier FFTF testing of decay heat removal by sodium natural circulation was reported in 1981. The main purpose of the 1986 test series was to demonstrate passive reactor shutdown during a loss-of-flow event when several inherent shutdown devices called gas expansion modules (GEMs) were installed in the reactor. However, these tests also provide further data on the natural circulation performance of the primary system, in particular the reactor core, and thus add to the data base available for checking the validity of available analytical tools

  2. Project of a binary breeder reactor and its inherent safety

    International Nuclear Information System (INIS)

    Nascimento, J.A. do; Dias, A.F.; Ishiguro, Y.

    1983-01-01

    A core layout for the binary breeder reactor (BBR) is developed based on the results of preliminary burnup calculations. The apparent breeding ratio, in the U 233 /Th fueled inner core, is low due to the accumulation of Pa-233 in the first few months of operation. The loss of reactivity during this time is around 3%. The BBR requires more reactivity control than Pu/U-fueled LMFBRs and the core layout developed has 19 control rod assemblies in the inner core. Three aspects related to the inherent safety of the Binary Breeder Reactor have been studied: the radial distribution of the sodium-void reactivity zone-wise Doppler reactivity and the fractions of delayed neutrons. The results show excellent characteristics for the BRB safety. (Author) [pt

  3. Contracting for independent evaluation: approaches to an inherent tension.

    Science.gov (United States)

    Klerman, Jacob Alex

    2010-08-01

    There has recently been discussion of whether independent contract evaluation is possible. This article acknowledges the inherent tension in contract evaluation and in response suggests a range of constructive approaches to improving the independence of contract evaluation. In particular, a clear separation between the official evaluation report and a contractor's own publication of analysis from the underlying evaluation appears to be a promising approach. In this approach, the funder would retain almost unfettered rights to the official contract report (including the right never to publish but not the right to change the contractor's text while leaving the contractor's authorship) and the contractor would retain clearly defined rights to publish any findings from the evaluation (subject only to the limitations of human subjects and proprietary data and some minimal notice).

  4. Development of inherent core technologies for advanced reactor

    International Nuclear Information System (INIS)

    Kim, Keung Koo; Noh, J.M.; Hwang, D.H.

    1999-03-01

    Recently, the developed countries made their effort on developing the advanced reactor which will result in significantly enhanced safety and economy. However, they will protect the advanced reactor and its design technology with patent and proprietary right. Therefore, it is very important to develop our own key core concepts and inherent core design technologies which can form a foundation of indigenous technologies for development of the domestic advanced reactor in order to keep the superiority in the nuclear plant building market among the developing countries. In order to provide the basic technology for the core design of advanced reactor, this project is for developing the inherent core design concepts with enhanced safety and economy, and associated methodologies and technologies for core analyses. The feasibility study of constructing domestic critical facilities are performed by surveying the status and utilization of foreign facilities and by investigating the demand for domestic facilities. The research results developed in this project, such as core analysis methodologies for hexagonal core, conceptual core design based on hexagonal fuel assemblies and soluble boron core design and control strategies, will provide a technical foundation in developing core design of domestic advanced reactor. Furthermore, they will strengthen the competitiveness of Korean nuclear technology. We also expect that some of the design concepts developed in this project to improve the reactor safety and economy can be applicable to the design of advanced reactor. This will significantly reduce the public anxiety on the nuclear power plant, and will contribute to the economy of construction and operation for the future domestic reactors. Even though the critical facility will not be constructed right now, the investigation of the status and utilization of foreign critical facility will contribute to the future critical facility construction. (author). 150 refs., 34 tabs., 103

  5. Development of inherent core technologies for advanced reactor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keung Koo; Noh, J.M.; Hwang, D.H. [and others

    1999-03-01

    Recently, the developed countries made their effort on developing the advanced reactor which will result in significantly enhanced safety and economy. However, they will protect the advanced reactor and its design technology with patent and proprietary right. Therefore, it is very important to develop our own key core concepts and inherent core design technologies which can form a foundation of indigenous technologies for development of the domestic advanced reactor in order to keep the superiority in the nuclear plant building market among the developing countries. In order to provide the basic technology for the core design of advanced reactor, this project is for developing the inherent core design concepts with enhanced safety and economy, and associated methodologies and technologies for core analyses. The feasibility study of constructing domestic critical facilities are performed by surveying the status and utilization of foreign facilities and by investigating the demand for domestic facilities. The research results developed in this project, such as core analysis methodologies for hexagonal core, conceptual core design based on hexagonal fuel assemblies and soluble boron core design and control strategies, will provide a technical foundation in developing core design of domestic advanced reactor. Furthermore, they will strengthen the competitiveness of Korean nuclear technology. We also expect that some of the design concepts developed in this project to improve the reactor safety and economy can be applicable to the design of advanced reactor. This will significantly reduce the public anxiety on the nuclear power plant, and will contribute to the economy of construction and operation for the future domestic reactors. Even though the critical facility will not be constructed right now, the investigation of the status and utilization of foreign critical facility will contribute to the future critical facility construction. (author). 150 refs., 34 tabs., 103

  6. Anomalous baroreflex functionality inherent in floxed and Cre-Lox mice: an overlooked physiological phenotype.

    Science.gov (United States)

    Tsai, Ching-Yi; Poon, Yan-Yuen; Chen, Chang-Han; Chan, Samuel H H

    2017-10-01

    The last two decades have seen the emergence of Cre-Lox recombination as one of the most powerful and versatile technologies for cell-specific genetic engineering of mammalian cells. Understandably, the primary concerns in the practice of Cre-Lox recombination are whether the predicted genome has been correctly modified and the targeted phenotypes expressed. Rarely are the physiological conditions of the animals routinely examined because the general assumption is that they are normal. Based on corroborative results from radiotelemetric recording, power spectral analysis, and magnetic resonance imaging/diffusion tensor imaging in brain-derived neurotrophic factor-floxed mice, the present study revealed that this assumption requires amendment. We found that despite comparable blood pressure and heart rate with C57BL/6 or Cre mice under the conscious state, floxed and Cre-Lox mice exhibited diminished baroreflex-mediated sympathetic vasomotor tone and cardiac vagal baroreflex. We further found that the capacity and plasticity of baroreflex of these two strains of mice under isoflurane anesthesia were retarded, as reflected by reduced connectivity between the nucleus tractus solitarii and rostral ventrolateral medulla or nucleus ambiguus. The identification of anomalous baroreflex functionality inherent in floxed and Cre-Lox mice points to the importance of incorporating physiological phenotypes into studies that engage gene manipulations such as Cre-Lox recombination. NEW & NOTEWORTHY We established that anomalous baroreflex functionality is inherent in floxed and Cre-Lox mice. These two mouse strains exhibited diminished baroreflex-mediated sympathetic vasomotor tone and cardiac vagal baroreflex under the conscious state, retarded capacity and plasticity of baroreflex under isoflurane anesthesia, and reduced connectivity between key nuclei in the baroreflex neural circuits. Copyright © 2017 the American Physiological Society.

  7. Communicating uncertainty: managing the inherent probabilistic character of hazard estimates

    Science.gov (United States)

    Albarello, Dario

    2013-04-01

    Science is much more fixing the limits of our knowledge about possible occurrences than the identification of any "truth". This is particularly true when scientific statements concern prediction of natural phenomena largely exceeding the laboratory scale as in the case of seismogenesis. In these cases, many scenarios about future occurrences result possible (plausible) and the contribution of scientific knowledge (based on the available knowledge about underlying processes or the phenomenological studies) mainly consists in attributing to each scenario a different level of likelihood (probability). In other terms, scientific predictions in the field of geosciences (hazard assessment) are inherently probabilistic. However, despite of this, many scientist (seismologists, etc.) in communicating their position in public debates tend to stress the " truth" of their statements against the fancy character of pseudo-scientific assertions: stronger is the opposition of science and pseudo-science, more hidden becomes the probabilistic character of scientific statements. The problem arises when this kind of "probabilistic" knowledge becomes the basis of any political action (e.g., to impose expensive form of risk reducing activities): in these cases the lack of any definitive "truth" requires a direct assumption of responsibility by the relevant decider (being the single citizen or the legitimate expression of a larger community) to choose among several possibilities (however characterized by different levels of likelihood). In many cases, this can be uncomfortable and strong is the attitude to delegate to the scientific counterpart the responsibility of these decisions. This "transfer" from the genuine political field to an improper scientific context is also facilitated by the lack of a diffuse culture of "probability" outside the scientific community (and in many cases inside also). This is partially the effect of the generalized adoption (by media and scientific

  8. El silenciamiento de la proteína priónica celular (PrPC mediante RNA de interferencia (siRNA reduce la infección por HSV-1 y HSV-2 en células SK-SY5Y

    Directory of Open Access Journals (Sweden)

    Elizabeth Ortega-Soto

    2012-01-01

    Full Text Available Las encefalopatías espongiformes transmisibles (EETs son enfermedades neurodegenerativas fatales que afectan a humanos y ciertas especies animales. La hipótesis más aceptada indica que el agente infeccioso, denotado como prion y compuesto principalmente por la Proteína Priónica Scrapie (PrPSc, corresponde a una conformación anormal de una proteína codificada por el huésped denominada Proteína Priónica Celular (PrPC, cuya función es aún desconocida; sin embargo, la expresión ubicua de PrPC así como su elevado grado de conservación entre especies, sugieren un papel importante para esta proteína. En este trabajo se detectó a la PrPC en diferentes tipos celulares incluyendo un cultivo primario de células de peces (Tilapia, Oreochromis spp.. Además, basándonos en la secuencia de la PrPC humana, se diseñó un RNA de interferencia (siRNA con el fin de silenciar el gen PRNP en células neuronales SK-SY5Y. El siRNA diseñado inhibió la expresión de PrPC a lo largo de las 96 h post-transfección y las células silenciadas fueron menos susceptibles a la infección por HSV-1 y HSV-2, en comparación con células no transfectadas con el siRNA.

  9. Experimental quantum control landscapes: Inherent monotonicity and artificial structure

    International Nuclear Information System (INIS)

    Roslund, Jonathan; Rabitz, Herschel

    2009-01-01

    Unconstrained searches over quantum control landscapes are theoretically predicted to generally exhibit trap-free monotonic behavior. This paper makes an explicit experimental demonstration of this intrinsic monotonicity for two controlled quantum systems: frequency unfiltered and filtered second-harmonic generation (SHG). For unfiltered SHG, the landscape is randomly sampled and interpolation of the data is found to be devoid of landscape traps up to the level of data noise. In the case of narrow-band-filtered SHG, trajectories are taken on the landscape to reveal a lack of traps. Although the filtered SHG landscape is trap free, it exhibits a rich local structure. A perturbation analysis around the top of these landscapes provides a basis to understand their topology. Despite the inherent trap-free nature of the landscapes, practical constraints placed on the controls can lead to the appearance of artificial structure arising from the resultant forced sampling of the landscape. This circumstance and the likely lack of knowledge about the detailed local landscape structure in most quantum control applications suggests that the a priori identification of globally successful (un)constrained curvilinear control variables may be a challenging task.

  10. Process Inherent Ultimate Safety (PIUS) reactor evaluation study: Final report

    International Nuclear Information System (INIS)

    1987-02-01

    This report presents the results of an independent study by United Engineers and Constructors (UNITED) of the SECURE-P Process Inherent Ultimate Safety (PIUS) Reactor Concept which is presently under development by the Swedish light water reactor vendor ASEA-ATOM of Vasteras, Sweden. This study was performed to investigate whether there is any realistic basis for believing that the PIUS reactor could be a viable competitor in the US energy market in the future. Assessments were limited to the technical, economic and licensing aspects of PIUS. Socio-political issues, while certainly important in answering this question, are so broad and elusive that it was considered that addressing them with the limited perspective of one small group from one company would be of questionable value and likely be misleading. Socio-political issues aside, the key issue is economics. For this reason, the specific objectives of this study were to determine if the estimated PIUS plant cost will be competitive in the US market and to identify and evaluate the technical and licensing risks that might make PIUS uneconomical or otherwise unacceptable

  11. Performance improvement CME for quality: challenges inherent to the process.

    Science.gov (United States)

    Vakani, Farhan Saeed; O'Beirne, Ronan

    2015-01-01

    The purpose of this paper is to discuss the perspective debates upon the real-time challenges for a three-staged Performance Improvement Continuing Medical Education (PI-CME) model, an innovative and potential approach for future CME, to inform providers to think, prepare and to act proactively. In this discussion, the challenges associated for adopting the American Medical Association's three-staged PI-CME model are reported. Not many institutions in USA are using a three-staged performance improvement model and then customizing it to their own healthcare context for the specific targeted audience. They integrate traditional CME methods with performance and quality initiatives, and linking with CME credits. Overall the US health system is interested in a structured PI-CME model with the potential to improve physicians practicing behaviors. Knowing the dearth of evidence for applying this structured performance improvement methodology into the design of CME activities, and the lack of clarity on challenges inherent to the process that learners and providers encounter. This paper establishes all-important first step to render the set of challenges for a three-staged PI-CME model.

  12. Conceptual design of Inherently Safe Fast Reactor (ISFR)

    International Nuclear Information System (INIS)

    Asahi, Yoshiro

    2003-01-01

    ISFR is a boiling heavy water fast reactor of process inherent ultimate safety (PIUS) type. ISFR may breed fuel in the core. Owing to a positive void coefficient, the application of the PIUS concept to ISFR is not straightforward. Thus, the gap conductance is small so that the time constant τ α of the positive void feedback process is sufficiently large, while the initially-closed two-way check valves to be used as passive switches to the pumps are installed at the lower honeycombs. As a result, the passive shutdown mechanisms can come into effect sufficiently soon to suppress the positive feedback reactivity. Both large τ α and the passive switches also help stabilize the system so that ISFR can perform a constant power operation with a simple control logic for the main coolant pump speed. In a steam generator tube rupture, fuel temperature was found to smoothly decrease to the decay heat level with nucleate boiling. The feasibility of ISFR was proved only to some extent. (author)

  13. Inherent safety features in balance-of-plant layout

    International Nuclear Information System (INIS)

    Wattelet, P.L.; Green, K.J.

    1992-01-01

    Future nuclear units must be more economical to construct and operate, and, at the same time, clearly incorporate advances in safety over the current generation of light water reactors. To achieve these goals, the root causes of safety issues must be addressed. In this way, global, cost-effective solutions can be implemented. With simple, direct design approaches, the licensing risk is minimized and configuration control is enhanced. With proper planning in the early stages of plant design, postulated accidents and events can often be mitigated by passive features inherent in the basic structure and layout, eliminating expensive added protective structures and components often found in current designs. Korea Electric Power Corporation's Yonggwang (YGN) Units 3 and 4, shown in an artist's rendering in Figure 1, are now under construction in Korea. Engineering is more than 85% complete, and Unit 3 construction is more than 50% complete. Significant steps toward design simplification and safety enhancement have been made by addressing safety concerns very early in the design effort. The tools used to achieve this were improved symmetry and separation, isolation of potential hazards, and an improved design process

  14. Demonstration of inherent safety features of HTGRs using the HTTR

    International Nuclear Information System (INIS)

    Tachibana, Yukio; Nakagawa, Shigeaki; Nakazawa, Toshio; Iyoku, Tatsuo

    2004-01-01

    Safety demonstration tests using the High Temperature Engineering Test Reactor (HTTR) are conducted for the purpose of demonstrating inherent safety features of High Temperature Gas-cooled Reactors (HTGRs) quantitatively as well as providing the core and plant transient data for validation of HTGR analysis codes for safety evaluation. The safety demonstration test are divided to the first phase and second phase tests. In the first phase tests, simulation tests of anticipated operational occurrences and anticipated transients without scram (ATWS) are conducted. The second phase tests will simulate accidents such as a depressurization accident (loss of coolant accident). The first phase test simulating reactivity insertion events and coolant flow reduction events stared in FY 2002. Post-test analyses have been conducted to reproduced the test results by using the core and plant dynamics analysis code, ACCORD and Monte Carlo code, MVP. The analysis results agreed fairly well with the test results of a control rod withdrawal test simulating reactivity insertion, and gas circulators trip test simulating coolant flow reduction, at power levels of 50% and 30% of the rated power, respectively. It is shown that improvement of the ACCORD code by taking into consideration vertical and horizontal temperature distribution gives better analysis results in the control rod withdrawal test. The fist phase safety demonstration tests will continue until FY 2005, and the second phase tests are planned to be started in FY 2006. (author)

  15. Accounting for inherent variability of growth in microbial risk assessment.

    Science.gov (United States)

    Marks, H M; Coleman, M E

    2005-04-15

    Risk assessments of pathogens need to account for the growth of small number of cells under varying conditions. In order to determine the possible risks that occur when there are small numbers of cells, stochastic models of growth are needed that would capture the distribution of the number of cells over replicate trials of the same scenario or environmental conditions. This paper provides a simple stochastic growth model, accounting only for inherent cell-growth variability, assuming constant growth kinetic parameters, for an initial, small, numbers of cells assumed to be transforming from a stationary to an exponential phase. Two, basic, microbial sets of assumptions are considered: serial, where it is assume that cells transform through a lag phase before entering the exponential phase of growth; and parallel, where it is assumed that lag and exponential phases develop in parallel. The model is based on, first determining the distribution of the time when growth commences, and then modelling the conditional distribution of the number of cells. For the latter distribution, it is found that a Weibull distribution provides a simple approximation to the conditional distribution of the relative growth, so that the model developed in this paper can be easily implemented in risk assessments using commercial software packages.

  16. Inherent aerobic capacity-dependent differences in breast carcinogenesis.

    Science.gov (United States)

    Thompson, Henry J; Jones, Lee W; Koch, Lauren G; Britton, Steven L; Neil, Elizabeth S; McGinley, John N

    2017-09-01

    Although regular physical activity is associated with improvement in aerobic capacity and lower breast cancer risk, there are heritable sets of traits that affect improvement in aerobic capacity in response to physical activity. Although aerobic capacity segregates risk for a number of chronic diseases, the effect of the heritable component on cancer risk has not been evaluated. Therefore, we investigated breast carcinogenesis in rodent models of heritable fitness in the absence of induced physical activity. Female offspring of N:NIH rats selectively bred for low (LIAC) or high (HIAC) inherent aerobic capacity were injected intraperitoneally with 1-methyl-1-nitrosurea (70 mg/kg body wt). At study termination 33 weeks post-carcinogen, cancer incidence (14.0 versus 47.3%; P < 0.001) and multiplicity (0.18 versus 0.85 cancers per rat; P < 0.0001) were significantly decreased in HIAC versus LIAC rats, respectively. HIAC had smaller visceral and subcutaneous body fat depots than LIAC and activity of two proteins that regulated the mammalian target of rapamycin, protein kinase B (Akt), and adenosine monophosphate-activated protein kinase were suppressed and activated, respectively, in HIAC. Although many factors distinguish between HIAC and LIAC, it appears that the protective effect of HIAC against breast carcinogenesis is mediated, at least in part, via alterations in core metabolic signaling pathways deregulated in the majority of human breast cancers. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Tumor inherent interferons: Impact on immune reactivity and immunotherapy.

    Science.gov (United States)

    Brockwell, Natasha K; Parker, Belinda S

    2018-04-19

    Immunotherapy has revolutionized cancer treatment, with sustained responses to immune checkpoint inhibitors reported in a number of malignancies. Such therapeutics are now being trialed in aggressive or advanced cancers that are heavily reliant on untargeted therapies, such as triple negative breast cancer. However, responses have been underwhelming to date and are very difficult to predict, leading to an inability to accurately weigh up the benefit-to-risk ratio for their implementation. The tumor immune microenvironment has been closely linked to immunotherapeutic response, with superior responses observed in patients with T cell-inflamed or 'hot' tumors. One class of cytokines, the type I interferons, are a major dictator of tumor immune infiltration and activation. Tumor cell inherent interferon signaling dramatically influences the immune microenvironment and the expression of immune checkpoint proteins, hence regulators and targets of this pathway are candidate biomarkers of immunotherapeutic response. In support of a link between IFN signaling and immunotherapeutic response, the combination of type I interferon inducers with checkpoint immunotherapy has recently been demonstrated critical for a sustained anti-tumor response in aggressive breast cancer models. Here we review evidence that links type I interferons with a hot tumor immune microenvironment, response to checkpoint inhibitors and reduced risk of metastasis that supports their use as biomarkers and therapeutics in oncology. Copyright © 2018. Published by Elsevier Ltd.

  18. Inherent Difference in Saliency for Generators with Different PM Materials

    Directory of Open Access Journals (Sweden)

    Sandra Eriksson

    2014-01-01

    Full Text Available The inherent differences between salient and nonsalient electrical machines are evaluated for two permanent magnet generators with different configurations. The neodymium based (NdFeB permanent magnets (PMs in a generator are substituted with ferrite magnets and the characteristics of the NdFeB generator and the ferrite generator are compared through FEM simulations. The NdFeB generator is a nonsalient generator, whereas the ferrite machine is a salient-pole generator, with small saliency. The two generators have almost identical properties at rated load operation. However, at overload the behaviour differs between the two generators. The salient-pole, ferrite generator has lower maximum torque than the NdFeB generator and a larger voltage drop at high current. It is concluded that, for applications where overload capability is important, saliency must be considered and the generator design adapted according to the behaviour at overload operation. Furthermore, if the maximum torque is the design criteria, additional PM mass will be required for the salient-pole machine.

  19. Inherent variation in multiple shoe-sole test impressions.

    Science.gov (United States)

    Shor, Yaron; Wiesner, Sarena; Tsach, Tsadok; Gurel, Ron; Yekutieli, Yoram

    2018-04-01

    Shoeprints left at crime scenes are seldom perfect. Many prints are distorted or contaminated by various materials. Noisy background often contributes to vagueness on the shoeprints as well. Test impressions made from the suspect's shoes in the laboratory are considered a genuine replication of the shoe-sole. This naïve attitude is far from being correct. Consecutive test impressions made in the laboratory under strict similar conditions revealed differences among the exemplars of the same sole. Some of them are minor, but some are major, and can mislead the less experienced practitioners during the comparison process. This article focuses on the inherent within source variability between controlled shoeprints made from the same shoe, as it appears on the RACs. To describe and analyze this variability, repeated test impressions were prepared, and datasets were created. Several RACs were marked on each test impression, using an expert assisting software tool (developed in the authors' lab). The variance in repeated test impressions is demonstrated and possible sources are discussed. This variance should be considered when trying to establish the degree of matching between individual characteristics. Copyright © 2017. Published by Elsevier B.V.

  20. Metal-fuel modeling for inherently safe reactor designs

    International Nuclear Information System (INIS)

    Miles, K.J. Jr.

    1987-01-01

    Current development of breeder reactor systems has led to the renewed interest in metal fuels. These fuels have properties that enhance the inherent safety of the system, such as high thermal conductivity, compatibility with liquid sodium, and low fuel/cladding mechanical interaction. While metal-fuel irradiation behavior is well understood, there are some areas where more information is needed to fully understand the various safety-related phenomena, such as fuel/cladding chemical interaction, eutectic melting and penetration, and axial relocation of molten fuel prior to cladding breach. Because many of these phenomena can cause changes in the reactivity state of the system, their effects on whole-core normal, anticipated, and hypothetical accident scenarios need to be studied. The metal-fuel behavior model DEFORM-5 is being developed to provide the necessary phenomenological basis for these studies. The first stage in the DEFORM-5 development has been completed. Presently, DEFORM-5 calculates the cladding strain, life fraction, and eutectic penetration thinning for Types D9, HT9, or 316 steels. This first stage of DEFORM-5 has been used to analyze the TREAT M2, M3, and M4 transients with irradiated Experimental Breeder Reactor-II driver fuel. The paper shows the DEFORM-5 and experimental results for failure times for the test pins. The results provide confidence and validation of the DEFORM-5 modeling of the cladding behavior

  1. Managing inherent complexity for sustainable walleye fisheries in Lake Erie

    Science.gov (United States)

    Roseman, Edward F.; Drouin, Richard; Gaden, Marc; Knight, Roger; Tyson, Jeff; Zhao, Yingming; Taylor, William W.; Lynch, Abigail J.; Léonard, Nancy J.

    2012-01-01

    In Lake Erie, Walleye (Sander vitreus vitreus) is king. The naturally occurring species is the foundation of commercial fishing operations on the Canadian side of the lake and is a much-prized sport fish on the American side. Management of Lake Erie walleye fisheries is complex and takes place in an inter-jurisdictional setting composed of resource agencies from the states of Michigan (MDNR), Ohio (ODNR), Pennsylvania (PFBC), and New York (NYDEC) and the province of Ontario (OMNR). The complexity of walleye management is exacerbated by interactions among environmental and ecological changes in Lake Erie, complex life-history characteristics of the species, public demand for walleye, and cultural/governance differences among managing groups and their respective constituents. Success of future management strategies will largely hinge upon our ability to understand these inherent complexities and to employ tactics that successfully accommodate stock productivity and human demand in a highly dynamic environment. In this report, we review the history of Lake Erie walleye management, outline the multi-jurisdictional process for international management of walleye, and discuss strategies to address challenges facing managers.

  2. Thermally responsive polymer electrolytes for inherently safe electrochemical energy storage

    Science.gov (United States)

    Kelly, Jesse C.

    Electrochemical double layer capacitors (EDLCs), supercapacitors and Li-ion batteries have emerged as premier candidates to meet the rising demands in energy storage; however, such systems are limited by thermal hazards, thermal runaway, fires and explosions, all of which become increasingly more dangerous in large-format devices. To prevent such scenarios, thermally-responsive polymer electrolytes (RPEs) that alter properties in electrochemical energy storage devices were designed and tested. These RPEs will be used to limit or halt device operation when temperatures increase beyond a predetermined threshold, therefore limiting further heating. The development of these responsive systems will offer an inherent safety mechanism in electrochemical energy storage devices, while preserving the performance, lifetimes, and versatility that large-format systems require. Initial work focused on the development of a model system that demonstrated the concept of RPEs in an electrochemical device. Aqueous electrolyte solutions of polymers exhibiting properties that change in response to temperature were developed for applications in EDLCs and supercapacitors. These "smart materials" provide a means to control electrochemical systems where polymer phase separation at high temperatures affects electrolyte properties and inhibits device performance. Aqueous RPEs were synthesized using N-isopropylacrylamide, which governs the thermal properties, and fractions of acrylic acid or vinyl sulfonic acids, which provide ions to the solution. The molecular properties of these aqueous RPEs, specifically the ionic composition, were shown to influence the temperature-dependent electrolyte properties and the extent to which these electrolytes control the energy storage characteristics of a supercapacitor device. Materials with high ionic content provided the highest room temperature conductivity and electrochemical activity; however, RPEs with low ionic content provided the highest "on

  3. Large Eddy Simulation for an inherent boron dilution transient

    International Nuclear Information System (INIS)

    Jayaraju, S.T.; Sathiah, P.; Komen, E.M.J.; Baglietto, E.

    2013-01-01

    Highlights: • Large Eddy Simulation is performed for a transient boron dilution scenario in the scaled experimental facility of ROCOM. • Fully conformal polyhedral grid of 14 million is created to capture all details of the domain. • Systematic multi-step validation methodology is followed to assess the accuracy of LES model. • For the presently simulated BDT scenario, the LES results lend support to its reliability in consistently predicting the slug transport in the RPV. -- Abstract: The present paper focuses on the validation and applicability of large eddy simulation (LES) to analyze the transport and mixing in the reactor pressure vessel (RPV) during an inherent boron dilution transient (BDT) scenario. Extensive validation data comes from relevant integral tests performed in the scaled ROCOM experimental facility. The modeling of sub-grid-scales is based on the WALE model. A fully conformal polyhedral grid of about 15 million cells is constructed to capture all details in the domain, including the complex structures of the lower-plenum. Detailed qualitative and quantitative validations are performed by following a systematic multi-step validation methodology. Qualitative comparisons to the experimental data in the cold legs, downcomer and the core inlet showed good predictions by the LES model. Minor deviations seen in the quantitative comparisons are rigorously quantified. A key parameter which is affecting the core neutron kinetics response is the value of highest deborated slug concentration that occurs at the core inlet during the transient. Detailed analyses are made at the core inlet to evaluate not only the value of the maximum slug concentration, but also the location and the time at which it occurs during the transient. The relative differences between the ensemble averaged experimental data and CFD predictions were within the range of relative differences seen within 10 different experimental realizations. For the studied scenario, the

  4. An inherently parallel method for solving discretized diffusion equations

    International Nuclear Information System (INIS)

    Eccleston, B.R.; Palmer, T.S.

    1999-01-01

    A Monte Carlo approach to solving linear systems of equations is being investigated in the context of the solution of discretized diffusion equations. While the technique was originally devised decades ago, changes in computer architectures (namely, massively parallel machines) have driven the authors to revisit this technique. There are a number of potential advantages to this approach: (1) Analog Monte Carlo techniques are inherently parallel; this is not necessarily true to today's more advanced linear equation solvers (multigrid, conjugate gradient, etc.); (2) Some forms of this technique are adaptive in that they allow the user to specify locations in the problem where resolution is of particular importance and to concentrate the work at those locations; and (3) These techniques permit the solution of very large systems of equations in that matrix elements need not be stored. The user could trade calculational speed for storage if elements of the matrix are calculated on the fly. The goal of this study is to compare the parallel performance of Monte Carlo linear solvers to that of a more traditional parallelized linear solver. The authors observe the linear speedup that they expect from the Monte Carlo algorithm, given that there is no domain decomposition to cause significant communication overhead. Overall, PETSc outperforms the Monte Carlo solver for the test problem. The PETSc parallel performance improves with larger numbers of unknowns for a given number of processors. Parallel performance of the Monte Carlo technique is independent of the size of the matrix and the number of processes. They are investigating modifications to the scheme to accommodate matrix problems with positive off-diagonal elements. They are also currently coding an on-the-fly version of the algorithm to investigate the solution of very large linear systems

  5. Inherent Reward and Risk (Part I): Towards a Universal Paradigm for Investment Analysis

    OpenAIRE

    Liang Zou

    2000-01-01

    In this paper, a new paradigm is developed for analyzinginvestment strategies and pricing financial assets. This paradigmassumes that any investment strategy has its own “inherent reward”and “inherent risk” that can be judged with common sense. Ijustify axiomatically the existence and uniqueness (ratio scale)of inherent reward (U) and inherent risk (D) that could beregarded as universal measures of reward and risk for any giveninvestment strategy. Incorporating the notion of “inherentefficien...

  6. Is it about "pink" or about "girls"? The inherence heuristic across social and nonsocial domains.

    Science.gov (United States)

    Kinzler, Katherine D; Sullivan, Kathleen R

    2014-10-01

    The inherence heuristic provides an intriguing and novel explanation for early thought in a variety of domains. Exploring similarities and differences in inherent reasoning across social and nonsocial domains can help us understand the role that inherent thinking plays in the development of human reasoning and the process by which more elaborate essentialist reasoning develops.

  7. Chemical looping combustion. Fuel conversion with inherent CO2 capture

    Energy Technology Data Exchange (ETDEWEB)

    Brandvoll, Oeyvind

    2005-07-01

    ONiAl do not rule out CLC as a viable alternative for CO2 capture, but long term durability studies along with realistic testing of the carrier in a continuous rig is needed to firmly conclude. For comparative purposes a perovskite was synthesized and tested in CLC, under similar conditions as NiONiAl. The results indicate that in a moving bed CLC application, perovskites have inherent disadvantages as compared to simpler compounds, by virtue of low relative oxygen content. (Author)

  8. Mitigation of Severe Accident Consequences Using Inherent Safety Principles

    International Nuclear Information System (INIS)

    Wigeland, R.A.; Cahalan, J.E.

    2009-01-01

    Sodium-cooled fast reactors are designed to have a high level of safety. Events of high probability of occurrence are typically handled without consequence through reliable engineering systems and good design practices. For accidents of lower probability, the initiating events are characterized by larger and more numerous challenges to the reactor system, such as failure of one or more major engineered systems and can also include a failure to scram the reactor in response. As the initiating conditions become more severe, they have the potential for creating serious consequences of potential safety significance, including fuel melting, fuel pin disruption and recriticality. If the progression of such accidents is not mitigated by design features of the reactor, energetic events and dispersal of radioactive materials may result. For severe accidents, there are several approaches that can be used to mitigate the consequences of such severe accident initiators, which typically include fuel pin failures and core disruption. One approach is to increase the reliability of the reactor protection system so that the probability of an ATWS event is reduced to less than 1 x 10-6 per reactor year, where larger accident consequences are allowed, meeting the U.S. NRC goal of relegating such accident consequences as core disruption to these extremely low probabilities. The main difficulty with this approach is to convincingly test and guarantee such increased reliability. Another approach is to increase the redundancy of the reactor scram system, which can also reduce the probability of an ATWS event to a frequency of less than 1 x 10-6 per reactor year or lower. The issues with this approach are more related to reactor core design, with the need for a greater number of control rod positions in the reactor core and the associated increase in complexity of the reactor protection system. A third approach is to use the inherent reactivity feedback that occurs in a fast reactor to

  9. Technology which led to the westinghouse inherently safe liquid metal reactor

    International Nuclear Information System (INIS)

    Schmidt, J.E.; Coffield, R.D.; Doncals, R.A.; Kalinowski, J.E.; Markley, R.A.

    1985-01-01

    The Fast Flux Test Facility (FFTF) and the Clinch River Breeder Reactor programs resulted in an understanding of liquid metal reactor behavior that is being used to design inherent safety capability into liquid metal reactors. Technological advances give the same beneficial operating characteristics of conventional liquid metal reactors, however, the addition of inherently safe design features precludes the initiation of hypothetical core disruptive accidents. These innovative features permit inherent safety capability to be demonstrated with more than adequate margins. Also, the variety of inherent safety features provides the designers with options in selecting inherent design features for a specific reactor application

  10. Understanding the Spatiotemporal Variability of Inherent Water Use Efficiency

    Science.gov (United States)

    Boese, Sven; Jung, Martin; Carvalhais, Nuno; Reichstein, Markus

    2015-04-01

    The global carbon and water cycles are coupled via plant physiology. However, the resulting spatial and temporal covariability of both fluxes on a global scale lacks sufficient understanding. This is required to estimate the impact of atmospheric drought on photosynthesis in water-limited ecosystems. Water use efficiency (WUE) is an essential ecosystem diagnostic defined as the ratio between gross primary productivity (GPP) and transpiration (T). WUE is known to vary with vapour-pressure deficit (VPD) and therefore also in time. The inherent water use efficiency (iWUE) accounts for the VPD effect on WUE and aims at representing a largely time-invariant ecosystem property. However, different ways of describing the functional response of iWUE to VPD are found in the literature. One established iWUE definition was proposed by Beer et al. (2009) and takes the form of iWUE = GPP--VPD- . T (1) A similar definition can be derived from stomatal conductance theories such as Katul et al. (2010) and takes the form of √ -- GPP---VPD- iWUE = T . (2) Here, we use eddy covariance measurements from the FLUXNET database to evaluate both approaches for a globally representative set of biomes including tropical, temperate and semi-arid ecosystems. Testing both definitions in a model-data fusion setup indicated that (2) is more consistent with FLUXNET observations than (1). However, there still remains considerable temporal variability of iWUE which is linked to seasonal changes in VPD. To explore up to which extent the temporal variability of iWUE may be related to the prescribed functional responses to VPD, we treated the exponent of VPD as a global parameter, here termed γ. When γ = 1 the functional response is equivalent to (1), while when γ = 0.5 it corresponds to formulation of model (2)). The global estimate was found to be significantly lower than 0.5, which would have been expected from stomatal conductance theory at leaf level. We assessed whether adding γ as site

  11. Mycobacteriophage genome database.

    Science.gov (United States)

    Joseph, Jerrine; Rajendran, Vasanthi; Hassan, Sameer; Kumar, Vanaja

    2011-01-01

    Mycobacteriophage genome database (MGDB) is an exclusive repository of the 64 completely sequenced mycobacteriophages with annotated information. It is a comprehensive compilation of the various gene parameters captured from several databases pooled together to empower mycobacteriophage researchers. The MGDB (Version No.1.0) comprises of 6086 genes from 64 mycobacteriophages classified into 72 families based on ACLAME database. Manual curation was aided by information available from public databases which was enriched further by analysis. Its web interface allows browsing as well as querying the classification. The main objective is to collect and organize the complexity inherent to mycobacteriophage protein classification in a rational way. The other objective is to browse the existing and new genomes and describe their functional annotation. The database is available for free at http://mpgdb.ibioinformatics.org/mpgdb.php.

  12. Concept of an inherently-safe high temperature gas-cooled reactor

    International Nuclear Information System (INIS)

    Ohashi, Hirofumi; Sato, Hiroyuki; Tachibana, Yukio; Kunitomi, Kazuhiko; Ogawa, Masuro

    2012-01-01

    As the challenge to ensure no harmful release of radioactive materials at the accidents by deterministic approach instead to satisfy acceptance criteria or safety goal for risk by probabilistic approach, new concept of advanced reactor, an inherently-safe high temperature gas-cooled reactor, is proposed based on the experience of the operation of the actual High Temperature Gas-cooled Reactor (HTGR) in Japan, High Temperature Engineering Test Reactor (HTTR), and the design of the commercial plant (GTHTR300), utilizing the inherent safety features of the HTGR (i.e., safety features based on physical phenomena). The safety design philosophy of the inherently-safe HTGR for the safety analysis of the radiological consequences is determined as the confinement of radioactive materials is assured by only inherent safety features without engineered safety features, AC power or prompt actions by plant personnel if the design extension conditions occur. Inherent safety features to prevent the loss or degradation of the confinement function are identified. It is proposed not to apply the probabilistic approach for the evaluation of the radiological consequences of the accidents in the safety analysis because no inherent safety features fail for the mitigation of the consequences of the accidents. Consequently, there are no event sequences to harmful release of radioactive materials if the design extension conditions occur in the inherently-safe HTGR concept. The concept and future R and D items for the inherently-safe HTGR are described in this paper.

  13. Inherent reward & risk (Part I): Towards a universal paradigm for investment analysis

    NARCIS (Netherlands)

    Zou, L.

    2000-01-01

    In this paper, a new paradigm is developed for analyzinginvestment strategies and pricing financial assets. This paradigmassumes that any investment strategy has its own "inherent reward"and "inherent risk" that can be judged with common sense. Ijustify axiomatically the existence and uniqueness

  14. Ordeals of Chernobyl and the rejustification of the inherently safe reactors

    International Nuclear Information System (INIS)

    Lu, Y.

    1989-01-01

    This paper presents the necessity of developing inherently safe economic reactors (ISERs). Two characteristics which define inherent safety are discussed on the basis of various applications of such a principle in practice. Different design concepts of ISERs are then evaluated and their possible role in the future nuclear program of PRC discussed. A three-stage development strategy of ISERs in PRC is proposed

  15. A case for inherent geometric and geodetic accuracy in remotely sensed VNIR and SWIR imaging products

    Science.gov (United States)

    Driver, J. M.

    1982-01-01

    Significant aberrations can occur in acquired images which, unless compensated on board the spacecraft, can seriously impair throughput and timeliness for typical Earth observation missions. Conceptual compensations options are advanced to enable acquisition of images with inherent geometric and geodetic accuracy. Research needs are identified which, when implemented, can provide inherently accurate images. Agressive pursuit of these research needs is recommended.

  16. Advances in Arachis genomics for peanut improvement

    Science.gov (United States)

    Peanut genomics is very challenging due to its inherent problem of genetic architecture. Blockage of gene flow from diploid wild relatives to tetraploid cultivated peanut, recent polyploidization combined with self pollination and narrow genetic base of primary gene pool resulted in low genetic dive...

  17. Safety assessment in plant layout design using indexing approach: Implementing inherent safety perspective

    International Nuclear Information System (INIS)

    Tugnoli, Alessandro; Khan, Faisal; Amyotte, Paul; Cozzani, Valerio

    2008-01-01

    Layout planning plays a key role in the inherent safety performance of process plants since this design feature controls the possibility of accidental chain-events and the magnitude of possible consequences. A lack of suitable methods to promote the effective implementation of inherent safety in layout design calls for the development of new techniques and methods. In the present paper, a safety assessment approach suitable for layout design in the critical early phase is proposed. The concept of inherent safety is implemented within this safety assessment; the approach is based on an integrated assessment of inherent safety guideword applicability within the constraints typically present in layout design. Application of these guidewords is evaluated along with unit hazards and control devices to quantitatively map the safety performance of different layout options. Moreover, the economic aspects related to safety and inherent safety are evaluated by the method. Specific sub-indices are developed within the integrated safety assessment system to analyze and quantify the hazard related to domino effects. The proposed approach is quick in application, auditable and shares a common framework applicable in other phases of the design lifecycle (e.g. process design). The present work is divided in two parts: Part 1 (current paper) presents the application of inherent safety guidelines in layout design and the index method for safety assessment; Part 2 (accompanying paper) describes the domino hazard sub-index and demonstrates the proposed approach with a case study, thus evidencing the introduction of inherent safety features in layout design

  18. Extreme genomes

    OpenAIRE

    DeLong, Edward F

    2000-01-01

    The complete genome sequence of Thermoplasma acidophilum, an acid- and heat-loving archaeon, has recently been reported. Comparative genomic analysis of this 'extremophile' is providing new insights into the metabolic machinery, ecology and evolution of thermophilic archaea.

  19. Long range stress correlations in the inherent structures of liquids at rest

    Energy Technology Data Exchange (ETDEWEB)

    Chowdhury, Sadrul; Abraham, Sneha; Hudson, Toby; Harrowell, Peter [School of Chemistry, University of Sydney, Sydney, NSW 2006 (Australia)

    2016-03-28

    Simulation studies of the atomic shear stress in the local potential energy minima (inherent structures) are reported for binary liquid mixtures in 2D and 3D. These inherent structure stresses are fundamental to slow stress relaxation and high viscosity in supercooled liquids. We find that the atomic shear stress in the inherent structures (IS’s) of both liquids at rest exhibits slowly decaying anisotropic correlations. We show that the stress correlations contribute significantly to the variance of the total shear stress of the IS configurations and consider the origins of the anisotropy and spatial extent of the stress correlations.

  20. The role of passive and inherent safety properties in Siemens/KWU nuclear power plants

    International Nuclear Information System (INIS)

    Gremm, O.

    1990-01-01

    In Siemens/KWU Nuclear Power Plants the applied safety concept consist of a well balanced combination of active, passive use well is inherent safety measures. In principle it is not possible to realise a safety concept exclusively with inherent and/or passive safety properties. The respective measures and arguments will be explained in detail in the presentation. In addition the Siemens/KWU safety concept with examples of the role of inherent and passive safety measures will be illustrated. (author). 9 refs, 9 figs

  1. Grass genomes

    OpenAIRE

    Bennetzen, Jeffrey L.; SanMiguel, Phillip; Chen, Mingsheng; Tikhonov, Alexander; Francki, Michael; Avramova, Zoya

    1998-01-01

    For the most part, studies of grass genome structure have been limited to the generation of whole-genome genetic maps or the fine structure and sequence analysis of single genes or gene clusters. We have investigated large contiguous segments of the genomes of maize, sorghum, and rice, primarily focusing on intergenic spaces. Our data indicate that much (>50%) of the maize genome is composed of interspersed repetitive DNAs, primarily nested retrotransposons that in...

  2. Cancer genomics

    DEFF Research Database (Denmark)

    Norrild, Bodil; Guldberg, Per; Ralfkiær, Elisabeth Methner

    2007-01-01

    Almost all cells in the human body contain a complete copy of the genome with an estimated number of 25,000 genes. The sequences of these genes make up about three percent of the genome and comprise the inherited set of genetic information. The genome also contains information that determines whe...

  3. Compact All Solid State Oceanic Inherent Optical Property Sensor, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Light propagation in the sea and the consequent remote sensing signals seen by aircraft and spacecraft is fundamentally governed by the inherent optical properties...

  4. Probabilities of inherent shutdown of unprotected events in innovative liquid metal reactors

    International Nuclear Information System (INIS)

    Mueller, C.J.; Wade, D.C.

    1988-01-01

    The uncertainty in predicting the effectiveness of inherent shutdown in innovative liquid metal cooled reactors with metallic fuel results from three broad contributing areas of uncertainty: (1) the inability to exactly predict the frequency of ATWS events with potential to challenge the safety systems and require inherent shutdown; (2) the approximation of representing all such events by a selected set of ''generic scenarios''; and (3) the inability to exactly calculate the core response to the selected generic scenarios. This paper discusses the work being done to address each of these contributing areas, identifies the design and research approaches being used at Argonne National Laboratory to reducing the key contributions to uncertainties in inherent shutdown, and presents results. The conditional probabilities (given ATWS initiation) of achieving temperatures capable of defeating inherent shutdown are shown to range from /approximately/0.1% to negligible for current designs

  5. Progress on PRISM, an inherently safe, economic, and testable advanced liquid metal reactor

    International Nuclear Information System (INIS)

    Tippets, F.E.; Salerno, L.N.; Boardman, C.E.; Kwant, W.; Murata, R.E.; Snyder, C.R.

    1987-01-01

    This paper reports progress on the design of PRISM (Power Reactor Inherently Safe Module) under the DOE-sponsored innovative reactor program now in its third year at General Electric. The purpose of this program is to develop a design for an inherently safe, reliable, and marketable liquid metal fast reactor power plant. The PRISM design approach includes the following key elements: Compact sodium-cooled pool-type reactor modules that are sized to enable factory fabrication, economical shipment to inland as well as water-side sites, and economical full-scale prototype testing for design certification; Nuclear safety-related envelope limited to the reactor modules and their service systems; Inherent, passive shutdown heat removal for loss-of-cooling events; Inherent, passive reactivity shutdown for failure-to-scram events

  6. Food plant toxicants and safety - Risk assessment and regulation of inherent toxicants in plant foods

    DEFF Research Database (Denmark)

    Essers, A.J.A.; Alink, G.M.; Speijers, G.J.A.

    1998-01-01

    The ADI as a tool for risk management and regulation of food additives and pesticide residues is not readily applicable to inherent food plant toxicants: The margin between actual intake and potentially toxic levels is often small; application of the default uncertainty factors used to derive ADI...... values, particularly when extrapolating from animal data, would prohibit the utilisation of the food, which may have an overall beneficial health effect. Levels of inherent toxicants are difficult to control; their complete removal is not always wanted, due to their function for the plant or for human...... health. The health impact of the inherent toxicant is often modified by factors in the food, e.g. the bioavailability from the matrix and interaction with other inherent constituents. Risk-benefit analysis should be made for different consumption scenarios, without the use of uncertainty factors. Crucial...

  7. Quantification of Inherent Respirable Dust Generation Potential (IRDGP) of South African Coals

    CSIR Research Space (South Africa)

    Phillips, H

    2003-08-01

    Full Text Available Advisory Committee Project Summary Project Title: Inherent Respirable Dust Generation Potential (IRDGP) of South African Coals-SIM020604 Author(s): H.R.Phillips and B. K. Belle Agency: University of Witwatersrand Report Date: July2003... Related Projects: Health 607, Sim 02-06-03 Category: Occupational Health Applied Research Occupational Hygiene Summary Project SIM020604 was formulated to determine the Inherent Respirable Dust Generation Potential (IRDGP) of various South...

  8. Novel OSNR Monitoring Technique in Dense WDM Systems using Inherently Generated CW Monitoring Channels

    DEFF Research Database (Denmark)

    Petersen, Martin Nordal

    2007-01-01

    We present a simple, yet effective OSNR monitoring technique based on an inherent effect in the optical modulator. Highly accurate OSNR monitoring is demonstrated in a 40 Gb/s dense WDM system with 50 GHz channel spacing.......We present a simple, yet effective OSNR monitoring technique based on an inherent effect in the optical modulator. Highly accurate OSNR monitoring is demonstrated in a 40 Gb/s dense WDM system with 50 GHz channel spacing....

  9. A real-life example of choosing an inherently safer process option

    International Nuclear Information System (INIS)

    Study, Karen

    2007-01-01

    While choosing an inherently safer alternative may seem straightforward, sometimes what seems to be the most obvious alternative may not provide the best risk reduction. The process designer must maintain a broad perspective to be able to recognize all potential hazards when evaluating design options. All aspects of operation such as start-up, shut-down, utility failure, as well as normal operation should be considered. Choosing the inherently safer option is best accomplished early in the option selection phase of a project; however, recycle back to the option selection phase may be needed if an option is not thoroughly evaluated early in the process. In this paper, a project to supply ammonia to a catalytic reactor will be reviewed. During the course of the project, an 'inherently safer' alternative was selected and later discarded due to issues uncovered during the detail design phase. The final option chosen will be compared to (1) the original design and (2) the initial 'inherently safer' alternative. The final option was inherently safer than both the original design and the initial 'inherently safer' alternative even though the design team initially believed that it would not be

  10. [THE CYTOMETRIC TECHNIQUE OF BINDING OF EOSIN-5-MALEIMIDE IN DIAGNOSTIC OF INHERENT SPHEROCYTOSIS].

    Science.gov (United States)

    Kuzminova, J A; Plyasunova, S A; Jogov, V V; Smetanina, N S

    2016-03-01

    The laboratory diagnostic of inherent spherocytosis is based on detection of spherocytes in peripheral blood, decreasing of index of sphericity, decreasing of osmotic resistance of erythrocytes. The new test of diagnostic of hereditary spherocytosis build on molecular defect was developed on the basis of binding extracellular fragments of protein of band 3 with eosin-5-maleimide (EMA-test). The study was carried out to implement comparative analysis of sensitivity and specificity of techniques applied to diagnose inherent spherocytosis. The sampling of 94 patients with various forms of anemias was analyzed All patients were applied complex clinical laboratory examination including analysis of osmotic resistance of erythrocytes, erythrocytometry and EMA-test as specific techniques of diagnostic of inherent spherocytosis. In 51 out of 94 patients (54%) decreasing of values of EMA-test was detected and in 47 patients diagnosis of inherent spherocytosis was confirmed. The standard values of EMA-test were established in 43 patients (46%) and 12 patients out of them with established diagnosis of inherent spherocytosis. Therefore, sensitivity of EMA-test made up to 79% and specificity - 80%. The most sensitive techniques of diagnostic remain osmotic resistance of erythrocytes (91%) and index of sphericity (up to 96%). But the highest specificity in this respect has EMA-test (80%). Nowadays, none of implemented techniques of diagnostic of inherent spherocytosis can be applied as a universal one. The implementation of complex examination is needed for proper diagnostic of disease.

  11. Development of quantitative goals for inherent safety feature design and licensing

    International Nuclear Information System (INIS)

    Kastenberg, W.E.; Apostolakis, G.; Dhir, V.K.; Okrent, D.

    1987-01-01

    There is now considerable interest in the development of advanced fast reactors whose major focus is inherent safety. The achievement of inherent safety can be viewed from several aspects. In the Integral Fast Reactor Concept the approach is to utilize the intrinsic characteristics of pool-type liquid metal fast breeder reactors (LMFBRs) and the properties of metal fuels to integrate a high degree of inherent safety into the design. The PRISM and SAFR concepts focus on other inherent safety features. The reactors discussed above represent a radical departure from existing LWR designs as well as previous LMFBR designs (e.g., CRBRP) which are based, for the most part, on the General Design Criteria found in 10CFR50 Appendix. In view of these parallel developments (advanced reactors exploiting inherent safety and the use of quantitative goals to augment licensing), there appears to be a need to perform research on the development of methods for designing, assessing, and licensing inherent safety features in advanced reactors. The objectives of such research are outlined

  12. Inherent work suit buoyancy distribution: effects on lifejacket self-righting performance.

    Science.gov (United States)

    Barwood, Martin J; Long, Geoffrey M; Lunt, Heather; Tipton, Michael J

    2014-09-01

    Accidental immersion in cold water is an occupational risk. Work suits and life jackets (LJ) should work effectively in combination to keep the airway clear of the water (freeboard) and enable self-righting. We hypothesized that inherent buoyancy, in the suit or LJ, would be beneficial for enabling freeboard, but its distribution may influence LJ self-righting. Six participants consented to complete nine immersions. Suits and LJ tested were: flotation suit (FLOAT; 85 N inherent buoyancy); oilskins 1 (OS-1) and 2 (OS-2), both with no inherent buoyancy; LJs (inherent buoyancy/buoyancy after inflation/total buoyancy), LJ-1 50/150/200 N, LJ-2 0/290/290 N, LJ-3 80/190/270 N. Once dressed, the subject entered an immersion pool where uninflated freeboard, self-righting performance, and inflated freeboard were measured. Data were compared using Friedman's test to the 0.05 alpha level. All suits and LJs enabled uninflated and inflated freeboard, but differences were seen between the suits and LJs. Self-righting was achieved on 43 of 54 occasions, irrespective of suit or LJ. On all occasions that self-righting was not achieved, this occurred in an LJ that included inherent buoyancy (11/54 occasions). Of these 11 failures, 8 occurred (73% of occasions) when the FLOAT suit was being worn. LJs that included inherent buoyancy, that are certified as effective on their own, worked less effectively from the perspective of self-righting in combination with a work suit that also included inherent buoyancy. Equipment that is approved for use in the workplace should be tested in combination to ensure adequate performance in an emergency scenario.

  13. Is the inherent potential of maize roots efficient for soil phosphorus acquisition?

    Science.gov (United States)

    Deng, Yan; Chen, Keru; Teng, Wan; Zhan, Ai; Tong, Yiping; Feng, Gu; Cui, Zhenling; Zhang, Fusuo; Chen, Xinping

    2014-01-01

    Sustainable agriculture requires improved phosphorus (P) management to reduce the overreliance on P fertilization. Despite intensive research of root adaptive mechanisms for improving P acquisition, the inherent potential of roots for efficient P acquisition remains unfulfilled, especially in intensive agriculture, while current P management generally focuses on agronomic and environmental concerns. Here, we investigated how levels of soil P affect the inherent potential of maize (Zea mays L.) roots to obtain P from soil. Responses of root morphology, arbuscular mycorrhizal colonization, and phosphate transporters were characterized and related to agronomic traits in pot and field experiments with soil P supply from deficiency to excess. Critical soil Olsen-P level for maize growth approximated 3.2 mg kg(-1), and the threshold indicating a significant environmental risk was about 15 mg kg(-1), which represented the lower and upper levels of soil P recommended in current P management. However, most root adaptations involved with P acquisition were triggered when soil Olsen-P was below 10 mg kg(-1), indicating a threshold for maximum root inherent potential. Therefore, to maintain efficient inherent potential of roots for P acquisition, we suggest that the target upper level of soil P in intensive agriculture should be reduced from the environmental risk threshold to the point maximizing the inherent potential of roots.

  14. Memory accessibility shapes explanation: Testing key claims of the inherence heuristic account.

    Science.gov (United States)

    Hussak, Larisa J; Cimpian, Andrei

    2018-01-01

    People understand the world by constructing explanations for what they observe. It is thus important to identify the cognitive processes underlying these judgments. According to a recent proposal, everyday explanations are often constructed heuristically: Because people need to generate explanations on a moment-by-moment basis, they cannot perform an exhaustive search through the space of possible reasons, but may instead use the information that is most easily accessible in memory (Cimpian & Salomon 2014a, b). In the present research, we tested two key claims of this proposal that have so far not been investigated. First, we tested whether-as previously hypothesized-the information about an entity that is most accessible in memory tends to consist of inherent or intrinsic facts about that entity, rather than extrinsic (contextual, historical, etc.) facts about it (Studies 1 and 2). Second, we tested the implications of this difference in the memory accessibility of inherent versus extrinsic facts for the process of generating explanations: Does the fact that inherent facts are more accessible than relevant extrinsic facts give rise to an inherence bias in the content of the explanations generated (Studies 3 and 4)? The findings supported the proposal that everyday explanations are generated in part via a heuristic process that relies on easily accessible-and often inherent-information from memory.

  15. Is the inherent potential of maize roots efficient for soil phosphorus acquisition?

    Directory of Open Access Journals (Sweden)

    Yan Deng

    Full Text Available Sustainable agriculture requires improved phosphorus (P management to reduce the overreliance on P fertilization. Despite intensive research of root adaptive mechanisms for improving P acquisition, the inherent potential of roots for efficient P acquisition remains unfulfilled, especially in intensive agriculture, while current P management generally focuses on agronomic and environmental concerns. Here, we investigated how levels of soil P affect the inherent potential of maize (Zea mays L. roots to obtain P from soil. Responses of root morphology, arbuscular mycorrhizal colonization, and phosphate transporters were characterized and related to agronomic traits in pot and field experiments with soil P supply from deficiency to excess. Critical soil Olsen-P level for maize growth approximated 3.2 mg kg(-1, and the threshold indicating a significant environmental risk was about 15 mg kg(-1, which represented the lower and upper levels of soil P recommended in current P management. However, most root adaptations involved with P acquisition were triggered when soil Olsen-P was below 10 mg kg(-1, indicating a threshold for maximum root inherent potential. Therefore, to maintain efficient inherent potential of roots for P acquisition, we suggest that the target upper level of soil P in intensive agriculture should be reduced from the environmental risk threshold to the point maximizing the inherent potential of roots.

  16. Construction of rat cell lines that contain potential morphologically transforming regions of the herpes simplex virus type 2 genome

    NARCIS (Netherlands)

    van den Berg, F. M.; van Amstel, P. J.; Walboomers, J. M.

    1985-01-01

    Hybrid recombinant plasmids were constructed; they were composed of the herpes simplex virus type 2 (HSV2) thymidine kinase (tk) gene and DNA sequences of HSV2 that have been reported to induce morphological and/or oncogenic transformation of rodent cells in culture. Several plasmids were made in

  17. Genomic Signatures of Sexual Conflict.

    Science.gov (United States)

    Kasimatis, Katja R; Nelson, Thomas C; Phillips, Patrick C

    2017-10-30

    Sexual conflict is a specific class of intergenomic conflict that describes the reciprocal sex-specific fitness costs generated by antagonistic reproductive interactions. The potential for sexual conflict is an inherent property of having a shared genome between the sexes and, therefore, is an extreme form of an environment-dependent fitness effect. In this way, many of the predictions from environment-dependent selection can be used to formulate expected patterns of genome evolution under sexual conflict. However, the pleiotropic and transmission constraints inherent to having alleles move across sex-specific backgrounds from generation to generation further modulate the anticipated signatures of selection. We outline methods for detecting candidate sexual conflict loci both across and within populations. Additionally, we consider the ability of genome scans to identify sexually antagonistic loci by modeling allele frequency changes within males and females due to a single generation of selection. In particular, we highlight the need to integrate genotype, phenotype, and functional information to truly distinguish sexual conflict from other forms of sexual differentiation. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Results and implications of the EBR-II inherent safety demonstration tests

    International Nuclear Information System (INIS)

    Planchon, H.P.; Golden, G.H.; Sackett, J.I.; Mohr, D.; Chang, L.K.; Feldman, E.E.; Betten, P.R.

    1987-01-01

    On April 3, 1986 two milestone tests were conducted in Experimental Breeder Reactor-2 (EBR-II). The first test was a loss of flow without scram and the second was a loss of heat sink without scram. Both tests were initiated from 100% power and in both tests the reactor was shut down by natural processes, principally thermal expansion, without automatic scram, operator intervention or the help of special in-core devices. The temperature transients during the tests were mild, as predicted, and there was no damage to the core or reactor plant structures. In a general sense, therefore, the tests plus supporting analysis demonstrated the feasibility of inherent passive shutdown for undercooling accidents in metal-fueled LMRs. The results provide a technical basis for future experiments in EBR-II to demonstrate inherent safety for overpower accidents and provide data for validation of computer codes used for design and safety analysis of inherently safe reactor plants

  19. [Distribution of herpes simplex virus type 1 and 2 genomes in the human spinal ganglia].

    Science.gov (United States)

    Obara, Y

    1994-09-01

    Herpes simplex virus (HSV) is well known for its propensity to cause recurrent oral or genital mucosal infections in humans. HSV-1 is involved primarily in oral lesions, whereas HSV-2 is more frequently involved in genital lesions. Based on this, it is thought that HSV-1 may produce latent infections in trigeminal ganglia, and HSV-2 in the sacral ganglia. However the distribution pattern of latent HSV-1 and HSV-2 infections in spinal ganglia remains unknown. Using the polymerase chain reaction we detected latent herpes HSV-1 and HSV-2 in human spinal ganglia obtained from autopsy material. A pair of primers which were specific for a part of the HSV-1 and HSV-2 DNA polymerase domain were employed. HSV-1 and HSV-2 DNAs were detected in 11 of 40 (28%) and 15 of 40 (38%) cervical ganglia, respectively, 52 of 103 (50%) and 47 of 103 (46%) thoracic ganglia, 16 of 53 (30%) and 17 of 53 (32%) lumbar ganglia, and 3 of 20 (15%) and 3 of 20 (15%) sacral ganglia. These findings suggest that latent HSV-1 and HSV-2 infections have a widespread distribution from the cervical ganglia to sacral ganglia. Importantly this study demonstrated latent HSV-1 infection of both the lumbar and sacral ganglia for the first time.

  20. Deliberate practice theory: perceived relevance, effort, and inherent enjoyment of music practice: study II.

    Science.gov (United States)

    Hyllegard, Randy; Bories, Tamara L

    2009-10-01

    This study, based on the theory of deliberate practice, examined the practice relevance, effort, and inherent enjoyment aspects of the theory. 25 college undergraduates practiced playing a melody on an electronic keyboard for three 20-min. practice sessions. Following each session, the perceived relevance of the practice for improving performance of the melody, the effort needed to learn the melody, and the inherent enjoyment of the practice were each rated on 10-point scales. Findings were consistent with theory and similar to previous studies also involving music practice and other tasks.

  1. Impacts of reactivity feedback uncertainties on inherent shutdown in innovative designs

    International Nuclear Information System (INIS)

    Mueller, C.J.

    1986-01-01

    The concept of inherent shutdown is emphasized in the approach to the design of innovative, small pool-type liquid-metal reactors (LMRs). This paper reports an evaluation of reactivity feedback uncertainties used in the analyses of anticipated transients without scram for innovative LMRs, and the associated impacts on safety margins and inherent shutdown success probabilities on unprotected loss-of-flow (LOF) events. It then assesses the ultimate importance of these uncertainties on LOF and transient overpower events in evolving metal and oxide innovative designs

  2. Chimera Type Behavior in Nonlocal Coupling System with Two Different Inherent Frequencies

    Science.gov (United States)

    Lin, Larry; Li, Ping-Cheng; Tseng, Hseng-Che

    2014-03-01

    From the research of Kuramoto and Strogatz, arrays of identical oscillators can display a remarkable pattern, named chimera state, in which phase-locked oscillators coexist with drifting ones in nonlocal coupling oscillator system. We consider further in this study, two groups of oscillators with different inherent frequencies and arrange them in a ring. When the difference of the inherent frequencies is within some specific parameter range, oscillators of nonlocal coupling system show two distinct chimera states. When the parameter value exceeds some threshold value, two chimera states disappear. They show different features. The statistical dynamic behavior of the system can be described by Kuramoto theory.

  3. Inherent safe design of advanced high temperature reactors - concepts for future nuclear power plants

    International Nuclear Information System (INIS)

    Hodzic, A.; Kugeler, K.

    1997-01-01

    This paper discusses the applicable solutions for a commercial size High Temperature Reactor (HTR) with inherent safety features. It describes the possible realization using an advanced concept which combines newly proposed design characteristics with some well known and proven HTR inherent safety features. The use of the HTR technology offers the conceivably best solution to meet the legal criteria, recently stated in Germany, for the future reactor generation. Both systems, block and pebble bed ,reactor, could be under certain design conditions self regulating in terms of core nuclear heat, mechanical stability and the environmental transfer. 23 refs., 7 figs

  4. Probabilities of inherent shutdown of unprotected events in innovative liquid metal reactors

    International Nuclear Information System (INIS)

    Mueller, C.J.

    1987-01-01

    The uncertainty in predicting the effectiveness of inherent shutdown (ISD) in innovative designs results from three broad contributing areas of uncertainty: (1) the inability to exactly predict the frequency of ATWS events with potential to challenge the safety systems and require ISD; (2) the approximation of representing all such ATWS events by a selected set of ''generic scenarios''; and (3) the inability to exactly calculate the core response to the selected generic scenarios. In this summary, the methodology and associated results of work used to establish probabilities of failure of inherent shutdown of innovative LMRs to the unprotected loss-of-flow (LOF) accident are discussed

  5. Government can regulate food advertising to children because cognitive research shows that it is inherently misleading.

    Science.gov (United States)

    Graff, Samantha; Kunkel, Dale; Mermin, Seth E

    2012-02-01

    The childhood obesity crisis has prompted repeated calls for government action to curb the marketing of unhealthy food to children. Food and entertainment industry groups have asserted that the First Amendment prohibits such regulation. However, case law establishes that the First Amendment does not protect "inherently misleading" commercial speech. Cognitive research indicates that young children cannot effectively recognize the persuasive intent of advertising or apply the critical evaluation required to comprehend commercial messages. Given this combination--that government can prohibit "inherently misleading" advertising and that children cannot adequately understand commercial messages--advertising to children younger than age twelve should be considered beyond the scope of constitutional protection.

  6. Inherent Limitations in Mid-Wave and Long-Wave-IR Upconversion Detector

    DEFF Research Database (Denmark)

    Barh, Ajanta; Tseng, Yu-Pei; Pedersen, Christian

    2017-01-01

    Inherent limitations in terms of optical losses, selection of nonlinear crystal(s), detection efficiency and pumping conditions in mid-wave (3-5 µm) and long-wave (8-12 µm) infrared frequency upconversion modules are investigated in this paper.......Inherent limitations in terms of optical losses, selection of nonlinear crystal(s), detection efficiency and pumping conditions in mid-wave (3-5 µm) and long-wave (8-12 µm) infrared frequency upconversion modules are investigated in this paper....

  7. Impacts of reactivity feedback uncertainties on inherent shutdown in innovative designs

    International Nuclear Information System (INIS)

    Mueller, C.J.

    1986-01-01

    The concept of ''inherent shutdown'' is emphasized in the approach to the design of innovative, small pool-type liquid metal reactors (LMRs). This paper reports an evaluation of reactivity feedback uncertainties used in the analyses of anticipated transients without scram (ATWS) for innovative LMRs, and the associated impacts on safety margins and inherent shutdown success probabilities on unprotected loss-of-flow (LOF) events. It then assesses the ultimate importance of these uncertainties on LOF and transient overpower (TOP) events in evolving metal and oxide innovative designs

  8. Genome Imprinting

    Indian Academy of Sciences (India)

    the cell nucleus (mitochondrial and chloroplast genomes), and. (3) traits governed ... tively good embryonic development but very poor development of membranes and ... Human homologies for the type of situation described above are naturally ..... imprint; (b) New modifications of the paternal genome in germ cells of each ...

  9. Baculovirus Genomics

    NARCIS (Netherlands)

    Oers, van M.M.; Vlak, J.M.

    2007-01-01

    Baculovirus genomes are covalently closed circles of double stranded-DNA varying in size between 80 and 180 kilobase-pair. The genomes of more than fourty-one baculoviruses have been sequenced to date. The majority of these (37) are pathogenic to lepidopteran hosts; three infect sawflies

  10. Genomic Testing

    Science.gov (United States)

    ... this database. Top of Page Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) In 2004, the Centers for Disease Control and Prevention launched the EGAPP initiative to establish and test a ... and other applications of genomic technology that are in transition from ...

  11. Ancient genomes

    OpenAIRE

    Hoelzel, A Rus

    2005-01-01

    Ever since its invention, the polymerase chain reaction has been the method of choice for work with ancient DNA. In an application of modern genomic methods to material from the Pleistocene, a recent study has instead undertaken to clone and sequence a portion of the ancient genome of the cave bear.

  12. The Market for Academic Knowledge: Its Historical Emergence and Inherent Tensions

    Science.gov (United States)

    Weik, Elke

    2014-01-01

    This paper contributes to the discussion about the marketisation of universities by providing a historical perspective. Going back to the time when the market for academic knowledge emerged, I argue that it was created through incorporating a number of inherent tensions that have been, and still are, shaping its development. I show how these…

  13. Generalizing a model beyond the inherence heuristic and applying it to beliefs about objective value.

    Science.gov (United States)

    Wood, Graham

    2014-10-01

    The inherence heuristic is characterized as part of an instantiation of a more general model that describes the interaction between undeveloped intuitions, produced by System 1 heuristics, and developed beliefs, constructed by System 2 reasoning. The general model is described and illustrated by examining another instantiation of the process that constructs belief in objective moral value.

  14. Remote sensing reflectance and inherent optical properties of oceanic waters derived from above-water measurements

    Science.gov (United States)

    Lee, Zhongping; Carder, Kendall L.; Steward, Robert G.; Peacock, Thomas G.; Davis, Curtiss O.; Mueller, James L.

    1997-02-01

    Remote-sensing reflectance and inherent optical properties of oceanic properties of oceanic waters are important parameters for ocean optics. Due to surface reflectance, Rrs or water-leaving radiance is difficult to measure from above the surface. It usually is derived by correcting for the reflected skylight in the measured above-water upwelling radiance using a theoretical Fresnel reflectance value. As it is difficult to determine the reflected skylight, there are errors in the Q and E derived Rrs, and the errors may get bigger for high chl_a coastal waters. For better correction of the reflected skylight,w e propose the following derivation procedure: partition the skylight into Rayleigh and aerosol contributions, remove the Rayleigh contribution using the Fresnel reflectance, and correct the aerosol contribution using an optimization algorithm. During the process, Rrs and in-water inherent optical properties are derived at the same time. For measurements of 45 sites made in the Gulf of Mexico and Arabian Sea with chl_a concentrations ranging from 0.07 to 49 mg/m3, the derived Rrs and inherent optical property values were compared with those from in-water measurements. These results indicate that for the waters studied, the proposed algorithm performs quite well in deriving Rrs and in- water inherent optical properties from above-surface measurements for clear and turbid waters.

  15. Thermosetting resins with high fractions of free volume and inherently low dielectric constants.

    Science.gov (United States)

    Lin, Liang-Kai; Hu, Chien-Chieh; Su, Wen-Chiung; Liu, Ying-Ling

    2015-08-18

    This work demonstrates a new class of thermosetting resins, based on Meldrum's acid (MA) derivatives, which have high fractions of free volume and inherently low k values of about 2.0 at 1 MHz. Thermal decomposition of the MA groups evolves CO2 and acetone to create air-trapped cavities so as to reduce the dielectric constants.

  16. An corrective method to correct of the inherent flaw of the asynchronization direct counting circuit

    International Nuclear Information System (INIS)

    Wang Renfei; Liu Congzhan; Jin Yongjie; Zhang Zhi; Li Yanguo

    2003-01-01

    As a inherent flaw of the Asynchronization Direct Counting Circuit, the crosstalk, which is resulted from the randomicity of the time-signal always exists between two adjacent channels. In order to reduce the counting error derived from the crosstalk, the author propose an effective method to correct the flaw after analysing the mechanism of the crosstalk

  17. Location estimation of approaching objects is modulated by the observer's inherent and momentary action capabilities

    NARCIS (Netherlands)

    Kandula, Manasa; Hofman, Dennis; Dijkerman, H Chris

    2016-01-01

    Action capability may be one of the factors that can influence our percept of the world. A distinction can be made between momentary action capability (action capability at that particular moment) and inherent action capability (representing a stable action capability). In the current study, we

  18. 16 CFR 1211.13 - Inherent force activated secondary door sensors.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Inherent force activated secondary door sensors. 1211.13 Section 1211.13 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT... across the door so that the axis is perpendicular to the plane of the door. See Figure 6 of this part...

  19. 40 CFR 88.312-93 - Inherently Low-Emission Vehicle labeling.

    Science.gov (United States)

    2010-07-01

    ... stroke width not less than 0.5 inches (1.3 centimeters). In addition, the words “INHERENTLY LOW-EMISSION..., the words “CLEAN AIR VEHICLE” must be present in lettering no smaller than 0.8 inches (2.0 centimeters... loan to someone who has not demonstrated eligibility for expanded TCMs available to ILEVs according to...

  20. [The concentration of growth factors in patients with inherent and acquired shortenings of limbs bones].

    Science.gov (United States)

    Strogov, M V; Luneva, S N; Novikov, K I

    2013-04-01

    The article deals with the results of study of level of growth factors in blood serum of patients with inherent and post-traumatic shortenings of limbs' bones. The detection in blood serum the level of epidermal growth factor insulin-like growth factor I and angiopoetins is proposed to monitor in given patients the reparative bone formation.

  1. Toxic release consequence analysis tool (TORCAT) for inherently safer design plant

    International Nuclear Information System (INIS)

    Shariff, Azmi Mohd; Zaini, Dzulkarnain

    2010-01-01

    Many major accidents due to toxic release in the past have caused many fatalities such as the tragedy of MIC release in Bhopal, India (1984). One of the approaches is to use inherently safer design technique that utilizes inherent safety principle to eliminate or minimize accidents rather than to control the hazard. This technique is best implemented in preliminary design stage where the consequence of toxic release can be evaluated and necessary design improvements can be implemented to eliminate or minimize the accidents to as low as reasonably practicable (ALARP) without resorting to costly protective system. However, currently there is no commercial tool available that has such capability. This paper reports on the preliminary findings on the development of a prototype tool for consequence analysis and design improvement via inherent safety principle by utilizing an integrated process design simulator with toxic release consequence analysis model. The consequence analysis based on the worst-case scenarios during process flowsheeting stage were conducted as case studies. The preliminary finding shows that toxic release consequences analysis tool (TORCAT) has capability to eliminate or minimize the potential toxic release accidents by adopting the inherent safety principle early in preliminary design stage.

  2. The Inherent Politics of Managing the Quality of Urban Green Spaces

    DEFF Research Database (Denmark)

    Lindholst, Christian; Sullivan, Sidney George; Konijnendijk van den Bosch, Cecil C.

    2015-01-01

    of such ‘inherent politics’ through a case study of a widespread approach to operationalizing quality in urban green space management. We conclude that adoption of any quality model has both limiting and enabling implications for public participation and decision-making and that a critical stance is needed within...

  3. Manson Chicks and Microskirted Cuties : Pornification in Thomas Pynchon's Inherent Vice

    NARCIS (Netherlands)

    Cook, S.J.|info:eu-repo/dai/nl/411939432

    2015-01-01

    Many sexual encounters in Thomas Pynchon’s fiction have occurred beyond the mainstream, generating theatres of perversity which dramatise the death wish and enact power relations from wider arenas. However, in Inherent Vice they change in nature. With the exception of scenes which use Charles Manson

  4. Development status of PIUS/ISER - a inherently safe reactor for the international use

    International Nuclear Information System (INIS)

    Wakabayashi, Hiroaki

    1987-01-01

    It is just in early 1980s that LWR-based nuclear power has become a substantial power source. Though the safety level of nuclear power is always claimed to be sufficiently high by the industry, it rests on the idea of defense in depth, the calculation by probabilistic risk assessment (PRA) or probabilistic safety assessment (PSA). The TMI-2 and Chernobyl-4 accidents occurred in the industrially most advanced countries. In this paper, an alternative way to safe nuclear power is sought in so-called inherently safe reactors (ISR) including the LWR type PIUS/ISER. With proper consideration into the design of nuclear reactor plants, those can be made basically safe through the use of passive safe mechanism for their design. In short, an ISR is a nuclear power reactor which has passive and intrinsic core cooling capability and automatic shutdown capability. As the nuclear power reactors which are currently claimed to be inherently safe, there are the process inherent and ultimately safe reactor (PIUS) of ASEA-ATOM Sweden and the inherently safe and economical reactor (ISER) of the University of Tokyo, Japan, of LWR type. The current status of the development, the reliability, and some technical problems of ISER/PIUS and the attitude of various countries toward ISER/PIUS are described. (Kako, I.)

  5. Food plant toxicants and safety: risk assessment and regulation of inherent toxicants in plant foods.

    NARCIS (Netherlands)

    Essers, A.J.; Alink, G.M.; Speijers, G.J.A.; Alexander, J.; Bouwmeister, P.J.; Brandt, van den P.A.; Ciere, S.; Gry, J.; Herrman, J.; Kuiper, H.A.; Mortby, E.; Renwickn, A.G.

    1998-01-01

    The ADI as a tool for risk management and regulation of food additives and pesticide residues is not readily applicable to inherent food plant toxicants: The margin between actual intake and potentially toxic levels is often small; application of the default uncertainty factors used to derive ADI

  6. Unlocking variability: inherent variation and developmental traits of garlic plants originated from sexual reproduction

    NARCIS (Netherlands)

    Shemesh, E.; Scholten, O.E.; Rabinowitch, H.D.; Kamenetsky, R.

    2008-01-01

    Recent collections of fertile garlic (Allium sativum) accessions from Central Asia allow a detailed study of seedling developments and the evaluation of inherent variations. We hereby provide a comprehensive account of the ontogenesis of a population of garlic seedlings and their vegetative and

  7. The attractive Achilles heel of germ cell tumours : an inherent sensitivity to apoptosis-inducing stimuli

    NARCIS (Netherlands)

    Spierings, DCJ; de Vries, EGE; Vellenga, E; de Jong, S

    Testicular germ cell tumours (TGCTs) are extremely sensitive to cisplatin-containing chemotherapy. The rapid time course of apoptosis induction after exposure to cisplatin suggests that TGCT cells are primed to undergo programmed cell death as an inherent property of the cell of origin. In fact,

  8. Efficiency of inherent protection mechanisms for an improved HTR safety concept

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, K.; Buescher, R.; Gerwin, H.; Schenk, W. [Kernforschungsanlage Juelich G.m.b.H. (Germany, F.R.). Inst. fuer Reaktorentwicklung

    1981-01-15

    For a preliminary design of a 350 MWsub(th) annular core derived from AVR-reactor the efficiency of inherent protection mechanisms is discussed. After-heat removal and auto-shut down potential are demonstrated for intact and complete failure of core heat sinks.

  9. Making the Grade: Describing Inherent Requirements for the Initial Teacher Education Practicum

    Science.gov (United States)

    Sharplin, Elaine; Peden, Sanna; Marais, Ida

    2016-01-01

    This study explores the development, description, and illustration of inherent requirement (IR) statements to make explicit the requirements for performance on an initial teacher education (ITE) practicum. Through consultative group processes with stakeholders involved in ITE, seven IR domains were identified. From interviews with academics,…

  10. Inherent Safety Feature of Hybrid Low Power Research Reactor during Reactivity Induced Accident

    Energy Technology Data Exchange (ETDEWEB)

    Kim, DongHyun; Yum, Soo Been; Hong, Sung Teak; Lim, In-Cheol [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    Hybrid low power research reactor(H-LPRR) is the new design concept of low power research reactor for critical facility as well as education and training. In the case of typical low power research reactor, the purposes of utilization are the experiments for education of nuclear engineering students, Neutron Activation Analysis(NAA) and radio-isotope production for research purpose. H-LPRR is a light-water cooled and moderated research reactor that uses rod-type LEU UO{sub 2} fuels same as those for commercial power plants. The maximum core thermal power is 70kW and, the core is placed in the bottom of open pool. There are 1 control rod and 2 shutdown rods in the core. It is designed to cool the core by natural convection, retain negative feedback coefficient for entire fuel periods and operate for 20 years without refueling. Inherent safety in H-LPRR is achieved by passive design features such as negative temperature feedback coefficient and core cooling by natural convection during normal and emergency conditions. The purpose of this study is to find out that the inherent safety characteristics of H-LPRR is able to control the power and protect the reactor from the RIA(Reactivity induced accident). RIA analysis was performed to investigate the inherent safety feature of H-LPRR. As a result, it was found that the reactor controls its power without fuel damage in the event and that the reactor remains safe states inherently. Therefore, it is believed that high degree of safety inheres in H-LPRR.

  11. Justice and the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, T.F.; Lappe, M. (eds.)

    1992-01-01

    Most of the essays gathered in this volume were first presented at a conference, Justice and the Human Genome, in Chicago in early November, 1991. The goal of the, conference was to consider questions of justice as they are and will be raised by the Human Genome Project. To achieve its goal of identifying and elucidating the challenges of justice inherent in genomic research and its social applications the conference drew together in one forum members from academia, medicine, and industry with interests divergent as rate-setting for insurance, the care of newborns, and the history of ethics. The essays in this volume address a number of theoretical and practical concerns relative to the meaning of genomic research.

  12. Justice and the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, T.F.; Lappe, M. [eds.

    1992-12-31

    Most of the essays gathered in this volume were first presented at a conference, Justice and the Human Genome, in Chicago in early November, 1991. The goal of the, conference was to consider questions of justice as they are and will be raised by the Human Genome Project. To achieve its goal of identifying and elucidating the challenges of justice inherent in genomic research and its social applications the conference drew together in one forum members from academia, medicine, and industry with interests divergent as rate-setting for insurance, the care of newborns, and the history of ethics. The essays in this volume address a number of theoretical and practical concerns relative to the meaning of genomic research.

  13. Herbarium genomics

    DEFF Research Database (Denmark)

    Bakker, Freek T.; Lei, Di; Yu, Jiaying

    2016-01-01

    Herbarium genomics is proving promising as next-generation sequencing approaches are well suited to deal with the usually fragmented nature of archival DNA. We show that routine assembly of partial plastome sequences from herbarium specimens is feasible, from total DNA extracts and with specimens...... up to 146 years old. We use genome skimming and an automated assembly pipeline, Iterative Organelle Genome Assembly, that assembles paired-end reads into a series of candidate assemblies, the best one of which is selected based on likelihood estimation. We used 93 specimens from 12 different...... correlation between plastome coverage and nuclear genome size (C value) in our samples, but the range of C values included is limited. Finally, we conclude that routine plastome sequencing from herbarium specimens is feasible and cost-effective (compared with Sanger sequencing or plastome...

  14. Multi-objective optimization of a cascade refrigeration system: Exergetic, economic, environmental, and inherent safety analysis

    International Nuclear Information System (INIS)

    Eini, Saeed; Shahhosseini, Hamidreza; Delgarm, Navid; Lee, Moonyong; Bahadori, Alireza

    2016-01-01

    Highlights: • A multi-objective optimization is performed for a cascade refrigeration cycle. • The optimization problem considers inherently safe design as well as 3E analysis. • As a measure of inherent safety level a quantitative risk analysis is utilized. • A CO 2 /NH 3 cascade refrigeration system is compared with a CO 2 /C 3 H 8 system. - Abstract: Inherently safer design is the new approach to maximize the overall safety of a process plant. This approach suggests some risk reduction strategies to be implemented in the early stages of design. In this paper a multi-objective optimization was performed considering economic, exergetic, and environmental aspects besides evaluation of the inherent safety level of a cascade refrigeration system. The capital costs, the processing costs, and the social cost due to CO 2 emission were considered to be included in the economic objective function. Exergetic efficiency of the plant was considered as the second objective function. As a measure of inherent safety level, Quantitative Risk Assessment (QRA) was performed to calculate total risk level of the cascade as the third objective function. Two cases (ammonia and propane) were considered to be compared as the refrigerant of the high temperature circuit. The achieved optimum solutions from the multi–objective optimization process were given as Pareto frontier. The ultimate optimal solution from available solutions on the Pareto optimal curve was selected using Decision-Makings approaches. NSGA-II algorithm was used to obtain Pareto optimal frontiers. Also, three decision-making approaches (TOPSIS, LINMAP, and Shannon’s entropy methods) were utilized to select the final optimum point. Considering continuous material release from the major equipment in the plant, flash and jet fire scenarios were considered for the CO 2 /C 3 H 8 cycle and toxic hazards were considered for the CO 2 /NH 3 cycle. The results showed no significant differences between CO 2 /NH 3 and

  15. Inherent optical properties of pollen particles: a case study for the morning glory pollen.

    Science.gov (United States)

    Liu, Chao; Yin, Yan

    2016-01-25

    Biological aerosols, such as bacteria, fungal spores, and pollens, play an important role on various atmospheric processes, whereas their inherent optical property is one of the most uncertainties that limit our ability to assess their effects on weather and climate. A numerical model with core-shell structure, hexagonal grids and barbs is developed to represent one kind of realistic pollen particles, and their inherent optical properties are simulated using a pseudo-spectral time domain method. Both the hexagonal grids and barbs substantially affect the modeled pollen optical properties. Results based on the realistic particle model are compared with two equivalent spherical approximations, and the significant differences indicate the importance of considering pollen geometries for their optical properties.

  16. Searching for Models Exhibiting High Circularly Polarized Luminescence: the Electroactive Inherently Chiral Oligothiophenes.

    Science.gov (United States)

    Benincori, Tiziana; Appoloni, Giulio; Mussini, Patrizia Romana; Arnaboldi, Serena; Cirilli, Roberto; Quartapelle Procopio, Elsa; Panigati, Monica; Abbate, Sergio; Mazzeo, Giuseppe; Longhi, Giovanna

    2018-05-02

    Two new inherently chiral oligothiophenes characterized by the atropisomeric 3,3'-bithianaphtene scaffold functionalized with fused ring bithiophene derivatives, namely 4H-cyclopenta [2,1-b3:4b']dithiophene (CPDT) and dithieno[3,3-b:2',3'-d]pyrrole (DTP), were synthesized. The racemates were fully characterized and resolved into antipodes by enantioselective HPLC. The enantiomers were analyzed through different chiroptical techniques: electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) were employed to attribute the absolute configuration (AC). Comparison of experimental and calculated VCD spectra confirmed the DFT calculated conformational characteristics. The compound functionalized with two CPDT units was oxidized with FeCl3 and ECD and CPL of the resulting material were measured. Circularly Polarized Luminescence (CPL) was measured in order to verify if inherently chiral oligothiophenes could be promising systems for chiral photonics applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Integral Inherently Safe Light Water Reactor (I2S-LWR)

    International Nuclear Information System (INIS)

    Petrovic, Bojan; Memmott, Matthew; Boy, Guy; Charit, Indrajit; Manera, Annalisa; Downar, Thomas; Lee, John; Muldrow, Lycurgus; Upadhyaya, Belle; Hines, Wesley; Haghighat, Alierza

    2017-01-01

    This final report summarizes results of the multi-year effort performed during the period 2/2013- 12/2016 under the DOE NEUP IRP Project ''Integral Inherently Safe Light Water Reactors (I 2 S-LWR)''. The goal of the project was to develop a concept of a 1 GWe PWR with integral configuration and inherent safety features, at the same time accounting for lessons learned from the Fukushima accident, and keeping in mind the economic viability of the new concept. Essentially (see Figure 1-1) the project aimed to implement attractive safety features, typically found only in SMRs, to a larger power (1 GWe) reactor, to address the preference of some utilities in the US power market for unit power level on the order of 1 GWe.

  18. Inherent wettability of different rock surfaces at nanoscale: a theoretical study

    Science.gov (United States)

    Chang, Xiao; Xue, Qingzhong; Li, Xiaofang; Zhang, Jianqiang; Zhu, Lei; He, Daliang; Zheng, Haixia; Lu, Shuangfang; Liu, Zilong

    2018-03-01

    Investigating the inherent wettability of rock surfaces at nanoscale is of great importance in ore floatation and oil recovery field. Using molecular dynamics simulations, we systematically study the wetting behavior of water on different rock surfaces (silica, calcite, gypsum, halite and graphite) at nanoscale. It is demonstrated that the inherent rock wettability follows the order of gypsum > calcite > halite > silica > graphite. Remarkably, we also manifest that the polarity of oil molecules can affect the water contact angles on silica surface. For example, the water contact angles on silica surface in hexane, dodecane, thiophene and toluene are 58 ± 2°, 63 ± 3°, 90 ± 1°, 118 ± 1°, respectively. Furthermore, we investigate the wetting behavior of water on heterogeneous rock surfaces and find that water molecules can move from hydrophobic surface to hydrophilic surface.

  19. Passive and inherent safety technologies for light-water nuclear reactors

    International Nuclear Information System (INIS)

    Forsberg, C.W.

    1990-07-01

    Passive/inherent safety implies a technical revolution in our approach to nuclear power safety. This direction is discussed herein for light-water reactors (LWRs) -- the predominant type of power reactor used in the world today. At Oak Ridge National Laboratory (ORNL) the approach to the development of passive/inherent safety for LWRs consists of four steps: identify and quantify safety requirements and goals; identify and quantify the technical functional requirements needed for safety; identify, invent, develop, and quantify technical options that meet both of the above requirements; and integrate safety systems into designs of economic and reliable nuclear power plants. Significant progress has been achieved in the first three steps of this program. The last step involves primarily the reactor vendors. These activities, as well as related activities worldwide, are described here. 27 refs., 7 tabs

  20. Integral Inherently Safe Light Water Reactor (I2S-LWR)

    Energy Technology Data Exchange (ETDEWEB)

    Petrovic, Bojan [Georgia Inst. of Technology, Atlanta, GA (United States); Memmott, Matthew [Brigham Young Univ., Provo, UT (United States); Boy, Guy [Florida Inst. of Technology, Melbourne, FL (United States); Charit, Indrajit [Univ. of Idaho, Moscow, ID (United States); Manera, Annalisa [Univ. of Michigan, Ann Arbor, MI (United States); Downar, Thomas [Univ. of Michigan, Ann Arbor, MI (United States); Lee, John [Univ. of Michigan, Ann Arbor, MI (United States); Muldrow, Lycurgus [Morehouse College, Atlanta, GA (United States); Upadhyaya, Belle [Univ. of Tennessee, Knoxville, TN (United States); Hines, Wesley [Univ. of Tennessee, Knoxville, TN (United States); Haghighat, Alierza [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States)

    2017-10-02

    This final report summarizes results of the multi-year effort performed during the period 2/2013- 12/2016 under the DOE NEUP IRP Project “Integral Inherently Safe Light Water Reactors (I2S-LWR)”. The goal of the project was to develop a concept of a 1 GWe PWR with integral configuration and inherent safety features, at the same time accounting for lessons learned from the Fukushima accident, and keeping in mind the economic viability of the new concept. Essentially (see Figure 1-1) the project aimed to implement attractive safety features, typically found only in SMRs, to a larger power (1 GWe) reactor, to address the preference of some utilities in the US power market for unit power level on the order of 1 GWe.

  1. Is damage to the common bile duct during laparoscopic cholecystectomy an inherent risk of the operation?

    Science.gov (United States)

    Fischer, Josef E

    2009-06-01

    Laparoscopic cholocystectomy has been practiced for close to 20 years. The rate of common duct injury remains somewhere between 0.4 to 0.7 percent and is approximately the same around the world. Recent papers have stressed ways in which laparoscopic common duct injury can be avoided, but none of the methods mentioned is foolproof. In addition, this complication can occur to even the most experienced laparoscopic surgeon. The author believes that injury to the common duct during laparoscopic cholocystectomy is not a result of the practice below the standard, but an inherent risk of the operation. This injury needs to be emphasized by the surgical community as an inherent risk of the operation, and patients should be fully informed of this potential complication.

  2. Role of FFTF in assessing structural feedbacks and inherent safety of LMR's

    International Nuclear Information System (INIS)

    Padilla, A.; Omberg, R.P.; O'Dell, L.D.; Harris, R.A.; Nguyen, D.H.; Waltar, A.E.

    1985-03-01

    The possibility of developing reactor designs with inherent safety characteristics sufficient to provide ''walk away'' safety is receiving additional emphasis in the LMR program. A key element in this effort is the recognition that LMR's possess safety characteristics above and beyond those employed in past safety review processes. Some of these additional safety characteristics are due to reactivity feedback effects caused by small structural movements during hypothetical severe design transients. The effect of these characteristics upon the behavior of the FFTF under such transients has been assessed and is discussed in this paper. The paper also presents a preliminary test matrix which might allow experimental verification of the structural reactivity feedback effects. Such experimental verification should be very useful to innovative designers seeking to optimize inherent safety. 8 refs., 1 fig., 2 tabs

  3. A simplified analysis of uncertainty propagation in inherently controlled ATWS events

    International Nuclear Information System (INIS)

    Wade, D.C.

    1987-01-01

    The quasi static approach can be used to provide useful insight concerning the propagation of uncertainties in the inherent response to ATWS events. At issue is how uncertainties in the reactivity coefficients and in the thermal-hydraulics and materials properties propagate to yield uncertainties in the asymptotic temperatures attained upon inherent shutdown. The basic notion to be quantified is that many of the same physical phenomena contribute to both the reactivity increase of power reduction and the reactivity decrease of core temperature rise. Since these reactivities cancel by definition, a good deal of uncertainty cancellation must also occur of necessity. For example, if the Doppler coefficient is overpredicted, too large a positive reactivity insertion is predicted upon power reduction and collapse of the ΔT across the fuel pin. However, too large a negative reactivity is also predicted upon the compensating increase in the isothermal core average temperature - which includes the fuel Doppler effect

  4. An assessment of the low seismic risk of the inherently safe sodium advanced fast reactor (SAFR)

    International Nuclear Information System (INIS)

    Rutherford, P.D.

    1988-01-01

    A recent probabilistic risk assessment (PRA) of the sodium advanced fast reactor (SAFR) demonstrated the inherently low risk of advanced liquid-metal, pool-type fast reactors with inherent safety systems. As a result, it was recognized that external events, especially seismic events, may not only be a major contributor to risk (as shown in several LWR PRAs) but also may completely dominate the risk. Accordingly, a seismic risk assessment has been completed for SAFR, which resulted in a core damage frequency of 2 x 10 -7 /year and a large release frequency of 4 x 10 -9 /year. This paper reports that public health risk in terms of early fatality risk and latent fatality risk were also several orders of magnitude below the NRC safety goals and below recent LWR risks reported in NUREB/CR1150

  5. [Differences of inherent optical properties of inland lake water body in typical seasons].

    Science.gov (United States)

    Sun, De-Yong; Li, Yun-Mei; Wang, Qiao; Le, Cheng-Fen; Huang, Chang-Chun; Wang, Li-Zhen

    2008-05-01

    Inherent optical property is one of the important properties of water body, which lays the foundation for the establishment of water color analytical models. By using quantity filter technology (QFT) and BB9 backscattering meter, the absorption coefficients of chromophoric dissolved organic matter (CDOM) and total suspended matters (TSM) and the backscattering coefficient of TSM in the water body at Meiliang Bay of Taihu Lake were measured in summer and winter. Based on the spectral comparison of the absorption and backscattering coefficients, their differences between the two seasons were demonstrated, and the reasons that caused these differences were also explored in the context of their relations to the changes in water quality. Consequently, water environment condition could be revealed by using the inherent optical property. The relationship between the backscattering coefficient and the TSM concentration was established, which could provide supporting coefficients to the analytical models to be developed.

  6. Acoustic resonance scattering by a system of concentrically multilayered shells: the inherent background and resonance coefficients

    CERN Document Server

    Choi, M S; Lee, S H

    1999-01-01

    The inherent background coefficients that exactly describe the background amplitudes in the scattered field have been presented for the scattering of plane acoustic waves by a system of concentrically multilayered solid and/or fluid shells submerged in a fluid. The coefficients have been obtained by replacing the mechanical surface admittance function with the zero-frequency limit of the admittance function for the analogous fluid system, where the shear wave speeds in the solid layers are set to zero. By taking advantage of the concept of incoming and outgoing waves, we find the surface admittance function for the fluid system in such a form that the analytical generalization for any number of layers and the physical interpretation are very easy. The background coefficients obtained are independent of the bulk wave speeds in the system: they depend on the mass densities and the thickness of the shells. With increasing frequency, the inherent background undergoes a transition from the soft to the rigid backgr...

  7. Disease resistance is related to inherent swimming performance in Atlantic salmon

    OpenAIRE

    Castro, Vicente; Grisdale-Helland, Barbara; Jørgensen, Sven Martin; Helgerud, Jan; Claireaux, Guy; Farrell, Anthony P.; Krasnov, Aleksei; Helland, Ståle; Takle, Harald Rune

    2013-01-01

    Background Like humans, fish can be classified according to their athletic performance. Sustained exercise training of fish can improve growth and physical capacity, and recent results have documented improved disease resistance in exercised Atlantic salmon. In this study we investigated the effects of inherent swimming performance and exercise training on disease resistance in Atlantic salmon. Atlantic salmon were first classified as either poor or good according to their swimming per...

  8. Ethical problems inherent in psychological research based on internet communication as stored information

    DEFF Research Database (Denmark)

    Øhrstrøm, Peter; Dyhrberg, Johan

    2007-01-01

    This paper deals with certain ethical problems inherent in psychological research based on internet communication as stored information. Section 1 contains an analysis of research on Internet debates. In particular, it takes into account a famous example of deception for psychology research...... purposes. In section 2, the focus is on research on personal data in texts published on the Internet. Section 3 includes an attempt to formulate some ethical principles and guidelines, which should be regarded as fundamental in research on stored information....

  9. Quantification of the inherent uncertainty in the relaxation modulus and creep compliance of asphalt mixes

    Science.gov (United States)

    Kassem, Hussein A.; Chehab, Ghassan R.; Najjar, Shadi S.

    2017-08-01

    Advanced material characterization of asphalt concrete is essential for realistic and accurate performance prediction of flexible pavements. However, such characterization requires rigorous testing regimes that involve mechanical testing of a large number of laboratory samples at various conditions and set-ups. Advanced measurement instrumentation in addition to meticulous and accurate data analysis and analytical representation are also of high importance. Such steps as well as the heterogeneous nature of asphalt concrete (AC) constitute major factors of inherent variability. Thus, it is imperative to model and quantify the variability of the needed asphalt material's properties, mainly the linear viscoelastic response functions such as: relaxation modulus, E(t), and creep compliance, D(t). The objective of this paper is to characterize the inherent uncertainty of both E(t) and D(t) over the time domain of their master curves. This is achieved through a probabilistic framework using Monte Carlo simulations and First Order approximations, utilizing E^{*} data for six AC mixes with at least eight replicates per mix. The study shows that the inherent variability, presented by the coefficient of variation (COV), in E(t) and D(t) is low at small reduced times, and increases with the increase in reduced time. At small reduced times, the COV in E(t) and D(t) are similar in magnitude; however, differences become significant at large reduced times. Additionally, the probability distributions and COVs of E(t) and D(t) are mix dependent. Finally, a case study is considered in which the inherent uncertainty in D(t) is forward propagated to assess the effect of variability on the predicted number of cycles to fatigue failure of an asphalt mix.

  10. Experimental evidence for inherent Lévy search behaviour in foraging animals.

    Science.gov (United States)

    Kölzsch, Andrea; Alzate, Adriana; Bartumeus, Frederic; de Jager, Monique; Weerman, Ellen J; Hengeveld, Geerten M; Naguib, Marc; Nolet, Bart A; van de Koppel, Johan

    2015-05-22

    Recently, Lévy walks have been put forward as a new paradigm for animal search and many cases have been made for its presence in nature. However, it remains debated whether Lévy walks are an inherent behavioural strategy or emerge from the animal reacting to its habitat. Here, we demonstrate signatures of Lévy behaviour in the search movement of mud snails (Hydrobia ulvae) based on a novel, direct assessment of movement properties in an experimental set-up using different food distributions. Our experimental data uncovered clusters of small movement steps alternating with long moves independent of food encounter and landscape complexity. Moreover, size distributions of these clusters followed truncated power laws. These two findings are characteristic signatures of mechanisms underlying inherent Lévy-like movement. Thus, our study provides clear experimental evidence that such multi-scale movement is an inherent behaviour rather than resulting from the animal interacting with its environment. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  11. Disease resistance is related to inherent swimming performance in Atlantic salmon.

    Science.gov (United States)

    Castro, Vicente; Grisdale-Helland, Barbara; Jørgensen, Sven M; Helgerud, Jan; Claireaux, Guy; Farrell, Anthony P; Krasnov, Aleksei; Helland, Ståle J; Takle, Harald

    2013-01-21

    Like humans, fish can be classified according to their athletic performance. Sustained exercise training of fish can improve growth and physical capacity, and recent results have documented improved disease resistance in exercised Atlantic salmon. In this study we investigated the effects of inherent swimming performance and exercise training on disease resistance in Atlantic salmon.Atlantic salmon were first classified as either poor or good according to their swimming performance in a screening test and then exercise trained for 10 weeks using one of two constant-velocity or two interval-velocity training regimes for comparison against control trained fish (low speed continuously). Disease resistance was assessed by a viral disease challenge test (infectious pancreatic necrosis) and gene expression analyses of the host response in selected organs. An inherently good swimming performance was associated with improved disease resistance, as good swimmers showed significantly better survival compared to poor swimmers in the viral challenge test. Differences in mortalities between poor and good swimmers were correlated with cardiac mRNA expression of virus responsive genes reflecting the infection status. Although not significant, fish trained at constant-velocity showed a trend towards higher survival than fish trained at either short or long intervals. Finally, only constant training at high intensity had a significant positive effect on fish growth compared to control trained fish. This is the first evidence suggesting that inherent swimming performance is associated with disease resistance in fish.

  12. Disease resistance is related to inherent swimming performance in Atlantic salmon

    Directory of Open Access Journals (Sweden)

    Castro Vicente

    2013-01-01

    Full Text Available Abstract Background Like humans, fish can be classified according to their athletic performance. Sustained exercise training of fish can improve growth and physical capacity, and recent results have documented improved disease resistance in exercised Atlantic salmon. In this study we investigated the effects of inherent swimming performance and exercise training on disease resistance in Atlantic salmon. Atlantic salmon were first classified as either poor or good according to their swimming performance in a screening test and then exercise trained for 10 weeks using one of two constant-velocity or two interval-velocity training regimes for comparison against control trained fish (low speed continuously. Disease resistance was assessed by a viral disease challenge test (infectious pancreatic necrosis and gene expression analyses of the host response in selected organs. Results An inherently good swimming performance was associated with improved disease resistance, as good swimmers showed significantly better survival compared to poor swimmers in the viral challenge test. Differences in mortalities between poor and good swimmers were correlated with cardiac mRNA expression of virus responsive genes reflecting the infection status. Although not significant, fish trained at constant-velocity showed a trend towards higher survival than fish trained at either short or long intervals. Finally, only constant training at high intensity had a significant positive effect on fish growth compared to control trained fish. Conclusions This is the first evidence suggesting that inherent swimming performance is associated with disease resistance in fish.

  13. Model development for the dynamic analysis of the OSU inherently safe reactor. Part 1

    International Nuclear Information System (INIS)

    Aybar, H.S.

    1992-01-01

    Faculty and students in the Nuclear Engineering Program at the Ohio State University (OSU) have proposed a conceptual design for an inherently safe 340 MWe power reactor. The design is based on the state-of-the-art technology of LWRs and the High Temperature Gas- cooled Reactors (HTGRs). The OSU Inherently Safe Reactor (OSU-ISR) concept uses shorter than standard BWR fuel elements in the reactor core. All the fluid on the primary side is contained within a Prestressed Concrete Reactor Vessel (PCRV). This important feature significantly reduces the probability of a LOCA. A new feature of the OSU-ISR is an operator independent steam driven Emergency Core Cooling System (ECCS) housed within the PCRV. In accident conditions where the steam generators are incapacitated, steam from the core drives a jet injector, which takes water from the suppression pool and pumps it into the core cavity to maintain core coverability. The preliminary analysis of the concept was performed as a design project in the Nuclear Engineering Program at the OSU during the Spring of 1985, and published in ''Nuclear Technology.'' The use of a PCRV for ducting and containment and the replacement of forced recirculation with natural circulation on the primary side significantly improve the inherent safety of the plant. Currently, work is in progress for the refinement of the OSU-ISR concept, partially supported by a grant from the U.S. Department of Energy

  14. Liver-inherent immune system: its role in blood-stage malaria.

    Science.gov (United States)

    Wunderlich, Frank; Al-Quraishy, Saleh; Dkhil, Mohamed A

    2014-01-01

    The liver is well known as that organ which is obligately required for the intrahepatocyte development of the pre-erythrocytic stages of the malaria-causative agent Plasmodium. However, largely neglected is the fact that the liver is also a central player of the host defense against the morbidity- and mortality-causing blood stages of the malaria parasites. Indeed, the liver is equipped with a unique immune system that acts locally, however, with systemic impact. Its main "antipodal" functions are to recognize and to generate effective immunoreactivity against pathogens on the one hand, and to generate tolerance to avoid immunoreactivity with "self" and harmless substances as dietary compounds on the other hand. This review provides an introductory survey of the liver-inherent immune system: its pathogen recognition receptors including Toll-like receptors (TLRs) and its major cell constituents with their different facilities to fight and eliminate pathogens. Then, evidence is presented that the liver is also an essential organ to overcome blood-stage malaria. Finally, we discuss effector responses of the liver-inherent immune system directed against blood-stage malaria: activation of TLRs, acute phase response, phagocytic activity, cytokine-mediated pro- and anti-inflammatory responses, generation of "protective" autoimmunity by extrathymic T cells and B-1 cells, and T cell-mediated repair of liver injuries mainly produced by malaria-induced overreactions of the liver-inherent immune system.

  15. Safety assessment in plant layout design using indexing approach: Implementing inherent safety perspective

    International Nuclear Information System (INIS)

    Tugnoli, Alessandro; Khan, Faisal; Amyotte, Paul; Cozzani, Valerio

    2008-01-01

    The design of layout plans requires adequate assessment tools for the quantification of safety performance. The general focus of the present work is to introduce an inherent safety perspective at different points of the layout design process. In particular, index approaches for safety assessment and decision-making in the early stages of layout design are developed and discussed in this two-part contribution. Part 1 (accompanying paper) of the current work presents an integrated index approach for safety assessment of early plant layout. In the present paper (Part 2), an index for evaluation of the hazard related to the potential of domino effects is developed. The index considers the actual consequences of possible escalation scenarios and scores or ranks the subsequent accident propagation potential. The effects of inherent and passive protection measures are also assessed. The result is a rapid quantification of domino hazard potential that can provide substantial support for choices in the early stages of layout design. Additionally, a case study concerning selection among various layout options is presented and analyzed. The case study demonstrates the use and applicability of the indices developed in both parts of the current work and highlights the value of introducing inherent safety features early in layout design

  16. Interdependency control : compensation strategies for the inherent vulnerability of critical infrastructure networks

    International Nuclear Information System (INIS)

    Mao, D.; Sotoodeh, M.; Monu, K.; Marti, J.R.; Srivastava, K.D.

    2009-01-01

    Today's increasingly interacting national critical infrastructures (NCIs) can tolerate most stochastic local disturbances. However, they are extremely fragile under global disturbances, as the latter may either push the whole system into a critical state or reveal many unexpected hidden interdependencies, inducing or triggering cascading failures among all possible layers. This robust yet fragile duality is an inherent vulnerability of modern infrastructures. It is therefore expected that weather-related disasters will be more frequent under a changing climate. This paper proposed an interdependency control strategy (ICS) that would maintain the survival of the most critical services, and compensate for this inherent vulnerability during emergency states. The paper also proposed a generalized adjacency matrix (GAM) to represent the physical interdependencies intra/inter of various infrastructure networks. The vulnerable section in the network can be identified, based on computed results of GAM, number of islands in the network, and influence domain(s) of each component. These features render ICS more effective and convincing. Last, the paper proposed a survivability index for isolated sub-networks and described relevant measures for improving this index during the four phases of emergency management. It was concluded that the proposed strategy is an effective means to reduce the inherent vulnerability and increase the resiliency of these critical infrastructures networks. 20 refs., 5 figs

  17. Possibility of a pressurized water reactor concept with highly inherent heat removal following capability

    International Nuclear Information System (INIS)

    Araya, Fumimasa; Murao, Yoshio

    1995-01-01

    If the core power inherently follows change in heat removal rate from the primary coolant system within small thermal expansion of the coolant which can be absorbed in a practical size of pressurizer, reactor systems may have more safety and load following capability. In order to know possibility and necessary conditions of a concept on reactor core and primary coolant system of a pressurized water reactor (PWR) with such 'highly inherent heat removal following capability', transient analyses on an ordinary two-loop PWR have been performed for a transient due to 50% change in heat removal with the RETRAN-02 code. The possibility of a PWR concept with the highly inherent heat removal following capability has been demonstrated under the conditions of the absolute value of ratio of the coolant density reactivity coefficient to the Doppler reactivity coefficient more than 10x10 3 kg·cm 3 which is two to three times larger than that at beginning of cycle (BOC) in an ordinary PWR and realized by elimination of the chemical shim, the 12% lower average linear heat generation rate of 17.9 kW/m, and the 1.5 times larger pressurizer volume than those of the ordinary PWR. (author)

  18. A compact, inherently safe liquid metal reactor plant concept for terrestrial defense power applications

    International Nuclear Information System (INIS)

    Magee, P.M.; Dubberley, A.E.; Lutz, D.E.; Palmer, R.S.

    1987-01-01

    A compact, inherently safe, liquid metal reactor concept based on the GE PRISM innovative LMR design has been developed for terrestrial defense power applications in the 2-50 MWe range. The concept uses a small, sodium-cooled, U-5%Zr metal fueled reactor contained within two redundant steel vessels. The core is designed to operate at a low power density and temperature (925 F) and can operate 30 years without refueling. One two primary coolant loops, depending upon the plant size, transport heat from the core to sodium-to-air, double-wall heat exchangers. Power is produced by a gas turbine operated in a closed ''bottoming'' cycle that employs intercoolers between the compressor stages and a recuperator. Inherent safety is provided by passive means only; operator action is not required to ensure plant safety even for events normally considered Beyond Design Basis Accidents. In addition to normal shutdown heat removal via the sodium-to-air heat exchangers, the design utilizes an inherently passive radiant vessel auxiliary cooling system similar to that designed for PRISM. The use of an air cycle gas turbine eliminates the cost and complexity of the sodium-water reactor pressure relief system required for a steam cycle sodium-cooled reactor

  19. Developing a model for hospital inherent safety assessment: Conceptualization and validation.

    Science.gov (United States)

    Yari, Saeed; Akbari, Hesam; Gholami Fesharaki, Mohammad; Khosravizadeh, Omid; Ghasemi, Mohammad; Barsam, Yalda; Akbari, Hamed

    2018-01-01

    Paying attention to the safety of hospitals, as the most crucial institute for providing medical and health services wherein a bundle of facilities, equipment, and human resource exist, is of significant importance. The present research aims at developing a model for assessing hospitals' safety based on principles of inherent safety design. Face validity (30 experts), content validity (20 experts), construct validity (268 examples), convergent validity, and divergent validity have been employed to validate the prepared questionnaire; and the items analysis, the Cronbach's alpha test, ICC test (to measure reliability of the test), composite reliability coefficient have been used to measure primary reliability. The relationship between variables and factors has been confirmed at 0.05 significance level by conducting confirmatory factor analysis (CFA) and structural equations modeling (SEM) technique with the use of Smart-PLS. R-square and load factors values, which were higher than 0.67 and 0.300 respectively, indicated the strong fit. Moderation (0.970), simplification (0.959), substitution (0.943), and minimization (0.5008) have had the most weights in determining the inherent safety of hospital respectively. Moderation, simplification, and substitution, among the other dimensions, have more weight on the inherent safety, while minimization has the less weight, which could be due do its definition as to minimize the risk.

  20. Cephalopod genomics

    DEFF Research Database (Denmark)

    Albertin, Caroline B.; Bonnaud, Laure; Brown, C. Titus

    2012-01-01

    The Cephalopod Sequencing Consortium (CephSeq Consortium) was established at a NESCent Catalysis Group Meeting, ``Paths to Cephalopod Genomics-Strategies, Choices, Organization,'' held in Durham, North Carolina, USA on May 24-27, 2012. Twenty-eight participants representing nine countries (Austria......, Australia, China, Denmark, France, Italy, Japan, Spain and the USA) met to address the pressing need for genome sequencing of cephalopod mollusks. This group, drawn from cephalopod biologists, neuroscientists, developmental and evolutionary biologists, materials scientists, bioinformaticians and researchers...... active in sequencing, assembling and annotating genomes, agreed on a set of cephalopod species of particular importance for initial sequencing and developed strategies and an organization (CephSeq Consortium) to promote this sequencing. The conclusions and recommendations of this meeting are described...

  1. Genome Sequencing

    DEFF Research Database (Denmark)

    Sato, Shusei; Andersen, Stig Uggerhøj

    2014-01-01

    The current Lotus japonicus reference genome sequence is based on a hybrid assembly of Sanger TAC/BAC, Sanger shotgun and Illumina shotgun sequencing data generated from the Miyakojima-MG20 accession. It covers nearly all expressed L. japonicus genes and has been annotated mainly based on transcr......The current Lotus japonicus reference genome sequence is based on a hybrid assembly of Sanger TAC/BAC, Sanger shotgun and Illumina shotgun sequencing data generated from the Miyakojima-MG20 accession. It covers nearly all expressed L. japonicus genes and has been annotated mainly based...

  2. The human genome; you gain some, you lose some

    NARCIS (Netherlands)

    Kriek, Marjolein

    2007-01-01

    Copy number variations (CNVs) in the human genome are inherent in both evolutionary progression as well as the etiology of disease. The introduction of this thesis will review CNVs that appear to be neutral as well as CNVs that appear to be related to a phenotypic trait. This will be followed by a

  3. DNA immunization with a herpes simplex virus 2 bacterial artificial chromosome

    International Nuclear Information System (INIS)

    Meseda, Clement A.; Schmeisser, Falko; Pedersen, Robin; Woerner, Amy; Weir, Jerry P.

    2004-01-01

    Construction of a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome (BAC) is described. BAC vector sequences were inserted into the thymidine kinase gene of HSV-2 by homologous recombination. DNA from cells infected with the resulting recombinant virus was transformed into E. coli, and colonies containing the HSV-2 BAC (HSV2-BAC) were isolated and analyzed for the expected genotype. HSV2-BAC DNA was infectious when transfected back into mammalian cells and the resulting virus was thymidine kinase negative. When used to immunize mice, the HSV2-BAC DNA elicited a strong HSV-2 specific antibody response that was equal to or greater than live virus immunization. Further, HSV2-BAC immunization was protective when animals were challenged with a lethal dose of virus. The utility of the HSV2-BAC for construction of recombinant virus genomes was demonstrated by elimination of the HSV-2 glycoprotein D (gD) gene. A recombinant HSV-2 BAC with the gD gene deleted was isolated and shown to be incapable of producing infectious virus following transfection unless an HSV gD gene was expressed in a complementing cell line. Immunization of mice with the HSV2 gD-BAC also elicited an HSV-2 specific antibody response and was protective. The results demonstrate the feasibility of DNA immunization with HSV-2 bacterial artificial chromosomes for replicating and nonreplicating candidate HSV-2 vaccines, as well as the utility of BAC technology for construction and maintenance of novel HSV-2 vaccines. The results further suggest that such technology will be a powerful tool for dissecting the immune response to HSV-2

  4. Comparative Genomics

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 11; Issue 8. Comparative Genomics - A Powerful New Tool in Biology. Anand K Bachhawat. General Article Volume 11 Issue 8 August 2006 pp 22-40. Fulltext. Click here to view fulltext PDF. Permanent link:

  5. Deliberate practice theory: relevance, effort, and inherent enjoyment of music practice.

    Science.gov (United States)

    Hyllegard, Randy; Bories, Tamara L

    2008-10-01

    This study examined three assumptions of the theory of deliberate practice for practice playing music on an electronic keyboard. 40 undergraduate students, divided into two separate groups, practiced one of two music sequences and rated the relevance of practice for improving performance on the sequences, the amount of effort needed to learn the sequences, and the inherent enjoyment of practice sessions. Findings for each assumption were consistent with those suggested by theory but also showed that perceptions are affected by the amount of practice completed and performance of the skill.

  6. Inherently safe SNR shutdown system with Curie point controlled sensor/switch unit

    International Nuclear Information System (INIS)

    Mueller, K.; Norajitra, P.; Reiser, H.

    1987-02-01

    Inherent shutdown due to increase in the sodium temperature at the core outlet is triggered by interruption of the current supply to the electromagnet coupling of absorber elements via curie point controlled sensor/switch units. These switches are arranged above suitable fuel element positions and spatially independent of the shutdown elements. Compared with other similar systems very short response times are achieved. A prototype switch unit has already undergone extensive testing. These tests have confirmed that switching takes place in a very narrow temperature range. (orig./HP) [de

  7. The development of a small inherently safe homogeneous reactor for the production of medical isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Carlin, G.E.; Bonin, H.W., E-mail: george.carlin@rmc.ca [Royal Military College of Canada, Kingston, Ontario (Canada)

    2013-07-01

    The use of radioisotopes for various procedures in the health care industry has become one of the most important practices in medicine. New interest has been found in the use of liquid fueled nuclear reactors to produce these isotopes due to the ease of fuel processing and ability to efficiently use LEU as the fuel source. A version of this reactor is being developed at the Royal Military College of Canada to act as a successor to the SLOWPOKE-2 platform. The thermal hydraulic and transient characteristics of a 20 kWt version are being studied to verify inherent safety abilities. (author)

  8. On the inherent self-excited macroscopic randomness of chaotic three-body system

    OpenAIRE

    Liao, Shijun; Li, Xiaoming

    2014-01-01

    What is the origin of macroscopic randomness (uncertainty)? This is one of the most fundamental open questions for human being. In this paper, 10000 samples of reliable (convergent), multiple-scale (from 1.0E-60 to 100) numerical simulations of a chaotic three-body system indicate that, without any external disturbance, the microscopic inherent uncertainty (in the level of 1.0E-60) due to physical fluctuation of initial positions of the three-body system enlarges exponentially into macroscopi...

  9. Treatment of inherently unstable open or infected fractures by open wound management and external skeletal fixation.

    Science.gov (United States)

    Ness, M G

    2006-02-01

    To assess the use of external skeletal fixation with open wound management for the treatment of inherently unstable open or infected fractures in dogs. A retrospective review of 10 cases. Fracture stabilisation and wound management required only a single anaesthetic, and despite the challenging nature of these injuries, the final outcome was acceptable or good in every case. However, minor complications associated with the fixator pins were quite common, and two dogs developed complications which required additional surgery. Open management of wounds, even when bone was exposed, proved to be an effective technique, and external skeletal fixators were usually effective at maintaining stability throughout an inevitably extended fracture healing period.

  10. Multiformity of inherent randomicity and visitation density in n symbolic dynamics

    International Nuclear Information System (INIS)

    Zhang Yagang; Wang Changjiang

    2007-01-01

    The multiformity of inherent randomicity and visitation density in n symbolic dynamics will be clarified in this paper. These stochastic symbolic sequences bear three features. The distribution of frequency, inter-occurrence times and the alignment of two random sequences are amplified in detail. The features of visitation density in surjective maps presents catholicity and the catholicity in n letters randomicity has the same measure foundation. We hope to offer a symbolic platform that satisfies these stochastic properties and to attempt to study certain properties of DNA base sequences, 20 amino acids symbolic sequences of proteid structure, and the time series that can be symbolic in finance market et al

  11. Dynamics and inherent safety features of small modular high temperature gas-cooled reactors

    International Nuclear Information System (INIS)

    Harrington, R.M.; Ball, S.J.; Cleveland, J.C.

    1986-01-01

    Investigations were made at Oak Ridge National Laboratory to characterize the dynamics and inherent safety features of various modular high temperature gas-cooled reactor (HTGR) designs. This work was sponsored by the US Nuclear Regulatory Commission's HTGR Safety Research program. The US Department of Energy (DOE) and the Gas Cooled Reactor Associates (GCRA) have sponsored studies of several modular HTGR concepts, each having it own unique advantageous economic and inherent safety features. The DOE design team has recently choses a 350-MW(t) annular core with prismatic, graphite matrix fuel for its reference plant. The various safety features of this plant and of the pebble-bed core designs similar to those currently being developed and operated in the Federal Republic of Germany (FRG) are described. A varity of postulated accident sequences involving combinations of loss of forced circulation of the helium primary coolant, loss of primary coolant pressurization, and loss of normal and backup heat sinks were studied and are discussed. Results demonstrate that each concept can withstand an uncontrolled heatup accident without reaching excessive peak fuel temperatures. Comparisons of calculated and measured response for a loss of forced circulation test on the FRG reactor, AVR, are also presented. 10 refs

  12. DEM Simulation of Biaxial Compression Experiments of Inherently Anisotropic Granular Materials and the Boundary Effects

    Directory of Open Access Journals (Sweden)

    Zhao-Xia Tong

    2013-01-01

    Full Text Available The reliability of discrete element method (DEM numerical simulations is significantly dependent on the particle-scale parameters and boundary conditions. To verify the DEM models, two series of biaxial compression tests on ellipse-shaped steel rods are used. The comparisons on the stress-strain relationship, strength, and deformation pattern of experiments and simulations indicate that the DEM models are able to capture the key macro- and micromechanical behavior of inherently anisotropic granular materials with high fidelity. By using the validated DEM models, the boundary effects on the macrodeformation, strain localization, and nonuniformity of stress distribution inside the specimens are investigated using two rigid boundaries and one flexible boundary. The results demonstrate that the boundary condition plays a significant role on the stress-strain relationship and strength of granular materials with inherent fabric anisotropy if the stresses are calculated by the force applied on the wall. However, the responses of the particle assembly measured inside the specimens are almost the same with little influence from the boundary conditions. The peak friction angle obtained from the compression tests with flexible boundary represents the real friction angle of particle assembly. Due to the weak lateral constraints, the degree of stress nonuniformity under flexible boundary is higher than that under rigid boundary.

  13. A fit method for the determination of inherent filtration with diagnostic x-ray units

    International Nuclear Information System (INIS)

    Meghzifene, K; Nowotny, R; Aiginger, H

    2006-01-01

    A method for the determination of total inherent filtration for clinical x-ray units using attenuation curves was devised. A model for the calculation of x-ray spectra is used to calculate kerma values which are then adjusted to the experimental data in minimizing the sum of the squared relative differences in kerma using a modified simplex fit process. The model considers tube voltage, voltage ripple, anode angle and additional filters. Fit parameters are the thickness of an additional inherent Al filter and a general normalization factor. Nineteen sets of measurements including attenuation data for three tube voltages and five Al-filter settings each were obtained. Relative differences of experimental and calculated kerma using the data for the additional filter thickness are within a range of -7.6% to 6.4%. Quality curves, i.e. the relationship of additional filtration to HVL, are often used to determine filtration but the results show that standard quality curves do not reflect the variety of conditions encountered in practice. To relate the thickness of the additional filter to the condition of the anode surface, the data fits were also made using tungsten as the filter material. These fits gave an identical fit quality compared to aluminium with a tungsten filter thickness of 2.12-8.21 μm which is within the range of the additional absorbing layers determined for rough anodes

  14. Are autobiographical memories inherently social? Evidence from an fMRI study.

    Directory of Open Access Journals (Sweden)

    Linda Wilbers

    Full Text Available The story of our lifetime - our narrative self - is constructed from our autobiographical memories. A central claim of social psychology is that this narrative self is inherently social: When we construct our lives, we do so in a real or imagined interaction. This predicts that self-referential processes which are involved in recall of autobiographical memories overlap with processes involved in social interactions. Indeed, previous functional MRI studies indicate that regions in the medial prefrontal cortex (mPFC are activated during autobiographical memory recall and virtual communication. However, no fMRI study has investigated recall of autobiographical memories in a real-life interaction. We developed a novel paradigm in which participants overtly reported self-related and other-related memories to an experimenter, whose non-verbal reactions were being filmed and online displayed to the participants in the scanner. We found that recall of autobiographical vs. non-autobiographical memories was associated with activation of the mPFC, as was recall in the social as compared to a non-social control condition; however, both contrasts involved different non-overlapping regions within the mPFC. These results indicate that self-referential processes involved in autobiographical memory recall are different from processes supporting social interactions, and argue against the hypothesis that autobiographical memories are inherently social.

  15. Worldwide advanced nuclear power reactors with passive and inherent safety: What, why, how, and who

    International Nuclear Information System (INIS)

    Forsberg, C.W.; Reich, W.J.

    1991-09-01

    The political controversy over nuclear power, the accidents at Three Mile Island (TMI) and Chernobyl, international competition, concerns about the carbon dioxide greenhouse effect and technical breakthroughs have resulted in a segment of the nuclear industry examining power reactor concepts with PRIME safety characteristics. PRIME is an acronym for Passive safety, Resilience, Inherent safety, Malevolence resistance, and Extended time after initiation of an accident for external help. The basic ideal of PRIME is to develop power reactors in which operator error, internal sabotage, or external assault do not cause a significant release of radioactivity to the environment. Several PRIME reactor concepts are being considered. In each case, an existing, proven power reactor technology is combined with radical innovations in selected plant components and in the safety philosophy. The Process Inherent Ultimate Safety (PIUS) reactor is a modified pressurized-water reactor, the Modular High Temperature Gas-Cooled Reactor (MHTGR) is a modified gas-cooled reactor, and the Advanced CANDU Project is a modified heavy-water reactor. In addition to the reactor concepts, there is parallel work on super containments. The objective is the development of a passive ''box'' that can contain radioactivity in the event of any type of accident. This report briefly examines: why a segment of the nuclear power community is taking this new direction, how it differs from earlier directions, and what technical options are being considered. A more detailed description of which countries and reactor vendors have undertaken activities follows. 41 refs

  16. Inherent Immunogenicity or Lack Thereof of Pluripotent Stem Cells: Implications for Cell Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Arvind Chhabra

    2017-08-01

    Full Text Available Donor-specific induced pluripotent stem cells (iPSCs offer opportunities for personalized cell replacement therapeutic approaches due to their unlimited self-renewal potential and ability to differentiate into different somatic cells. A significant progress has been made toward generating iPSC lines that are free of integrating viral vectors, development of xeno-free culture conditions, and differentiation of pluripotent stem cells (PSCs into functional somatic cell lineages. Since donor-specific iPSC lines are genetically identical to the individual, they are expected to be immunologically matched and these iPSC lines and their cellular derivatives are not expected to be immunologically rejected. However, studies in mouse models, utilizing rejection of teratomas as a model, have claimed that syngenic iPSC lines, especially the iPSC lines derived with integrating viral vectors, could be inherently immunogenic. This manuscript reviews current understanding of inherent immunogenicity of PSC lines, especially that of the human iPSC lines and their cellular derivatives, and strategies to overcome it.

  17. Indispensable role of biochar-inherent mineral constituents in its environmental applications: A review.

    Science.gov (United States)

    Xu, Xiaoyun; Zhao, Yinghao; Sima, Jingke; Zhao, Ling; Mašek, Ondřej; Cao, Xinde

    2017-10-01

    Biochar typically consists of both carbon and mineral fractions, and the carbon fraction has been generally considered to determine its properties and applications. Recently, an increasing body of research has demonstrated that mineral components inherent in biochar, such as alkali or alkaline earth metals in the form of carbonates, phosphates, or oxides, could also influence the properties and thus the applications. The review articles published thus far have mainly focused on multiple environmental and agronomic applications of biochar, including carbon sequestration, soil improvement, environmental remediation, etc. This review aims to highlight the indispensable role of the mineral fraction of biochar in these different applications, especially in environmental applications. Specifically, it provides a critical review of current research findings related to the mineral composition of biochar and the effect of the mineral fraction on the physicochemical properties, contaminant sorption, carbon retention and stability, and nutrient bioavailability of biochar. Furthermore, the role of minerals in the emerging applications of biochar, as a precursor for fuel cells, supercapacitors, and photoactive components, is also summarized. Overall, inherent minerals should be fully considered while determining the most appropriate application for any given biochar. A thorough understanding of the role of biochar-bound minerals in different applications will also allow the design or selection of the most suitable biochar for specific applications based on the consideration of feedstock composition, production parameters, and post-treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. INHERENT ASPECT: A SOCIOFUNCTIONALIST APPROACH OF PAST IMPERFECTIVE VERBAL FORMS IN SPANISH

    Directory of Open Access Journals (Sweden)

    Márluce Coan

    2014-03-01

    Full Text Available : We deal with the category aspect in a lexical dimension – an inherent aspect - and its interaction with the grammatical aspect, in order to inquire the convergences and divergences in the compositional shaping of the aspect. Our data come from twenty four short stories written in Spanish language, selected based on the cultural region parameter: Caribe; Mexico and Central America; Andes, Rio of the Prata; Chile and Spain. It was obtained a total of 2.093 data: 290 of them are imperfective periphrasis of past, that is, 13,85% of the total. These forms encode variably the descriptive, narrative, habitual and desiderative functions. The other identified functions – interactive, politeness, present, future, simultaneity, contrariety and playful – were only encoded by the imperfective past tense. The analysis of the correlation between the inherent aspect and the grammatical one corroborates the range of imperfectiviness by Givón (2001, which issupported by criteria of Vendler’s typology (2005 [1967]: states, the ones less marked and predicable, present more occurrences; followed at scale by activities, culminated processes, and culminations, the ones which are more marked and less predictable.

  19. INHERENT ASPECT: A SOCIOFUNCTIONALIST APPROACH OF PAST IMPERFECTIVE VERBAL FORMS IN SPANISH

    Directory of Open Access Journals (Sweden)

    Márluce COAN

    2013-12-01

    Full Text Available We deal with the category aspect in a lexical dimension – an inherent aspect - and its interaction with the grammatical aspect, in order to inquire the convergences and divergences in the compositional shaping of the aspect. Our data come from twenty four short stories written in Spanish language, selected based on the cultural region parameter: Caribe; Mexico and Central America; Andes, Rio of the Prata; Chile and Spain. It was obtained a total of 2.093 data: 290 of them are imperfective periphrasis of past, that is, 13,85% of the total. These forms encode variably the descriptive, narrative, habitual and desiderative functions. The other identified functions – interactive, politeness, present, future, simultaneity, contrariety and playful – were only encoded by the imperfective past tense. The analysis of the correlation between the inherent aspect and the grammatical one corroborates the range of imperfectiviness by Givón (2001, which issupported by criteria of Vendler’s typology (2005 [1967]: states, the ones less marked and predicable, present more occurrences; followed at scale by activities, culminated processes, and culminations, the ones which are more marked and less predictable.

  20. Problems in the assessment of inherent safety characteristics of nuclear reactors

    International Nuclear Information System (INIS)

    Garribba, S.F.; Vivante, C.

    1988-01-01

    A number of proposals are being made for an increased RD and D effort on advanced nuclear power reactors that would display outstanding safety performance. A common characteristic of the different reactor concepts would be their limited reliance upon active engineered systems under major accident conditions. However, when submitted to a more close scrutiny reactor concept options may reveal diverging safety behaviors and also development opportunities. In this respect, three issues are explored in this paper. A first question is the meaning of non-active, i.e. inherent and passive safety features. Next, is the ranking of advanced and new reactor concepts from the viewpoint of inherent and passive safety. Multiple correspondence analysis may provide a simple tool, whose use is shown for the case of HTR-500, AP600 and PRISM. Conversely, probabilistic risk assessment would allow quantitative comparisons, although lack of information and data is an obstacle. Finally, is demonstration of safety performances as a step toward market deployment of the new reactor systems

  1. Optimal control of quantum systems: Origins of inherent robustness to control field fluctuations

    International Nuclear Information System (INIS)

    Rabitz, Herschel

    2002-01-01

    The impact of control field fluctuations on the optimal manipulation of quantum dynamics phenomena is investigated. The quantum system is driven by an optimal control field, with the physical focus on the evolving expectation value of an observable operator. A relationship is shown to exist between the system dynamics and the control field fluctuations, wherein the process of seeking optimal performance assures an inherent degree of system robustness to such fluctuations. The presence of significant field fluctuations breaks down the evolution of the observable expectation value into a sequence of partially coherent robust steps. Robustness occurs because the optimization process reduces sensitivity to noise-driven quantum system fluctuations by taking advantage of the observable expectation value being bilinear in the evolution operator and its adjoint. The consequences of this inherent robustness are discussed in the light of recent experiments and numerical simulations on the optimal control of quantum phenomena. The analysis in this paper bodes well for the future success of closed-loop quantum optimal control experiments, even in the presence of reasonable levels of field fluctuations

  2. Inherent safety features of the HTTR revealed in the accident condition

    International Nuclear Information System (INIS)

    Kunitomi, K.; Shinozaki, M.; Baba, O.; Saito, S.

    1992-01-01

    The High Temperature Engineering Test Reactor (HTTR) being constructed by JAERI (Japan Atomic Energy Research Institute) is a graphite-moderated and helium-cooled reactor with an outlet gas temperature of 950degC. The inherent safety characteristics in the HTTR prevent temperature increase of reactor fuels and fission product release from the reactor core in postulated accident conditions. The reactor core can be cooled by a Vessel Cooling System (VCS) indirectly, even in the case that no forced cooling is expected during the accident such as primary pipe break. The VCS consists of independent water cooling loop and cooling panel around the reactor pressure vessel. The cooling panel whose temperature of 60-90degC cools the reactor pressure vessel by radiation and removes the decay heat from the core indirectly. Furthermore, even if failure of VCS is assumed during this accident as a severe accident, the reactor core is remained safe despite the temperature increase of biological concrete shield around the reactor pressure vessel. This paper describes the inherent safety features of the HTTR specially focused on the accident condition without forced cooling. The detailed analytical results of such an accident are described together with clarifying the role of the VCS. (author)

  3. Dealing with uncertainty and pursuing superior technology options in risk management-The inherency risk analysis

    International Nuclear Information System (INIS)

    Helland, Aasgeir

    2009-01-01

    Current regulatory systems focus on the state of scientific evidence as the predominant factor for how to handle risks to human health and the environment. However, production and assessment of risk information are costly and time-consuming, and firms have an intrinsic disincentive to produce and distribute information about risks of their products as this could endanger their production opportunities and sales. An emphasis on more or better science may result in insufficient thought and attention going into the exploration of technology alternatives, and that risk management policies miss out on the possible achievement of a more favorable set of consequences. In this article, a method is proposed that combines risk assessment with the search for alternative technological options as a part of the risk management procedure. The method proposed is the inherency risk analysis where the first stage focuses on the original agent subject to investigation, the second stage focuses on identifying technological options whereas the third stage reviews the different alternatives, searching for the most attractive tradeoffs between costs and inherent safety. This is then used as a fundament for deciding which technology option to pursue. This method aims at providing a solution-focused, systematic technology-based approach for addressing and setting priorities for environmental problems. By combining risk assessment with a structured approach to identify superior technology options within a risk management system, the result could very well be a win-win situation for both company and the environment.

  4. The development of an inherent safety approach to the prevention of domino accidents.

    Science.gov (United States)

    Cozzani, Valerio; Tugnoli, Alessandro; Salzano, Ernesto

    2009-11-01

    The severity of industrial accidents in which a domino effect takes place is well known in the chemical and process industry. The application of an inherent safety approach for the prevention of escalation events leading to domino accidents was explored in the present study. Reference primary scenarios were analyzed and escalation vectors were defined. Inherent safety distances were defined and proposed as a metric to express the intensity of the escalation vectors. Simple rules of thumb were presented for a preliminary screening of these distances. Swift reference indices for layout screening with respect to escalation hazard were also defined. Two case studies derived from existing layouts of oil refineries were selected to understand the potentialities coming from the application in the methodology. The results evidenced that the approach allows a first comparative assessment of the actual domino hazard in a layout, and the identification of critical primary units with respect to escalation events. The methodology developed also represents a useful screening tool to identify were to dedicate major efforts in the design of add-on measures, optimizing conventional passive and active measures for the prevention of severe domino accidents.

  5. Synthesis and Characterization of Pure Copper Nanostructures Using Wood Inherent Architecture as a Natural Template

    Science.gov (United States)

    Dong, Youming; Wang, Kaili; Tan, Yi; Wang, Qingchun; Li, Jianzhang; Mark, Hughes; Zhang, Shifeng

    2018-04-01

    The inherent sophisticated structure of wood inspires researchers to use it as a natural template for synthesizing functional nanoparticles. In this study, pure copper nanoparticles were synthesized using poplar wood as a natural inexpensive and renewable template. The crystal structure and morphologies of the copper nanoparticles were characterized by X-ray diffraction and field emission scanning electron microscopy. The optical properties, antibacterial properties, and stability of the hybrid wood materials were also tested. Due to the hierarchical and anisotropic structure and electron-rich components of wood, pure copper nanoparticles with high stability were synthesized with fcc structure and uniform sizes and then assembled into corncob-like copper deposits along the wood cell lumina. The products of nanoparticles depended strongly on the initial OH- concentration. With an increase in OH- concentration, Cu2O gradually decreased and Cu remained. Due to the restrictions inherent in wood structure, the derived Cu nanoparticles showed similar grain size in spite of increased Cu2+ concentration. This combination of Cu nanostructures and wood exhibited remarkable optical and antibacterial properties.

  6. Effective material parameter retrieval of anisotropic elastic metamaterials with inherent nonlocality

    Science.gov (United States)

    Lee, Hyung Jin; Lee, Heung Son; Ma, Pyung Sik; Kim, Yoon Young

    2016-09-01

    In this paper, the scattering (S-) parameter retrieval method is presented specifically for anisotropic elastic metamaterials; so far, no retrieval has been accomplished when elastic metamaterials exhibit fully anisotropic behavior. Complex constitutive property and intrinsic scattering behavior of elastic metamaterials make their characterization far more complicated than that for acoustic and electromagnetic metamaterials. In particular, elastic metamaterials generally exhibit anisotropic scattering behavior due to higher scattering modes associated with shear deformation. They also exhibit nonlocal responses to some degrees, which originate from strong multiple scattering interactions even in the long wavelength limit. Accordingly, the conventional S-parameter retrieval methods cannot be directly used for elastic metamaterials, because they determine only the diagonal components in effective tensor property. Also, the conventional methods simply use the analytic inversion formulae for the material characterization so that inherent nonlocality cannot be taken into account. To establish a retrieval method applicable to anisotropic elastic metamaterials, we propose an alternative S-parameter method to deal with full anisotropy of elastic metamaterials. To retrieve the whole effective anisotropic parameter, we utilize not only normal but also oblique wave incidences. For the retrieval, we first retrieve the ratio of the effective stiffness tensor to effective density and then determine the effective density. The proposed retrieval method is validated by characterizing the effective material parameters of various types of non-resonant anisotropic metamaterials. It is found that the whole effective parameters are retrieved consistently regardless of used retrieval conditions in spite of inherent nonlocality.

  7. Personal genomics services: whose genomes?

    Science.gov (United States)

    Gurwitz, David; Bregman-Eschet, Yael

    2009-07-01

    New companies offering personal whole-genome information services over the internet are dynamic and highly visible players in the personal genomics field. For fees currently ranging from US$399 to US$2500 and a vial of saliva, individuals can now purchase online access to their individual genetic information regarding susceptibility to a range of chronic diseases and phenotypic traits based on a genome-wide SNP scan. Most of the companies offering such services are based in the United States, but their clients may come from nearly anywhere in the world. Although the scientific validity, clinical utility and potential future implications of such services are being hotly debated, several ethical and regulatory questions related to direct-to-consumer (DTC) marketing strategies of genetic tests have not yet received sufficient attention. For example, how can we minimize the risk of unauthorized third parties from submitting other people's DNA for testing? Another pressing question concerns the ownership of (genotypic and phenotypic) information, as well as the unclear legal status of customers regarding their own personal information. Current legislation in the US and Europe falls short of providing clear answers to these questions. Until the regulation of personal genomics services catches up with the technology, we call upon commercial providers to self-regulate and coordinate their activities to minimize potential risks to individual privacy. We also point out some specific steps, along the trustee model, that providers of DTC personal genomics services as well as regulators and policy makers could consider for addressing some of the concerns raised below.

  8. Visualization for genomics: the Microbial Genome Viewer.

    NARCIS (Netherlands)

    Kerkhoven, R.; Enckevort, F.H.J. van; Boekhorst, J.; Molenaar, D; Siezen, R.J.

    2004-01-01

    SUMMARY: A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a

  9. Safety assessment in plant layout design using indexing approach: implementing inherent safety perspective. Part 1 - guideword applicability and method description.

    Science.gov (United States)

    Tugnoli, Alessandro; Khan, Faisal; Amyotte, Paul; Cozzani, Valerio

    2008-12-15

    Layout planning plays a key role in the inherent safety performance of process plants since this design feature controls the possibility of accidental chain-events and the magnitude of possible consequences. A lack of suitable methods to promote the effective implementation of inherent safety in layout design calls for the development of new techniques and methods. In the present paper, a safety assessment approach suitable for layout design in the critical early phase is proposed. The concept of inherent safety is implemented within this safety assessment; the approach is based on an integrated assessment of inherent safety guideword applicability within the constraints typically present in layout design. Application of these guidewords is evaluated along with unit hazards and control devices to quantitatively map the safety performance of different layout options. Moreover, the economic aspects related to safety and inherent safety are evaluated by the method. Specific sub-indices are developed within the integrated safety assessment system to analyze and quantify the hazard related to domino effects. The proposed approach is quick in application, auditable and shares a common framework applicable in other phases of the design lifecycle (e.g. process design). The present work is divided in two parts: Part 1 (current paper) presents the application of inherent safety guidelines in layout design and the index method for safety assessment; Part 2 (accompanying paper) describes the domino hazard sub-index and demonstrates the proposed approach with a case study, thus evidencing the introduction of inherent safety features in layout design.

  10. European Constitutional Identity “Inside Out”: Inherent Risks of the Pluralist Structure

    DEFF Research Database (Denmark)

    Cebulak, Pola Paula

    2012-01-01

    The jurisprudence of the CJEU and the national constitutional courts referring to the national constitutional identities of the Members States fits into the framework of constitutional pluralism as modus vivendi of the European legal order. This paper focuses in particular on the recent judgments...... the tensions inherent in the pluralist structure of the relationships between legal orders in the European arena. Constitutional identity is yet another concept used in this debate about the ultimate authority. Pluralism assumes that the courts will compete over the ultimate authority and will try to use...... for fruitful interaction of competing visions of Europe. Single criticisable judgments do not put in question the viability of the whole framework, but it is important to be aware of the systemic risks....

  11. Evaluation of design variants for improved inherent regulation of advanced small modular reactors - 15325

    International Nuclear Information System (INIS)

    Vilim, R.B.; Passerini, S.

    2015-01-01

    This paper examines design variants that can improve inherent regulation in Advanced Small Modular Reactors (ASMR). It looks at the nature of unprotected upsets and then develops appropriate design measures to ensure that no upset can override a capability for safe self-regulation. This work adopts a reference sodium fast reactor (SFR) design to serve as a baseline for operational and safety performance and for comparison with variants on this design. The effect of design measures on plant stability is then examined. It is found that compared to full-power operation, the stability margin is reduced under islanded-operation. Islanded-operation is more likely for an ASMR deployed in a small regional electric grid with high penetration of renewable energy sources. The stability of core power production is a function of the inlet temperature coefficient, coolant transport times, and temperature-front attenuation in heat exchangers. The interaction of these phenomena with the control system is described

  12. Design of a Single Motor Based Leg Structure with the Consideration of Inherent Mechanical Stability

    Science.gov (United States)

    Taha Manzoor, Muhammad; Sohail, Umer; Noor-e-Mustafa; Nizami, Muhammad Hamza Asif; Ayaz, Yasar

    2017-07-01

    The fundamental aspect of designing a legged robot is constructing a leg design that is robust and presents a simple control problem. In this paper, we have successfully designed a robotic leg based on a unique four bar mechanism with only one motor per leg. The leg design parameters used in our platform are extracted from design principles used in biological systems, multiple iterations and previous research findings. These principles guide a robotic leg to have minimal mechanical passive impedance, low leg mass and inertia, a suitable foot trajectory utilizing a practical balance between leg kinematics and robot usage, and the resultant inherent mechanical stability. The designed platform also exhibits the key feature of self-locking. Theoretical tools and software iterations were used to derive these practical features and yield an intuitive sense of the required leg design parameters.

  13. On the fundamentals of nuclear reactor safety assessment. Inherent threats and their implications

    Energy Technology Data Exchange (ETDEWEB)

    Hyvaerinen, J. [Finnish Centre for Radiation and Nuclear Safety, Helsinki (Finland). Nuclear Safety Dept.

    1996-12-01

    The thesis addresses some fundamental questions related to implementation and assessment of nuclear safety. The safety principles and assessment methods are described, followed by descriptions of selected novel technical challenges to nuclear safety. The novel challenges encompass a wide variety of technical issues, thus providing insights on the limitations of conventional safety assessment methods. Study of the limitations suggests means to improve nuclear reactor design criteria and safety assessment practices. The novel safety challenges discussed are (1) inherent boron dilution in PWRs, (2) metallic insulation performance with respect to total loss of emergency cooling systems in a loss-of-coolant accident, and (3) horizontal steam generator heat transfer performance at natural circulation conditions. (50 refs.).

  14. Utopia and Debt in Postmodernity; or, Time Management in Inherent Vice

    Directory of Open Access Journals (Sweden)

    James Liner

    2016-05-01

    Full Text Available The category of postmodernism has come under renewed scrutiny in recent years. Indeed, it has become rather commonplace to pronounce the death or obsolescence of postmodernism today. Unsurprisingly, the increasingly questioned status of postmodernism also impacts the field of Pynchon studies. This article reads 'Inherent Vice' as symptomatic not of the end but of a transformation of postmodernism and postmodernity. Pynchon’s novel simultaneously registers a contemporary intensification of postmodern/late capitalism and, crucially, participates in a minor current in postmodernism, one which insists on collective agency and utopian thinking despite the atomization and isolation of subjects accomplished by late capitalism and which, against all odds, remembers how to think historically—or better, invents new ways of thinking historically.

  15. Comments on the variability of inherent bioelement contents of spruce needles

    International Nuclear Information System (INIS)

    Wyttenbach, A.; Tobler, L.; Bajo, S.

    1991-01-01

    Inherent needle contents are the relevant concentrations within the needle, excluding surface contaminations by aerosols. The error arising from the analysis of unwashed needles is quantified. For many elements it is the source of a large apparent variability. Spatial variability is discussed under the aspects of variability among trees within a plot and of variability among different plots. Both terms have implications as to the number of trees that should be sampled for the characterization of a plot. Variability with time is investigated by following the needle concentrations from an age of 1 to 23 months. The results give indications on favourable sampling dates and on the physiology of the different elements. All investigations refer to 20 elements, which have been determined by neutron activation analysis. (author) 6 figs., 5 tabs., 16 refs

  16. A level III PSA for the inherently safe CAREM-25 nuclear power station

    International Nuclear Information System (INIS)

    Baron, Jorge H.; Nunez McLeod, J.; Rivera, S.S.

    2000-01-01

    A Level III PSA has been performed for the inherently safe CAREM-25 nuclear power station, as a requirement for licensing according to argentinian regulations. The CAREM-25 project is still at a detailed design state, therefore only internal events have been considered, and a representative site has been assumed for dose estimations. Several conservative hypothesis have been formulated, but even so an overall core melt frequency of 2.3E -5 per reactor year has been obtained. The risk estimations comply with the regulations. The risk values obtained are compared to the 700MW(e) nuclear power plant Atucha II PSA result, showing an effective risk reduction not only in the severe accident probability but alto in the consequence component of the risk estimation. (author)

  17. Why infest the loved ones--inherent human behaviour indicates former mutualism with head lice.

    Science.gov (United States)

    Rózsa, Lajos; Apari, Péter

    2012-05-01

    Head lice transmit to new hosts when people lean their heads together. Humans frequently touch their heads to express friendship or love, while this behaviour is absent in apes. We hypothesize that this behaviour was adaptive because it enabled people to acquire head lice infestations as early as possible to provoke an immune response effective against both head lice and body lice throughout the subsequent periods of their life. This cross-immunity could provide some defence against the body-louse-borne lethal diseases like epidemic typhus, trench fever, relapsing fever and the classical plague. Thus the human 'touching heads' behaviour probably acts as an inherent and unconscious 'vaccination' against body lice to reduce the threat exposed by the pathogens they may transmit. Recently, the eradication of body-louse-borne diseases rendered the transmission of head lice a maladaptive, though still widespread, behaviour in developed societies.

  18. Inherently safe aircooling for the storage of self-heating configurations of radionuclides

    International Nuclear Information System (INIS)

    Hame, W.; Klein, D.; Pirk, H.

    1980-01-01

    NUKEM developed a technical concept of a radionuclide storage facility based on aircooling, which provides that - the radionuclides, i.e. spent fuel elements, are tightly canned in steel canisters - the canned elements are put into individual cooling channels, which form the storage rack within the storage cell - the produced heat is removed from the surface of the canisters through free convection. This cooling concept shows the following advantages: - The cooling is inherently safe, as the driving force of the coolant is reliably supplied by the heat production of the system to be cooled. - The system is self-controlled and self-regulated because of the physically based correlation of heat production, heat transfer coefficients and air flow resistances. (orig.) 891 RB/orig. 892 MKO [de

  19. Dynamic operator actions analysis for inherently safe fast reactors and light water reactors

    International Nuclear Information System (INIS)

    Ho, V.; Apostolakis, G.

    1988-01-01

    A comparative dynamic human actions analysis of inherently safe fast reactors (ISFRs) and light water reactors (LWRs) in terms of systems response and estimated human error rates is presented. Brief overviews of the ISFR and LWR systems are given to illustrate the design differences. Key operator actions required by the ISFR reactor shutdown and decay heat removal systems are identified and are compared with those of the LWR. It is observed that, because of the passive nature of the ISFR safety-related systems, a large time window is available for operator actions during transient events. Furthermore, these actions are fewer in number, are less complex, and have lower error rates and less severe consequences than those of the LWRs. We expect the ISFR operator errors' contribution to risk is smaller (at least in the context of the existing human reliability models) than that of the LWRs. (author)

  20. On the fundamentals of nuclear reactor safety assessment. Inherent threats and their implications

    International Nuclear Information System (INIS)

    Hyvaerinen, J.

    1996-12-01

    The thesis addresses some fundamental questions related to implementation and assessment of nuclear safety. The safety principles and assessment methods are described, followed by descriptions of selected novel technical challenges to nuclear safety. The novel challenges encompass a wide variety of technical issues, thus providing insights on the limitations of conventional safety assessment methods. Study of the limitations suggests means to improve nuclear reactor design criteria and safety assessment practices. The novel safety challenges discussed are (1) inherent boron dilution in PWRs, (2) metallic insulation performance with respect to total loss of emergency cooling systems in a loss-of-coolant accident, and (3) horizontal steam generator heat transfer performance at natural circulation conditions. (50 refs.)

  1. Quick and Easy Measurements of the Inherent Optical Property of Water by Laser

    International Nuclear Information System (INIS)

    Izadi, Dina; Hajiesmaeilbaigi, Fereshteh

    2009-01-01

    To generate realistic images of natural waters, one must consider in some detail the interaction of light with the water body. The reflectance and attenuation coefficient of the second harmonic of Nd:YAG laser light through distilled water and a sample of water from the Oman Sea were measured in a solid-state laser laboratory to estimate inherent optical properties of natural waters. These measurements determined the bottom conditions and the impurities of the water. The water's reflectivity varied depending on the angle of incidence, height of the laser from water surface, wavelength of laser light, radiant intensities, and depth of water. In these experiments laser light propagated through the water nonlinearly, and different reflectance showed different bottom slopes. The differences among various water samples were obtained taking into account the exponential equation in attenuation coefficient versus depth graphs.

  2. Evaluation of different in vitro assays of inherent sensitivity as predictors of radiotherapy response

    International Nuclear Information System (INIS)

    Schwartz, J.L.; Chicago Univ., IL; Beckett, M.A.; Mustafi, R.; Weichselbaum, R.R.; Vaughan, A.T.M.

    1991-01-01

    The inherent sensitivity of cells within a tumor plays an important role in the response of the tumor to radiotherapy. Clonogenic assays show that cells established from in-field radiotherapy failures are significantly more resistant to radiation than cell lines established from pre-treatment samples. Clonogenic assays fail to predict tumor response to radiotherapy, however. The failure might be due to the small sample size in this study, or the complicating factors of staging, surgery, and chemotherapy, and/or in vivo selection by radiotherapy for resistant tumor cells. In vitro selection for resistant cell lines does not appear to be a complicating factor. Nonclonogenic assays such as those that measure DNA strand break rejoining rates (filter elution, pulse-field gel electrophoresis) or chromosome structure (flow cytometric analysis) show promise as alternative rapid assays of radiation sensitivity and possibly tumor response. 16 refs., 2 figs

  3. Contrasting Inherent Optical Properties and Carbon Metabolism Between Five Northeastern (USA) Estuary-plume Systems

    Science.gov (United States)

    Vandemark, Doug; Salisbury, Joe; Hunt, Chris; McGillis, Wade R.

    2004-01-01

    We have recently developed the ability to rapidly assess Surface inherent optical properties (IOP), oxygen concentration and pCO2 in estuarine-plume systems using flow-through instrumentation. During the summer of 2004, several estuarine-plume systems were surveyed which include the Pleasant (ME), Penobscot (ME), Kennebec-Androscoggin (ME), Merrimack (NH-MA) and Hudson (NY). Continuous measurements of surface chlorophyll and colored dissolved organic carbon (CDOM) fluorescence, beam attenuation, temperature, salinity, oxygen and pC02 were taken at each system along a salinity gradient from fresh water to near oceanic endmembers. CTD and IOP profiles were also taken at predetermined surface salinity intervals. These were accompanied by discrete determinations of chlorophyll (HPLC and fluorometric), total suspended solids (TSS), dissolved organic carbon (DOC) and alkalinity. IOP data were calibrated using chlorophyll, DOC and TSS data to enable the retrieval of these constituents from IOP data. Considerable differences in the data sets were observed between systems. These ranged from the DOC-enriched, strongly heterotrophic Pleasant River System to the high-chlorophyll autotrophic Merrimack River System. Using pCO2 and oxygen saturation measurements as proxies for water column metabolism, distinct relationships were found between trophic status and inherent optical properties. The nature of these relationships varies between systems and is likely a function of watershed and estuarine attributes including carbon and nutrient loading, in-situ production and related autochthonous inputs of DOC and alkalinity. Our results suggest that IOP data may contain significant information about the trophic status of estuarine and plume systems.

  4. Analysis Relationship Among Descriptor, References and Citation to Contruct the Inherent Structure of Document Collection

    International Nuclear Information System (INIS)

    Hasibuan, Zainal A.; Mustangimah

    2001-01-01

    There are many characteristics can be used to identify a document which cover characteristics of the documents, cited documents, and citing documents This research explored the inherent structure of a document collection as one of main components of information retrieval system. The characteristics examined are: descriptors, references (cited documents), and citations (citing documents). Three independent variables were studied: co-descriptor, bibliographic coupling, and co-citation. A test collection was constructed by searching on a single descriptor i nformation retrieval i n the CD-ROM version of Education Resource Information Clearinghouse (ERIC), covering the period 1981 through 1985. Descriptors were extracted from ERIC; cited and citing documents associated with the test collection were derived from Social Sciences Citation Index (SSCI), covering the period 1981 through 1990. Three hypothesis were tested in this study, that are: (1) the higher the frequency of co-descriptors between documents, the higher the frequencies of their bibliographic coupling and co-citation; (2) the higher the frequency of bibliographic coupling between documents, the higher the frequencies of their co-citation and co-descriptors; and (3) the higher the frequency of co-citation between documents, the higher the frequencies of their co-descriptors and bibliographic coupling. The results showed that all of three hypothesis are supported statistically and there is a significant linear relationship among the observed variables. It is mean that there is a significant relationship among descriptors, references, and citation, so that it can be used to construct the inherent structure of document collection in order to improve information retrieval system performance

  5. Nuclear desalination in the Arab world - Part II: Advanced inherent and passive safe nuclear reactors

    International Nuclear Information System (INIS)

    Karameldin, A.; Samer S. Mekhemar

    2004-01-01

    Rapid increases in population levels have led to greater demands for fresh water and electricity in the Arab World. Different types of energies are needed to contribute to bridging the gap between increased demand and production. Increased levels of safeguards in nuclear power plants have became reliable due to their large operational experience, which now exceeds 11,000 years of operation. Thus, the nuclear power industry should be attracting greater attention. World electricity production from nuclear power has risen from 1.7% in 1970 to 17%-20% today. This ratio had increased in June 2002 to reach more than 30%, 33% and 42% in Europe, Japan, and South Korea respectively. In the Arab World, both the public acceptance and economic viability of nuclear power as a major source of energy are greatly dependent on the achievement of a high level of safety and environmental protection. An assessment of the recent generation of advanced reactor safety criteria requirements has been carried out. The promising reactor designs adapted for the Arab world and other similar developing countries are those that profit from the enhanced and passive safety features of the new generation of reactors, with a stronger focus on the effective use of intrinsic characteristics, simplified plant design, and easy construction, operation and maintenance. In addition, selected advanced reactors with a full spectrum from small to large capacities, and from evolutionary to radical types, which have inherent and passive safety features, are discussed. The relevant economic assessment of these reactors adapted for water/electricity cogeneration have been carried out and compared with non-nuclear desalination methods. This assessment indicates that, water/electricity cogeneration by the nuclear method with advanced inherent and passive safe nuclear power plants, is viable and competitive. (author)

  6. The inherent weaknesses in industrial control systems devices; hacking and defending SCADA systems

    Science.gov (United States)

    Bianco, Louis J.

    The North American Electric Reliability Corporation (NERC) is about to enforce their NERC Critical Infrastructure Protection (CIP) Version Five and Six requirements on July 1st 2016. The NERC CIP requirements are a set of cyber security standards designed to protect cyber assets essential the reliable operation of the electric grid. The new Version Five and Six requirements are a major revision to the Version Three (currently enforced) requirements. The new requirements also bring substations into scope alongside Energy Control Centers. When the Version Five requirements were originally drafted they were vague, causing in depth discussions throughout the industry. The ramifications of these requirements has made owners look at their systems in depth, questioning how much money it will take to meet these requirements. Some owners saw backing down from routable networks to non-routable as a means to save money as they would be held to less requirements within the standards. Some owners saw removing routable connections as a proper security move. The purpose of this research was to uncover the inherent weaknesses in Industrial Control Systems (ICS) devices; to show how ICS devices can be hacked and figure out potential protections for these Critical Infrastructure devices. In addition, this research also aimed to validate the decision to move from External Routable connectivity to Non-Routable connectivity, as a security measure and not as a means of savings. The results reveal in order to ultimately protect Industrial Control Systems they must be removed from the Internet and all bi-directional external routable connections must be removed. Furthermore; non-routable serial connections should be utilized, and these non-routable serial connections should be encrypted on different layers of the OSI model. The research concluded that most weaknesses in SCADA systems are due to the inherent weaknesses in ICS devices and because of these weaknesses, human intervention is

  7. Seeds of Brassicaceae weeds have an inherent or inducible response to the germination stimulant karrikinolide.

    Science.gov (United States)

    Long, Rowena L; Stevens, Jason C; Griffiths, Erin M; Adamek, Markus; Gorecki, Marta J; Powles, Stephen B; Merritt, David J

    2011-10-01

    Karrikinolide (KAR(1)) is a smoke-derived chemical that can trigger seeds to germinate. A potential application for KAR(1) is for synchronizing the germination of weed seeds, thereby enhancing the efficiency of weed control efforts. Yet not all species germinate readily with KAR(1), and it is not known whether seemingly non-responsive species can be induced to respond. Here a major agronomic weed family, the Brassicaceae, is used to test the hypothesis that a stimulatory response to KAR(1) may be present in physiologically dormant seeds but may not be expressed under all circumstances. Seeds of eight Brassicaceae weed species (Brassica tournefortii, Raphanus raphanistrum, Sisymbrium orientale, S. erysimoides, Rapistrum rugosum, Lepidium africanum, Heliophila pusilla and Carrichtera annua) were tested for their response to 1 µm KAR(1) when freshly collected and following simulated and natural dormancy alleviation, which included wet-dry cycling, dry after-ripening, cold and warm stratification and a 2 year seed burial trial. Seven of the eight Brassicaceae species tested were stimulated to germinate with KAR(1) when the seeds were fresh, and the remaining species became responsive to KAR(1) following wet-dry cycling and dry after-ripening. Light influenced the germination response of seeds to KAR(1), with the majority of species germinating better in darkness. Germination with and without KAR(1) fluctuated seasonally throughout the seed burial trial. KAR(1) responses are more complex than simply stating whether a species is responsive or non-responsive; light and temperature conditions, dormancy state and seed lot all influence the sensitivity of seeds to KAR(1), and a response to KAR(1) can be induced. Three response types for generalizing KAR(1) responses are proposed, namely inherent, inducible and undetected. Given that responses to KAR(1) were either inherent or inducible in all 15 seed lots included in this study, the Brassicaceae may be an ideal target for

  8. PRISM [Power Reactor Inherently Safe Module] design concept enhances waste management

    International Nuclear Information System (INIS)

    Thompson, M.L.; Berglund, R.C.

    1989-01-01

    PRISM, a modular advanced liquid metal reactor (ALMR), has been designed conceptually by GE under the US Department of Energy sponsorship. The concept design and analyses have been primarily focused on passive safety and improved construction and operating costs. Significantly, the unique design of multiple modules and features of PRISM enhance waste management over conventional reactor systems. This paper provides an overview of PRISM of these enhancements. Inherent to the ALMR's, the sodium coolant precludes crud buildup on reactor surfaces and in components and waste for disposal. Preliminary evaluations indicate this fundamental feature results in factors of 2-4 less waste volume and 2-3 orders of magnitude less curies per megawatt-electric for ultimate disposal. For example, the tap designed for sodium cleanup is expected to be exchanged only once every thirty years. Also, inherent to ALMR's, burning waste actinides and selected fission products to preclude their accumulation and burial is very attractive. The hard neutron spectrum of ALMR burns the actinides efficiently and is not poisoned by the actinides and fission products. The modular design of PRISM components (and the fuel cycle equipment) permit replacement without expensive and potentially hazardous volume reduction. For example, the functional components of the reference electromagnetic pump and IHK can be removed intact for waste disposal. Although development of the reference metal fuel is not completed, it is estimated that (low-level) waste from recycle of the fuel will result in significantly less volume than would be generated by aqueous recycle of oxide fuel. 6 refs., 10 figs

  9. Ancient genomics

    DEFF Research Database (Denmark)

    Der Sarkissian, Clio; Allentoft, Morten Erik; Avila Arcos, Maria del Carmen

    2015-01-01

    throughput of next generation sequencing platforms and the ability to target short and degraded DNA molecules. Many ancient specimens previously unsuitable for DNA analyses because of extensive degradation can now successfully be used as source materials. Additionally, the analytical power obtained...... by increasing the number of sequence reads to billions effectively means that contamination issues that have haunted aDNA research for decades, particularly in human studies, can now be efficiently and confidently quantified. At present, whole genomes have been sequenced from ancient anatomically modern humans...

  10. Marine genomics

    DEFF Research Database (Denmark)

    Oliveira Ribeiro, Ângela Maria; Foote, Andrew David; Kupczok, Anne

    2017-01-01

    Marine ecosystems occupy 71% of the surface of our planet, yet we know little about their diversity. Although the inventory of species is continually increasing, as registered by the Census of Marine Life program, only about 10% of the estimated two million marine species are known. This lag......-throughput sequencing approaches have been helping to improve our knowledge of marine biodiversity, from the rich microbial biota that forms the base of the tree of life to a wealth of plant and animal species. In this review, we present an overview of the applications of genomics to the study of marine life, from...

  11. The nature of inherent bactericidal activity: insights from the nanotopology of three species of dragonfly

    Science.gov (United States)

    Mainwaring, David E.; Nguyen, Song Ha; Webb, Hayden; Jakubov, Timur; Tobin, Mark; Lamb, Robert N.; Wu, Alex H.-F.; Marchant, Richard; Crawford, Russell J.; Ivanova, Elena P.

    2016-03-01

    While insect wings are widely recognised as multi-functional, recent work showed that this extends to extensive bactericidal activity brought about by cell deformation and lysis on the wing nanotopology. We now quantitatively show that subtle changes to this topography result in substantial changes in bactericidal activity that are able to span an order of magnitude. Notably, the chemical composition of the lipid nanopillars was seen by XPS and synchrotron FTIR microspectroscopy to be similar across these activity differences. Modelling the interaction between bacterial cells and the wing surface lipids of 3 species of dragonflies, that inhabit similar environments, but with distinctly different behavioural repertoires, provided the relationship between surface structure and antibacterial functionality. In doing so, these principal behavioural patterns correlated with the demands for antimicrobial efficiency dictated by differences in their foraging strategies. This work now reveals a new feature in the design elegance of natural multi-functional surfaces as well providing insights into the bactericidal mechanism underlying inherently antimicrobial materials, while suggesting that nanotopology is related to the evolutionary development of a species through the demands of its behavioural repertoire. The underlying relationship between the processes of wetting, adhesion and capillarity of the lipid nanopillars and bactericidal efficiency suggests new prospects for purely mechano-responsive antibacterial surfaces.While insect wings are widely recognised as multi-functional, recent work showed that this extends to extensive bactericidal activity brought about by cell deformation and lysis on the wing nanotopology. We now quantitatively show that subtle changes to this topography result in substantial changes in bactericidal activity that are able to span an order of magnitude. Notably, the chemical composition of the lipid nanopillars was seen by XPS and synchrotron

  12. Dissociable Changes of Frontal and Parietal Cortices in Inherent Functional Flexibility across the Human Life Span.

    Science.gov (United States)

    Yin, Dazhi; Liu, Wenjing; Zeljic, Kristina; Wang, Zhiwei; Lv, Qian; Fan, Mingxia; Cheng, Wenhong; Wang, Zheng

    2016-09-28

    Extensive evidence suggests that frontoparietal regions can dynamically update their pattern of functional connectivity, supporting cognitive control and adaptive implementation of task demands. However, it is largely unknown whether this flexibly functional reconfiguration is intrinsic and occurs even in the absence of overt tasks. Based on recent advances in dynamics of resting-state functional resonance imaging (fMRI), we propose a probabilistic framework in which dynamic reconfiguration of intrinsic functional connectivity between each brain region and others can be represented as a probability distribution. A complexity measurement (i.e., entropy) was used to quantify functional flexibility, which characterizes heterogeneous connectivity between a particular region and others over time. Following this framework, we identified both functionally flexible and specialized regions over the human life span (112 healthy subjects from 13 to 76 years old). Across brainwide regions, we found regions showing high flexibility mainly in the higher-order association cortex, such as the lateral prefrontal cortex (LPFC), lateral parietal cortex, and lateral temporal lobules. In contrast, visual, auditory, and sensory areas exhibited low flexibility. Furthermore, we observed that flexibility of the right LPFC improved during maturation and reduced due to normal aging, with the opposite occurring for the left lateral parietal cortex. Our findings reveal dissociable changes of frontal and parietal cortices over the life span in terms of inherent functional flexibility. This study not only provides a new framework to quantify the spatiotemporal behavior of spontaneous brain activity, but also sheds light on the organizational principle behind changes in brain function across the human life span. Recent neuroscientific research has demonstrated that the human capability of adaptive task control is primarily the result of the flexible operation of frontal brain networks. However

  13. No inherent left and right side in human 'mental number line': evidence from right brain damage.

    Science.gov (United States)

    Aiello, Marilena; Jacquin-Courtois, Sophie; Merola, Sheila; Ottaviani, Teresa; Tomaiuolo, Francesco; Bueti, Domenica; Rossetti, Yves; Doricchi, Fabrizio

    2012-08-01

    Spatial reasoning has a relevant role in mathematics and helps daily computational activities. It is widely assumed that in cultures with left-to-right reading, numbers are organized along the mental equivalent of a ruler, the mental number line, with small magnitudes located to the left of larger ones. Patients with right brain damage can disregard smaller numbers while mentally setting the midpoint of number intervals. This has been interpreted as a sign of spatial neglect for numbers on the left side of the mental number line and taken as a strong argument for the intrinsic left-to-right organization of the mental number line. Here, we put forward the understanding of this cognitive disability by discovering that patients with right brain damage disregard smaller numbers both when these are mapped on the left side of the mental number line and on the right side of an imagined clock face. This shows that the right hemisphere supports the representation of small numerical magnitudes independently from their mapping on the left or the right side of a spatial-mental layout. In addition, the study of the anatomical correlates through voxel-based lesion-symptom mapping and the mapping of lesion peaks on the diffusion tensor imaging-based reconstruction of white matter pathways showed that the rightward bias in the imagined clock-face was correlated with lesions of high-level middle temporal visual areas that code stimuli in object-centred spatial coordinates, i.e. stimuli that, like a clock face, have an inherent left and right side. In contrast, bias towards higher numbers on the mental number line was linked to white matter damage in the frontal component of the parietal-frontal number network. These anatomical findings show that the human brain does not represent the mental number line as an object with an inherent left and right side. We conclude that the bias towards higher numbers in the mental bisection of number intervals does not depend on left side spatial

  14. Underwater Inherent Optical Properties Estimation Using a Depth Aided Deep Neural Network

    Directory of Open Access Journals (Sweden)

    Zhibin Yu

    2017-01-01

    Full Text Available Underwater inherent optical properties (IOPs are the fundamental clues to many research fields such as marine optics, marine biology, and underwater vision. Currently, beam transmissometers and optical sensors are considered as the ideal IOPs measuring methods. But these methods are inflexible and expensive to be deployed. To overcome this problem, we aim to develop a novel measuring method using only a single underwater image with the help of deep artificial neural network. The power of artificial neural network has been proved in image processing and computer vision fields with deep learning technology. However, image-based IOPs estimation is a quite different and challenging task. Unlike the traditional applications such as image classification or localization, IOP estimation looks at the transparency of the water between the camera and the target objects to estimate multiple optical properties simultaneously. In this paper, we propose a novel Depth Aided (DA deep neural network structure for IOPs estimation based on a single RGB image that is even noisy. The imaging depth information is considered as an aided input to help our model make better decision.

  15. Simple frequency-dependent tools for analysis of inherent control limitations

    Directory of Open Access Journals (Sweden)

    Sigurd Skogestad

    1991-10-01

    Full Text Available By a plant's inherent control limitations we mean the characteristics of the plant which will cause poor control performance irrespective of what controller is used. Another frequently used term is 'dynamic resilience' which is the best closed-loop performance achievable using any controller. Since a plant's dynamic resilience cannot be altered by change of the control algorithm, but only by design modifications, it follows that the term controllability provides a link between process design and process control. In this paper we focus on two aspects of controllability. The plants' sensitivity to disturbances and the limitations imposed by interactions when using decentralized control. We use simple tools such as the RGA, the PRGA (Performance RGA and the closely related Closed Loop Disturbance Gain (CLDG. For example, if kth column of the CLDG is large, then this indicates that disturbance k will be difficult to reject. This may pinpoint the need for modifying the process. The PRGA provides a measure of interaction which also includes one-way coupling. In the paper we apply these measures to distillation column control and fluid catalytic cracker (FCC control.

  16. Distinct Short-Range Order Is Inherent to Small Amorphous Calcium Carbonate Clusters (<2 nm)

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Shengtong [Physical Chemistry, University of Konstanz, Universitätsstrasse 10 78457 Konstanz Germany; School of Chemical Engineering, State Key Laboratory of Chemical Engineering, Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, East China University of Science and Technology, 130 Meilong Road Shanghai 200237 P.R. China; Chevrier, Daniel M. [Department of Chemistry and Institute for Research in Materials, Dalhousie University, Halifax Nova Scotia B3H 4R2 Canada; Zhang, Peng [Department of Chemistry and Institute for Research in Materials, Dalhousie University, Halifax Nova Scotia B3H 4R2 Canada; Gebauer, Denis [Physical Chemistry, University of Konstanz, Universitätsstrasse 10 78457 Konstanz Germany; Cölfen, Helmut [Physical Chemistry, University of Konstanz, Universitätsstrasse 10 78457 Konstanz Germany

    2016-09-09

    Amorphous intermediate phases are vital precursors in the crystallization of many biogenic minerals. While inherent short-range orders have been found in amorphous calcium carbonates (ACCs) relating to different crystalline forms, it has never been clarified experimentally whether such orders already exist in very small clusters less than 2 nm in size. Here, we studied the stability and structure of 10,12-pentacosadiynoic acid (PCDA) protected ACC clusters with a core size of ca. 1.4 nm consisting of only seven CaCO3 units. Ligand concentration and structure are shown to be key factors in stabilizing the ACC clusters. More importantly, even in such small CaCO3 entities, a proto-calcite short-range order can be identified but with a relatively high degree of disorder that arises from the very small size of the CaCO3 core. Our findings support the notion of a structural link between prenucleation clusters, amorphous intermediates, and final crystalline polymorphs, which appears central to the understanding of polymorph selection.

  17. A Mechanistic Reliability Assessment of RVACS and Metal Fuel Inherent Reactivity Feedbacks

    Energy Technology Data Exchange (ETDEWEB)

    Grabaskas, David; Brunett, Acacia J.; Passerini, Stefano; Grelle, Austin

    2017-09-24

    GE Hitachi Nuclear Energy (GEH) and Argonne National Laboratory (Argonne) participated in a two year collaboration to modernize and update the probabilistic risk assessment (PRA) for the PRISM sodium fast reactor. At a high level, the primary outcome of the project was the development of a next-generation PRA that is intended to enable risk-informed prioritization of safety- and reliability-focused research and development. A central Argonne task during this project was a reliability assessment of passive safety systems, which included the Reactor Vessel Auxiliary Cooling System (RVACS) and the inherent reactivity feedbacks of the metal fuel core. Both systems were examined utilizing a methodology derived from the Reliability Method for Passive Safety Functions (RMPS), with an emphasis on developing success criteria based on mechanistic system modeling while also maintaining consistency with the Fuel Damage Categories (FDCs) of the mechanistic source term assessment. This paper provides an overview of the reliability analyses of both systems, including highlights of the FMEAs, the construction of best-estimate models, uncertain parameter screening and propagation, and the quantification of system failure probability. In particular, special focus is given to the methodologies to perform the analysis of uncertainty propagation and the determination of the likelihood of violating FDC limits. Additionally, important lessons learned are also reviewed, such as optimal sampling methodologies for the discovery of low likelihood failure events and strategies for the combined treatment of aleatory and epistemic uncertainties.

  18. Bayesian estimation inherent in a Mexican-hat-type neural network

    Science.gov (United States)

    Takiyama, Ken

    2016-05-01

    Brain functions, such as perception, motor control and learning, and decision making, have been explained based on a Bayesian framework, i.e., to decrease the effects of noise inherent in the human nervous system or external environment, our brain integrates sensory and a priori information in a Bayesian optimal manner. However, it remains unclear how Bayesian computations are implemented in the brain. Herein, I address this issue by analyzing a Mexican-hat-type neural network, which was used as a model of the visual cortex, motor cortex, and prefrontal cortex. I analytically demonstrate that the dynamics of an order parameter in the model corresponds exactly to a variational inference of a linear Gaussian state-space model, a Bayesian estimation, when the strength of recurrent synaptic connectivity is appropriately stronger than that of an external stimulus, a plausible condition in the brain. This exact correspondence can reveal the relationship between the parameters in the Bayesian estimation and those in the neural network, providing insight for understanding brain functions.

  19. Circumvention of inherent or acquired cytotoxic drug resistance in vitro using combinations of modulating agents.

    Science.gov (United States)

    Cadagan, David; Merry, Stephen

    2013-10-01

    Modulating agents are used to circumvent drug resistance in the clinical setting. However achievable serum concentrations are often lower than those which are optimal in vitro. Combination of modulating agents with non-overlapping toxicities may overcome this obstacle. We have investigated combinations of three modulating agents (quinine, verapamil, and cinnarizine) to circumvent inherent or acquired resistance to the cytotoxic drugs doxorubicin, vincristine and paclitaxel. Dose-response curves to cytotoxic drugs in the presence/absence of modulating agents were determined using colony formation and cell proliferation assays. Doxorubicin accumulation into cell monolayers was measured by fluorescence spectrophotometry. Greater (1.9-fold) sensitisation to particular cytotoxic drugs was observed for certain combinations of modulating agents compared to individual effects. The most effective combination was quinine-plus-verapamil with the cytotoxic drug doxorubicin. This increase in sensitivity was associated with increased doxorubicin accumulation. Such enhanced activity was, however, not observed for all combinations of modulating agents or for all studied cytotoxic drugs. The findings of the present study suggest certain combinations of modulating agents to have a clinical role in circumventing drug resistance. Particular combinations of modulating agents must be carefully chosen to suit particular cytotoxic drug treatments.

  20. Bionic Ears: Their Development and Future Advances Using Neurotrophins and Inherently Conducting Polymers

    Directory of Open Access Journals (Sweden)

    Graeme M. Clark

    2004-01-01

    Full Text Available The development of the multiple-channel bionic ear for hearing and speech understanding in profoundly deaf people is the result of integrating biological and physical sciences with engineering. It is the first clinically successful restoration of sensory and brain function, and brings electronic technology into a direct functional relationship with human consciousness. It presently transmits essential place and coarse temporal information for the coding of frequency, but the fine temporal and place excitation of groups of nerve fibres is inadequate for high-fidelity sound. This is required for adequate musical appreciation and hearing in noise. Research has demonstrated that nerve growth factors preserve the peripheral processes of the auditory nerves so that an electrode array placed close to these fibres could produce this fine temporal and spatial coding. The nerve growth factors can be incorporated into inherently conducting polymers that are part of the array so the peripheral processes can be preserved at the same time as they are electrically stimulated.

  1. Retrieving Marine Inherent Optical Properties from Satellites Using Temperature and Salinity-dependent Backscattering by Seawater

    Science.gov (United States)

    Werdell, Paul J.; Franz, Bryan Alden; Lefler, Jason Travis; Robinson, Wayne D.; Boss, Emmanuel

    2013-01-01

    Time-series of marine inherent optical properties (IOPs) from ocean color satellite instruments provide valuable data records for studying long-term time changes in ocean ecosystems. Semi-analytical algorithms (SAAs) provide a common method for estimating IOPs from radiometric measurements of the marine light field. Most SAAs assign constant spectral values for seawater absorption and backscattering, assume spectral shape functions of the remaining constituent absorption and scattering components (e.g., phytoplankton, non-algal particles, and colored dissolved organic matter), and retrieve the magnitudes of each remaining constituent required to match the spectral distribution of measured radiances. Here, we explore the use of temperature- and salinity-dependent values for seawater backscattering in lieu of the constant spectrum currently employed by most SAAs. Our results suggest that use of temperature- and salinity-dependent seawater spectra elevate the SAA-derived particle backscattering, reduce the non-algal particles plus colored dissolved organic matter absorption, and leave the derived absorption by phytoplankton unchanged.

  2. An analytic framework for developing inherently-manufacturable pop-up laminate devices

    International Nuclear Information System (INIS)

    Aukes, Daniel M; Goldberg, Benjamin; Wood, Robert J; Cutkosky, Mark R

    2014-01-01

    Spurred by advances in manufacturing technologies developed around layered manufacturing technologies such as PC-MEMS, SCM, and printable robotics, we propose a new analytic framework for capturing the geometry of folded composite laminate devices and the mechanical processes used to manufacture them. These processes can be represented by combining a small set of geometric operations which are general enough to encompass many different manufacturing paradigms. Furthermore, such a formulation permits one to construct a variety of geometric tools which can be used to analyze common manufacturability concepts, such as tool access, part removability, and device support. In order to increase the speed of development, reduce the occurrence of manufacturing problems inherent with current design methods, and reduce the level of expertise required to develop new devices, the framework has been implemented in a new design tool called popupCAD, which is suited for the design and development of complex folded laminate devices. We conclude with a demonstration of utility of the tools by creating a folded leg mechanism. (paper)

  3. Conservatism inherent to simplified qualification techniques used for piping steady state vibration

    International Nuclear Information System (INIS)

    Olson, D.E.; Smetters, J.L.

    1983-01-01

    This paper examines some of the qualification techniques currently used by the power industry, including the techniques specified in a recently issued standard related to this subject (ANSI/ASME OM-3, Requirements for Preoperational and Initial Startup Vibration Testing of Nuclear Power Plant Piping Systems). Several methods are used to demonstrate the amount of conservatism inherent in these techniques. Allowable limits calculated by the use of simplified techniques are compared to limits calculated by more detailed computer analysis. A portion of a reactor feedwater piping system along with the results of a piping vibration monitoring program recently completed in a nuclear power plant are used as case studies. The limits determined by the use of simplified criteria are also compared to limits determined empirically through the use of strain gauges. The simple beam analogies that use vibrational displacement as acceptance criteria were found to be conservative for all the examples studied. However, when velocity was used as a criterion, it was not always conservative. Simplified techniques that result in displacement allowables appear to be the most viable method of qualifying piping vibrations. Quantities referred to in the paper are cited in British units throughout. These may be converted to the International System of Units (SI) as follows: 1 foot=0.3048 meter; 1 inch=0.0254 meter=1,000 mils; 1 psi=6,894 pascals; and 1 inch/second=0.0254 meter/second. (orig.)

  4. Generalized Ocean Color Inversion Model for Retrieving Marine Inherent Optical Properties

    Science.gov (United States)

    Werdell, P. Jeremy; Franz, Bryan A.; Bailey, Sean W.; Feldman, Gene C.; Boss, Emmanuel; Brando, Vittorio E.; Dowell, Mark; Hirata, Takafumi; Lavender, Samantha J.; Lee, ZhongPing; hide

    2013-01-01

    Ocean color measured from satellites provides daily, global estimates of marine inherent optical properties (IOPs). Semi-analytical algorithms (SAAs) provide one mechanism for inverting the color of the water observed by the satellite into IOPs. While numerous SAAs exist, most are similarly constructed and few are appropriately parameterized for all water masses for all seasons. To initiate community-wide discussion of these limitations, NASA organized two workshops that deconstructed SAAs to identify similarities and uniqueness and to progress toward consensus on a unified SAA. This effort resulted in the development of the generalized IOP (GIOP) model software that allows for the construction of different SAAs at runtime by selection from an assortment of model parameterizations. As such, GIOP permits isolation and evaluation of specific modeling assumptions, construction of SAAs, development of regionally tuned SAAs, and execution of ensemble inversion modeling. Working groups associated with the workshops proposed a preliminary default configuration for GIOP (GIOP-DC), with alternative model parameterizations and features defined for subsequent evaluation. In this paper, we: (1) describe the theoretical basis of GIOP; (2) present GIOP-DC and verify its comparable performance to other popular SAAs using both in situ and synthetic data sets; and, (3) quantify the sensitivities of their output to their parameterization. We use the latter to develop a hierarchical sensitivity of SAAs to various model parameterizations, to identify components of SAAs that merit focus in future research, and to provide material for discussion on algorithm uncertainties and future ensemble applications.

  5. Chronic kidney disease: an inherent risk factor for acute kidney injury?

    Science.gov (United States)

    Singh, Prabhleen; Rifkin, Dena E; Blantz, Roland C

    2010-09-01

    Epidemiologic evidence suggests that chronic kidney disease (CKD) is a risk factor for acute kidney injury (AKI) due to the prevalence of CKD in patients who have episodes of AKI. However, the high burden of comorbidities such as age, diabetes, peripheral vascular, cardiovascular, and liver disease accompanying CKD, and the difficulties of defining AKI in the setting of CKD make these observations difficult to interpret. These comorbidities not only could alter the course of AKI but also may be the driving force behind the epidemiologic association between CKD and AKI because of systemic changes and/or increased exposure to potential nephrotoxic risks. Here, we contend that studies suggesting that CKD is a risk factor for AKI may suffer from residual confounding and reflect an overall susceptibility to illness rather than biologic susceptibility of the kidney parenchyma to injury. In support of our argument, we discuss the clinical evidence from epidemiologic studies, and the knowledge obtained from animal models on the pathophysiology of AKI and CKD, demonstrating a preconditioning influence of the previously impaired kidneys against subsequent injury. We conclude that, under careful analysis, factors apart from the inherent pathophysiology of the diseased kidney may be responsible for the increased frequency of AKI in CKD patients, and the impact of CKD on the risk and severity of AKI needs further investigation. Moreover, certain elements in the pathophysiology of a previously injured kidney may, surprisingly, bear out to be protective against AKI.

  6. Preliminary risk assessment of the Integral Inherently-Safe Light Water Reactor

    International Nuclear Information System (INIS)

    McCarroll, Kellen R.; Lee, John C.; Manera, Annalisa; Memmott, Matthew J.; Ferroni, Paolo

    2017-01-01

    The Integral, Inherently Safe Light Water Reactor (I 2 S-LWR) concept seeks to significantly increase nuclear power plant safety. The project implements a safety-by-design philosophy, eliminating several initiating events and providing novel, passive safety systems at the conceptual phase. Pursuit of unparalleled safety employs an integrated development process linking design with deterministic and probabilistic safety analyses. Unique aspects of the I 2 S-LWR concept and design process present challenges to the probabilistic risk assessment (PRA), particularly regarding overall flexibility, auditability and resolution of results. Useful approaches to initiating events and conditional failures are presented. To exemplify the risk-informed design process using PRA, a trade-off study of two safety system configurations is presented. Although further optimization is required, preliminary results indicate that the I 2 S-LWR can achieve a core damage frequency (CDF) from internal events less than 1.01 × 10 −8 /ry, including reactor vessel ruptures. Containment bypass frequency due to primary heat exchanger rupture is found to be comparable to non-vessel rupture CDF.

  7. Congenital short QT syndrome and implantable cardioverter defibrillator treatment: inherent risk for inappropriate shock delivery.

    Science.gov (United States)

    Schimpf, Rainer; Wolpert, Christian; Bianchi, Francesca; Giustetto, Carla; Gaita, Florenzo; Bauersfeld, Urs; Borggrefe, Martin

    2003-12-01

    A congenital short QT interval constitutes a new primary electrical abnormality associated with syncope and/or sudden cardiac death. We report on the initial use of implantable cardioverter defibrillator (ICD) therapy in patients with inherited short QT interval and discuss sensing abnormalities and detection issues. In five consecutive patients from two unrelated European families who had structurally normal hearts, excessively shortened QT intervals, and a strong positive family history of sudden cardiac death, ICDs were placed for primary and secondary prevention. Mean QT intervals were 252 +/- 13 ms (QTc 287 +/- 13 ms). Despite normal sensing behavior during intraoperative and postoperative device testing, 3 of 5 patients experienced inappropriate shock therapies for T wave oversensing 30 +/- 26 days after implantation. Programming lower sensitivities and decay delays prevented further inappropriate discharges. The congenital short QT syndrome constitutes a new clinical entity with an increased risk for sudden cardiac death. Currently, ICD treatment is the only therapeutic option. In patients with short QT interval and implanted ICD, increased risk for inappropriate therapy is inherent due to the detection of short-coupled and prominent T waves. Careful testing of ICD function and adaptation of sensing levels and decay delays without sacrificing correct arrhythmia detection are essential.

  8. Inherent Tumor Characteristics That Limit Effective and Safe Resection of Giant Nonfunctioning Pituitary Adenomas.

    Science.gov (United States)

    Nishioka, Hiroshi; Hara, Takayuki; Nagata, Yuichi; Fukuhara, Noriaki; Yamaguchi-Okada, Mitsuo; Yamada, Shozo

    2017-10-01

    Surgical treatment of giant pituitary adenomas is sometimes challenging. We present our surgical series of giant nonfunctioning adenomas to shed light on the limitations of effective and safe tumor resection. The preoperative tumor characteristics, surgical approaches, outcome, and histology of giant nonfunctioning adenoma (>40 mm) in 128 consecutive surgical patients are reviewed. The follow-up period ranged from 19 to 113 months (mean 62.2 months). A transsphenoidal approach was used in the treatment of 109 patients and a combined transsphenoidal transcranial approach in 19 patients. A total of 93 patients (72.7%) underwent total resection or subtotal resection apart from the cavernous sinus (CS). The degree of tumor resection, excluding the marked CS invasion, was lower in tumors that were larger (P = 0.0107), showed massive intracranial extension (P = 0.0352), and had an irregular configuration (P = 0.0016). Permanent surgical complications developed in 28 patients (22.0%). Long-term tumor control was achieved in all patients by single surgery, including 43 patients with adjuvant radiotherapy. Most tumors were histologically benign, with a low MIB-1 index (inherent factors that independently limit effective resection. These high-risk tumors require an individualized therapeutic strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Late-onset Alzheimer's disease is associated with inherent changes in bioenergetics profiles.

    Science.gov (United States)

    Sonntag, Kai-C; Ryu, Woo-In; Amirault, Kristopher M; Healy, Ryan A; Siegel, Arthur J; McPhie, Donna L; Forester, Brent; Cohen, Bruce M

    2017-10-25

    Body-wide changes in bioenergetics, i.e., energy metabolism, occur in normal aging and disturbed bioenergetics may be an important contributing mechanism underlying late-onset Alzheimer's disease (LOAD). We investigated the bioenergetic profiles of fibroblasts from LOAD patients and healthy controls, as a function of age and disease. LOAD cells exhibited an impaired mitochondrial metabolic potential and an abnormal redox potential, associated with reduced nicotinamide adenine dinucleotide metabolism and altered citric acid cycle activity, but not with disease-specific changes in mitochondrial mass, production of reactive oxygen species, transmembrane instability, or DNA deletions. LOAD fibroblasts demonstrated a shift in energy production to glycolysis, despite an inability to increase glucose uptake in response to IGF-1. The increase of glycolysis and the abnormal mitochondrial metabolic potential in LOAD appeared to be inherent, as they were disease- and not age-specific. Our findings support the hypothesis that impairment in multiple interacting components of bioenergetic metabolism may be a key mechanism contributing to the risk and pathophysiology of LOAD.

  10. Widespread protein aggregation as an inherent part of aging in C. elegans.

    Directory of Open Access Journals (Sweden)

    Della C David

    Full Text Available Aberrant protein aggregation is a hallmark of many age-related diseases, yet little is known about whether proteins aggregate with age in a non-disease setting. Using a systematic proteomics approach, we identified several hundred proteins that become more insoluble with age in the multicellular organism Caenorhabditis elegans. These proteins are predicted to be significantly enriched in beta-sheets, which promote disease protein aggregation. Strikingly, these insoluble proteins are highly over-represented in aggregates found in human neurodegeneration. We examined several of these proteins in vivo and confirmed their propensity to aggregate with age. Different proteins aggregated in different tissues and cellular compartments. Protein insolubility and aggregation were significantly delayed or even halted by reduced insulin/IGF-1-signaling, which also slows aging. We found a significant overlap between proteins that become insoluble and proteins that influence lifespan and/or polyglutamine-repeat aggregation. Moreover, overexpressing one aggregating protein enhanced polyglutamine-repeat pathology. Together our findings indicate that widespread protein insolubility and aggregation is an inherent part of aging and that it may influence both lifespan and neurodegenerative disease.

  11. Visual analytics of inherently noisy crowdsourced data on ultra high resolution displays

    Science.gov (United States)

    Huynh, Andrew; Ponto, Kevin; Lin, Albert Yu-Min; Kuester, Falko

    The increasing prevalence of distributed human microtasking, crowdsourcing, has followed the exponential increase in data collection capabilities. The large scale and distributed nature of these microtasks produce overwhelming amounts of information that is inherently noisy due to the nature of human input. Furthermore, these inputs create a constantly changing dataset with additional information added on a daily basis. Methods to quickly visualize, filter, and understand this information over temporal and geospatial constraints is key to the success of crowdsourcing. This paper present novel methods to visually analyze geospatial data collected through crowdsourcing on top of remote sensing satellite imagery. An ultra high resolution tiled display system is used to explore the relationship between human and satellite remote sensing data at scale. A case study is provided that evaluates the presented technique in the context of an archaeological field expedition. A team in the field communicated in real-time with and was guided by researchers in the remote visual analytics laboratory, swiftly sifting through incoming crowdsourced data to identify target locations that were identified as viable archaeological sites.

  12. Improvement of inherent safety features in CSR (Coupled Spectrum Reactor) for treating MA

    International Nuclear Information System (INIS)

    Aziz, F.; Kitamoto, Asashi.

    1996-01-01

    Burning and/or transmutation (B/T) of MA is proposed here using a CSR (Coupled Spectrum Reactor) concept. CSR was based on a modified conventional 1150 MWe-PWR system, and consisted of two core regions for thermal and fast neutrons, respectively. The B/T fuel used was supposed such that MA discharged from 1 GWe-LWR were mixed homogeneously in LWR fuel. The geometry of B/T fuel in the outer region was left the same with that of PWR, while in the inner region the B/T fuel was arranged in a tight-lattice geometry that allowed a higher fuel to coolant volume ratio, (V m /V f ). In order to improve its inherent safety features, several cases of CSR were studied and compared, each case used different fuel type in the inner region. The result of the calculations showed that safety features can be improved by using composite fuel of ( 235 U-Pu- 238 U) in the inner region. The equilibrium of main isotopes in CSR can be achieved after about 5 recycle stages. This study also showed that the CSR can burn and transmute MA up to 808 kg/stage in a single reactor operated with a reactivity swing of 2.8 % Δk/kk'. (author)

  13. Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells.

    Science.gov (United States)

    Huang, Szu-Han; Ren, Yanqin; Thomas, Allison S; Chan, Dora; Mueller, Stefanie; Ward, Adam R; Patel, Shabnum; Bollard, Catherine M; Cruz, Conrad Russell; Karandish, Sara; Truong, Ronald; Macedo, Amanda B; Bosque, Alberto; Kovacs, Colin; Benko, Erika; Piechocka-Trocha, Alicja; Wong, Hing; Jeng, Emily; Nixon, Douglas F; Ho, Ya-Chi; Siliciano, Robert F; Walker, Bruce D; Jones, R Brad

    2018-02-01

    The presence of persistent, latent HIV reservoirs in CD4+ T cells obstructs current efforts to cure infection. The so-called kick-and-kill paradigm proposes to purge these reservoirs by combining latency-reversing agents with immune effectors such as cytotoxic T lymphocytes. Support for this approach is largely based on success in latency models, which do not fully reflect the makeup of latent reservoirs in individuals on long-term antiretroviral therapy (ART). Recent studies have shown that CD8+ T cells have the potential to recognize defective proviruses, which comprise the vast majority of all infected cells, and that the proviral landscape can be shaped over time due to in vivo clonal expansion of infected CD4+ T cells. Here, we have shown that treating CD4+ T cells from ART-treated individuals with combinations of potent latency-reversing agents and autologous CD8+ T cells consistently reduced cell-associated HIV DNA, but failed to deplete replication-competent virus. These CD8+ T cells recognized and potently eliminated CD4+ T cells that were newly infected with autologous reservoir virus, ruling out a role for both immune escape and CD8+ T cell dysfunction. Thus, our results suggest that cells harboring replication-competent HIV possess an inherent resistance to CD8+ T cells that may need to be addressed to cure infection.

  14. Readjusting one's life in the tension inherent in work and motherhood.

    Science.gov (United States)

    Alstveit, Marit; Severinsson, Elisabeth; Karlsen, Bjørg

    2011-10-01

    This paper is a report on a study undertaken to interpret employed first-time mothers' experiences of returning to work after maternity leave, in a Norwegian context. Despite the increasing rate of employed fertile women and increasing welfare benefits to support the work-life balance, the first years after giving birth are described as being the most demanding on mothers' health. However, little is known about mothers' experiences of returning to work after maternity leave. The study included nine Norwegian employees who were individually interviewed during the first months after their return to work following maternity leave. The interviews were conducted during 2009 and interpreted using a method grounded in hermeneutics. Overall, the meaning of returning to work was interpreted as 'Readjusting one's life in the tension inherent in work and motherhood'. This comprehensive theme was based on three sub-themes: (a) Striving to manage the workload and taking responsibility for the best interests of the child, (b) Struggling with feelings of not being a good enough mother, and (c) Maintaining a balance between sensitivity and self-confidence. Returning to work after maternity leave appears to be a transitional phase that can be critical to the well-being of first-time mothers. To support women during this phase, employers and public health nurses should monitor the work in relation to the women's capacity and value their competence both as employees and mothers. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

  15. Underwater Inherent Optical Properties Estimation Using a Depth Aided Deep Neural Network.

    Science.gov (United States)

    Yu, Zhibin; Wang, Yubo; Zheng, Bing; Zheng, Haiyong; Wang, Nan; Gu, Zhaorui

    2017-01-01

    Underwater inherent optical properties (IOPs) are the fundamental clues to many research fields such as marine optics, marine biology, and underwater vision. Currently, beam transmissometers and optical sensors are considered as the ideal IOPs measuring methods. But these methods are inflexible and expensive to be deployed. To overcome this problem, we aim to develop a novel measuring method using only a single underwater image with the help of deep artificial neural network. The power of artificial neural network has been proved in image processing and computer vision fields with deep learning technology. However, image-based IOPs estimation is a quite different and challenging task. Unlike the traditional applications such as image classification or localization, IOP estimation looks at the transparency of the water between the camera and the target objects to estimate multiple optical properties simultaneously. In this paper, we propose a novel Depth Aided (DA) deep neural network structure for IOPs estimation based on a single RGB image that is even noisy. The imaging depth information is considered as an aided input to help our model make better decision.

  16. Uncovering inherent cellular plasticity of multiciliated ependyma leading to ventricular wall transformation and hydrocephalus.

    Science.gov (United States)

    Abdi, Khadar; Lai, Chun-Hsiang; Paez-Gonzalez, Patricia; Lay, Mark; Pyun, Joon; Kuo, Chay T

    2018-04-25

    Specialized, differentiated cells often perform unique tasks that require them to maintain a stable phenotype. Multiciliated ependymal cells (ECs) are unique glial cells lining the brain ventricles, important for cerebral spinal fluid circulation. While functional ECs are needed to prevent hydrocephalus, they have also been reported to generate new neurons: whether ECs represent a stable cellular population remains unclear. Via a chemical screen we found that mature ECs are inherently plastic, with their multiciliated state needing constant maintenance by the Foxj1 transcription factor, which paradoxically is rapidly turned over by the ubiquitin-proteasome system leading to cellular de-differentiation. Mechanistic analyses revealed a novel NF-κB-independent IKK2 activity stabilizing Foxj1 in mature ECs, and we found that known IKK2 inhibitors including viruses and growth factors robustly induced Foxj1 degradation, EC de-differentiation, and hydrocephalus. Although mature ECs upon de-differentiation can divide and regenerate multiciliated ECs, we did not detect evidence supporting EC's neurogenic potential.

  17. The Development and Evaluation of Inherent RPCS for the APR1400

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jae D.; Ryu, Seok H.; Jung, Dong C.; Kim, Joon S.; Baek, Byung C.; Sung, Song K.; You, Guk J. [KNF, Daejeon (Korea, Republic of); Kim, Han G. [KHNP, Daejeon (Korea, Republic of); Chi, Sung G. [KOPEC, Daejeon (Korea, Republic of)

    2008-10-15

    The APR1400 RPCS (Reactor Power Cutback System) is designed to rapidly reduce the core power to eliminate the need for a reactor trip following a large load rejection or a loss of two main feedwater pumps at high power. GDC (General Design Criteria) 25 says 'Protection system requirements for reactivity control malfunctions. The protection system shall be designed to assure that SAFDL (Specified Acceptable Fuel Design Limits) are not exceeded for any single malfunction of the reactivity control systems, such as accidental withdrawal (not ejection or dropout) of control rods.' In order to comply GDC 25, CPCS (Core Protection Calculator System) will apply a big power penalty({approx} 1.3) to determine the minimum DNBR (Departure from Nucleate Boiling Ratio), the maximum LPD(Local Power Density) and reactor may immediately trip by CPCS low DNBR and high LPD during high power operation for 12-finger CEA drop. The purpose of this study is to develop the inherent RPCS to avoid unwanted reactor trips due to a 12-finger CEA drop. In order to accomplish this purpose, the CPCS should be modified to send RPCS actuation signal and not to apply power penalty due to 12-finger CEA drop for a shot period. During this period which is determined by assessment of safety, the SAFDL will not be violated without any CPCS trip function. The system and CPCS performance is evaluated to verify that CPCS trip does not occurred during 12-finger CEA drop event.

  18. Stable Regulation of Cell Cycle Events in Mycobacteria: Insights From Inherently Heterogeneous Bacterial Populations.

    Science.gov (United States)

    Logsdon, Michelle M; Aldridge, Bree B

    2018-01-01

    Model bacteria, such as E. coli and B. subtilis , tightly regulate cell cycle progression to achieve consistent cell size distributions and replication dynamics. Many of the hallmark features of these model bacteria, including lateral cell wall elongation and symmetric growth and division, do not occur in mycobacteria. Instead, mycobacterial growth is characterized by asymmetric polar growth and division. This innate asymmetry creates unequal birth sizes and growth rates for daughter cells with each division, generating a phenotypically heterogeneous population. Although the asymmetric growth patterns of mycobacteria lead to a larger variation in birth size than typically seen in model bacterial populations, the cell size distribution is stable over time. Here, we review the cellular mechanisms of growth, division, and cell cycle progression in mycobacteria in the face of asymmetry and inherent heterogeneity. These processes coalesce to control cell size. Although Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) utilize a novel model of cell size control, they are similar to previously studied bacteria in that initiation of DNA replication is a key checkpoint for cell division. We compare the regulation of DNA replication initiation and strategies used for cell size homeostasis in mycobacteria and model bacteria. Finally, we review the importance of cellular organization and chromosome segregation relating to the physiology of mycobacteria and consider how new frameworks could be applied across the wide spectrum of bacterial diversity.

  19. Stable Regulation of Cell Cycle Events in Mycobacteria: Insights From Inherently Heterogeneous Bacterial Populations

    Directory of Open Access Journals (Sweden)

    Michelle M. Logsdon

    2018-03-01

    Full Text Available Model bacteria, such as E. coli and B. subtilis, tightly regulate cell cycle progression to achieve consistent cell size distributions and replication dynamics. Many of the hallmark features of these model bacteria, including lateral cell wall elongation and symmetric growth and division, do not occur in mycobacteria. Instead, mycobacterial growth is characterized by asymmetric polar growth and division. This innate asymmetry creates unequal birth sizes and growth rates for daughter cells with each division, generating a phenotypically heterogeneous population. Although the asymmetric growth patterns of mycobacteria lead to a larger variation in birth size than typically seen in model bacterial populations, the cell size distribution is stable over time. Here, we review the cellular mechanisms of growth, division, and cell cycle progression in mycobacteria in the face of asymmetry and inherent heterogeneity. These processes coalesce to control cell size. Although Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG utilize a novel model of cell size control, they are similar to previously studied bacteria in that initiation of DNA replication is a key checkpoint for cell division. We compare the regulation of DNA replication initiation and strategies used for cell size homeostasis in mycobacteria and model bacteria. Finally, we review the importance of cellular organization and chromosome segregation relating to the physiology of mycobacteria and consider how new frameworks could be applied across the wide spectrum of bacterial diversity.

  20. Architecture and inherent robustness of a bacterial cell-cycle control system.

    Science.gov (United States)

    Shen, Xiling; Collier, Justine; Dill, David; Shapiro, Lucy; Horowitz, Mark; McAdams, Harley H

    2008-08-12

    A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory proteins with tight coupling to processive chromosome replication and cell division subsystems. We report a hybrid simulation of the coupled cell-cycle control system, including asymmetric cell division and responses to external starvation signals, that replicates mRNA and protein concentration patterns and is consistent with observed mutant phenotypes. An asynchronous sequential digital circuit model equivalent to the validated simulation model was created. Formal model-checking analysis of the digital circuit showed that the cell-cycle control is robust to intrinsic stochastic variations in reaction rates and nutrient supply, and that it reliably stops and restarts to accommodate nutrient starvation. Model checking also showed that mechanisms involving methylation-state changes in regulatory promoter regions during DNA replication increase the robustness of the cell-cycle control. The hybrid cell-cycle simulation implementation is inherently extensible and provides a promising approach for development of whole-cell behavioral models that can replicate the observed functionality of the cell and its responses to changing environmental conditions.

  1. Computability, Gödel's incompleteness theorem, and an inherent limit on the predictability of evolution.

    Science.gov (United States)

    Day, Troy

    2012-04-07

    The process of evolutionary diversification unfolds in a vast genotypic space of potential outcomes. During the past century, there have been remarkable advances in the development of theory for this diversification, and the theory's success rests, in part, on the scope of its applicability. A great deal of this theory focuses on a relatively small subset of the space of potential genotypes, chosen largely based on historical or contemporary patterns, and then predicts the evolutionary dynamics within this pre-defined set. To what extent can such an approach be pushed to a broader perspective that accounts for the potential open-endedness of evolutionary diversification? There have been a number of significant theoretical developments along these lines but the question of how far such theory can be pushed has not been addressed. Here a theorem is proven demonstrating that, because of the digital nature of inheritance, there are inherent limits on the kinds of questions that can be answered using such an approach. In particular, even in extremely simple evolutionary systems, a complete theory accounting for the potential open-endedness of evolution is unattainable unless evolution is progressive. The theorem is closely related to Gödel's incompleteness theorem, and to the halting problem from computability theory.

  2. Ensembl Genomes 2016: more genomes, more complexity.

    Science.gov (United States)

    Kersey, Paul Julian; Allen, James E; Armean, Irina; Boddu, Sanjay; Bolt, Bruce J; Carvalho-Silva, Denise; Christensen, Mikkel; Davis, Paul; Falin, Lee J; Grabmueller, Christoph; Humphrey, Jay; Kerhornou, Arnaud; Khobova, Julia; Aranganathan, Naveen K; Langridge, Nicholas; Lowy, Ernesto; McDowall, Mark D; Maheswari, Uma; Nuhn, Michael; Ong, Chuang Kee; Overduin, Bert; Paulini, Michael; Pedro, Helder; Perry, Emily; Spudich, Giulietta; Tapanari, Electra; Walts, Brandon; Williams, Gareth; Tello-Ruiz, Marcela; Stein, Joshua; Wei, Sharon; Ware, Doreen; Bolser, Daniel M; Howe, Kevin L; Kulesha, Eugene; Lawson, Daniel; Maslen, Gareth; Staines, Daniel M

    2016-01-04

    Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including reference sequence, gene models, transcriptional data, genetic variation and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments. These include the development of new analyses and views to represent polyploid genomes (of which bread wheat is the primary exemplar); and the continued up-scaling of the resource, which now includes over 23 000 bacterial genomes, 400 fungal genomes and 100 protist genomes, in addition to 55 genomes from invertebrate metazoa and 39 genomes from plants. This dramatic increase in the number of included genomes is one part of a broader effort to automate the integration of archival data (genome sequence, but also associated RNA sequence data and variant calls) within the context of reference genomes and make it available through the Ensembl user interfaces. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Rodent malaria parasites : genome organization & comparative genomics

    NARCIS (Netherlands)

    Kooij, Taco W.A.

    2006-01-01

    The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P.

  4. Predicting welding distortion in a panel structure with longitudinal stiffeners using inherent deformations obtained by inverse analysis method.

    Science.gov (United States)

    Liang, Wei; Murakawa, Hidekazu

    2014-01-01

    Welding-induced deformation not only negatively affects dimension accuracy but also degrades the performance of product. If welding deformation can be accurately predicted beforehand, the predictions will be helpful for finding effective methods to improve manufacturing accuracy. Till now, there are two kinds of finite element method (FEM) which can be used to simulate welding deformation. One is the thermal elastic plastic FEM and the other is elastic FEM based on inherent strain theory. The former only can be used to calculate welding deformation for small or medium scale welded structures due to the limitation of computing speed. On the other hand, the latter is an effective method to estimate the total welding distortion for large and complex welded structures even though it neglects the detailed welding process. When the elastic FEM is used to calculate the welding-induced deformation for a large structure, the inherent deformations in each typical joint should be obtained beforehand. In this paper, a new method based on inverse analysis was proposed to obtain the inherent deformations for weld joints. Through introducing the inherent deformations obtained by the proposed method into the elastic FEM based on inherent strain theory, we predicted the welding deformation of a panel structure with two longitudinal stiffeners. In addition, experiments were carried out to verify the simulation results.

  5. Factors contributing to inherent varus alignment of lower limb in normal Asian adults: role of tibial plateau inclination.

    Science.gov (United States)

    Shetty, Gautam M; Mullaji, Arun; Bhayde, Sagar; Nha, Kyung Wook; Oh, Hyoung Keun

    2014-03-01

    This prospective study aimed to evaluate radiographically, mechanical or hip-knee-ankle (HKA) axis in healthy, asymptomatic, Asian (Indian and Korean) adults between 20 and 40 years of age to determine the incidence of inherent varus (mechanical limb alignment of >3° varus) and the factors influencing it. Three hundred and eighty-eight lower limbs were evaluated using full length, standing hip-to-ankle radiographs in 198 healthy, asymptomatic, Asian (Indian and Korean) adults between 20 and 40 years of age to assess the hip-knee-ankle (HKA) angle, medial proximal tibial angle (MPTA), femoral bowing and femoral neck-shaft angle to determine the incidence of inherent varus (mechanical limb alignment of >3° varus) and the factors influencing it. Overall, the mean HKA angle was 177.6°±2.6° with 34.5% of limbs in inherent varus (mean HKA angle 174.9°±1.8°). The incidence of inherent varus was significantly higher (p=0.01) in males (40%) compared to females (28%) but similar among Indian (34%) and Korean subjects (35%). The hip-knee-ankle (HKA) angle showed significant positive correlation (r=0.82, palignment of the lower limb is fairly common among asymptomatic, Asian adults. These results raise several pertinent questions regarding the role of inherent varus in the aetiopathogenesis of knee osteoarthritis and in lower limb realignment procedures. © 2013 Elsevier B.V. All rights reserved.

  6. Identification and characterization of passive safety system and inherent safety feature building blocks for advanced light-water reactors

    International Nuclear Information System (INIS)

    Forsberg, C.W.

    1989-01-01

    Oak Ridge National Laboratory (ORNL) is investigating passive and inherent safety options for Advanced Light-Water Reactors (ALWRs). A major activity in 1989 includes identification and characterization of passive safety system and inherent safety feature building blocks, both existing and proposed, for ALWRs. Preliminary results of this work are reported herein. This activity is part of a larger effort by the US Department of Energy, reactor vendors, utilities, and others in the United States to develop improved LWRs. The Advanced Boiling Water Reactor (ABWR) program and the Advanced Pressurized Water Reactor (APWR) program have as goals improved, commercially available LWRs in the early 1990s. The Advanced Simplified Boiling Water Reactor (ASBWR) program and the AP-600 program are developing more advanced reactors with increased use of passive safety systems. It is planned that these reactors will become commercially available in the mid 1990s. The ORNL program is an exploratory research program for LWRs beyond the year 2000. Desired long-term goals for such reactors include: (1) use of only passive and inherent safety, (2) foolproof against operator errors, (3) malevolence resistance against internal sabotage and external assault and (4) walkaway safety. The acronym ''PRIME'' [Passive safety, Resilient operation, Inherent safety, Malevolence resistance, and Extended (walkaway) safety] is used to summarize these desired characteristics. Existing passive and inherent safety options are discussed in this document

  7. Sexual violence, HSV-2 and HIV are important predictors for infertility in Rwanda

    NARCIS (Netherlands)

    Dhont, N.; van de Wijgert, J.; Luchters, S.; Muvunyi, C.; Vyankandondera, J.; Temmerman, M.

    2010-01-01

    In order to formulate cost-effective health interventions aimed at preventing infertility it is necessary to identify modifiable risk factors for infertility in sub-Saharan Africa. This case-control study examined potential predictors and their population attributable fraction (PAF%) for various

  8. Inherently variable responses to glucocorticoid stress among endogenous retroviruses isolated from 23 mouse strains.

    Science.gov (United States)

    Hsu, Karen; Lee, Young-Kwan; Chew, Alex; Chiu, Sophia; Lim, Debora; Greenhalgh, David G; Cho, Kiho

    2017-10-01

    Active participation of endogenous retroviruses (ERVs) in disease processes has been exemplified by the finding that the HERV (human ERV)-W envelope protein is involved in the pathogenesis of multiple sclerosis, an autoimmune disease. We also demonstrated that injury-elicited stressors alter the expression of murine ERVs (MuERVs), both murine leukemia virus-type and mouse mammary tumor virus (MMTV)-type (MMTV-MuERV). In this study, to evaluate MMTV-MuERVs' responses to stress (e.g., injury, infection)-elicited systemic glucocorticoid (GC) levels, we examined the GC-stress response of 64 MMTV-MuERV promoters isolated from the genomes of 23 mouse strains. All 64 promoters responded to treatment with a synthetic GC, dexamethasone (DEX), at a wide range from a 0.6- to 85.7-fold increase in reporter activity compared to no treatment. An analysis of the 10 lowest and 10 highest DEX responders revealed specific promoter elements exclusively present in either the three lowest or the two highest responders. Each promoter had a unique profile of transcription regulatory elements and the glucocorticoid response element (GRE) was identified in all promoters with the number of GREs ranging from 2 to 7. The three lowest DEX responders were the only promoters with two GREs. The findings from this study suggest that certain MMTV-MuERVs are more responsive to stress-elicited systemic GC elevation compared to the others. The mouse strain-specific genomic MMTV-MuERV profiles and individual MMTV-MuERVs' differential responses to GC-stress might explain, at least in part, the variable inflammatory responses to injury and/or infection, often observed among different mouse strains. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis edited by Dr. Raghavan Raju. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Improving Coastal Ocean Color Validation Capabilities through Application of Inherent Optical Properties (IOPs)

    Science.gov (United States)

    Mannino, Antonio

    2008-01-01

    Understanding how the different components of seawater alter the path of incident sunlight through scattering and absorption is essential to using remotely sensed ocean color observations effectively. This is particularly apropos in coastal waters where the different optically significant components (phytoplankton, detrital material, inorganic minerals, etc.) vary widely in concentration, often independently from one another. Inherent Optical Properties (IOPs) form the link between these biogeochemical constituents and the Apparent Optical Properties (AOPs). understanding this interrelationship is at the heart of successfully carrying out inversions of satellite-measured radiance to biogeochemical properties. While sufficient covariation of seawater constituents in case I waters typically allows empirical algorithms connecting AOPs and biogeochemical parameters to behave well, these empirical algorithms normally do not hold for case I1 regimes (Carder et al. 2003). Validation in the context of ocean color remote sensing refers to in-situ measurements used to verify or characterize algorithm products or any assumption used as input to an algorithm. In this project, validation capabilities are considered those measurement capabilities, techniques, methods, models, etc. that allow effective validation. Enhancing current validation capabilities by incorporating state-of-the-art IOP measurements and optical models is the purpose of this work. Involved in this pursuit is improving core IOP measurement capabilities (spectral, angular, spatio-temporal resolutions), improving our understanding of the behavior of analytical AOP-IOP approximations in complex coastal waters, and improving the spatial and temporal resolution of biogeochemical data for validation by applying biogeochemical-IOP inversion models so that these parameters can be computed from real-time IOP sensors with high sampling rates. Research cruises supported by this project provides for collection and

  10. The in vitro digestibility of beef varies with its inherent ultimate pH.

    Science.gov (United States)

    Farouk, Mustafa M; Wu, Guojie; Frost, Deborah A; Clerens, Stefan; Knowles, Scott O

    2014-11-01

    Animal carcasses and cuts of meat are usually differentiated and valued according to size and compositional attributes. An underappreciated variable of red meat is its inherent ultimate pH (pHu) value, which affects organoleptic and processing characteristics. This study tests the hypothesis that high pHu aged meat would be more digestible than low pHu unaged (fresh) meat. Longissimus dorsi muscles collected from 59 bull carcasses had pHu values of 5.6-6.9. These were aged for 21 days at -1.5 °C, then raw and cooked (72 °C) samples were enzymatically digested at 37 °C with pepsin (pH 1.9 for 90 min) followed by pancreatin (pH 8.0 for an additional 120 min) to simulate conditions in the stomach and small intestine, respectively. Meat proteins and peptides in the digests were separated by 1D SDS PAGE. Regardless of pHu, ageing or cooking, most sarcoplasmic and myofibrillar proteins were rapidly digested by pepsin, with concomitant release of products identified by LC-MS/MS as mainly myosin-1, -2 and -7, α-actinin-2 or -3 and tropomyosin beta and alpha chains. These products were resistant to further digestion for the entire 210 min duration of the incubation. In terms of rate and extent of digestibility of these resistant products, high pHu > low pHu (P unaged (P meat samples increased with increasing pHu (P meat was highly digestible but could be further differentiated on the basis of its pHu and the ease of digestibility of proteins. Specific carcasses or cuts could be targeted to consumer groups in order to provide benefits and add value.

  11. An optimized power conversion system concept of the integral, inherently-safe light water reactor

    International Nuclear Information System (INIS)

    Memmott, Matthew J.; Wilding, Paul R.; Petrovic, Bojan

    2017-01-01

    Highlights: • Three power conversion systems (PCS) for the I"2S-LWR are presented. • An optimization analyses was performed to evaluate these PCS alternatives. • The ideal PCS consists of 5 turbines, and obtains an overall efficiency of 35.7%. - Abstract: The integral, inherently safe light water reactor (I"2S-LWR) has been developed to significantly enhance passive safety capabilities while maintaining cost competitiveness relative to the current light water reactor (LWR) fleet. The compact heat exchangers of the I"2S-LWR preclude boiling of the secondary fluid, which decreases the probability of heat exchanger failure, but this requires the addition of a flash drum, which negatively affects the overall plant thermodynamic efficiency. A state of the art Rankine cycle is proposed for the I"2S-LWR to increase the thermodynamic efficiency by utilizing a flash drum with optimized operational parameters. In presenting this option for power conversion in the I"2S-LWR power plant, the key metric used in rating the performance is the overall net thermodynamic efficiency of the cycle. In evaluating the flash-Rankine cycle, three basic industrial concepts are evaluated, one without an intermediate pressure turbine, one with an intermediate turbine and one reheat stream, and one with an intermediate turbine and two reheat streams. For each configuration, a single-path multi-variable optimization is undertaken to maximize the thermal efficiency. The third configuration with an intermediate turbine and 2 reheat streams is the most effective concept, with an optimized efficiency of 35.7%.

  12. Impact of calcification state on the inherent optical properties of Emiliania huxleyi coccoliths and coccolithophores

    Science.gov (United States)

    Bi, Lei; Yang, Ping

    2015-04-01

    Understanding the inherent optical properties (IOPs) of coccoliths and coccolithophores is important in oceanic radiative transfer simulations and remote sensing implementations. In this study, the invariant imbedding T-matrix method (II-TM) is employed to investigate the IOPs of coccoliths and coccolithophores. The Emiliania huxleyi (Ehux) coccolith and coccolithophore models are built based on observed biometric parameters including the eccentricity, the number of slits, and the rim width of detached coccoliths. The calcification state that specifies the amount of calcium of a single coccolith is critical in the determination of the size-volume/mass relationship (note, the volume/mass of coccoltihs at different calcification states are different although the diameters are the same). The present results show that the calcification state, namely, under-calcification, normal-calcification, or over-calcification, significantly influences the backscattering cross section and the phase matrix. Furthermore, the linear depolarization ratio of the light scattered by coccoliths is sensitive to the degree of calcification, and provides a potentially valuable parameter for interpreting oceanic remote sensing data. The phase function of an ensemble of randomly oriented coccolithophores has a similar pattern to that of individual coccoliths, but the forward scattering is dominant in the coccolithophores due to the large geometric cross sections. The linear depolarization ratio associated with coccolithophores is found to be larger than that for coccoliths as polarization is more sensitive to multiple scattering than the phase function. The simulated coccolithophore phase matrix numerical results are compared with laboratory measurements. For scattering angles larger than 100°, an increase of the phase function with respect to the scattering angle is confirmed based on the present coccolithophore model while the spherical approximation fails.

  13. Impact of calcification state on the inherent optical properties of Emiliania huxleyi coccoliths and coccolithophores

    International Nuclear Information System (INIS)

    Bi, Lei; Yang, Ping

    2015-01-01

    Understanding the inherent optical properties (IOPs) of coccoliths and coccolithophores is important in oceanic radiative transfer simulations and remote sensing implementations. In this study, the invariant imbedding T-matrix method (II-TM) is employed to investigate the IOPs of coccoliths and coccolithophores. The Emiliania huxleyi (Ehux) coccolith and coccolithophore models are built based on observed biometric parameters including the eccentricity, the number of slits, and the rim width of detached coccoliths. The calcification state that specifies the amount of calcium of a single coccolith is critical in the determination of the size–volume/mass relationship (note, the volume/mass of coccoltihs at different calcification states are different although the diameters are the same). The present results show that the calcification state, namely, under-calcification, normal-calcification, or over-calcification, significantly influences the backscattering cross section and the phase matrix. Furthermore, the linear depolarization ratio of the light scattered by coccoliths is sensitive to the degree of calcification, and provides a potentially valuable parameter for interpreting oceanic remote sensing data. The phase function of an ensemble of randomly oriented coccolithophores has a similar pattern to that of individual coccoliths, but the forward scattering is dominant in the coccolithophores due to the large geometric cross sections. The linear depolarization ratio associated with coccolithophores is found to be larger than that for coccoliths as polarization is more sensitive to multiple scattering than the phase function. The simulated coccolithophore phase matrix numerical results are compared with laboratory measurements. For scattering angles larger than 100°, an increase of the phase function with respect to the scattering angle is confirmed based on the present coccolithophore model while the spherical approximation fails. - Highlights: • Realistic

  14. Measuring situational awareness and resolving inherent high-level fusion obstacles

    Science.gov (United States)

    Sudit, Moises; Stotz, Adam; Holender, Michael; Tagliaferri, William; Canarelli, Kathie

    2006-04-01

    Information Fusion Engine for Real-time Decision Making (INFERD) is a tool that was developed to supplement current graph matching techniques in Information Fusion models. Based on sensory data and a priori models, INFERD dynamically generates, evolves, and evaluates hypothesis on the current state of the environment. The a priori models developed are hierarchical in nature lending them to a multi-level Information Fusion process whose primary output provides a situational awareness of the environment of interest in the context of the models running. In this paper we look at INFERD's multi-level fusion approach and provide insight on the inherent problems such as fragmentation in the approach and the research being undertaken to mitigate those deficiencies. Due to the large variance of data in disparate environments, the awareness of situations in those environments can be drastically different. To accommodate this, the INFERD framework provides support for plug-and-play fusion modules which can be developed specifically for domains of interest. However, because the models running in INFERD are graph based, some default measurements can be provided and will be discussed in the paper. Among these are a Depth measurement to determine how much danger is presented by the action taking place, a Breadth measurement to gain information regarding the scale of an attack that is currently happening, and finally a Reliability measure to tell the user the credibility of a particular hypothesis. All of these results will be demonstrated in the Cyber domain where recent research has shown to be an area that is welldefined and bounded, so that new models and algorithms can be developed and evaluated.

  15. Demonstrated operational and inherent safety of the prototype fast reactor (PFR)

    International Nuclear Information System (INIS)

    Smedley, J.A.; Gregory, C.V.; Judd, A.M.

    1983-01-01

    The Prototype Fast Reactor (PFR) is sited at Dounreay, on the north coast of Scotland in the United Kingdom, and has been in operation since 1974. Three aspects of the safety of the reactor are described, including the all-important practical consideration of operational safety, a demonstration of the limited consequences of a sodium/water reaction in a steam generator and the ability of the reactor to protect itself against highly improbable incidents. Attention is drawn to the low radiation levels in the plant and the correspondingly low dose rate to personnel. A feature of PFR operation has been the stable and predictable behaviour of its core together with the high degree of reliability exhibited by the engineered safety system. No failures have occurred within the standard driver charge but two experimental fuel pins suffered cladding failure, which was detected easily by the fission gas and delayed neutron detection systems. In the steam generating units sodium and water are separated by the single steel wall of the steam tubes. Although no under-sodium leak has occurred, an experimental programme is continuing and demonstrates that were any such leak to occur its consequences would be containable and would not result in the release of sodium to the environment or any breach of the reactor containment. The final section describes the inherent safety features of the reactor which enable it to survive a range of very improbable incidents even when the engineered safeguards fail. The features considered are natural circulation, which has been demonstrated by reactor experiment; the reactor's negative power coefficient, which, for example, enables the reactor to survive a complete loss of heat sink; and the durability of the fuel pins, demonstrated by a series of boiling experiments in the Dounreay Fast Reactor (DFR). (author)

  16. Influence of the inherent properties of drinking water treatment residuals on their phosphorus adsorption capacities.

    Science.gov (United States)

    Bai, Leilei; Wang, Changhui; He, Liansheng; Pei, Yuansheng

    2014-12-01

    Batch experiments were conducted to investigate the phosphorus (P) adsorption and desorption on five drinking water treatment residuals (WTRs) collected from different regions in China. The physical and chemical characteristics of the five WTRs were determined. Combined with rotated principal component analysis, multiple regression analysis was used to analyze the relationship between the inherent properties of the WTRs and their P adsorption capacities. The results showed that the maximum P adsorption capacities of the five WTRs calculated using the Langmuir isotherm ranged from 4.17 to 8.20mg/g at a pH of 7 and further increased with a decrease in pH. The statistical analysis revealed that a factor related to Al and 200 mmol/L oxalate-extractable Al (Alox) accounted for 36.5% of the variations in the P adsorption. A similar portion (28.5%) was attributed to an integrated factor related to the pH, Fe, 200 mmol/L oxalate-extractable Fe (Feox), surface area and organic matter (OM) of the WTRs. However, factors related to other properties (Ca, P and 5 mmol/L oxalate-extractable Fe and Al) were rejected. In addition, the quantity of P desorption was limited and had a significant negative correlation with the (Feox+Alox) of the WTRs (p<0.05). Overall, WTRs with high contents of Alox, Feox and OM as well as large surface areas were proposed to be the best choice for P adsorption in practical applications. Copyright © 2014. Published by Elsevier B.V.

  17. Inherent and passive safety measures in accelerator driven systems: a safety strategy for ADS

    International Nuclear Information System (INIS)

    Maschek, W.; Rineiski, A.; Morita, K.; Flad, M.

    2001-01-01

    The efficiency of Accelerator Driven Systems (ADSs) for the transmutation and incineration of nuclear waste is strongly related to the utilization of so-called dedicated fuels. In the ideal case these fuels should consist of pure TRUs without fertile materials as 238 U or 232 Th to achieve highest incineration/transmutation rates. Dedicated fuels still have to be developed and programs are under way for their fabrication, irradiation and testing. These fertile-free fuels may suffer from deteriorated thermal or thermo-mechanical properties, as a reduced melting point, reduced thermal conductivity or even thermal instability. First analyses have shown that the use of dedicated fuels may lead to a strong deterioration of the safety parameters of the reactor core as e.g. the void worth, the Doppler or the kinetics quantities as neutron generation time and β eff . In addition, a dedicated core may contain multiple ''critical'' fuel masses, resulting in a considerable recriticality potential. Current knowledge on these dedicated fuels suggests that ''critical'' reactors may not be feasible, because of safety reasons. However, for ADSs, the salient hope has been promoted that due to the subcriticality of the system the poor safety features of such fuels could be coped with. Analyses are presented which show potential safety problems for such dedicated cores. Respecting the results of these analyses a safety strategy is proposed along the lines of defense approach in analogy with ideas formerly developed for fast reactors. Inherent and passive safety measures are integrated into the various defense lines. (author)

  18. The hype cycle in 3D displays: inherent limits of autostereoscopy

    Science.gov (United States)

    Grasnick, Armin

    2013-06-01

    Since a couple of years, a renaissance of 3dimensional cinema can be observed. Even though the stereoscopy was quite popular within the last 150 years, the 3d cinema has disappeared and re-established itself several times. The first boom in the late 19th century stagnated and vanished after a few years of success, the same happened again in 50's and 80's of the 20th century. With the commercial success of the 3d blockbuster "Avatar" in 2009, at the latest, it is obvious that the 3d cinema is having a comeback. How long will it last this time? There are already some signs of a declining interest in 3d movies, as the discrepancy between expectations and the results delivered becomes more evident. From the former hypes it is known: After an initial phase of curiosity (high expectations and excessive fault tolerance), a phase of frustration and saturation (critical analysis and subsequent disappointment) will follow. This phenomenon is known as "Hype Cycle" The everyday experienced evolution of technology has conditioned the consumers. The expectation "any technical improvement will preserve all previous properties" cannot be fulfilled with present 3d technologies. This is an inherent problem of stereoscopy and autostereoscopy: The presentation of an additional dimension caused concessions in relevant characteristics (i.e. resolution, brightness, frequency, viewing area) or leads to undesirable physical side effects (i.e. subjective discomfort, eye strain, spatial disorientation, feeling of nausea). It will be verified that the 3d apparatus (3d glasses or 3d display) is also the source for these restrictions and a reason for decreasing fascination. The limitations of present autostereoscopic technologies will be explained.

  19. Funding Opportunity: Genomic Data Centers

    Science.gov (United States)

    Funding Opportunity CCG, Funding Opportunity Center for Cancer Genomics, CCG, Center for Cancer Genomics, CCG RFA, Center for cancer genomics rfa, genomic data analysis network, genomic data analysis network centers,

  20. Deep ancestry of programmed genome rearrangement in lampreys.

    Science.gov (United States)

    Timoshevskiy, Vladimir A; Lampman, Ralph T; Hess, Jon E; Porter, Laurie L; Smith, Jeramiah J

    2017-09-01

    In most multicellular organisms, the structure and content of the genome is rigorously maintained over the course of development. However some species have evolved genome biologies that permit, or require, developmentally regulated changes in the physical structure and content of the genome (programmed genome rearrangement: PGR). Relatively few vertebrates are known to undergo PGR, although all agnathans surveyed to date (several hagfish and one lamprey: Petromyzon marinus) show evidence of large scale PGR. To further resolve the ancestry of PGR within vertebrates, we developed probes that allow simultaneous tracking of nearly all sequences eliminated by PGR in P. marinus and a second lamprey species (Entosphenus tridentatus). These comparative analyses reveal conserved subcellular structures (lagging chromatin and micronuclei) associated with PGR and provide the first comparative embryological evidence in support of the idea that PGR represents an ancient and evolutionarily stable strategy for regulating inherent developmental/genetic conflicts between germline and soma. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Exploring Other Genomes: Bacteria.

    Science.gov (United States)

    Flannery, Maura C.

    2001-01-01

    Points out the importance of genomes other than the human genome project and provides information on the identified bacterial genomes Pseudomonas aeuroginosa, Leprosy, Cholera, Meningitis, Tuberculosis, Bubonic Plague, and plant pathogens. Considers the computer's use in genome studies. (Contains 14 references.) (YDS)

  2. Selective nature and inherent variability of interrill erosion across prolonged rainfall simulation

    Science.gov (United States)

    Hu, Y.; Kuhn, N. J.; Fister, W.

    2012-04-01

    Sediment of interrill erosion has been generally recognized to be selectively enriched with soil organic carbon (SOC) and fine fractions (clay/silt-sized particles or aggregates) in comparison to source area soil. Limited kinetic energy and lack of concentrated runoff are the dominant factors causing selective detachment and transportation. Although enrichment ratios of SOC (ERsoc) in eroded sediment were generally reported > 1, the values varied widely. Causal factors to variation, such as initial soil properties, rainfall properties and experimental conditions, have been extensively discussed. But less attention was directed to the potential influence of prolonged rainfall time onto the temporal pattern of ERsoc. Conservation of mass dictates that ERsoc must be balanced by a decline in the source material which should also lead to a reduced or even negative ERsoc in sediment over time. Besides, the stabilizing effects of structural crust on reducing erosional variation, and the unavoidable variations of erosional response induced by the inherent complexity of interrill erosion, have scarcely been integrated. Moreover, during a prolonged rainfall event surface roughness evolves and affects the movement of eroded aggregates and mineral particles. In this study, two silt loams from Möhlin, Switzerland, organically (OS) and conventionally farmed (CS), were exposed to simulated rainfall of 30 mm h-1 for up to 6 hours. Round donut-flumes with a confined eroding area (1845 cm2) and limited transporting distance (20 cm) were used. Sediments, runoff and subsurface flow were collected in intervals of 30 min. Loose aggregates left on the eroded soil surface, crusts and the soil underneath the crusts were collected after the experiment. All the samples were analyzed for total organic carbon (TOC) content, and texture. Laser scanning of soil surface was applied before and after the rainfall event. The whole experiment was repeated for 10 times. Results from this study showed

  3. MOX-fuel inherent proliferation-protection due to {sup 231}Pa admixture

    Energy Technology Data Exchange (ETDEWEB)

    Kryuchkov, E.F.; Glebov, V.B.; Apse, V.A.; Shmelev, A.N. [Moscow Engineering Physics Institute (State University), Moscow (Russian Federation)

    2003-07-01

    The proliferation protection levels of MOX-fuel containing small additions of protactinium are evaluated for equilibrium closed and open cycles of a light-water reactor (LWR).Analysis of the ways to the proliferation protection of MOX-fuel by small {sup 231}Pa addition and comparison of this way with another options for giving MOX-fuel the proliferation self-protection property enable us to make the 3 following conclusions: -1) Unique nature of protactinium as a small addition to MOX-fuel is determined by the following properties: - Protactinium is available in the nature (uranium ore) as a long-lived mono-isotope {sup 231}Pa, - under neutron irradiation, {sup 231}Pa is converted into {sup 232}U, which is a long-term source of high energy gamma-radiation and practically non-separable from main fuel mass, - essentially, {sup 231}Pa is a high-quality burnable neutron absorber. -2) From the proliferation self-protection point of view, nuclear fuel cycle closure with fuel recycle is a preferable option because, under this condition, introduction of protactinium into MOX-fuel allows to create the inherent radiation barrier which is in action during full cycle of fuel management at the level corresponding to the accepted today criterion of the Spent Fuel Standard (SFS). In particular, the considered example of multiple MOX-fuel recycle with small addition of {sup 231}Pa (0.2% HM) at each cycle demonstrates a possibility to reach the proliferation protection level of fresh MOX-fuel corresponding to once irradiated fuel with the same cooling time. In this case, the lethal dose (at 30 cm distance from fuel assembly) is received within the minute range. -3) Introduction of {sup 231}Pa into MOX-fuel composition in amount of 0.5% HM allows to prolong action of the SFS from 100 to 200 years. If {sup 231}Pa content is increased up to 5% HM, then MOX-fuel conserves the proliferation self-protection property in respect to short-term unauthorized actions for 200-year period of its

  4. Genomics With Cloud Computing

    OpenAIRE

    Sukhamrit Kaur; Sandeep Kaur

    2015-01-01

    Abstract Genomics is study of genome which provides large amount of data for which large storage and computation power is needed. These issues are solved by cloud computing that provides various cloud platforms for genomics. These platforms provides many services to user like easy access to data easy sharing and transfer providing storage in hundreds of terabytes more computational power. Some cloud platforms are Google genomics DNAnexus and Globus genomics. Various features of cloud computin...

  5. Genome Maps, a new generation genome browser.

    Science.gov (United States)

    Medina, Ignacio; Salavert, Francisco; Sanchez, Rubén; de Maria, Alejandro; Alonso, Roberto; Escobar, Pablo; Bleda, Marta; Dopazo, Joaquín

    2013-07-01

    Genome browsers have gained importance as more genomes and related genomic information become available. However, the increase of information brought about by new generation sequencing technologies is, at the same time, causing a subtle but continuous decrease in the efficiency of conventional genome browsers. Here, we present Genome Maps, a genome browser that implements an innovative model of data transfer and management. The program uses highly efficient technologies from the new HTML5 standard, such as scalable vector graphics, that optimize workloads at both server and client sides and ensure future scalability. Thus, data management and representation are entirely carried out by the browser, without the need of any Java Applet, Flash or other plug-in technology installation. Relevant biological data on genes, transcripts, exons, regulatory features, single-nucleotide polymorphisms, karyotype and so forth, are imported from web services and are available as tracks. In addition, several DAS servers are already included in Genome Maps. As a novelty, this web-based genome browser allows the local upload of huge genomic data files (e.g. VCF or BAM) that can be dynamically visualized in real time at the client side, thus facilitating the management of medical data affected by privacy restrictions. Finally, Genome Maps can easily be integrated in any web application by including only a few lines of code. Genome Maps is an open source collaborative initiative available in the GitHub repository (https://github.com/compbio-bigdata-viz/genome-maps). Genome Maps is available at: http://www.genomemaps.org.

  6. Summary of advanced LMR [Liquid Metal Reactor] evaluations: PRISM [Power Reactor Inherently Safe Module] and SAFR [Sodium Advanced Fast Reactor

    International Nuclear Information System (INIS)

    Van Tuyle, G.J.; Slovik, G.C.; Chan, B.C.; Kennett, R.J.; Cheng, H.S.; Kroeger, P.G.

    1989-10-01

    In support of the US Nuclear Regulatory Commission (NRC), Brookhaven National Laboratory (BNL) has performed independent analyses of two advanced Liquid Metal Reactor (LMR) concepts. The designs, sponsored by the US Department of Energy (DOE), the Power Reactor Inherently Safe Module (PRISM) [Berglund, 1987] and the Sodium Advanced Fast Reactor (SAFR) [Baumeister, 1987], were developed primarily by General Electric (GE) and Rockwell International (RI), respectively. Technical support was provided to DOE, RI, and GE, by the Argonne National Laboratory (ANL), particularly with respect to the characteristics of the metal fuels. There are several examples in both PRISM and SAFR where inherent or passive systems provide for a safe response to off-normal conditions. This is in contrast to the engineered safety systems utilized on current US Light Water Reactor (LWR) designs. One important design inherency in the LMRs is the ''inherent shutdown'', which refers to the tendency of the reactor to transition to a much lower power level whenever temperatures rise significantly. This type of behavior was demonstrated in a series of unscrammed tests at EBR-II [NED, 1986]. The second key design feature is the passive air cooling of the vessel to remove decay heat. These systems, designated RVACS in PRISM and RACS in SAFR, always operate and are believed to be able to prevent core damage in the event that no other means of heat removal is available. 27 refs., 78 figs., 3 tabs

  7. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome.

    Science.gov (United States)

    Sharp, Andrew J; Hansen, Sierra; Selzer, Rebecca R; Cheng, Ze; Regan, Regina; Hurst, Jane A; Stewart, Helen; Price, Sue M; Blair, Edward; Hennekam, Raoul C; Fitzpatrick, Carrie A; Segraves, Rick; Richmond, Todd A; Guiver, Cheryl; Albertson, Donna G; Pinkel, Daniel; Eis, Peggy S; Schwartz, Stuart; Knight, Samantha J L; Eichler, Evan E

    2006-09-01

    Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic disorders. We tested 290 individuals with mental retardation by BAC array comparative genomic hybridization and identified 16 pathogenic rearrangements, including de novo microdeletions of 17q21.31 found in four individuals. Using oligonucleotide arrays, we refined the breakpoints of this microdeletion, defining a 478-kb critical region containing six genes that were deleted in all four individuals. We mapped the breakpoints of this deletion and of four other pathogenic rearrangements in 1q21.1, 15q13, 15q24 and 17q12 to flanking segmental duplications, suggesting that these are also sites of recurrent rearrangement. In common with the 17q21.31 deletion, these breakpoint regions are sites of copy number polymorphism in controls, indicating that these may be inherently unstable genomic regions.

  8. JGI Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2011-03-14

    Genomes of energy and environment fungi are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 50 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such 'parts' suggested by comparative genomics and functional analysis in these areas are presented here

  9. Genomic Encyclopedia of Fungi

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-08-10

    Genomes of fungi relevant to energy and environment are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 150 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such parts suggested by comparative genomics and functional analysis in these areas are presented here.

  10. The inherence heuristic: an intuitive means of making sense of the world, and a potential precursor to psychological essentialism.

    Science.gov (United States)

    Cimpian, Andrei; Salomon, Erika

    2014-10-01

    We propose that human reasoning relies on an inherence heuristic, an implicit cognitive process that leads people to explain observed patterns (e.g., girls wear pink) predominantly in terms of the inherent features of their constituents (e.g., pink is a delicate color). We then demonstrate how this proposed heuristic can provide a unified account for a broad set of findings spanning areas of research that might at first appear unrelated (e.g., system justification, nominal realism, is-ought errors in moral reasoning). By revealing the deep commonalities among the diverse phenomena that fall under its scope, our account is able to generate new insights into these phenomena, as well as new empirical predictions. A second main goal of this article, aside from introducing the inherence heuristic, is to articulate the proposal that the heuristic serves as a foundation for the development of psychological essentialism. More specifically, we propose that essentialism - which is the common belief that natural and social categories are underlain by hidden, causally powerful essences - emerges over the first few years of life as an elaboration of the earlier, and more open-ended, intuitions supplied by the inherence heuristic. In the final part of the report, we distinguish our proposal from competing accounts (e.g., Strevens's K-laws) and clarify the relationship between the inherence heuristic and related cognitive tendencies (e.g., the correspondence bias). In sum, this article illuminates a basic cognitive process that emerges early in life and is likely to have profound effects on many aspects of human psychology.

  11. Plant-based assessment of inherent soil productivity and contributions to China's cereal crop yield increase since 1980.

    Directory of Open Access Journals (Sweden)

    Mingsheng Fan

    Full Text Available OBJECTIVE: China's food production has increased 6-fold during the past half-century, thanks to increased yields resulting from the management intensification, accomplished through greater inputs of fertilizer, water, new crop strains, and other Green Revolution's technologies. Yet, changes in underlying quality of soils and their effects on yield increase remain to be determined. Here, we provide a first attempt to quantify historical changes in inherent soil productivity and their contributions to the increase in yield. METHODS: The assessment was conducted based on data-set derived from 7410 on-farm trials, 8 long-term experiments and an inventory of soil organic matter concentrations of arable land. RESULTS: Results show that even without organic and inorganic fertilizer addition crop yield from on-farm trials conducted in the 2000s was significantly higher compared with those in the 1980s - the increase ranged from 0.73 to 1.76 Mg/ha for China's major irrigated cereal-based cropping systems. The increase in on-farm yield in control plot since 1980s was due primarily to the enhancement of soil-related factors, and reflected inherent soil productivity improvement. The latter led to higher and stable yield with adoption of improved management practices, and contributed 43% to the increase in yield for wheat and 22% for maize in the north China, and, 31%, 35% and 22% for early and late rice in south China and for single rice crop in the Yangtze River Basin since 1980. CONCLUSIONS: Thus, without an improvement in inherent soil productivity, the 'Agricultural Miracle in China' would not have happened. A comprehensive strategy of inherent soil productivity improvement in China, accomplished through combining engineering-based measures with biological-approaches, may be an important lesson for the developing world. We propose that advancing food security in 21st century for both China and other parts of world will depend on continuously improving

  12. NRGC: a novel referential genome compression algorithm.

    Science.gov (United States)

    Saha, Subrata; Rajasekaran, Sanguthevar

    2016-11-15

    Next-generation sequencing techniques produce millions to billions of short reads. The procedure is not only very cost effective but also can be done in laboratory environment. The state-of-the-art sequence assemblers then construct the whole genomic sequence from these reads. Current cutting edge computing technology makes it possible to build genomic sequences from the billions of reads within a minimal cost and time. As a consequence, we see an explosion of biological sequences in recent times. In turn, the cost of storing the sequences in physical memory or transmitting them over the internet is becoming a major bottleneck for research and future medical applications. Data compression techniques are one of the most important remedies in this context. We are in need of suitable data compression algorithms that can exploit the inherent structure of biological sequences. Although standard data compression algorithms are prevalent, they are not suitable to compress biological sequencing data effectively. In this article, we propose a novel referential genome compression algorithm (NRGC) to effectively and efficiently compress the genomic sequences. We have done rigorous experiments to evaluate NRGC by taking a set of real human genomes. The simulation results show that our algorithm is indeed an effective genome compression algorithm that performs better than the best-known algorithms in most of the cases. Compression and decompression times are also very impressive. The implementations are freely available for non-commercial purposes. They can be downloaded from: http://www.engr.uconn.edu/~rajasek/NRGC.zip CONTACT: rajasek@engr.uconn.edu. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. ERGC: an efficient referential genome compression algorithm.

    Science.gov (United States)

    Saha, Subrata; Rajasekaran, Sanguthevar

    2015-11-01

    Genome sequencing has become faster and more affordable. Consequently, the number of available complete genomic sequences is increasing rapidly. As a result, the cost to store, process, analyze and transmit the data is becoming a bottleneck for research and future medical applications. So, the need for devising efficient data compression and data reduction techniques for biological sequencing data is growing by the day. Although there exists a number of standard data compression algorithms, they are not efficient in compressing biological data. These generic algorithms do not exploit some inherent properties of the sequencing data while compressing. To exploit statistical and information-theoretic properties of genomic sequences, we need specialized compression algorithms. Five different next-generation sequencing data compression problems have been identified and studied in the literature. We propose a novel algorithm for one of these problems known as reference-based genome compression. We have done extensive experiments using five real sequencing datasets. The results on real genomes show that our proposed algorithm is indeed competitive and performs better than the best known algorithms for this problem. It achieves compression ratios that are better than those of the currently best performing algorithms. The time to compress and decompress the whole genome is also very promising. The implementations are freely available for non-commercial purposes. They can be downloaded from http://engr.uconn.edu/∼rajasek/ERGC.zip. rajasek@engr.uconn.edu. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. SVBR-75/100 multi-purpose modular inherent-safety fast reactor

    International Nuclear Information System (INIS)

    Dragunov, Yu.G.; Stepanov, V.S.; Klimov, N.N.; Dedul, A.V.; Zrodnokov, A.V.; Toshinsky, G.I.; Komlev, O.G.; Krushelnitsky, V.N.; Takh, S.M.

    2006-01-01

    In this century energy consumption, including electric power, will continue growing on a large scale especially in developing countries. Significant changes in electric power market needs are to be expected in the direction of decreasing and varying the capacity of power sources. To satisfy the expected growth of demand for electric power and to take a decision concerning the ways of further development of global power, including nuclear engineering, it is very important to continue the development of innovative concepts of nuclear power sources, which might successfully compete with alternative power technologies at the future power markets. The proposed nuclear power source (or in other words - reactor plant) of new generation is supposed: - to have small power capacity in the range of 10 - 100 MW (electric) and possibility of its multi-purpose application (independent nuclear power source for desalination installations and electricity supply, nuclear power plants (NPP) of various capacity and purpose; - to use modular principle of construction of NPP of various capacity on the basis of unified 'typical' reactor plants; - to have qualitatively new level of passive safety and possess properties of inherent safety, deterministically excluding any opportunity of severe accidents; - to have an opportunity to use different kinds of fuel and to work in various fuel cycles at various stages of development of nuclear power without change in the design. And also to have long (7-10 years, and in the long term 15-20 years) core life time and enrichment on U-235 not higher than 20 % (which is in compliance with recommendations of IAEA under non-proliferation condition); - to be completely factory-manufactured, and an opportunity of its safe transportation to and from the NPP site shall be provided. Unified multi-purpose reactor plant SVBR-75/100 (Lead-Bismuth Fast Reactor with equivalent electric power of 75 - 100 MW-e depending on the steam parameters) meets the set of the

  15. Genome-wide identification of significant aberrations in cancer genome.

    Science.gov (United States)

    Yuan, Xiguo; Yu, Guoqiang; Hou, Xuchu; Shih, Ie-Ming; Clarke, Robert; Zhang, Junying; Hoffman, Eric P; Wang, Roger R; Zhang, Zhen; Wang, Yue

    2012-07-27

    Somatic Copy Number Alterations (CNAs) in human genomes are present in almost all human cancers. Systematic efforts to characterize such structural variants must effectively distinguish significant consensus events from random background aberrations. Here we introduce Significant Aberration in Cancer (SAIC), a new method for characterizing and assessing the statistical significance of recurrent CNA units. Three main features of SAIC include: (1) exploiting the intrinsic correlation among consecutive probes to assign a score to each CNA unit instead of single probes; (2) performing permutations on CNA units that preserve correlations inherent in the copy number data; and (3) iteratively detecting Significant Copy Number Aberrations (SCAs) and estimating an unbiased null distribution by applying an SCA-exclusive permutation scheme. We test and compare the performance of SAIC against four peer methods (GISTIC, STAC, KC-SMART, CMDS) on a large number of simulation datasets. Experimental results show that SAIC outperforms peer methods in terms of larger area under the Receiver Operating Characteristics curve and increased detection power. We then apply SAIC to analyze structural genomic aberrations acquired in four real cancer genome-wide copy number data sets (ovarian cancer, metastatic prostate cancer, lung adenocarcinoma, glioblastoma). When compared with previously reported results, SAIC successfully identifies most SCAs known to be of biological significance and associated with oncogenes (e.g., KRAS, CCNE1, and MYC) or tumor suppressor genes (e.g., CDKN2A/B). Furthermore, SAIC identifies a number of novel SCAs in these copy number data that encompass tumor related genes and may warrant further studies. Supported by a well-grounded theoretical framework, SAIC has been developed and used to identify SCAs in various cancer copy number data sets, providing useful information to study the landscape of cancer genomes. Open-source and platform-independent SAIC software is

  16. Genome-wide identification of significant aberrations in cancer genome

    Directory of Open Access Journals (Sweden)

    Yuan Xiguo

    2012-07-01

    Full Text Available Abstract Background Somatic Copy Number Alterations (CNAs in human genomes are present in almost all human cancers. Systematic efforts to characterize such structural variants must effectively distinguish significant consensus events from random background aberrations. Here we introduce Significant Aberration in Cancer (SAIC, a new method for characterizing and assessing the statistical significance of recurrent CNA units. Three main features of SAIC include: (1 exploiting the intrinsic correlation among consecutive probes to assign a score to each CNA unit instead of single probes; (2 performing permutations on CNA units that preserve correlations inherent in the copy number data; and (3 iteratively detecting Significant Copy Number Aberrations (SCAs and estimating an unbiased null distribution by applying an SCA-exclusive permutation scheme. Results We test and compare the performance of SAIC against four peer methods (GISTIC, STAC, KC-SMART, CMDS on a large number of simulation datasets. Experimental results show that SAIC outperforms peer methods in terms of larger area under the Receiver Operating Characteristics curve and increased detection power. We then apply SAIC to analyze structural genomic aberrations acquired in four real cancer genome-wide copy number data sets (ovarian cancer, metastatic prostate cancer, lung adenocarcinoma, glioblastoma. When compared with previously reported results, SAIC successfully identifies most SCAs known to be of biological significance and associated with oncogenes (e.g., KRAS, CCNE1, and MYC or tumor suppressor genes (e.g., CDKN2A/B. Furthermore, SAIC identifies a number of novel SCAs in these copy number data that encompass tumor related genes and may warrant further studies. Conclusions Supported by a well-grounded theoretical framework, SAIC has been developed and used to identify SCAs in various cancer copy number data sets, providing useful information to study the landscape of cancer genomes

  17. Genomics With Cloud Computing

    Directory of Open Access Journals (Sweden)

    Sukhamrit Kaur

    2015-04-01

    Full Text Available Abstract Genomics is study of genome which provides large amount of data for which large storage and computation power is needed. These issues are solved by cloud computing that provides various cloud platforms for genomics. These platforms provides many services to user like easy access to data easy sharing and transfer providing storage in hundreds of terabytes more computational power. Some cloud platforms are Google genomics DNAnexus and Globus genomics. Various features of cloud computing to genomics are like easy access and sharing of data security of data less cost to pay for resources but still there are some demerits like large time needed to transfer data less network bandwidth.

  18. Long-read sequencing and de novo assembly of a Chinese genome

    Science.gov (United States)

    Short-read sequencing has enabled the de novo assembly of several individual human genomes, but with inherent limitations in characterizing repeat elements. Here we sequence a Chinese individual HX1 by single-molecule real-time (SMRT) long-read sequencing, construct a physical map by NanoChannel arr...

  19. Inherent Safety Features and Passive Prevention Approaches for Pb/Bi-cooled Accelerator-Driven Systems

    Energy Technology Data Exchange (ETDEWEB)

    Carlsson, Johan

    2003-03-01

    This thesis is devoted to the investigation of passive safety and inherent features of subcritical nuclear transmutation systems - accelerator-driven systems. The general objective of this research has been to improve the safety performance and avoid elevated coolant temperatures in worst-case scenarios like unprotected loss-of-flow accidents, loss-of-heat-sink accidents, and a combination of both these accident initiators. The specific topics covered are emergency decay heat removal by reactor vessel auxiliary cooling systems, beam shut-off by a melt-rupture disc, safety aspects from locating heat-exchangers in the riser of a pool-type reactor system, and reduction of pressure resistance in the primary circuit by employing bypass routes. The initial part of the research was focused on reactor vessel auxiliary cooling systems. It was shown that an 80 MW{sub th} Pb/Bi-cooled accelerator-driven system of 8 m height and 6 m diameter vessel can be well cooled in the case of loss-of-flow accidents in which the accelerator proton beam is not switched off. After a loss-of-heat-sink accident the proton beam has to be interrupted within 40 minutes in order to avoid fast creep of the vessel. If a melt-rupture disc is included in the wall of the beam pipe, which breaks at 150 K above the normal core outlet temperature, the grace period until the beam has to be shut off is increased to 6 hours. For the same vessel geometry, but an operating power of 250 MW{sub th} the structural materials can still avoid fast creep in case the proton beam is shut off immediately. If beam shut-off is delayed, additional cooling methods are needed to increase the heat removal. Investigations were made on the filling of the gap between the guard and the reactor vessel with liquid metal coolant and using water spray cooling on the guard vessel surface. The second part of the thesis presents examinations regarding an accelerator-driven system also cooled with Pb/Bi but with heat-exchangers located

  20. Inherent Safety Features and Passive Prevention Approaches for Pb/Bi-cooled Accelerator-Driven Systems

    International Nuclear Information System (INIS)

    Carlsson, Johan

    2003-03-01

    This thesis is devoted to the investigation of passive safety and inherent features of subcritical nuclear transmutation systems - accelerator-driven systems. The general objective of this research has been to improve the safety performance and avoid elevated coolant temperatures in worst-case scenarios like unprotected loss-of-flow accidents, loss-of-heat-sink accidents, and a combination of both these accident initiators. The specific topics covered are emergency decay heat removal by reactor vessel auxiliary cooling systems, beam shut-off by a melt-rupture disc, safety aspects from locating heat-exchangers in the riser of a pool-type reactor system, and reduction of pressure resistance in the primary circuit by employing bypass routes. The initial part of the research was focused on reactor vessel auxiliary cooling systems. It was shown that an 80 MW th Pb/Bi-cooled accelerator-driven system of 8 m height and 6 m diameter vessel can be well cooled in the case of loss-of-flow accidents in which the accelerator proton beam is not switched off. After a loss-of-heat-sink accident the proton beam has to be interrupted within 40 minutes in order to avoid fast creep of the vessel. If a melt-rupture disc is included in the wall of the beam pipe, which breaks at 150 K above the normal core outlet temperature, the grace period until the beam has to be shut off is increased to 6 hours. For the same vessel geometry, but an operating power of 250 MW th the structural materials can still avoid fast creep in case the proton beam is shut off immediately. If beam shut-off is delayed, additional cooling methods are needed to increase the heat removal. Investigations were made on the filling of the gap between the guard and the reactor vessel with liquid metal coolant and using water spray cooling on the guard vessel surface. The second part of the thesis presents examinations regarding an accelerator-driven system also cooled with Pb/Bi but with heat-exchangers located in the

  1. Comparative Genome Analysis and Genome Evolution

    NARCIS (Netherlands)

    Snel, Berend

    2002-01-01

    This thesis described a collection of bioinformatic analyses on complete genome sequence data. We have studied the evolution of gene content and find that vertical inheritance dominates over horizontal gene trasnfer, even to the extent that we can use the gene content to make genome phylogenies.

  2. Genomic Data Commons launches

    Science.gov (United States)

    The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

  3. Rat Genome Database (RGD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Rat Genome Database (RGD) is a collaborative effort between leading research institutions involved in rat genetic and genomic research to collect, consolidate,...

  4. Visualization for genomics: the Microbial Genome Viewer.

    Science.gov (United States)

    Kerkhoven, Robert; van Enckevort, Frank H J; Boekhorst, Jos; Molenaar, Douwe; Siezen, Roland J

    2004-07-22

    A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a MySQL database. The generated images are in scalable vector graphics (SVG) format, which is suitable for creating high-quality scalable images and dynamic Web representations. Gene-related data such as transcriptome and time-course microarray experiments can be superimposed on the maps for visual inspection. The Microbial Genome Viewer 1.0 is freely available at http://www.cmbi.kun.nl/MGV

  5. Genomic prediction using subsampling

    OpenAIRE

    Xavier, Alencar; Xu, Shizhong; Muir, William; Rainey, Katy Martin

    2017-01-01

    Background Genome-wide assisted selection is a critical tool for the?genetic improvement of plants and animals. Whole-genome regression models in Bayesian framework represent the main family of prediction methods. Fitting such models with a large number of observations involves a prohibitive computational burden. We propose the use of subsampling bootstrap Markov chain in genomic prediction. Such method consists of fitting whole-genome regression models by subsampling observations in each rou...

  6. Finite-time and fixed-time leader-following consensus for multi-agent systems with discontinuous inherent dynamics

    Science.gov (United States)

    Ning, Boda; Jin, Jiong; Zheng, Jinchuan; Man, Zhihong

    2018-06-01

    This paper is concerned with finite-time and fixed-time consensus of multi-agent systems in a leader-following framework. Different from conventional leader-following tracking approaches where inherent dynamics satisfying the Lipschitz continuous condition is required, a more generalised case is investigated: discontinuous inherent dynamics. By nonsmooth techniques, a nonlinear protocol is first proposed to achieve the finite-time leader-following consensus. Then, based on fixed-time stability strategies, the fixed-time leader-following consensus problem is solved. An upper bound of settling time is obtained by using a new protocol, and such a bound is independent of initial states, thereby providing additional options for designers in practical scenarios where initial conditions are unavailable. Finally, numerical simulations are provided to demonstrate the effectiveness of the theoretical results.

  7. Ebolavirus comparative genomics

    DEFF Research Database (Denmark)

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms...

  8. Increasing Soil Organic Matter Enhances Inherent Soil Productivity while Offsetting Fertilization Effect under a Rice Cropping System

    Directory of Open Access Journals (Sweden)

    Ya-Nan Zhao

    2016-09-01

    Full Text Available Understanding the role of soil organic matter (SOM in soil quality and subsequent crop yield and input requirements is useful for agricultural sustainability. SOM is widely considered to affect a wide range of soil properties, however, great uncertainty still remains in identifying the relationships between SOM and crop yield due to the difficulty in separating the effect of SOM from other yield-limiting factors. Based on 543 on-farm experiments, where paired treatments with and without NPK fertilizer were conducted during 2005–2009, we quantified the inherent soil productivity, fertilization effect, and their contribution to rice yield and further evaluated their relationships with SOM contents under a rice cropping system in the Sichuan Basin of China. The inherent soil productivity assessed by rice grain yield under no fertilization (Y-CK was 5.8 t/ha, on average, and contributed 70% to the 8.3 t/ha of rice yield under NPK fertilization (Y-NPK while the other 30% was from the fertilization effect (FE. No significant correlation between SOM content and Y-NPK was observed, however, SOM content positively related to Y-CK and its contribution to Y-NPK but negatively to FE and its contribution to Y-NPK, indicating an increased soil contribution but a decreased fertilizer contribution to rice yield with increasing SOM. There were significantly positive relationships between SOM and soil available N, P, and K, indicating the potential contribution of SOM to inherent soil productivity by supplying nutrients from mineralization. As a result, approaches for SOM accumulation are practical to improve the inherent soil productivity and thereafter maintain a high crop productivity with less dependence on chemical fertilizers, while fertilization recommendations need to be adjusted with the temporal and spatial SOM variation.

  9. Navigating the Interface Between Landscape Genetics and Landscape Genomics

    Directory of Open Access Journals (Sweden)

    Andrew Storfer

    2018-03-01

    Full Text Available As next-generation sequencing data become increasingly available for non-model organisms, a shift has occurred in the focus of studies of the geographic distribution of genetic variation. Whereas landscape genetics studies primarily focus on testing the effects of landscape variables on gene flow and genetic population structure, landscape genomics studies focus on detecting candidate genes under selection that indicate possible local adaptation. Navigating the transition between landscape genomics and landscape genetics can be challenging. The number of molecular markers analyzed has shifted from what used to be a few dozen loci to thousands of loci and even full genomes. Although genome scale data can be separated into sets of neutral loci for analyses of gene flow and population structure and putative loci under selection for inference of local adaptation, there are inherent differences in the questions that are addressed in the two study frameworks. We discuss these differences and their implications for study design, marker choice and downstream analysis methods. Similar to the rapid proliferation of analysis methods in the early development of landscape genetics, new analytical methods for detection of selection in landscape genomics studies are burgeoning. We focus on genome scan methods for detection of selection, and in particular, outlier differentiation methods and genetic-environment association tests because they are the most widely used. Use of genome scan methods requires an understanding of the potential mismatches between the biology of a species and assumptions inherent in analytical methods used, which can lead to high false positive rates of detected loci under selection. Key to choosing appropriate genome scan methods is an understanding of the underlying demographic structure of study populations, and such data can be obtained using neutral loci from the generated genome-wide data or prior knowledge of a species

  10. Genetic Diversity within Alphaherpesviruses: Characterization of a Novel Variant of Herpes Simplex Virus 2.

    Science.gov (United States)

    Burrel, Sonia; Désiré, Nathalie; Marlet, Julien; Dacheux, Laurent; Seang, Sophie; Caumes, Eric; Bourhy, Hervé; Agut, Henri; Boutolleau, David

    2015-12-01

    Very low levels of variability have been reported for the herpes simplex virus 2 (HSV-2) genome. We recently described a new genetic variant of HSV-2 (HSV-2v) characterized by a much higher degree of variability for the UL30 gene (DNA polymerase) than observed for the HG52 reference strain. Retrospective screening of 505 clinical isolates of HSV-2 by a specific real-time PCR assay targeting the UL30 gene led to the identification of 13 additional HSV-2v isolates, resulting in an overall prevalence of 2.8%. Phylogenetic analyses on the basis of microsatellite markers and gene sequences showed clear differences between HSV-2v and classical HSV-2. Thirteen of the 14 patients infected with HSV-2v originated from West or Central Africa, and 9 of these patients were coinfected with HIV. These results raise questions about the origin of this new virus. Preliminary results suggest that HSV-2v may have acquired genomic segments from chimpanzee alphaherpesvirus (ChHV) by recombination. This article deals with the highly topical question of the origin of this new HSV-2 variant identified in patients with HIV coinfection originating mostly from West or Central Africa. HSV-2v clearly differed from classical HSV-2 isolates in phylogenetic analyses and may be linked to simian ChHV. This new HSV-2 variant highlights the possible occurrence of recombination between human and simian herpesviruses under natural conditions, potentially presenting greater challenges for the future. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. The Sequenced Angiosperm Genomes and Genome Databases.

    Science.gov (United States)

    Chen, Fei; Dong, Wei; Zhang, Jiawei; Guo, Xinyue; Chen, Junhao; Wang, Zhengjia; Lin, Zhenguo; Tang, Haibao; Zhang, Liangsheng

    2018-01-01

    Angiosperms, the flowering plants, provide the essential resources for human life, such as food, energy, oxygen, and materials. They also promoted the evolution of human, animals, and the planet earth. Despite the numerous advances in genome reports or sequencing technologies, no review covers all the released angiosperm genomes and the genome databases for data sharing. Based on the rapid advances and innovations in the database reconstruction in the last few years, here we provide a comprehensive review for three major types of angiosperm genome databases, including databases for a single species, for a specific angiosperm clade, and for multiple angiosperm species. The scope, tools, and data of each type of databases and their features are concisely discussed. The genome databases for a single species or a clade of species are especially popular for specific group of researchers, while a timely-updated comprehensive database is more powerful for address of major scientific mysteries at the genome scale. Considering the low coverage of flowering plants in any available database, we propose construction of a comprehensive database to facilitate large-scale comparative studies of angiosperm genomes and to promote the collaborative studies of important questions in plant biology.

  12. Genomics: Looking at Life in New Ways

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Mark D. (Case-Western Reserve University)

    2003-10-22

    The availability of complete or nearly complete mouse, human, and rat genomes (in addition to those from many other species) has resulted in a series of new and powerful opportunities to apply the technologies and approaches developed for large-scale genome sequencing to the study of disease. New approaches to biological problems are being explored that involve concepts from computer science such as systems theory and modern large scale computing techniques. A recent project at Celera Genomics involved sequencing protein coding regions from several humans and a chimpanzee. Computational models of evolutionary divergence enabled us to identify genes with unique evolutionary signatures. These genes give us some insight into features that may be uniquely human. The laboratory mouse and rat have long been favorite mammalian models of human disease. Integrated approaches to the study of disease that combine genetics, DNA sequence analysis, and careful analysis of phenotype at a molecular level are becoming more common and powerful. In addition, evaluation of the variation inherent in normal populations is now being used to build networks to describe heart function based on the interaction of multiple phenotypes in randomized populations using a factorial design.

  13. Evaluation of three automated genome annotations for Halorhabdus utahensis.

    Directory of Open Access Journals (Sweden)

    Peter Bakke

    2009-07-01

    Full Text Available Genome annotations are accumulating rapidly and depend heavily on automated annotation systems. Many genome centers offer annotation systems but no one has compared their output in a systematic way to determine accuracy and inherent errors. Errors in the annotations are routinely deposited in databases such as NCBI and used to validate subsequent annotation errors. We submitted the genome sequence of halophilic archaeon Halorhabdus utahensis to be analyzed by three genome annotation services. We have examined the output from each service in a variety of ways in order to compare the methodology and effectiveness of the annotations, as well as to explore the genes, pathways, and physiology of the previously unannotated genome. The annotation services differ considerably in gene calls, features, and ease of use. We had to manually identify the origin of replication and the species-specific consensus ribosome-binding site. Additionally, we conducted laboratory experiments to test H. utahensis growth and enzyme activity. Current annotation practices need to improve in order to more accurately reflect a genome's biological potential. We make specific recommendations that could improve the quality of microbial annotation projects.

  14. Survey and evaluation of inherent safety characteristics and passive safety systems for use in probabilistic safety analyses

    International Nuclear Information System (INIS)

    Wetzel, N.; Scharfe, A.

    1998-01-01

    The present report examines the possibilities and limits of a probabilistic safety analysis to evaluate passive safety systems and inherent safety characteristics. The inherent safety characteristics are based on physical principles, that together with the safety system lead to no damage. A probabilistic evaluation of the inherent safety characteristic is not made. An inventory of passive safety systems of accomplished nuclear power plant types in the Federal Republic of Germany was drawn up. The evaluation of the passive safety system in the analysis of the accomplished nuclear power plant types was examined. The analysis showed that the passive manner of working was always assumed to be successful. A probabilistic evaluation was not performed. The unavailability of the passive safety system was determined by the failure of active components which are necessary in order to activate the passive safety system. To evaluate the passive safety features in new concepts of nuclear power plants the AP600 from Westinghouse, the SBWR from General Electric and the SWR 600 from Siemens, were selected. Under these three reactor concepts, the SWR 600 is specially attractive because the safety features need no energy sources and instrumentation in this concept. First approaches for the assessment of the reliability of passively operating systems are summarized. Generally it can be established that the core melt frequency for the passive concepts AP600 and SBWR is advantageous in comparison to the probabilistic objectives from the European Pressurized Water Reactor (EPR). Under the passive concepts is the SWR 600 particularly interesting. In this concept the passive systems need no energy sources and instrumentation, and has active operational systems and active safety equipment. Siemens argues that with this concept the frequency of a core melt will be two orders of magnitude lower than for the conventional reactors. (orig.) [de

  15. Making the invisible, visible: challenging the knowledge structures inherent in International Relations Theory in order to create knowledge plural curricula

    Directory of Open Access Journals (Sweden)

    Jacqueline de Matos-Ala

    2018-02-01

    Full Text Available Abstract This article problematizes the lack of plurality of knowledges in International Relations theory curricula. The increase in knowledges and scholarship from the South has not seemingly filtered into International Relations theory curricula significantly. Thus Western knowledges still dominates the narrative. It investigates how knowledge structures inherent in the discipline coupled with Western centric ontology and epistemology function to exclude or marginalize knowledge that does not conform to specific criteria. I demonstrate how the third year IR theory curriculum at Wits University, has engaged with discipline’s knowledge structures as well as its ontology and epistemology to develop a knowledge plural curricula.

  16. Bioinformatics decoding the genome

    CERN Multimedia

    CERN. Geneva; Deutsch, Sam; Michielin, Olivier; Thomas, Arthur; Descombes, Patrick

    2006-01-01

    Extracting the fundamental genomic sequence from the DNA From Genome to Sequence : Biology in the early 21st century has been radically transformed by the availability of the full genome sequences of an ever increasing number of life forms, from bacteria to major crop plants and to humans. The lecture will concentrate on the computational challenges associated with the production, storage and analysis of genome sequence data, with an emphasis on mammalian genomes. The quality and usability of genome sequences is increasingly conditioned by the careful integration of strategies for data collection and computational analysis, from the construction of maps and libraries to the assembly of raw data into sequence contigs and chromosome-sized scaffolds. Once the sequence is assembled, a major challenge is the mapping of biologically relevant information onto this sequence: promoters, introns and exons of protein-encoding genes, regulatory elements, functional RNAs, pseudogenes, transposons, etc. The methodological ...

  17. Genomic research in Eucalyptus.

    Science.gov (United States)

    Poke, Fiona S; Vaillancourt, René E; Potts, Brad M; Reid, James B

    2005-09-01

    Eucalyptus L'Hérit. is a genus comprised of more than 700 species that is of vital importance ecologically to Australia and to the forestry industry world-wide, being grown in plantations for the production of solid wood products as well as pulp for paper. With the sequencing of the genomes of Arabidopsis thaliana and Oryza sativa and the recent completion of the first tree genome sequence, Populus trichocarpa, attention has turned to the current status of genomic research in Eucalyptus. For several eucalypt species, large segregating families have been established, high-resolution genetic maps constructed and large EST databases generated. Collaborative efforts have been initiated for the integration of diverse genomic projects and will provide the framework for future research including exploiting the sequence of the entire eucalypt genome which is currently being sequenced. This review summarises the current position of genomic research in Eucalyptus and discusses the direction of future research.

  18. Genome packaging in viruses

    OpenAIRE

    Sun, Siyang; Rao, Venigalla B.; Rossmann, Michael G.

    2010-01-01

    Genome packaging is a fundamental process in a viral life cycle. Many viruses assemble preformed capsids into which the genomic material is subsequently packaged. These viruses use a packaging motor protein that is driven by the hydrolysis of ATP to condense the nucleic acids into a confined space. How these motor proteins package viral genomes had been poorly understood until recently, when a few X-ray crystal structures and cryo-electron microscopy structures became available. Here we discu...

  19. Between Two Fern Genomes

    Science.gov (United States)

    2014-01-01

    Ferns are the only major lineage of vascular plants not represented by a sequenced nuclear genome. This lack of genome sequence information significantly impedes our ability to understand and reconstruct genome evolution not only in ferns, but across all land plants. Azolla and Ceratopteris are ideal and complementary candidates to be the first ferns to have their nuclear genomes sequenced. They differ dramatically in genome size, life history, and habit, and thus represent the immense diversity of extant ferns. Together, this pair of genomes will facilitate myriad large-scale comparative analyses across ferns and all land plants. Here we review the unique biological characteristics of ferns and describe a number of outstanding questions in plant biology that will benefit from the addition of ferns to the set of taxa with sequenced nuclear genomes. We explain why the fern clade is pivotal for understanding genome evolution across land plants, and we provide a rationale for how knowledge of fern genomes will enable progress in research beyond the ferns themselves. PMID:25324969

  20. Causes of genome instability

    DEFF Research Database (Denmark)

    Langie, Sabine A S; Koppen, Gudrun; Desaulniers, Daniel

    2015-01-01

    function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make......Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus...

  1. Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-03-12

    The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scale genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.

  2. MIPS plant genome information resources.

    Science.gov (United States)

    Spannagl, Manuel; Haberer, Georg; Ernst, Rebecca; Schoof, Heiko; Mayer, Klaus F X

    2007-01-01

    The Munich Institute for Protein Sequences (MIPS) has been involved in maintaining plant genome databases since the Arabidopsis thaliana genome project. Genome databases and analysis resources have focused on individual genomes and aim to provide flexible and maintainable data sets for model plant genomes as a backbone against which experimental data, for example from high-throughput functional genomics, can be organized and evaluated. In addition, model genomes also form a scaffold for comparative genomics, and much can be learned from genome-wide evolutionary studies.

  3. 1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    International Nuclear Information System (INIS)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D.

    2011-01-01

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in 1 H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  4. The inherent dynamics of a molecular liquid: Geodesic pathways through the potential energy landscape of a liquid of linear molecules

    Science.gov (United States)

    Jacobson, Daniel; Stratt, Richard M.

    2014-05-01

    Because the geodesic pathways that a liquid follows through its potential energy landscape govern its slow, diffusive motion, we suggest that these pathways are logical candidates for the title of a liquid's "inherent dynamics." Like their namesake "inherent structures," these objects are simply features of the system's potential energy surface and thus provide views of the system's structural evolution unobstructed by thermal kinetic energy. This paper shows how these geodesic pathways can be computed for a liquid of linear molecules, allowing us to see precisely how such molecular liquids mix rotational and translational degrees of freedom into their dynamics. The ratio of translational to rotational components of the geodesic path lengths, for example, is significantly larger than would be expected on equipartition grounds, with a value that scales with the molecular aspect ratio. These and other features of the geodesics are consistent with a picture in which molecular reorientation adiabatically follows translation—molecules largely thread their way through narrow channels available in the potential energy landscape.

  5. Inherent unsharpness of neutron radiographic image on X-ray films; Notranja neostrina nevtronografke slike na roentgenskih filmih

    Energy Technology Data Exchange (ETDEWEB)

    Ilic, R; Najzer, M [Institut Jozef Stefan, Ljubljana (Yugoslavia)

    1979-07-01

    The inherent unsharpness of the AGFA GEVART Structurix D-4 X-ray film was determined in terms of the unsharpness of the image of the knife edge test object for Gd converter 25 {mu}m In converters 50, 150 and 250 {mu}m and by Dy converters 7, 12, 25 and 60 {mu}m thick. The unsharpness of single coated film for Gd converter was found to be 56{+-}5 {mu}m. For In and Dy a value of 230 {+-} was obtained which was found to be independent on the converter type or thickness at least in the range of measuring error. The Inherent unsharpness of double coated film was 440 {+-} for In and 550{+-}50 {mu}m for Dy converter and was not dependent on the converter thickness. Comparing with single coated film the sensitivity was for a factor 1.6 higher for In and Dy converters. For Gd converter there was no gain in sensitivity and even the contrast was worse due to higher gamma ray background. (author)

  6. {sup 1}H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    Energy Technology Data Exchange (ETDEWEB)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D., E-mail: bernard.lemire@ualberta.ca [University of Alberta, Department of Biochemistry, School of Molecular and Systems Medicine (Canada)

    2011-04-15

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in {sup 1}H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  7. Feasibility study of a dedicate nuclear desalination system: Low-pressure inherent heat sink nuclear desalination plant (LIND)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ho Sik; No, Hee Cheon; Jo, Yu Gwan; Wivisono, Andhika Feri; Park, Byung Ha; Choi, Jin Young; Lee, Jeong Ik; Jeong, Yong Hoon; Cho, Nam Zin [Dept. of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2015-04-15

    In this paper, we suggest the conceptual design of a water-cooled reactor system for a low-pressure inherent heat sink nuclear desalination plant (LIND) that applies the safety-related design concepts of high temperature gas-cooled reactors to a water-cooled reactor for inherent and passive safety features. Through a scoping analysis, we found that the current LIND design satisfied several essential thermal-hydraulic and neutronic design requirements. In a thermal-hydraulic analysis using an analytical method based on the Wooton-Epstein correlation, we checked the possibility of safely removing decay heat through the steel containment even if all the active safety systems failed. In a neutronic analysis using the Monte Carlo N-particle transport code, we estimated a cycle length of approximately 6 years under 200 MW{sub th} and 4.5% enrichment. The very long cycle length and simple safety features minimize the burdens from the operation, maintenance, and spent-fuel management, with a positive impact on the economic feasibility. Finally, because a nuclear reactor should not be directly coupled to a desalination system to prevent the leakage of radioactive material into the desalinated water, three types of intermediate systems were studied: a steam producing system, a hot water system, and an organic Rankine cycle system.

  8. Feasibility study of a dedicated nuclear desalination system: Low-pressure Inherent heat sink Nuclear Desalination plant (LIND

    Directory of Open Access Journals (Sweden)

    Ho Sik Kim

    2015-04-01

    Full Text Available In this paper, we suggest the conceptual design of a water-cooled reactor system for a low-pressure inherent heat sink nuclear desalination plant (LIND that applies the safety-related design concepts of high temperature gas-cooled reactors to a water-cooled reactor for inherent and passive safety features. Through a scoping analysis, we found that the current LIND design satisfied several essential thermal–hydraulic and neutronic design requirements. In a thermal–hydraulic analysis using an analytical method based on the Wooton–Epstein correlation, we checked the possibility of safely removing decay heat through the steel containment even if all the active safety systems failed. In a neutronic analysis using the Monte Carlo N-particle transport code, we estimated a cycle length of approximately 6 years under 200 MWth and 4.5% enrichment. The very long cycle length and simple safety features minimize the burdens from the operation, maintenance, and spent-fuel management, with a positive impact on the economic feasibility. Finally, because a nuclear reactor should not be directly coupled to a desalination system to prevent the leakage of radioactive material into the desalinated water, three types of intermediate systems were studied: a steam producing system, a hot water system, and an organic Rankine cycle system.

  9. Herpes simplex virus type 2 infections of the central nervous system

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; Vestergaard, Bent Faber; Wandall, Johan

    2008-01-01

    Herpes simplex virus type 2 (HSV-2) infections of the central nervous system (CNS) are rare with meningitis as the most common clinical presentation. We have investigated the clinical spectrum of CNS infections in 49 adult consecutive patients with HSV-2 genome in the cerebrospinal fluid (CSF). HSV......-2 in the CSF was determined by polymerase chain reaction (PCR), and patients were diagnosed as encephalitis or meningitis according to predefined clinical criteria by retrospective data information from consecutive clinical journals. The annual crude incidence rate of HSV-2 CNS disease was 0.26 per...... 100,000. 43 (88%) had meningitis of whom 8 (19%) had recurring lymphocytic meningitis. Six patients (12%) had encephalitis. 11 of 49 patients (22%) had sequelae recorded during follow-up. None died as a result of HSV-2 CNS disease. Thus, the clinical presentation of HSV-2 infection of the CNS...

  10. Operation Inherent Resolve

    Science.gov (United States)

    2015-04-01

    a revised certification with Jordan’s Water Author- ity to inform funding decisions, in particular, for a new plant in Tafilah Governorate worth...Germany Moldova Slovakia Bahrain Greece Montenegro Slovenia Belgium Hungary Morocco Somalia Bosnia and Herzegovina Iceland The Netherlands...treatment plant in Tafilah Governorate worth about $18 million. Certification is required by Section 611(e) of the Foreign Assistance Act of 1961, as

  11. Nuclear deterrence: Inherent escalation?

    International Nuclear Information System (INIS)

    Bergbauer, J.R. Jr.

    1993-01-01

    Despite 40 years of peace between the super powers, there is increasing clamor to the effect that nuclear war between the super powers is imminent; or could occur through escalation from a minor conflict; or could result from harsh rhetoric (but only on the part of the U.S.) in the super power dialogue. The factor that is ignored is that a massive nuclear attack would be rational ONLY if that attack could inflict such damage that the other super power could not launch a significant retaliatory nuclear attack. ONLY in this circumstance would there be any profit in launching an initial Strategic Nuclear Attack. This First Strike capability is not now possessed nor projected to be developed by either super power. As long as ANY possible Strategic Nuclear Attack against the national territory of one super power would be insufficient to prevent an equally destructive retaliatory attack, then a Strategic Nuclear Attack would inevitably result in the destruction of both and would be profitless, hence, pointless. This situation describes Mutually Assured Destruction (MAD), the governing conflict paradigm applicable to both super powers. The only convential attack that would even remotely rival the national-destruction potential of a Strategic Nuclear Attack and could cause the attacked power to consider launching a retaliatory Strategic Nuclear Attack would be a massive land-air invasion/occupation of one super power by the other. Since neither super power can successfully execute such a conventional invasion/occupation, this situation is moot. The geo-political environments of the two super powers are so asymmetrical and their military positions so symmetrical that the probability of ANY forseeable situation resulting in their resorting to a Strategic Nuclear Exchange is vanishingly small. It is possible escape the Chicken-Little syndrome and, instead, devote energy to ensuring the maintenance of this favorable, but fragile, world system

  12. Computational genomics of hyperthermophiles

    NARCIS (Netherlands)

    Werken, van de H.J.G.

    2008-01-01

    With the ever increasing number of completely sequenced prokaryotic genomes and the subsequent use of functional genomics tools, e.g. DNA microarray and proteomics, computational data analysis and the integration of microbial and molecular data is inevitable. This thesis describes the computational

  13. Safeguarding genome integrity

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Syljuåsen, Randi G

    2012-01-01

    Mechanisms that preserve genome integrity are highly important during the normal life cycle of human cells. Loss of genome protective mechanisms can lead to the development of diseases such as cancer. Checkpoint kinases function in the cellular surveillance pathways that help cells to cope with D...

  14. Human genome I

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    An international conference, Human Genome I, was held Oct. 2-4, 1989 in San Diego, Calif. Selected speakers discussed: Current Status of the Genome Project; Technique Innovations; Interesting regions; Applications; and Organization - Different Views of Current and Future Science and Procedures. Posters, consisting of 119 presentations, were displayed during the sessions. 119 were indexed for inclusion to the Energy Data Base

  15. Effect of x-ray treatments on pathogenic bacteria, inherent microbiota, color, and texture on parsley leaves.

    Science.gov (United States)

    Mahmoud, Barakat S M

    2012-10-01

    This work is a part of systematic studies of the effect of X-ray treatments on fresh produce. The main objective of this investigation was to study the effects of X-ray treatments in reducing the concentration of artificially inoculated Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica, and Shigella flexneri, and inherent microbiota on parsley leaves. The secondary objective was to study the effects of X-ray treatments on color and texture parameters on treated parsley leaves. The Dip-inoculated method was used to inoculate parsley leaves with a mixture of two or three strains of each tested organism at 10(8) to 10(9) colony-forming unit (CFU)/mL; the inoculated parsley leaves were then air-dried and followed by treatment with different doses of X-ray (0, 0.1, 0.5, 1.0, and 1.5 kGy) at 22°C and 55-60% relative humidity. Surviving bacterial populations on parsley leaves were evaluated using a nonselective medium (tryptic soy agar) with a selective medium overlay for each bacterium: E. coli O157:H7 (CT-SMAC agar), L. monocytogenes (MOA), and S. enterica and S. flexneri (XLD). Approximately 5.8, 3.1, 5.7, and 5.2 log CFU reductions of E. coli O157:H7, L. monocytogenes, S. enterica, and Shigella flexneri were achieved by treatment with 1.0 kGy X-ray, respectively. Furthermore, the populations of E. coli O157:H7, L. monocytogenes, S. enterica, and Shigella flexneri were reduced to less than the detectable limit (1.0 log CFU/g) by treatment with 1.5 kGy X-ray. Treatment with 1.5 kGy X-ray significantly reduced the initial inherent microbiota on parsley leaves, and inherent levels were significantly (p 0.05) in color or texture of control and treated samples with 0.1-1.5 X-ray were observed. The results of investigation indicated that X-ray is an effective technology to eliminate E. coli O157:H7, L. monocytogenes, S. enterica, and Shigella flexneri, and to extend the shelf life of parsley leaves.

  16. Rumen microbial genomics

    International Nuclear Information System (INIS)

    Morrison, M.; Nelson, K.E.

    2005-01-01

    Improving microbial degradation of plant cell wall polysaccharides remains one of the highest priority goals for all livestock enterprises, including the cattle herds and draught animals of developing countries. The North American Consortium for Genomics of Fibrolytic Ruminal Bacteria was created to promote the sequencing and comparative analysis of rumen microbial genomes, offering the potential to fully assess the genetic potential in a functional and comparative fashion. It has been found that the Fibrobacter succinogenes genome encodes many more endoglucanases and cellodextrinases than previously isolated, and several new processive endoglucanases have been identified by genome and proteomic analysis of Ruminococcus albus, in addition to a variety of strategies for its adhesion to fibre. The ramifications of acquiring genome sequence data for rumen microorganisms are profound, including the potential to elucidate and overcome the biochemical, ecological or physiological processes that are rate limiting for ruminal fibre degradation. (author)

  17. Microbial Genomes Multiply

    Science.gov (United States)

    Doolittle, Russell F.

    2002-01-01

    The publication of the first complete sequence of a bacterial genome in 1995 was a signal event, underscored by the fact that the article has been cited more than 2,100 times during the intervening seven years. It was a marvelous technical achievement, made possible by automatic DNA-sequencing machines. The feat is the more impressive in that complete genome sequencing has now been adopted in many different laboratories around the world. Four years ago in these columns I examined the situation after a dozen microbial genomes had been completed. Now, with upwards of 60 microbial genome sequences determined and twice that many in progress, it seems reasonable to assess just what is being learned. Are new concepts emerging about how cells work? Have there been practical benefits in the fields of medicine and agriculture? Is it feasible to determine the genomic sequence of every bacterial species on Earth? The answers to these questions maybe Yes, Perhaps, and No, respectively.

  18. Musa sebagai Model Genom

    Directory of Open Access Journals (Sweden)

    RITA MEGIA

    2005-12-01

    Full Text Available During the meeting in Arlington, USA in 2001, the scientists grouped in PROMUSA agreed with the launching of the Global Musa Genomics Consortium. The Consortium aims to apply genomics technologies to the improvement of this important crop. These genome projects put banana as the third model species after Arabidopsis and rice that will be analyzed and sequenced. Comparing to Arabidopsis and rice, banana genome provides a unique and powerful insight into structural and in functional genomics that could not be found in those two species. This paper discussed these subjects-including the importance of banana as the fourth main food in the world, the evolution and biodiversity of this genetic resource and its parasite.

  19. The genome editing revolution

    DEFF Research Database (Denmark)

    Stella, Stefano; Montoya, Guillermo

    2016-01-01

    -Cas system has become the main tool for genome editing in many laboratories. Currently the targeted genome editing technology has been used in many fields and may be a possible approach for human gene therapy. Furthermore, it can also be used to modifying the genomes of model organisms for studying human......In the last 10 years, we have witnessed a blooming of targeted genome editing systems and applications. The area was revolutionized by the discovery and characterization of the transcription activator-like effector proteins, which are easier to engineer to target new DNA sequences than...... sequence). This ribonucleoprotein complex protects bacteria from invading DNAs, and it was adapted to be used in genome editing. The CRISPR ribonucleic acid (RNA) molecule guides to the specific DNA site the Cas9 nuclease to cleave the DNA target. Two years and more than 1000 publications later, the CRISPR...

  20. Denoising and dimensionality reduction of genomic data

    Science.gov (United States)

    Capobianco, Enrico

    2005-05-01

    Genomics represents a challenging research field for many quantitative scientists, and recently a vast variety of statistical techniques and machine learning algorithms have been proposed and inspired by cross-disciplinary work with computational and systems biologists. In genomic applications, the researcher deals with noisy and complex high-dimensional feature spaces; a wealth of genes whose expression levels are experimentally measured, can often be observed for just a few time points, thus limiting the available samples. This unbalanced combination suggests that it might be hard for standard statistical inference techniques to come up with good general solutions, likewise for machine learning algorithms to avoid heavy computational work. Thus, one naturally turns to two major aspects of the problem: sparsity and intrinsic dimensionality. These two aspects are studied in this paper, where for both denoising and dimensionality reduction, a very efficient technique, i.e., Independent Component Analysis, is used. The numerical results are very promising, and lead to a very good quality of gene feature selection, due to the signal separation power enabled by the decomposition technique. We investigate how the use of replicates can improve these results, and deal with noise through a stabilization strategy which combines the estimated components and extracts the most informative biological information from them. Exploiting the inherent level of sparsity is a key issue in genetic regulatory networks, where the connectivity matrix needs to account for the real links among genes and discard many redundancies. Most experimental evidence suggests that real gene-gene connections represent indeed a subset of what is usually mapped onto either a huge gene vector or a typically dense and highly structured network. Inferring gene network connectivity from the expression levels represents a challenging inverse problem that is at present stimulating key research in biomedical

  1. A model for roll stall and the inherent stability modes of low aspect ratio wings at low Reynolds numbers

    Science.gov (United States)

    Shields, Matt

    The development of Micro Aerial Vehicles has been hindered by the poor understanding of the aerodynamic loading and stability and control properties of the low Reynolds number regime in which the inherent low aspect ratio (LAR) wings operate. This thesis experimentally evaluates the static and damping aerodynamic stability derivatives to provide a complete aerodynamic model for canonical flat plate wings of aspect ratios near unity at Reynolds numbers under 1 x 105. This permits the complete functionality of the aerodynamic forces and moments to be expressed and the equations of motion to solved, thereby identifying the inherent stability properties of the wing. This provides a basis for characterizing the stability of full vehicles. The influence of the tip vortices during sideslip perturbations is found to induce a loading condition referred to as roll stall, a significant roll moment created by the spanwise induced velocity asymmetry related to the displacement of the vortex cores relative to the wing. Roll stall is manifested by a linearly increasing roll moment with low to moderate angles of attack and a subsequent stall event similar to a lift polar; this behavior is not experienced by conventional (high aspect ratio) wings. The resulting large magnitude of the roll stability derivative, Cl,beta and lack of roll damping, Cl ,rho, create significant modal responses of the lateral state variables; a linear model used to evaluate these modes is shown to accurately reflect the solution obtained by numerically integrating the nonlinear equations. An unstable Dutch roll mode dominates the behavior of the wing for small perturbations from equilibrium, and in the presence of angle of attack oscillations a previously unconsidered coupled mode, referred to as roll resonance, is seen develop and drive the bank angle? away from equilibrium. Roll resonance requires a linear time variant (LTV) model to capture the behavior of the bank angle, which is attributed to the

  2. Prostaglandin E2 enhances long-term repopulation but does not permanently alter inherent stem cell competitiveness.

    Science.gov (United States)

    Hoggatt, Jonathan; Mohammad, Khalid S; Singh, Pratibha; Pelus, Louis M

    2013-10-24

    Hematopoietic stem cell (HSC) transplantation is a lifesaving therapy for malignant and nonmalignant hematologic diseases and metabolic disorders. Although successful, hematopoietic transplantation can be hindered by inadequate stem cell number or poor engrafting efficiency. To overcome these deficits, we and others have previously reported the HSC-enhancing ability of a short-term exposure of prostaglandin E2 (PGE2); this strategy has now progressed to phase 1 clinical trials in double cord blood transplantation. To further analyze the short- and long-term effects of HSC exposure to PGE2, we followed the repopulation kinetics of PGE2-treated hematopoietic grafts through 5 serial transplantations and compared inherent long-term competitiveness in a HSC head-to-head secondary transplantation model. Treatment with PGE2 did not result in a long-term increase in HSC competitiveness, lineage bias, or enhanced proliferative potential, demonstrating that pulse exposure to PGE2 results in transient increases in HSC homing and engraftment potential.

  3. Inherent Electrochemistry and Charge Transfer Properties of Few-Layer Two Dimensional Ti3C2Tx MXene

    KAUST Repository

    Nayak, Pranati

    2018-05-25

    We report the effect of Ti3C2Tx MXene flake thickness on its inherent electrochemistry and heterogeneous charge transfer characteristics. It is shown that the Ti3C2Tx undergoes irreversible oxidation in the positive potential window, which strongly depends on the flake thickness and pH of the electrolyte. Few-layer Ti3C2Tx exhibits faster electron transfer kinetics (k0=0.09533 cm/s) with Fe(CN)64−/3− redox mediator compared to multi-layer Ti3C2Tx (k0= 0.00503 cm/s). In addition, few-layer free standing Ti3C2Tx film electrode remains intact after enduring irreversible oxidation.

  4. Movie Popularity Classification based on Inherent Movie Attributes using C4.5, PART and Correlation Coefficient

    DEFF Research Database (Denmark)

    Ibnal Asad, Khalid; Ahmed, Tanvir; Rahman, Md. Saiedur

    2012-01-01

    Abundance of movie data across the internet makes it an obvious candidate for machine learning and knowledge discovery. But most researches are directed towards bi-polar classification of movie or generation of a movie recommendation system based on reviews given by viewers on various internet...... sites. Classification of movie popularity based solely on attributes of a movie i.e. actor, actress, director rating, language, country and budget etc. has been less highlighted due to large number of attributes that are associated with each movie and their differences in dimensions. In this paper, we...... propose classification scheme of pre-release movie popularity based on inherent attributes using C4.S and PART classifier algorithm and define the relation between attributes of post release movies using correlation coefficient....

  5. Generating millimeter-wave Bessel beam with orbital angular momentum using reflective-type metasurface inherently integrated with source

    Science.gov (United States)

    Shen, Yizhu; Yang, Jiawei; Meng, Hongfu; Dou, Wenbin; Hu, Sanming

    2018-04-01

    Metasurfaces, orbital angular momenta (OAM), and non-diffractive Bessel beams have been attracting worldwide research. Combining the benefits of these three promising techniques, this paper proposes a metasurface-based reflective-type approach to generate a first-order Bessel beam carrying OAM. To validate this approach, a millimeter-wave metasurface is analyzed, designed, fabricated, and measured. Experimental results agree well with simulation. Moreover, this reflective-type metasurface, generating a Bessel beam with OAM, is inherently integrated with a planar feeding source in the same single-layer printed circuit board. Therefore, the proposed design features low profile, low cost, easy integration with front-end active circuits, and no alignment error between the feeding source and the metasurface.

  6. Inherent Electrochemistry and Charge Transfer Properties of Few-Layer Two Dimensional Ti3C2Tx MXene

    KAUST Repository

    Nayak, Pranati; Jiang, Qiu; Mohanraman, Rajeshkumar; Anjum, Dalaver H.; Hedhili, Mohamed N.; Alshareef, Husam N.

    2018-01-01

    We report the effect of Ti3C2Tx MXene flake thickness on its inherent electrochemistry and heterogeneous charge transfer characteristics. It is shown that the Ti3C2Tx undergoes irreversible oxidation in the positive potential window, which strongly depends on the flake thickness and pH of the electrolyte. Few-layer Ti3C2Tx exhibits faster electron transfer kinetics (k0=0.09533 cm/s) with Fe(CN)64−/3− redox mediator compared to multi-layer Ti3C2Tx (k0= 0.00503 cm/s). In addition, few-layer free standing Ti3C2Tx film electrode remains intact after enduring irreversible oxidation.

  7. Phytozome Comparative Plant Genomics Portal

    Energy Technology Data Exchange (ETDEWEB)

    Goodstein, David; Batra, Sajeev; Carlson, Joseph; Hayes, Richard; Phillips, Jeremy; Shu, Shengqiang; Schmutz, Jeremy; Rokhsar, Daniel

    2014-09-09

    The Dept. of Energy Joint Genome Institute is a genomics user facility supporting DOE mission science in the areas of Bioenergy, Carbon Cycling, and Biogeochemistry. The Plant Program at the JGI applies genomic, analytical, computational and informatics platforms and methods to: 1. Understand and accelerate the improvement (domestication) of bioenergy crops 2. Characterize and moderate plant response to climate change 3. Use comparative genomics to identify constrained elements and infer gene function 4. Build high quality genomic resource platforms of JGI Plant Flagship genomes for functional and experimental work 5. Expand functional genomic resources for Plant Flagship genomes

  8. TDP-43 inclusion bodies formed in bacteria are structurally amorphous, non-amyloid and inherently toxic to neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Claudia Capitini

    Full Text Available Accumulation of ubiquitin-positive, tau- and α-synuclein-negative intracellular inclusions of TDP-43 in the central nervous system represents the major hallmark correlated to amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. Such inclusions have variably been described as amorphous aggregates or more structured deposits having an amyloid structure. Following the observations that bacterial inclusion bodies generally consist of amyloid aggregates, we have overexpressed full-length TDP-43 and C-terminal TDP-43 in E. coli, purified the resulting full-length and C-terminal TDP-43 containing inclusion bodies (FL and Ct TDP-43 IBs and subjected them to biophysical analyses to assess their structure/morphology. We show that both FL and Ct TDP-43 aggregates contained in the bacterial IBs do not bind amyloid dyes such as thioflavin T and Congo red, possess a disordered secondary structure, as inferred using circular dichroism and infrared spectroscopies, and are susceptible to proteinase K digestion, thus possessing none of the hallmarks for amyloid. Moreover, atomic force microscopy revealed an irregular structure for both types of TDP-43 IBs and confirmed the absence of amyloid-like species after proteinase K treatment. Cell biology experiments showed that FL TDP-43 IBs were able to impair the viability of cultured neuroblastoma cells when added to their extracellular medium and, more markedly, when transfected into their cytosol, where they are at least in part ubiquitinated and phosphorylated. These data reveal an inherently high propensity of TDP-43 to form amorphous aggregates, which possess, however, an inherently high ability to cause cell dysfunction. This indicates that a gain of toxic function caused by TDP-43 deposits is effective in TDP-43 pathologies, in addition to possible loss of function mechanisms originating from the cellular mistrafficking of the protein.

  9. SU-F-J-47: Inherent Uncertainty in the Positional Shifts Determined by a Volumetric Cone Beam Imaging System

    International Nuclear Information System (INIS)

    Giri, U; Ganesh, T; Saini, V; Munshi, A; Sarkar, B; Mohanti, B

    2016-01-01

    Purpose: To quantify inherent uncertainty associated with a volumetric imaging system in its determination of positional shifts. Methods: The study was performed on an Elekta Axesse™ linac’s XVI cone beam computed tomography (CBCT) system. A CT image data set of a Penta- Guide phantom was used as reference image by placing isocenter at the center of the phantom.The phantom was placed arbitrarily on the couch close to isocenter and CBCT images were obtained. The CBCT dataset was matched with the reference image using XVI software and the shifts were determined in 6-dimensions. Without moving the phantom, this process was repeated 20 times consecutively within 30 minutes on a single day. Mean shifts and their standard deviations in all 6-dimensions were determined for all the 20 instances of imaging. For any given day, the first set of shifts obtained was kept as reference and the deviations of the subsequent 19 sets from the reference set were scored. Mean differences and their standard deviations were determined. In this way, data were obtained for 30 consecutive working days. Results: Tabulating the mean deviations and their standard deviations observed on each day for the 30 measurement days, systematic and random errors in the determination of shifts by XVI software were calculated. The systematic errors were found to be 0.03, 0.04 and 0.03 mm while random errors were 0.05, 0.06 and 0.06 mm in lateral, craniocaudal and anterio-posterior directions respectively. For rotational shifts, the systematic errors were 0.02°, 0.03° and 0.03° and random errors were 0.06°, 0.05° and 0.05° in pitch, roll and yaw directions respectively. Conclusion: The inherent uncertainties in every image guidance system should be assessed and baseline values established at the time of its commissioning. These shall be periodically tested as part of the QA protocol.

  10. New Markov Model Approaches to Deciphering Microbial Genome Function and Evolution: Comparative Genomics of Laterally Transferred Genes

    Energy Technology Data Exchange (ETDEWEB)

    Borodovsky, M.

    2013-04-11

    Algorithmic methods for gene prediction have been developed and successfully applied to many different prokaryotic genome sequences. As the set of genes in a particular genome is not homogeneous with respect to DNA sequence composition features, the GeneMark.hmm program utilizes two Markov models representing distinct classes of protein coding genes denoted "typical" and "atypical". Atypical genes are those whose DNA features deviate significantly from those classified as typical and they represent approximately 10% of any given genome. In addition to the inherent interest of more accurately predicting genes, the atypical status of these genes may also reflect their separate evolutionary ancestry from other genes in that genome. We hypothesize that atypical genes are largely comprised of those genes that have been relatively recently acquired through lateral gene transfer (LGT). If so, what fraction of atypical genes are such bona fide LGTs? We have made atypical gene predictions for all fully completed prokaryotic genomes; we have been able to compare these results to other "surrogate" methods of LGT prediction.

  11. INHIBITORY EFFECT OF SALVIA SCLAREA

    African Journals Online (AJOL)

    rakoe

    2011-11-02

    Nov 2, 2011 ... This study demonstrated anti-herpes simplex virus (HSV) activity of lavender, sage and ... Green monkey kidney cells were protected from HSV-2 infection by ... The highest inhibitory effect against HSV-2 was observed after treatment ..... some nuclear-replicating eukaryotic DNA viruses with large genomes.

  12. Genome-derived vaccines.

    Science.gov (United States)

    De Groot, Anne S; Rappuoli, Rino

    2004-02-01

    Vaccine research entered a new era when the complete genome of a pathogenic bacterium was published in 1995. Since then, more than 97 bacterial pathogens have been sequenced and at least 110 additional projects are now in progress. Genome sequencing has also dramatically accelerated: high-throughput facilities can draft the sequence of an entire microbe (two to four megabases) in 1 to 2 days. Vaccine developers are using microarrays, immunoinformatics, proteomics and high-throughput immunology assays to reduce the truly unmanageable volume of information available in genome databases to a manageable size. Vaccines composed by novel antigens discovered from genome mining are already in clinical trials. Within 5 years we can expect to see a novel class of vaccines composed by genome-predicted, assembled and engineered T- and Bcell epitopes. This article addresses the convergence of three forces--microbial genome sequencing, computational immunology and new vaccine technologies--that are shifting genome mining for vaccines onto the forefront of immunology research.

  13. The Banana Genome Hub

    Science.gov (United States)

    Droc, Gaëtan; Larivière, Delphine; Guignon, Valentin; Yahiaoui, Nabila; This, Dominique; Garsmeur, Olivier; Dereeper, Alexis; Hamelin, Chantal; Argout, Xavier; Dufayard, Jean-François; Lengelle, Juliette; Baurens, Franc-Christophe; Cenci, Alberto; Pitollat, Bertrand; D’Hont, Angélique; Ruiz, Manuel; Rouard, Mathieu; Bocs, Stéphanie

    2013-01-01

    Banana is one of the world’s favorite fruits and one of the most important crops for developing countries. The banana reference genome sequence (Musa acuminata) was recently released. Given the taxonomic position of Musa, the completed genomic sequence has particular comparative value to provide fresh insights about the evolution of the monocotyledons. The study of the banana genome has been enhanced by a number of tools and resources that allows harnessing its sequence. First, we set up essential tools such as a Community Annotation System, phylogenomics resources and metabolic pathways. Then, to support post-genomic efforts, we improved banana existing systems (e.g. web front end, query builder), we integrated available Musa data into generic systems (e.g. markers and genetic maps, synteny blocks), we have made interoperable with the banana hub, other existing systems containing Musa data (e.g. transcriptomics, rice reference genome, workflow manager) and finally, we generated new results from sequence analyses (e.g. SNP and polymorphism analysis). Several uses cases illustrate how the Banana Genome Hub can be used to study gene families. Overall, with this collaborative effort, we discuss the importance of the interoperability toward data integration between existing information systems. Database URL: http://banana-genome.cirad.fr/ PMID:23707967

  14. Genomic instability following irradiation

    International Nuclear Information System (INIS)

    Hacker-Klom, U.B.; Goehde, W.

    2001-01-01

    Ionising irradiation may induce genomic instability. The broad spectrum of stress reactions in eukaryontic cells to irradiation complicates the discovery of cellular targets and pathways inducing genomic instability. Irradiation may initiate genomic instability by deletion of genes controlling stability, by induction of genes stimulating instability and/or by activating endogeneous cellular viruses. Alternatively or additionally it is discussed that the initiation of genomic instability may be a consequence of radiation or other agents independently of DNA damage implying non nuclear targets, e.g. signal cascades. As a further mechanism possibly involved our own results may suggest radiation-induced changes in chromatin structure. Once initiated the process of genomic instability probably is perpetuated by endogeneous processes necessary for proliferation. Genomic instability may be a cause or a consequence of the neoplastic phenotype. As a conclusion from the data available up to now a new interpretation of low level radiation effects for radiation protection and in radiotherapy appears useful. The detection of the molecular mechanisms of genomic instability will be important in this context and may contribute to a better understanding of phenomenons occurring at low doses <10 cSv which are not well understood up to now. (orig.)

  15. Traditional medicine and genomics

    Directory of Open Access Journals (Sweden)

    Kalpana Joshi

    2010-01-01

    Full Text Available ′Omics′ developments in the form of genomics, proteomics and metabolomics have increased the impetus of traditional medicine research. Studies exploring the genomic, proteomic and metabolomic basis of human constitutional types based on Ayurveda and other systems of oriental medicine are becoming popular. Such studies remain important to developing better understanding of human variations and individual differences. Countries like India, Korea, China and Japan are investing in research on evidence-based traditional medicines and scientific validation of fundamental principles. This review provides an account of studies addressing relationships between traditional medicine and genomics.

  16. Traditional medicine and genomics.

    Science.gov (United States)

    Joshi, Kalpana; Ghodke, Yogita; Shintre, Pooja

    2010-01-01

    'Omics' developments in the form of genomics, proteomics and metabolomics have increased the impetus of traditional medicine research. Studies exploring the genomic, proteomic and metabolomic basis of human constitutional types based on Ayurveda and other systems of oriental medicine are becoming popular. Such studies remain important to developing better understanding of human variations and individual differences. Countries like India, Korea, China and Japan are investing in research on evidence-based traditional medicines and scientific validation of fundamental principles. This review provides an account of studies addressing relationships between traditional medicine and genomics.

  17. Bacillus subtilis genome diversity.

    Science.gov (United States)

    Earl, Ashlee M; Losick, Richard; Kolter, Roberto

    2007-02-01

    Microarray-based comparative genomic hybridization (M-CGH) is a powerful method for rapidly identifying regions of genome diversity among closely related organisms. We used M-CGH to examine the genome diversity of 17 strains belonging to the nonpathogenic species Bacillus subtilis. Our M-CGH results indicate that there is considerable genetic heterogeneity among members of this species; nearly one-third of Bsu168-specific genes exhibited variability, as measured by the microarray hybridization intensities. The variable loci include those encoding proteins involved in antibiotic production, cell wall synthesis, sporulation, and germination. The diversity in these genes may reflect this organism's ability to survive in diverse natural settings.

  18. Genomic taxonomy of vibrios

    Directory of Open Access Journals (Sweden)

    Iida Tetsuya

    2009-10-01

    Full Text Available Abstract Background Vibrio taxonomy has been based on a polyphasic approach. In this study, we retrieve useful taxonomic information (i.e. data that can be used to distinguish different taxonomic levels, such as species and genera from 32 genome sequences of different vibrio species. We use a variety of tools to explore the taxonomic relationship between the sequenced genomes, including Multilocus Sequence Analysis (MLSA, supertrees, Average Amino Acid Identity (AAI, genomic signatures, and Genome BLAST atlases. Our aim is to analyse the usefulness of these tools for species identification in vibrios. Results We have generated four new genome sequences of three Vibrio species, i.e., V. alginolyticus 40B, V. harveyi-like 1DA3, and V. mimicus strains VM573 and VM603, and present a broad analyses of these genomes along with other sequenced Vibrio species. The genome atlas and pangenome plots provide a tantalizing image of the genomic differences that occur between closely related sister species, e.g. V. cholerae and V. mimicus. The vibrio pangenome contains around 26504 genes. The V. cholerae core genome and pangenome consist of 1520 and 6923 genes, respectively. Pangenomes might allow different strains of V. cholerae to occupy different niches. MLSA and supertree analyses resulted in a similar phylogenetic picture, with a clear distinction of four groups (Vibrio core group, V. cholerae-V. mimicus, Aliivibrio spp., and Photobacterium spp.. A Vibrio species is defined as a group of strains that share > 95% DNA identity in MLSA and supertree analysis, > 96% AAI, ≤ 10 genome signature dissimilarity, and > 61% proteome identity. Strains of the same species and species of the same genus will form monophyletic groups on the basis of MLSA and supertree. Conclusion The combination of different analytical and bioinformatics tools will enable the most accurate species identification through genomic computational analysis. This endeavour will culminate in

  19. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  20. Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  1. Genomic signal processing

    CERN Document Server

    Shmulevich, Ilya

    2007-01-01

    Genomic signal processing (GSP) can be defined as the analysis, processing, and use of genomic signals to gain biological knowledge, and the translation of that knowledge into systems-based applications that can be used to diagnose and treat genetic diseases. Situated at the crossroads of engineering, biology, mathematics, statistics, and computer science, GSP requires the development of both nonlinear dynamical models that adequately represent genomic regulation, and diagnostic and therapeutic tools based on these models. This book facilitates these developments by providing rigorous mathema

  2. Distribution of herpes simplex virus types 1 and 2 genomes in human spinal ganglia studied by PCR and in situ hybridization.

    Science.gov (United States)

    Obara, Y; Furuta, Y; Takasu, T; Suzuki, S; Suzuki, H; Matsukawa, S; Fujioka, Y; Takahashi, H; Kurata, T; Nagashima, K

    1997-06-01

    Clinical data indicate that the recurring herpes simplex virus (HSV) from oro-labial lesions is HSV subtype 1 and that the virus from genital lesions is HSV-2. This suggests that HSV-1 and HSV-2 reside in latent forms in the trigeminal ganglia and sacral ganglia, respectively. However, the distribution of latent HSV-1 and HSV-2 infections in human spinal ganglia has not been fully examined. This report concerns the application of polymerase chain reaction (PCR) and in situ hybridization (ISH) to such a study. By using PCR and employing the respective primers, HSV-1 and HSV-2 DNAs were detected in 207 of 524 samples from 262 spinal ganglia (from the cervical to the sacral ganglia) examined on both sides. The percentages of HSV-1 and HSV-2 detected in a given set of ganglia were similar, indicating an absence of site preference. By ISH, few but positive hybridization signals were detected evenly in sacral ganglia sections. The data suggest that regional specificity of recurrent HSV infections is not due to regional distribution of latent virus, but that local host factors may be important for recurrences.

  3. Genomics and fish adaptation

    Directory of Open Access Journals (Sweden)

    Agostinho Antunes

    2015-12-01

    Full Text Available The completion of the human genome sequencing in 2003 opened a new perspective into the importance of whole genome sequencing projects, and currently multiple species are having their genomes completed sequenced, from simple organisms, such as bacteria, to more complex taxa, such as mammals. This voluminous sequencing data generated across multiple organisms provides also the framework to better understand the genetic makeup of such species and related ones, allowing to explore the genetic changes underlining the evolution of diverse phenotypic traits. Here, recent results from our group retrieved from comparative evolutionary genomic analyses of varied fish species will be considered to exemplify how gene novelty and gene enhancement by positive selection might have been determinant in the success of adaptive radiations into diverse habitats and lifestyles.

  4. Lophotrochozoan mitochondrial genomes

    Energy Technology Data Exchange (ETDEWEB)

    Valles, Yvonne; Boore, Jeffrey L.

    2005-10-01

    Progress in both molecular techniques and phylogeneticmethods has challenged many of the interpretations of traditionaltaxonomy. One example is in the recognition of the animal superphylumLophotrochozoa (annelids, mollusks, echiurans, platyhelminthes,brachiopods, and other phyla), although the relationships within thisgroup and the inclusion of some phyla remain uncertain. While much ofthis progress in phylogenetic reconstruction has been based on comparingsingle gene sequences, we are beginning to see the potential of comparinglarge-scale features of genomes, such as the relative order of genes.Even though tremendous progress is being made on the sequencedetermination of whole nuclear genomes, the dataset of choice forgenome-level characters for many animals across a broad taxonomic rangeremains mitochondrial genomes. We review here what is known aboutmitochondrial genomes of the lophotrochozoans and discuss the promisethat this dataset will enable insight into theirrelationships.

  5. Mouse Genome Informatics (MGI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  6. Genomic definition of species

    Energy Technology Data Exchange (ETDEWEB)

    Crkvenjakov, R.; Drmanac, R.

    1991-07-01

    The subject of this paper is the definition of species based on the assumption that genome is the fundamental level for the origin and maintenance of biological diversity. For this view to be logically consistent it is necessary to assume the existence and operation of the new law which we call genome law. For this reason the genome law is included in the explanation of species phenomenon presented here even if its precise formulation and elaboration are left for the future. The intellectual underpinnings of this definition can be traced to Goldschmidt. We wish to explore some philosophical aspects of the definition of species in terms of the genome. The point of proposing the definition on these grounds is that any real advance in evolutionary theory has to be correct in both its philosophy and its science.

  7. Structural genomics in endocrinology

    NARCIS (Netherlands)

    Smit, J. W.; Romijn, J. A.

    2001-01-01

    Traditionally, endocrine research evolved from the phenotypical characterisation of endocrine disorders to the identification of underlying molecular pathophysiology. This approach has been, and still is, extremely successful. The introduction of genomics and proteomics has resulted in a reversal of

  8. Epidemiology & Genomics Research Program

    Science.gov (United States)

    The Epidemiology and Genomics Research Program, in the National Cancer Institute's Division of Cancer Control and Population Sciences, funds research in human populations to understand the determinants of cancer occurrence and outcomes.

  9. Annotating individual human genomes.

    Science.gov (United States)

    Torkamani, Ali; Scott-Van Zeeland, Ashley A; Topol, Eric J; Schork, Nicholas J

    2011-10-01

    Advances in DNA sequencing technologies have made it possible to rapidly, accurately and affordably sequence entire individual human genomes. As impressive as this ability seems, however, it will not likely amount to much if one cannot extract meaningful information from individual sequence data. Annotating variations within individual genomes and providing information about their biological or phenotypic impact will thus be crucially important in moving individual sequencing projects forward, especially in the context of the clinical use of sequence information. In this paper we consider the various ways in which one might annotate individual sequence variations and point out limitations in the available methods for doing so. It is arguable that, in the foreseeable future, DNA sequencing of individual genomes will become routine for clinical, research, forensic, and personal purposes. We therefore also consider directions and areas for further research in annotating genomic variants. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. ANNOTATING INDIVIDUAL HUMAN GENOMES*

    Science.gov (United States)

    Torkamani, Ali; Scott-Van Zeeland, Ashley A.; Topol, Eric J.; Schork, Nicholas J.

    2014-01-01

    Advances in DNA sequencing technologies have made it possible to rapidly, accurately and affordably sequence entire individual human genomes. As impressive as this ability seems, however, it will not likely to amount to much if one cannot extract meaningful information from individual sequence data. Annotating variations within individual genomes and providing information about their biological or phenotypic impact will thus be crucially important in moving individual sequencing projects forward, especially in the context of the clinical use of sequence information. In this paper we consider the various ways in which one might annotate individual sequence variations and point out limitations in the available methods for doing so. It is arguable that, in the foreseeable future, DNA sequencing of individual genomes will become routine for clinical, research, forensic, and personal purposes. We therefore also consider directions and areas for further research in annotating genomic variants. PMID:21839162

  11. Yeast genome sequencing:

    DEFF Research Database (Denmark)

    Piskur, Jure; Langkjær, Rikke Breinhold

    2004-01-01

    For decades, unicellular yeasts have been general models to help understand the eukaryotic cell and also our own biology. Recently, over a dozen yeast genomes have been sequenced, providing the basis to resolve several complex biological questions. Analysis of the novel sequence data has shown...... of closely related species helps in gene annotation and to answer how many genes there really are within the genomes. Analysis of non-coding regions among closely related species has provided an example of how to determine novel gene regulatory sequences, which were previously difficult to analyse because...... they are short and degenerate and occupy different positions. Comparative genomics helps to understand the origin of yeasts and points out crucial molecular events in yeast evolutionary history, such as whole-genome duplication and horizontal gene transfer(s). In addition, the accumulating sequence data provide...

  12. Genetical Genomics for Evolutionary Studies

    NARCIS (Netherlands)

    Prins, J.C.P.; Smant, G.; Jansen, R.C.

    2012-01-01

    Genetical genomics combines acquired high-throughput genomic data with genetic analysis. In this chapter, we discuss the application of genetical genomics for evolutionary studies, where new high-throughput molecular technologies are combined with mapping quantitative trait loci (QTL) on the genome

  13. SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Ma, L; Braunstein, S; Chiu, J [University of California San Francisco, San Francisco, CA (United States); Sahgal, A [Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario (Canada)

    2016-06-15

    Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive an EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.

  14. The human genome project

    International Nuclear Information System (INIS)

    Worton, R.

    1996-01-01

    The Human Genome Project is a massive international research project, costing 3 to 5 billion dollars and expected to take 15 years, which will identify the all the genes in the human genome - i.e. the complete sequence of bases in human DNA. The prize will be the ability to identify genes causing or predisposing to disease, and in some cases the development of gene therapy, but this new knowledge will raise important ethical issues

  15. Decoding the human genome

    CERN Multimedia

    CERN. Geneva. Audiovisual Unit; Antonerakis, S E

    2002-01-01

    Decoding the Human genome is a very up-to-date topic, raising several questions besides purely scientific, in view of the two competing teams (public and private), the ethics of using the results, and the fact that the project went apparently faster and easier than expected. The lecture series will address the following chapters: Scientific basis and challenges. Ethical and social aspects of genomics.

  16. Molluscan Evolutionary Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Simison, W. Brian; Boore, Jeffrey L.

    2005-12-01

    In the last 20 years there have been dramatic advances in techniques of high-throughput DNA sequencing, most recently accelerated by the Human Genome Project, a program that has determined the three billion base pair code on which we are based. Now this tremendous capability is being directed at other genome targets that are being sampled across the broad range of life. This opens up opportunities as never before for evolutionary and organismal biologists to address questions of both processes and patterns of organismal change. We stand at the dawn of a new 'modern synthesis' period, paralleling that of the early 20th century when the fledgling field of genetics first identified the underlying basis for Darwin's theory. We must now unite the efforts of systematists, paleontologists, mathematicians, computer programmers, molecular biologists, developmental biologists, and others in the pursuit of discovering what genomics can teach us about the diversity of life. Genome-level sampling for mollusks to date has mostly been limited to mitochondrial genomes and it is likely that these will continue to provide the best targets for broad phylogenetic sampling in the near future. However, we are just beginning to see an inroad into complete nuclear genome sequencing, with several mollusks and other eutrochozoans having been selected for work about to begin. Here, we provide an overview of the state of molluscan mitochondrial genomics, highlight a few of the discoveries from this research, outline the promise of broadening this dataset, describe upcoming projects to sequence whole mollusk nuclear genomes, and challenge the community to prepare for making the best use of these data.

  17. Human Germline Genome Editing

    OpenAIRE

    Ormond, Kelly E.; Mortlock, Douglas P.; Scholes, Derek T.; Bombard, Yvonne; Brody, Lawrence C.; Faucett, W. Andrew; Garrison, Nanibaa’ A.; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E.

    2017-01-01

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Gen...

  18. RadGenomics project

    Energy Technology Data Exchange (ETDEWEB)

    Iwakawa, Mayumi; Imai, Takashi; Harada, Yoshinobu [National Inst. of Radiological Sciences, Chiba (Japan). Frontier Research Center] [and others

    2002-06-01

    Human health is determined by a complex interplay of factors, predominantly between genetic susceptibility, environmental conditions and aging. The ultimate aim of the RadGenomics (Radiation Genomics) project is to understand the implications of heterogeneity in responses to ionizing radiation arising from genetic variation between individuals in the human population. The rapid progression of the human genome sequencing and the recent development of new technologies in molecular genetics are providing us with new opportunities to understand the genetic basis of individual differences in susceptibility to natural and/or artificial environmental factors, including radiation exposure. The RadGenomics project will inevitably lead to improved protocols for personalized radiotherapy and reductions in the potential side effects of such treatment. The project will contribute to future research into the molecular mechanisms of radiation sensitivity in humans and will stimulate the development of new high-throughput technologies for a broader application of biological and medical sciences. The staff members are specialists in a variety of fields, including genome science, radiation biology, medical science, molecular biology, and informatics, and have joined the RadGenomics project from various universities, companies, and research institutes. The project started in April 2001. (author)

  19. Comparative Genome Viewer

    International Nuclear Information System (INIS)

    Molineris, I.; Sales, G.

    2009-01-01

    The amount of information about genomes, both in the form of complete sequences and annotations, has been exponentially increasing in the last few years. As a result there is the need for tools providing a graphical representation of such information that should be comprehensive and intuitive. Visual representation is especially important in the comparative genomics field since it should provide a combined view of data belonging to different genomes. We believe that existing tools are limited in this respect as they focus on a single genome at a time (conservation histograms) or compress alignment representation to a single dimension. We have therefore developed a web-based tool called Comparative Genome Viewer (Cgv): it integrates a bidimensional representation of alignments between two regions, both at small and big scales, with the richness of annotations present in other genome browsers. We give access to our system through a web-based interface that provides the user with an interactive representation that can be updated in real time using the mouse to move from region to region and to zoom in on interesting details.

  20. Human social genomics.

    Directory of Open Access Journals (Sweden)

    Steven W Cole

    2014-08-01

    Full Text Available A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.