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Sample records for integration host factor

  1. Requirement for Vibrio cholerae Integration Host Factor in Conjugative DNA Transfer

    OpenAIRE

    McLeod, Sarah M.; Burrus, Vincent; Waldor, Matthew K.

    2006-01-01

    The requirement for host factors in the transmission of integrative and conjugative elements (ICEs) has not been extensively explored. Here we tested whether integration host factor (IHF) or Fis, two host-encoded nucleoid proteins, are required for transfer of SXT, a Vibrio cholerae-derived ICE that can be transmitted to many gram-negative species. Fis did not influence the transfer of SXT to or from V. cholerae. In contrast, IHF proved to be required for V. cholerae to act as an SXT donor. I...

  2. Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

    Directory of Open Access Journals (Sweden)

    Sudhir Kumar Rai

    2017-12-01

    Full Text Available Retroviruses and Long Terminal Repeat (LTR-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

  3. Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

    Science.gov (United States)

    Rai, Sudhir Kumar; Sangesland, Maya; Lee, Michael; Esnault, Caroline; Cui, Yujin; Chatterjee, Atreyi Ghatak; Levin, Henry L

    2017-12-01

    Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

  4. Requirement for Vibrio cholerae integration host factor in conjugative DNA transfer.

    Science.gov (United States)

    McLeod, Sarah M; Burrus, Vincent; Waldor, Matthew K

    2006-08-01

    The requirement for host factors in the transmission of integrative and conjugative elements (ICEs) has not been extensively explored. Here we tested whether integration host factor (IHF) or Fis, two host-encoded nucleoid proteins, are required for transfer of SXT, a Vibrio cholerae-derived ICE that can be transmitted to many gram-negative species. Fis did not influence the transfer of SXT to or from V. cholerae. In contrast, IHF proved to be required for V. cholerae to act as an SXT donor. In the absence of IHF, V. cholerae displayed a modest defect for serving as an SXT recipient. Surprisingly, SXT integration into or excision from the V. cholerae chromosome, which requires an SXT-encoded integrase related to lambda integrase, did not require IHF. Therefore, the defect in SXT transmission in the V. cholerae IHF mutant is probably not related to IHF's ability to promote DNA recombination. The V. cholerae IHF mutant was also highly impaired as a donor of RP4, a broad-host-range conjugative plasmid. Thus, the V. cholerae IHF mutant appears to have a general defect in conjugation. Escherichia coli IHF mutants were not impaired as donors or recipients of SXT or RP4, indicating that IHF is a V. cholerae-specific conjugation factor.

  5. Two-step interrogation then recognition of DNA binding site by Integration Host Factor: an architectural DNA-bending protein.

    Science.gov (United States)

    Velmurugu, Yogambigai; Vivas, Paula; Connolly, Mitchell; Kuznetsov, Serguei V; Rice, Phoebe A; Ansari, Anjum

    2018-02-28

    The dynamics and mechanism of how site-specific DNA-bending proteins initially interrogate potential binding sites prior to recognition have remained elusive for most systems. Here we present these dynamics for Integration Host factor (IHF), a nucleoid-associated architectural protein, using a μs-resolved T-jump approach. Our studies show two distinct DNA-bending steps during site recognition by IHF. While the faster (∼100 μs) step is unaffected by changes in DNA or protein sequence that alter affinity by >100-fold, the slower (1-10 ms) step is accelerated ∼5-fold when mismatches are introduced at DNA sites that are sharply kinked in the specific complex. The amplitudes of the fast phase increase when the specific complex is destabilized and decrease with increasing [salt], which increases specificity. Taken together, these results indicate that the fast phase is non-specific DNA bending while the slow phase, which responds only to changes in DNA flexibility at the kink sites, is specific DNA kinking during site recognition. Notably, the timescales for the fast phase overlap with one-dimensional diffusion times measured for several proteins on DNA, suggesting that these dynamics reflect partial DNA bending during interrogation of potential binding sites by IHF as it scans DNA.

  6. Guidelines for Hosted Payload Integration

    Science.gov (United States)

    2014-06-06

    reduces risk. Need to consider mass simulator to protect host launch window. Average Payload Power Both BOL and EOL . Host must consider orbit...acceptance testing. Peak Payload Power Both BOL and EOL . Host must consider orbit constraints. Typically driven by Payload operations but must...post-retirement failure might cause damage to the Spacecraft Host or its payloads. Safe conditions at EOL should consider thermal and radiation

  7. Purification, crystallization and preliminary X-ray analysis of SGR6054, a Streptomyces homologue of the mycobacterial integration host factor mIHF

    International Nuclear Information System (INIS)

    Nomoto, Ryohei; Tezuka, Takeaki; Miyazono, Ken-ichi; Tanokura, Masaru; Horinouchi, Sueharu; Ohnishi, Yasuo

    2012-01-01

    A Streptomyces homologue of the mycobacterial integration host factor mIHF was heterologously produced, purified and crystallized in the presence of a 16-mer duplex DNA by the sitting-drop vapour-diffusion method. The best crystal diffracted X-rays to 2.22 Å resolution and belonged to space group C2. The mycobacterial integration host factor (mIHF) is a small nonspecific DNA-binding protein that is essential for the growth of Mycobacterium smegmatis. mIHF homologues are widely distributed among Actinobacteria, and a Streptomyces homologue of mIHF is involved in control of sporulation and antibiotic production in S. coelicolor A3(2). Despite their important biological functions, a structure of mIHF or its homologues has not been elucidated to date. Here, the S. griseus mIHF homologue (SGR6054) was expressed and purified from Escherichia coli and crystallized in the presence of a 16-mer duplex DNA by the sitting-drop vapour-diffusion method. The plate-shaped crystal belonged to space group C2, with unit-cell parameters a = 88.53, b = 69.35, c = 77.71 Å, β = 96.63°, and diffracted X-rays to 2.22 Å resolution

  8. Purification, crystallization and preliminary X-ray analysis of SGR6054, a Streptomyces homologue of the mycobacterial integration host factor mIHF

    Energy Technology Data Exchange (ETDEWEB)

    Nomoto, Ryohei; Tezuka, Takeaki; Miyazono, Ken-ichi; Tanokura, Masaru; Horinouchi, Sueharu; Ohnishi, Yasuo [Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan)

    2012-08-31

    A Streptomyces homologue of the mycobacterial integration host factor mIHF was heterologously produced, purified and crystallized in the presence of a 16-mer duplex DNA by the sitting-drop vapour-diffusion method. The best crystal diffracted X-rays to 2.22 Å resolution and belonged to space group C2. The mycobacterial integration host factor (mIHF) is a small nonspecific DNA-binding protein that is essential for the growth of Mycobacterium smegmatis. mIHF homologues are widely distributed among Actinobacteria, and a Streptomyces homologue of mIHF is involved in control of sporulation and antibiotic production in S. coelicolor A3(2). Despite their important biological functions, a structure of mIHF or its homologues has not been elucidated to date. Here, the S. griseus mIHF homologue (SGR6054) was expressed and purified from Escherichia coli and crystallized in the presence of a 16-mer duplex DNA by the sitting-drop vapour-diffusion method. The plate-shaped crystal belonged to space group C2, with unit-cell parameters a = 88.53, b = 69.35, c = 77.71 Å, β = 96.63°, and diffracted X-rays to 2.22 Å resolution.

  9. Host Factors in Ebola Infection.

    Science.gov (United States)

    Rasmussen, Angela L

    2016-08-31

    Ebola virus (EBOV) emerged in West Africa in 2014 to devastating effect, and demonstrated that infection can cause a broad range of severe disease manifestations. As the virus itself was genetically similar to other Zaire ebolaviruses, the spectrum of pathology likely resulted from variable responses to infection in a large and genetically diverse population. This review comprehensively summarizes current knowledge of the host response to EBOV infection, including pathways hijacked by the virus to facilitate replication, host processes that contribute directly to pathogenesis, and host-pathogen interactions involved in subverting or antagonizing host antiviral immunity.

  10. Host factors in nidovirus replication

    NARCIS (Netherlands)

    Wilde, Adriaan Hugo de

    2013-01-01

    The interplay between nidoviruses and the infected host cell was investigated. Arterivirus RNA-synthesising activity was shown to depend on intact membranes and on a cytosolic host protein which does not cosediment with the RTC. Furthermore, the immunosuppressant drug cyclosporin A (CsA) blocks

  11. Integration Host Factor (IHF binds to the promoter region of the phtD operon involved in phaseolotoxin synthesis in P. syringae pv. phaseolicola NPS3121

    Directory of Open Access Journals (Sweden)

    Álvarez-Morales Ariel

    2011-05-01

    Full Text Available Abstract Background Pseudomonas syringae pv. phaseolicola, the causal agent of halo blight disease in beans, produces a toxin known as phaseolotoxin, in whose synthesis participate a group of genes organized within the genome in a region known as the "Pht cluster". This region, which is thought to have been acquired by horizontal gene transfer, includes 5 transcriptional units, two monocistronic (argK, phtL and three polycistronic (phtA, phtD, phtM, whose expression is temperature dependent. So far, the regulatory mechanisms involved in phaseolotoxin synthesis have not been elucidated and the only well-established fact is the requirement of low temperatures for its synthesis. In this work, we searched for regulatory proteins that could be involved in phaseolotoxin synthesis, focusing on the regulation of the phtD operon. Results In this study we identified the global regulator IHF (Integration Host Factor, which binds to the promoter region of the phtD operon, exerting a negative effect on the expression of this operon. This is the first regulatory protein identified as part of the phaseolotoxin synthesis system. Our findings suggest that the Pht cluster was similarly regulated in the ancestral cluster by IHF or similar protein, and integrated into the global regulatory mechanism of P. syringae pv. phaseolicola, after the horizontal gene transfer event by using the host IHF protein. Conclusion This study identifies the IHF protein as one element involved in the regulation of phaseolotoxin synthesis in P. syringae pv. phaseolicola NPS3121 and provides new insights into the regulatory mechanisms involved in phaseolotoxin production.

  12. Host factors influencing viral persistence

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Nansen, A; Ørding Andreasen, Susanne

    2000-01-01

    host were used. Our results reveal that very different outcomes may be observed depending on virus strain and immunocompetence of the host. Thus while CD4+ cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4+ cells, B cells or CD40 ligand...... replication, mice lacking the ability to produce interferon-gamma may develop either a severe, mostly fatal, T-cell mediated wasting syndrome or a chronic infection characterized by long-term coexistence of antiviral cytotoxic T lymphocytes and infectious virus. Mathematical modelling indicates...

  13. PHIDIAS- Pathogen Host Interaction Data Integration and Analysis

    Indian Academy of Sciences (India)

    PHIDIAS- Pathogen Host Interaction Data Integration and Analysis- allows searching of integrated genome sequences, conserved domains and gene expressions data related to pathogen host interactions in high priority agents for public health and security ...

  14. Late effects of radiation: host factors

    International Nuclear Information System (INIS)

    Fry, R.J.M.; Storer, J.B.

    1983-01-01

    The paper discusses the influence of host factors on radiation late effects and in particular cancer. Radiation induces cellular changes that result in initiated cells with a potential to become cancers. The expression of the initiated cells as tumors is influenced, if not determined, by both tissue and systemic factors that are sex-, age-, and species-dependent

  15. Novel host restriction factors implicated in HIV-1 replication.

    Science.gov (United States)

    Ghimire, Dibya; Rai, Madhu; Gaur, Ritu

    2018-04-01

    Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

  16. The Poxvirus C7L Host Range Factor Superfamily

    OpenAIRE

    Liu, Jia; Rothenburg, Stefan; McFadden, Grant

    2012-01-01

    Host range factors, expressed by the poxvirus family, determine the host tropism of species, tissue, and cell specificity. C7L family members exist in the genomes of most sequenced mammalian poxviruses, suggesting an evolutionarily conserved effort adapting to the hosts. In general, C7L orthologs influence the host tropism in mammalian cell culture, and for some poxviruses it is essential for the complete viral life cycle in vitro and in vivo. The C7L family members lack obvious sequence homo...

  17. Host Competence: An Organismal Trait to Integrate Immunology and Epidemiology.

    Science.gov (United States)

    Martin, Lynn B; Burgan, S C; Adelman, James S; Gervasi, Stephanie S

    2016-12-01

    The new fields of ecological immunology and disease ecology have begun to merge, and the classic fields of immunology and epidemiology are beginning to blend with them. This merger is occurring because the integrative study of host-parasite interactions is providing insights into disease in ways that traditional methods have not. With the advent of new tools, mathematical and technological, we could be on the verge of developing a unified theory of infectious disease, one that supersedes the barriers of jargon and tradition. Here we argue that a cornerstone of any such synthesis will be host competence, the propensity of an individual host to generate new infections in other susceptible hosts. In the last few years, the emergence of systems immunology has led to novel insight into how hosts control or eliminate pathogens. Most such efforts have stopped short of considering transmission and the requisite behaviors of infected individuals that mediate it, and few have explicitly incorporated ecological and evolutionary principles. Ultimately though, we expect that the use of a systems immunology perspective will help link suborganismal processes (i.e., health of hosts and selection on genes) to superorganismal outcomes (i.e., community-level disease dynamics and host-parasite coevolution). Recently, physiological regulatory networks (PRNs) were cast as whole-organism regulatory systems that mediate homeostasis and hence link suborganismal processes with the fitness of individuals. Here, we use the PRN construct to develop a roadmap for studying host competence, taking guidance from systems immunology and evolutionary ecology research. We argue that PRN variation underlies heterogeneity in individual host competence and hence host-parasite dynamics. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  18. Data integration aids understanding of butterfly-host plant networks.

    Science.gov (United States)

    Muto-Fujita, Ai; Takemoto, Kazuhiro; Kanaya, Shigehiko; Nakazato, Takeru; Tokimatsu, Toshiaki; Matsumoto, Natsushi; Kono, Mayo; Chubachi, Yuko; Ozaki, Katsuhisa; Kotera, Masaaki

    2017-03-06

    Although host-plant selection is a central topic in ecology, its general underpinnings are poorly understood. Here, we performed a case study focusing on the publicly available data on Japanese butterflies. A combined statistical analysis of plant-herbivore relationships and taxonomy revealed that some butterfly subfamilies in different families feed on the same plant families, and the occurrence of this phenomenon more than just by chance, thus indicating the independent acquisition of adaptive phenotypes to the same hosts. We consequently integrated plant-herbivore and plant-compound relationship data and conducted a statistical analysis to identify compounds unique to host plants of specific butterfly families. Some of the identified plant compounds are known to attract certain butterfly groups while repelling others. The additional incorporation of insect-compound relationship data revealed potential metabolic processes that are related to host plant selection. Our results demonstrate that data integration enables the computational detection of compounds putatively involved in particular interspecies interactions and that further data enrichment and integration of genomic and transcriptomic data facilitates the unveiling of the molecular mechanisms involved in host plant selection.

  19. Data integration aids understanding of butterfly–host plant networks

    Science.gov (United States)

    Muto-Fujita, Ai; Takemoto, Kazuhiro; Kanaya, Shigehiko; Nakazato, Takeru; Tokimatsu, Toshiaki; Matsumoto, Natsushi; Kono, Mayo; Chubachi, Yuko; Ozaki, Katsuhisa; Kotera, Masaaki

    2017-01-01

    Although host-plant selection is a central topic in ecology, its general underpinnings are poorly understood. Here, we performed a case study focusing on the publicly available data on Japanese butterflies. A combined statistical analysis of plant–herbivore relationships and taxonomy revealed that some butterfly subfamilies in different families feed on the same plant families, and the occurrence of this phenomenon more than just by chance, thus indicating the independent acquisition of adaptive phenotypes to the same hosts. We consequently integrated plant–herbivore and plant–compound relationship data and conducted a statistical analysis to identify compounds unique to host plants of specific butterfly families. Some of the identified plant compounds are known to attract certain butterfly groups while repelling others. The additional incorporation of insect–compound relationship data revealed potential metabolic processes that are related to host plant selection. Our results demonstrate that data integration enables the computational detection of compounds putatively involved in particular interspecies interactions and that further data enrichment and integration of genomic and transcriptomic data facilitates the unveiling of the molecular mechanisms involved in host plant selection. PMID:28262809

  20. Integrated Factors Correlating Undergraduate Academic ...

    African Journals Online (AJOL)

    Integrated Factors Correlating Undergraduate Academic Achievement in Bayelsa State, Nigeria. ... AFRREV IJAH: An International Journal of Arts and Humanities ... Thus, it is study investigated the integrated factors determining academic performance of students in public secondary schools in Bayelsa State, Nigeria.

  1. Host restriction factors in retroviral infection: promises in virus-host interaction

    Directory of Open Access Journals (Sweden)

    Zheng Yong-Hui

    2012-12-01

    Full Text Available Abstract Retroviruses have an intricate life cycle. There is much to be learned from studying retrovirus-host interactions. Among retroviruses, the primate lentiviruses have one of the more complex genome structures with three categories of viral genes: structural, regulatory, and accessory genes. Over time, we have gained increasing understanding of the lentivirus life cycle from studying host factors that support virus replication. Similarly, studies on host restriction factors that inhibit viral replication have also made significant contributions to our knowledge. Here, we review recent progress on the rapidly growing field of restriction factors, focusing on the antiretroviral activities of APOBEC3G, TRIM5, tetherin, SAMHD1, MOV10, and cellular microRNAs (miRNAs, and the counter-activities of Vif, Vpu, Vpr, Vpx, and Nef.

  2. Factorization of Behavioral Integrity

    DEFF Research Database (Denmark)

    Li, Ximeng; Nielson, Flemming; Nielson, Hanne Riis

    2015-01-01

    We develop a bisimulation-based nonintereference property that describes the allowed dependencies between communication behaviors of different integrity levels. The property is able to capture all possible combinations of integrity levels for the “presence” and “content” of actual communications...

  3. Foreign Direct Investment, Host Country Factors and Economic Growth

    OpenAIRE

    Edna Maeyen Solomon

    2011-01-01

    This paper analyses how the levels of economic development, human capital, financial development and the qualities of the economic and political environments in host countries simultaneously affects the impact of aggregate inflows of Foreign Direct Investment (FDI) on economic growth. Multiple interaction terms are employed between inward FDI and each of the host country factors mentioned above. The System GMM estimator is applied to a panel of 111 countries from 1981 to 2005. The results sho...

  4. VERSE: a novel approach to detect virus integration in host genomes through reference genome customization.

    Science.gov (United States)

    Wang, Qingguo; Jia, Peilin; Zhao, Zhongming

    2015-01-01

    Fueled by widespread applications of high-throughput next generation sequencing (NGS) technologies and urgent need to counter threats of pathogenic viruses, large-scale studies were conducted recently to investigate virus integration in host genomes (for example, human tumor genomes) that may cause carcinogenesis or other diseases. A limiting factor in these studies, however, is rapid virus evolution and resulting polymorphisms, which prevent reads from aligning readily to commonly used virus reference genomes, and, accordingly, make virus integration sites difficult to detect. Another confounding factor is host genomic instability as a result of virus insertions. To tackle these challenges and improve our capability to identify cryptic virus-host fusions, we present a new approach that detects Virus intEgration sites through iterative Reference SEquence customization (VERSE). To the best of our knowledge, VERSE is the first approach to improve detection through customizing reference genomes. Using 19 human tumors and cancer cell lines as test data, we demonstrated that VERSE substantially enhanced the sensitivity of virus integration site detection. VERSE is implemented in the open source package VirusFinder 2 that is available at http://bioinfo.mc.vanderbilt.edu/VirusFinder/.

  5. Factors affecting host range in a generalist seed pathogen of semi-arid shrublands

    Science.gov (United States)

    Julie Beckstead; Susan E. Meyer; Kurt O. Reinhart; Kellene M. Bergen; Sandra R. Holden; Heather F. Boekweg

    2014-01-01

    Generalist pathogens can exhibit differential success on different hosts, resulting in complex host range patterns. Several factors operate to reduce realized host range relative to potential host range, particularly under field conditions. We explored factors influencing host range of the naturally occurring generalist ascomycete grass seed pathogen Pyrenophora...

  6. Host and Viral Factors in HIV-Mediated Bystander Apoptosis

    Science.gov (United States)

    Garg, Himanshu; Joshi, Anjali

    2017-01-01

    Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis. PMID:28829402

  7. Host and Environmental Factors Affecting the Intestinal Microbiota in Chickens.

    Science.gov (United States)

    Kers, Jannigje G; Velkers, Francisca C; Fischer, Egil A J; Hermes, Gerben D A; Stegeman, J A; Smidt, Hauke

    2018-01-01

    The initial development of intestinal microbiota in poultry plays an important role in production performance, overall health and resistance against microbial infections. Multiplexed sequencing of 16S ribosomal RNA gene amplicons is often used in studies, such as feed intervention or antimicrobial drug trials, to determine corresponding effects on the composition of intestinal microbiota. However, considerable variation of intestinal microbiota composition has been observed both within and across studies. Such variation may in part be attributed to technical factors, such as sampling procedures, sample storage, DNA extraction, the choice of PCR primers and corresponding region to be sequenced, and the sequencing platforms used. Furthermore, part of this variation in microbiota composition may also be explained by different host characteristics and environmental factors. To facilitate the improvement of design, reproducibility and interpretation of poultry microbiota studies, we have reviewed the literature on confounding factors influencing the observed intestinal microbiota in chickens. First, it has been identified that host-related factors, such as age, sex, and breed, have a large effect on intestinal microbiota. The diversity of chicken intestinal microbiota tends to increase most during the first weeks of life, and corresponding colonization patterns seem to differ between layer- and meat-type chickens. Second, it has been found that environmental factors, such as biosecurity level, housing, litter, feed access and climate also have an effect on the composition of the intestinal microbiota. As microbiota studies have to deal with many of these unknown or hidden host and environmental variables, the choice of study designs can have a great impact on study outcomes and interpretation of the data. Providing details on a broad range of host and environmental factors in articles and sequence data repositories is highly recommended. This creates opportunities to

  8. Host and Environmental Factors Affecting the Intestinal Microbiota in Chickens

    Directory of Open Access Journals (Sweden)

    Jannigje G. Kers

    2018-02-01

    Full Text Available The initial development of intestinal microbiota in poultry plays an important role in production performance, overall health and resistance against microbial infections. Multiplexed sequencing of 16S ribosomal RNA gene amplicons is often used in studies, such as feed intervention or antimicrobial drug trials, to determine corresponding effects on the composition of intestinal microbiota. However, considerable variation of intestinal microbiota composition has been observed both within and across studies. Such variation may in part be attributed to technical factors, such as sampling procedures, sample storage, DNA extraction, the choice of PCR primers and corresponding region to be sequenced, and the sequencing platforms used. Furthermore, part of this variation in microbiota composition may also be explained by different host characteristics and environmental factors. To facilitate the improvement of design, reproducibility and interpretation of poultry microbiota studies, we have reviewed the literature on confounding factors influencing the observed intestinal microbiota in chickens. First, it has been identified that host-related factors, such as age, sex, and breed, have a large effect on intestinal microbiota. The diversity of chicken intestinal microbiota tends to increase most during the first weeks of life, and corresponding colonization patterns seem to differ between layer- and meat-type chickens. Second, it has been found that environmental factors, such as biosecurity level, housing, litter, feed access and climate also have an effect on the composition of the intestinal microbiota. As microbiota studies have to deal with many of these unknown or hidden host and environmental variables, the choice of study designs can have a great impact on study outcomes and interpretation of the data. Providing details on a broad range of host and environmental factors in articles and sequence data repositories is highly recommended. This creates

  9. Factorization-algebraization-path integration

    International Nuclear Information System (INIS)

    Inomata, A.; Wilson, R.

    1986-01-01

    The authors review the method of factorization proposed by Schroedinger of a quantum mechanical second-order linear differential equation into a product of two first-order differential operators, often referred to as ladder operators, as well as the modifications made to Schroedinger's method by Infeld and Hull. They then review the group theoretical treatments proposed by Miller of the Schroedinger-Infeld-Hull factorizations and go on to demonstrate the application of dynamical symmetry to path integral calculations. 30 references

  10. Host Cell Restriction Factors that Limit Influenza A Infection

    Directory of Open Access Journals (Sweden)

    Fernando Villalón-Letelier

    2017-12-01

    Full Text Available Viral infection of different cell types induces a unique spectrum of host defence genes, including interferon-stimulated genes (ISGs and genes encoding other proteins with antiviral potential. Although hundreds of ISGs have been described, the vast majority have not been functionally characterised. Cellular proteins with putative antiviral activity (hereafter referred to as “restriction factors” can target various steps in the virus life-cycle. In the context of influenza virus infection, restriction factors have been described that target virus entry, genomic replication, translation and virus release. Genome wide analyses, in combination with ectopic overexpression and/or gene silencing studies, have accelerated the identification of restriction factors that are active against influenza and other viruses, as well as providing important insights regarding mechanisms of antiviral activity. Herein, we review current knowledge regarding restriction factors that mediate anti-influenza virus activity and consider the viral countermeasures that are known to limit their impact. Moreover, we consider the strengths and limitations of experimental approaches to study restriction factors, discrepancies between in vitro and in vivo studies, and the potential to exploit restriction factors to limit disease caused by influenza and other respiratory viruses.

  11. Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins

    OpenAIRE

    Meng, Xiangzhi; Krumm, Brian; Li, Yongchao; Deng, Junpeng; Xiang, Yan

    2015-01-01

    Productive viral replication requires overcoming many barriers posed by the host innate immune system. Human sterile alpha motif domain-containing 9 (SAMD9) is a newly identified antiviral factor that is specifically targeted by poxvirus proteins belonging to the C7 family of host-range factors. Here we provide the first, to our knowledge, atomic view of two functionally divergent proteins from the C7 family and determine the molecular basis that dictates whether they can target SAMD9 effecti...

  12. Integrated Detection of Pathogens and Host Biomarkers for Wounds

    Energy Technology Data Exchange (ETDEWEB)

    Jaing, C

    2012-03-19

    The increasing incidence and complications arising from combat wounds has necessitated a reassessment of methods for effective treatment. Infection, excessive inflammation, and incidence of drug-resistant organisms all contribute toward negative outcomes for afflicted individuals. The organisms and host processes involved in wound progression, however, are incompletely understood. We therefore set out, using our unique technical resources, to construct a profile of combat wounds which did or did not successfully resolve. We employed the Lawrence Livermore Microbial Detection Array and identified a number of nosocomial pathogens present in wound samples. Some of these identities corresponded with bacterial isolates previously cultured, while others were not obtained via standard microbiology. Further, we optimized proteomics protocols for the identification of host biomarkers indicative of various stages in wound progression. In combination with our pathogen data, our biomarker discovery efforts will provide a profile corresponding to wound complications, and will assist significantly in treatment of these complex cases.

  13. A computational tool integrating host immunity with antibiotic dynamics to study tuberculosis treatment.

    Science.gov (United States)

    Pienaar, Elsje; Cilfone, Nicholas A; Lin, Philana Ling; Dartois, Véronique; Mattila, Joshua T; Butler, J Russell; Flynn, JoAnne L; Kirschner, Denise E; Linderman, Jennifer J

    2015-02-21

    While active tuberculosis (TB) is a treatable disease, many complex factors prevent its global elimination. Part of the difficulty in developing optimal therapies is the large design space of antibiotic doses, regimens and combinations. Computational models that capture the spatial and temporal dynamics of antibiotics at the site of infection can aid in reducing the design space of costly and time-consuming animal pre-clinical and human clinical trials. The site of infection in TB is the granuloma, a collection of immune cells and bacteria that form in the lung, and new data suggest that penetration of drugs throughout granulomas is problematic. Here we integrate our computational model of granuloma formation and function with models for plasma pharmacokinetics, lung tissue pharmacokinetics and pharmacodynamics for two first line anti-TB antibiotics. The integrated model is calibrated to animal data. We make four predictions. First, antibiotics are frequently below effective concentrations inside granulomas, leading to bacterial growth between doses and contributing to the long treatment periods required for TB. Second, antibiotic concentration gradients form within granulomas, with lower concentrations toward their centers. Third, during antibiotic treatment, bacterial subpopulations are similar for INH and RIF treatment: mostly intracellular with extracellular bacteria located in areas non-permissive for replication (hypoxic areas), presenting a slowly increasing target population over time. Finally, we find that on an individual granuloma basis, pre-treatment infection severity (including bacterial burden, host cell activation and host cell death) is predictive of treatment outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. PHIDIAS: a pathogen-host interaction data integration and analysis system

    OpenAIRE

    Xiang, Zuoshuang; Tian, Yuying; He, Yongqun

    2007-01-01

    The Pathogen-Host Interaction Data Integration and Analysis System (PHIDIAS) is a web-based database system that serves as a centralized source to search, compare, and analyze integrated genome sequences, conserved domains, and gene expression data related to pathogen-host interactions (PHIs) for pathogen species designated as high priority agents for public health and biological security. In addition, PHIDIAS allows submission, search and analysis of PHI genes and molecular networks curated ...

  15. An integrating factor matrix method to find first integrals

    International Nuclear Information System (INIS)

    Saputra, K V I; Quispel, G R W; Van Veen, L

    2010-01-01

    In this paper we develop an integrating factor matrix method to derive conditions for the existence of first integrals. We use this novel method to obtain first integrals, along with the conditions for their existence, for two- and three-dimensional Lotka-Volterra systems with constant terms. The results are compared to previous results obtained by other methods.

  16. Host Proteins Determine MRSA Biofilm Structure and Integrity

    DEFF Research Database (Denmark)

    Dreier, Cindy; Nielsen, Astrid; Jørgensen, Nis Pedersen

    Human extracellular matrix (hECM) proteins aids the initial attachment and initiation of an infection, by specific binding to bacterial cell surface proteins. However, the importance of hECM proteins in structure, integrity and antibiotic resilience of a biofilm is unknown. This study aims...... to determine how specific hECM proteins affect S. aureus USA300 JE2 biofilms. Biofilms were grown in the presence of synovial fluid from rheumatoid arteritis patients to mimic in vivo conditions, where bacteria incorporate hECM proteins into the biofilm matrix. Difference in biofilm structure, with and without...... addition of hECM to growth media, was visualized by confocal laser scanning microscopy. Two enzymatic degradation experiments were used to study biofilm matrix composition and importance of hECM proteins: enzymatic removal of specific hECM proteins from growth media, before biofilm formation, and enzymatic...

  17. The herbaceous landlord: integrating the effects of symbiont consortia within a single host

    Directory of Open Access Journals (Sweden)

    Roo Vandegrift

    2015-11-01

    Full Text Available Plants are typically infected by a consortium of internal fungal associates, including endophytes in their leaves, as well as arbuscular mycorrhizal fungi (AMF and dark septate endophytes (DSE in their roots. It is logical that these organisms will interact with each other and the abiotic environment in addition to their host, but there has been little work to date examining the interactions of multiple symbionts within single plant hosts, or how the relationships among symbionts and their host change across environmental conditions. We examined the grass Agrostis capillaris in the context of a climate manipulation experiment in prairies in the Pacific Northwest, USA. Each plant was tested for presence of foliar endophytes in the genus Epichloë, and we measured percent root length colonized (PRLC by AMF and DSE. We hypothesized that the symbionts in our system would be in competition for host resources, that the outcome of that competition could be driven by the benefit to the host, and that the host plants would be able to allocate carbon to the symbionts in such a way as to maximize fitness benefit within a particular environmental context. We found a correlation between DSE and AMF PRLC across climatic conditions; we also found a fitness cost to increasing DSE colonization, which was negated by presence of Epichloë endophytes. These results suggest that selective pressure on the host is likely to favor host/symbiont relationships that structure the community of symbionts in the most beneficial way possible for the host, not necessarily favoring the individual symbiont that is most beneficial to the host in isolation. These results highlight the need for a more integrative, systems approach to the study of host/symbiont consortia.

  18. DMPD: Macrophage migration inhibitory factor and host innate immune responses tomicrobes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14620137 Macrophage migration inhibitory factor and host innate immune responses to...microbes. Calandra T. Scand J Infect Dis. 2003;35(9):573-6. (.png) (.svg) (.html) (.csml) Show Macrophage migration... inhibitory factor and host innate immune responses tomicrobes. PubmedID 14620137 Title Macrophage migration

  19. Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins.

    Science.gov (United States)

    Meng, Xiangzhi; Krumm, Brian; Li, Yongchao; Deng, Junpeng; Xiang, Yan

    2015-12-01

    Human sterile alpha motif domain-containing 9 (SAMD9) protein is a host restriction factor for poxviruses, but it can be overcome by some poxvirus host-range proteins that share homology with vaccinia virus C7 protein. To understand the mechanism of action for this important family of host-range factors, we determined the crystal structures of C7 and myxoma virus M64, a C7 family member that is unable to antagonize SAMD9. Despite their different functions and only 23% sequence identity, the two proteins have very similar overall structures, displaying a previously unidentified fold comprised of a compact 12-stranded antiparallel β-sandwich wrapped in two short α helices. Extensive structure-guided mutagenesis of C7 identified three loops clustered on one edge of the β sandwich as critical for viral replication and binding with SAMD9. The loops are characterized with functionally important negatively charged, positively charged, and hydrophobic residues, respectively, together forming a unique "three-fingered molecular claw." The key residues of the claw are not conserved in two C7 family members that do not antagonize SAMD9 but are conserved in distantly related C7 family members from four poxvirus genera that infect diverse mammalian species. Indeed, we found that all in the latter group of proteins bind SAMD9. Taken together, our data indicate that diverse mammalian poxviruses use a conserved molecular claw in a C7-like protein to target SAMD9 and overcome host restriction.

  20. PHIDIAS: a pathogen-host interaction data integration and analysis system.

    Science.gov (United States)

    Xiang, Zuoshuang; Tian, Yuying; He, Yongqun

    2007-01-01

    The Pathogen-Host Interaction Data Integration and Analysis System (PHIDIAS) is a web-based database system that serves as a centralized source to search, compare, and analyze integrated genome sequences, conserved domains, and gene expression data related to pathogen-host interactions (PHIs) for pathogen species designated as high priority agents for public health and biological security. In addition, PHIDIAS allows submission, search and analysis of PHI genes and molecular networks curated from peer-reviewed literature. PHIDIAS is publicly available at http://www.phidias.us.

  1. Marek’s disease herpesvirus vaccines integrate into chicken host chromosomes yet lack a virus-host phenotype associated with oncogenic transformation

    Science.gov (United States)

    Marek's disease (MD) is a lymphotrophic and oncogenic disease of chickens that can lead to death in susceptible and unimmunized host birds. The causative pathogen, Marek's disease virus (MDV), a highly oncogenic alphaherpesvirus, integrates into host genome near the telomeres during viral latency an...

  2. Study on integrated evaluation of sandstone-hosted uranium metallogenic potential in southern Yili basin

    International Nuclear Information System (INIS)

    Han Shaoyang; Ke Dan; Xu Jianguo; Zheng Enjiu; Li Shengxiang

    2008-01-01

    Plenty of geological data have been accumulated during mineral resource survey in China; under the guidance of new metallogenic theories, it is an important task of how to use these data most effectively for the new cycle uranium survey. In this paper, the flow of establishing the integrated mineral deposits prospecting model for sandstone-hosted uranium deposits is put forward. Based on studying geologic, hydrogeologic and regional geophysical field characteristics of representative uranium deposits No. 512 in southern Yili basin, its multi-source information descriptive model has been established, from which 512-type integrated prospecting models of sandstone-hosted uranium orefield and deposits are summarized. According to the established integrated prospecting models, the metallogenic information extraction of sandstone-hosted uranium deposits has completed in the study area. Finally, the integrated quantitative evaluation of sandstone-hosted uranium metallogenic potential is performed by using the evidence weighing method to integrate middle scale multi-source metallogenic information in the southern Yili basin, and good prediction effect is obtained. (authors)

  3. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease.

    Science.gov (United States)

    Ogino, Shuji; Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M; Meyerhardt, Jeffrey A; Meissner, Alexander; Schernhammer, Eva S; Fuchs, Charles S; Giovannucci, Edward

    2013-04-01

    Epigenetics acts as an interface between environmental/exogenous factors, cellular responses, and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases (including neoplasms and malignancies such as leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver, and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. In particular, DNA methylation assays are widely applied to formalin-fixed, paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiological factors, cellular molecular characteristics, and disease evolution, the field of 'molecular pathological epidemiology (MPE)' has emerged as an interdisciplinary integration of 'molecular pathology' and 'epidemiology'. In contrast to traditional epidemiological research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle, that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macroenvironment and tissue microenvironment. MPE may represent a logical evolution of GWAS, termed 'GWAS-MPE approach'. Although epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell within one individual has a unique, time-varying epigenome. Having a similar conceptual framework to systems biology, the holistic MPE approach enables us to link potential etiological factors to specific molecular pathology, and gain novel pathogenic insights on causality. The widespread application of epigenome (eg, methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator

  4. Ultrasonic longitudinal waves to monitor the integration of titanium rods with host bone

    Science.gov (United States)

    Wang, Wentao; Lynch, Jerome P.

    2017-04-01

    Osseointegrated prostheses which integrate the prosthesis directly to the limb bone are being developed for patients that are unable to wear traditional socket prostheses. While osseointegration of the prosthesis offers amputees improvement in their quality of life, there remains a need to better understand the integration process that occurs between the bone and the prosthesis. Quantification of the degree of integration is important to track the recuperation process of the amputee, guide physical therapy regimes, and to identify when the state of integration may change (due to damage to the bone). This study explores the development of an assessment strategy for quantitatively assessing the degree of integration between an osseointegrated prosthesis and host bone. Specifically, the strategy utilizes a titanium rod prosthesis as a waveguide with guided waves used to assess the degree of integration. By controlling waveforms launched by piezoelectric wafers bonded on the percutaneous tip of the prosthesis, body waves are introduced into the waveguide with wave reflections at the boneprosthesis interface recorded by the same array. Changes in wave energy are correlated to changes at the contact interface between the titanium rod and the bone material. Both simulation and experimental tests are presented in this paper. Experimental testing is performed using a high-density polyethylene (HDPE) host because the elastic modulus and density of HDPE are close to that of human and animal bone. Results indicate high sensitivity of the longitudinal wave energy to rod penetration depth and confinement stress issued by the host bone.

  5. Targeting Host Factors to Treat West Nile and Dengue Viral Infections

    Directory of Open Access Journals (Sweden)

    Manoj N. Krishnan

    2014-02-01

    Full Text Available West Nile (WNV and Dengue (DENV viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

  6. Targeting host factors to treat West Nile and dengue viral infections.

    Science.gov (United States)

    Krishnan, Manoj N; Garcia-Blanco, Mariano A

    2014-02-10

    West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

  7. A Trematode Parasite Derived Growth Factor Binds and Exerts Influences on Host Immune Functions via Host Cytokine Receptor Complexes.

    Directory of Open Access Journals (Sweden)

    Azad A Sulaiman

    2016-11-01

    Full Text Available The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allowing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory receptor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is dependent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs in their evasion of antibody-dependent cell cytotoxicity (ADCC by reducing the NO response of macrophages-again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for dampened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow

  8. PISCO: The PMAS/PPak Integral-field Supernova Hosts Compilation

    Science.gov (United States)

    Galbany, L.; Anderson, J. P.; Sánchez, S. F.; Kuncarayakti, H.; Pedraz, S.; González-Gaitán, S.; Stanishev, V.; Domínguez, I.; Moreno-Raya, M. E.; Wood-Vasey, W. M.; Mourão, A. M.; Ponder, K. A.; Badenes, C.; Mollá, M.; López-Sánchez, A. R.; Rosales-Ortega, F. F.; Vílchez, J. M.; García-Benito, R.; Marino, R. A.

    2018-03-01

    We present the PMAS/PPak Integral-field Supernova hosts COmpilation (PISCO), which comprises integral field spectroscopy (IFS) of 232 supernova (SN) host galaxies that hosted 272 SNe, observed over several semesters with the 3.5 m telescope at the Calar Alto Observatory (CAHA). PISCO is the largest collection of SN host galaxies observed with wide-field IFS, totaling 466,347 individual spectra covering a typical spatial resolution of ∼380 pc. Focused studies regarding specific SN Ia-related topics will be published elsewhere; this paper aims to present the properties of the SN environments, using stellar population (SP) synthesis, and the gas-phase interstellar medium, providing additional results separating stripped-envelope SNe into their subtypes. With 11,270 H II regions detected in all galaxies, we present for the first time a statistical analysis of H II regions, which puts H II regions that have hosted SNe in context with all other star-forming clumps within their galaxies. SNe Ic are associated with environments that are more metal-rich and have higher EW(Hα) and higher star formation rate within their host galaxies than the mean of all H II regions detected within each host. This in contrast to SNe IIb, which occur in environments that are very different compared to other core-collapse SNe types. We find two clear components of young and old SPs at SNe IIn locations. We find that SNe II fast decliners tend to explode at locations where the ΣSFR is more intense. Finally, we outline how a future dedicated IFS survey of galaxies in parallel to an untargeted SN search would overcome the biases in current environmental studies.

  9. Host-derived, pore-forming toxin-like protein and trefoil factor complex protects the host against microbial infection.

    Science.gov (United States)

    Xiang, Yang; Yan, Chao; Guo, Xiaolong; Zhou, Kaifeng; Li, Sheng'an; Gao, Qian; Wang, Xuan; Zhao, Feng; Liu, Jie; Lee, Wen-Hui; Zhang, Yun

    2014-05-06

    Aerolysins are virulence factors belonging to the bacterial β-pore-forming toxin superfamily. Surprisingly, numerous aerolysin-like proteins exist in vertebrates, but their biological functions are unknown. βγ-CAT, a complex of an aerolysin-like protein subunit (two βγ-crystallin domains followed by an aerolysin pore-forming domain) and two trefoil factor subunits, has been identified in frogs (Bombina maxima) skin secretions. Here, we report the rich expression of this protein, in the frog blood and immune-related tissues, and the induction of its presence in peritoneal lavage by bacterial challenge. This phenomena raises the possibility of its involvement in antimicrobial infection. When βγ-CAT was administrated in a peritoneal infection model, it greatly accelerated bacterial clearance and increased the survival rate of both frogs and mice. Meanwhile, accelerated Interleukin-1β release and enhanced local leukocyte recruitments were determined, which may partially explain the robust and effective antimicrobial responses observed. The release of interleukin-1β was potently triggered by βγ-CAT from the frog peritoneal cells and murine macrophages in vitro. βγ-CAT was rapidly endocytosed and translocated to lysosomes, where it formed high molecular mass SDS-stable oligomers (>170 kDa). Lysosomal destabilization and cathepsin B release were detected, which may explain the activation of caspase-1 inflammasome and subsequent interleukin-1β maturation and release. To our knowledge, these results provide the first functional evidence of the ability of a host-derived aerolysin-like protein to counter microbial infection by eliciting rapid and effective host innate immune responses. The findings will also largely help to elucidate the possible involvement and action mechanisms of aerolysin-like proteins and/or trefoil factors widely existing in vertebrates in the host defense against pathogens.

  10. Host factors that modify Plasmodium falciparum adhesion to endothelial receptors.

    Science.gov (United States)

    Mahamar, Almahamoudou; Attaher, Oumar; Swihart, Bruce; Barry, Amadou; Diarra, Bacary S; Kanoute, Moussa B; Cisse, Kadidia B; Dembele, Adama B; Keita, Sekouba; Gamain, Benoît; Gaoussou, Santara; Issiaka, Djibrilla; Dicko, Alassane; Duffy, Patrick E; Fried, Michal

    2017-10-24

    P. falciparum virulence is related to adhesion and sequestration of infected erythrocytes (IE) in deep vascular beds, but the endothelial receptors involved in severe malaria remain unclear. In the largest ever study of clinical isolates, we surveyed adhesion of freshly collected IE from children under 5 years of age in Mali to identify novel vascular receptors, and examined the effects of host age, hemoglobin type, blood group and severe malaria on levels of IE adhesion to a panel of endothelial receptors. Several novel molecules, including integrin α3β1, VE-cadherin, ICAM-2, junctional adhesion molecule-B (JAM-B), laminin, and cellular fibronectin, supported binding of IE from children. Severe malaria was not significantly associated with levels of IE adhesion to any of the 19 receptors. Hemoglobin AC, which reduces severe malaria risk, reduced IE binding to the receptors CD36 and integrin α5β1, while hemoglobin AS did not modify IE adhesion to any receptors. Blood groups A, AB and B significantly reduced IE binding to ICAM-1. Severe malaria risk varies with age, but age significantly impacted the level of IE binding to only a few receptors: IE binding to JAM-B decreased with age, while binding to CD36 and integrin α5β1 significantly increased with age.

  11. DMPD: The interferon regulatory factor family in host defense: mechanism of action. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17502370 The interferon regulatory factor family in host defense: mechanism of acti....html) (.csml) Show The interferon regulatory factor family in host defense: mechanism of action. PubmedID 1...7502370 Title The interferon regulatory factor family in host defense: mechanism

  12. Validation of human factor engineering integrated system

    International Nuclear Information System (INIS)

    Fang Zhou

    2013-01-01

    Apart from hundreds of thousands of human-machine interface resources, the control room of a nuclear power plant is a complex system integrated with many factors such as procedures, operators, environment, organization and management. In the design stage, these factors are considered by different organizations separately. However, whether above factors could corporate with each other well in operation and whether they have good human factors engineering (HFE) design to avoid human error, should be answered in validation of the HFE integrated system before delivery of the plant. This paper addresses the research and implementation of the ISV technology based on case study. After introduction of the background, process and methodology of ISV, the results of the test are discussed. At last, lessons learned from this research are summarized. (authors)

  13. Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease

    Science.gov (United States)

    Darzi, Youssef; Mongodin, Emmanuel F.; Pan, Chongle; Shah, Manesh; Halfvarson, Jonas; Tysk, Curt; Henrissat, Bernard; Raes, Jeroen; Verberkmoes, Nathan C.; Jansson, Janet K.

    2012-01-01

    Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers. PMID:23209564

  14. Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn's disease.

    Directory of Open Access Journals (Sweden)

    Alison R Erickson

    Full Text Available Crohn's disease (CD is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD or colon (CCD. Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.

  15. Citizen science data reveal ecological, historical and evolutionary factors shaping interactions between woody hosts and wood-inhabiting fungi.

    Science.gov (United States)

    Heilmann-Clausen, Jacob; Maruyama, Pietro K; Bruun, Hans Henrik; Dimitrov, Dimitar; Laessøe, Thomas; Frøslev, Tobias Guldberg; Dalsgaard, Bo

    2016-12-01

    Woody plants host diverse communities of associated organisms, including wood-inhabiting fungi. In this group, host effects on species richness and interaction network structure are not well understood, especially not at large geographical scales. We investigated ecological, historical and evolutionary determinants of fungal species richness and network modularity, that is, subcommunity structure, across woody hosts in Denmark, using a citizen science data set comprising > 80 000 records of > 1000 fungal species on 91 genera of woody plants. Fungal species richness was positively related to host size, wood pH, and the number of species in the host genus, with limited influence of host frequency and host history, that is, time since host establishment in the area. Modularity patterns were unaffected by host history, but largely reflected host phylogeny. Notably, fungal communities differed substantially between angiosperm and gymnosperm hosts. Host traits and evolutionary history appear to be more important than host frequency and recent history in structuring interactions between hosts and wood-inhabiting fungi. High wood acidity appears to act as a stress factor reducing fungal species richness, while large host size, providing increased niche diversity, enhances it. In some fungal groups that are known to interact with live host cells in the establishment phase, host selectivity is common, causing a modular community structure. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  16. Cycle Inhibiting Factors (Cifs: Cyclomodulins That Usurp the Ubiquitin-Dependent Degradation Pathway of Host Cells

    Directory of Open Access Journals (Sweden)

    Eric Oswald

    2011-03-01

    Full Text Available Cycle inhibiting factors (Cifs are type III secreted effectors produced by diverse pathogenic bacteria. Cifs are “cyclomodulins” that inhibit the eukaryotic host cell cycle and also hijack other key cellular processes such as those controlling the actin network and apoptosis. This review summarizes current knowledge on Cif since its first characterization in enteropathogenic Escherichia coli, the identification of several xenologues in distant pathogenic bacteria, to its structure elucidation and the recent deciphering of its mode of action. Cif impairs the host ubiquitin proteasome system through deamidation of ubiquitin or the ubiquitin-like protein NEDD8 that regulates Cullin-Ring-ubiquitin Ligase (CRL complexes. The hijacking of the ubiquitin-dependent degradation pathway of host cells results in the modulation of various cellular functions such as epithelium renewal, apoptosis and immune response. Cif is therefore a powerful weapon in the continuous arm race that characterizes host-bacteria interactions.

  17. Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense?

    NARCIS (Netherlands)

    van der Poll, T.; Lowry, S. F.

    1995-01-01

    Tumor necrosis factor-alpha (TNF) exerts numerous influences which, in association with severe infection, subserve both detrimental as well as beneficial host responses. The current review addresses recent insights into the structure and function of this pleiotropic cytokine, with a particular

  18. Integrating Data and Networks: Human Factors

    Science.gov (United States)

    Chen, R. S.

    2012-12-01

    The development of technical linkages and interoperability between scientific networks is a necessary but not sufficient step towards integrated use and application of networked data and information for scientific and societal benefit. A range of "human factors" must also be addressed to ensure the long-term integration, sustainability, and utility of both the interoperable networks themselves and the scientific data and information to which they provide access. These human factors encompass the behavior of both individual humans and human institutions, and include system governance, a common framework for intellectual property rights and data sharing, consensus on terminology, metadata, and quality control processes, agreement on key system metrics and milestones, the compatibility of "business models" in the short and long term, harmonization of incentives for cooperation, and minimization of disincentives. Experience with several national and international initiatives and research programs such as the International Polar Year, the Group on Earth Observations, the NASA Earth Observing Data and Information System, the U.S. National Spatial Data Infrastructure, the Global Earthquake Model, and the United Nations Spatial Data Infrastructure provide a range of lessons regarding these human factors. Ongoing changes in science, technology, institutions, relationships, and even culture are creating both opportunities and challenges for expanded interoperability of scientific networks and significant improvement in data integration to advance science and the use of scientific data and information to achieve benefits for society as a whole.

  19. Industrial production of clotting factors: Challenges of expression, and choice of host cells.

    Science.gov (United States)

    Kumar, Sampath R

    2015-07-01

    The development of recombinant forms of blood coagulation factors as safer alternatives to plasma derived factors marked a major advance in the treatment of common coagulation disorders. These are complex proteins, mostly enzymes or co-enzymes, involving multiple post-translational modifications, and therefore are difficult to express. This article reviews the nature of the expression challenges for the industrial production of these factors, vis-à-vis the translational and post-translational bottlenecks, as well as the choice of host cell lines for high-fidelity production. For achieving high productivities of vitamin K dependent proteins, which include factors II (prothrombin), VII, IX and X, and protein C, host cell limitation of γ-glutamyl carboxylation is a major bottleneck. Despite progress in addressing this, involvement of yet unidentified protein(s) impedes a complete cell engineering solution. Human factor VIII expresses at very low levels due to limitations at several steps in the protein secretion pathway. Protein and cell engineering, vector improvement and alternate host cells promise improvement in the productivity. Production of Von Willebrand factor is constrained by its large size, complex structure, and the need for extensive glycosylation and disulfide-bonded oligomerization. All the licensed therapeutic factors are produced in CHO, BHK or HEK293 cells. While HEK293 is a recent adoption, BHK cells appear to be disfavored. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Borrelia host adaptation Regulator (BadR) regulates rpoS to modulate host adaptation and virulence factors in Borrelia burgdorferi

    OpenAIRE

    Miller, Christine L.; Rajasekhar Karna, S. L.; Seshu, J.

    2013-01-01

    The RpoS transcription factor of Borrelia burgdorferi is a “gatekeeper” because it activates genes required for spirochetes to transition from tick to vertebrate hosts. However, it remains unknown how RpoS becomes repressed to allow the spirochetes to transition back from the vertebrate host to the tick vector. Here we show that a putative carbohydrate-responsive regulatory protein, designated BadR (Borrelia host adaptation Regulator), is a transcriptional repressor of rpoS. BadR levels are e...

  1. Global change integrating factors: Tropical tropopause trends

    International Nuclear Information System (INIS)

    Reck, R.A.

    1994-01-01

    This research proposes new criteria, shifts in the height and temperature of the tropical tropopause, as measures of global climate change. The search for signs of global warming in the temperature signal near the earth's surface is extremely difficult, largely because numerous factors contribute to surface temperature forcing with only a small signal-to-noise ratio relative to long-term effects. In the long term, no part of the atmosphere can be considered individually because the evolution will be a function of all states of all portions. A large surface greenhouse signal might ultimately be expected, but the analysis of surface temperature may not be particularly useful for early detection. What is suggested here is not an analysis of trends in the surface temperature field or any of its spatial averages, but rather an integrating factor or integrator, a single measure of global change that could be considered a test of significant change for the entire global system. Preferably, this global change integrator would vary slowly and would take into account many of the causes of climate change, with a relatively large signal-to-noise ratio. Such an integrator could be monitored, and abrupt or accelerated changes could serve as an early warning signal for policy makers and the public. Earlier work has suggested that temperature has much less short-term and small-scale noise in the lower stratosphere, and thus the global warming signal at that level might be more easily deconvoluted, because the cooling rate near the 200-mb level is almost constant with latitude. A study of the temperature signal at this pressure level might show a clearer trend due to increased levels of greenhouse gases, but it would yield information about the troposphere only by inference

  2. Host transcription factors in the immediate pro-inflammatory response to the parasitic mite Psoroptes ovis.

    Directory of Open Access Journals (Sweden)

    Stewart T G Burgess

    Full Text Available BACKGROUND: Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, results in the rapid development of cutaneous inflammation and leads to the crusted skin lesions characteristic of the disease. We described previously the global host transcriptional response to infestation with P. ovis, elucidating elements of the inflammatory processes which lead to the development of a rapid and profound immune response. However, the mechanisms by which this response is instigated remain unclear. To identify novel methods of intervention a better understanding of the early events involved in triggering the immune response is essential. The objective of this study was to gain a clearer understanding of the mechanisms and signaling pathways involved in the instigation of the immediate pro-inflammatory response. RESULTS: Through a combination of transcription factor binding site enrichment and pathway analysis we identified key roles for a number of transcription factors in the instigation of cutaneous inflammation. In particular, defined roles were elucidated for the transcription factors NF-kB and AP-1 in the orchestration of the early pro-inflammatory response, with these factors being implicated in the activation of a suite of inflammatory mediators. CONCLUSIONS: Interrogation of the host temporal response to P. ovis infestation has enabled the further identification of the mechanisms underlying the development of the immediate host pro-inflammatory response. This response involves key regulatory roles for the transcription factors NF-kB and AP-1. Pathway analysis demonstrated that the activation of these transcription factors may be triggered following a host LPS-type response, potentially involving TLR4-signalling and also lead to the intriguing possibility that this could be triggered by a P. ovis allergen.

  3. Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

    Science.gov (United States)

    Allan, Kristina J; Mahoney, Douglas J; Baird, Stephen D; Lefebvre, Charles A; Stojdl, David F

    2018-04-03

    High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. This protocol describes the development and validation of an assay for high-throughput RNAi screening in mammalian cells, the key considerations and preparation steps important for conducting a primary high-throughput RNAi screen, and a step-by-step guide for conducting a primary high-throughput RNAi screen; in addition, it broadly outlines the methods for conducting secondary screen validation and tertiary validation studies. The benefit of high-throughput RNAi screening is that it allows one to catalogue, in an extensive and unbiased fashion, host factors that modulate any aspect of virus replication for which one can develop an in vitro assay such as infectivity, burst size, and cytotoxicity. It has the power to uncover biotherapeutic targets unforeseen based on current knowledge.

  4. Demethylation of host-cell DNA at the site of avian retrovirus integration

    Czech Academy of Sciences Publication Activity Database

    Hejnar, Jiří; Elleder, Daniel; Hájková, P.; Walter, J.; Blažková, Jana; Svoboda, Jan

    2003-01-01

    Roč. 2003, č. 311 (2003), s. 641-648 ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915 Keywords : DNA methylation and demethylation * integration of retroviruses * gene silencing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.836, year: 2003

  5. Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors

    Science.gov (United States)

    Rahme, Laurence G.; Tan, Man-Wah; Le, Long; Wong, Sandy M.; Tompkins, Ronald G.; Calderwood, Stephen B.; Ausubel, Frederick M.

    1997-01-01

    We used plants as an in vivo pathogenesis model for the identification of virulence factors of the human opportunistic pathogen Pseudomonas aeruginosa. Nine of nine TnphoA mutant derivatives of P. aeruginosa strain UCBPP-PA14 that were identified in a plant leaf assay for less pathogenic mutants also exhibited significantly reduced pathogenicity in a burned mouse pathogenicity model, suggesting that P. aeruginosa utilizes common strategies to infect both hosts. Seven of these nine mutants contain TnphoA insertions in previously unknown genes. These results demonstrate that an alternative nonvertebrate host of a human bacterial pathogen can be used in an in vivo high throughput screen to identify novel bacterial virulence factors involved in mammalian pathogenesis. PMID:9371831

  6. Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors.

    Science.gov (United States)

    Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A

    2016-09-01

    The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

  7. Host and environmental factors influencing "Candidatus Liberibacter asiaticus" acquisition in Diaphorina citri.

    Science.gov (United States)

    Wu, Fengnian; Huang, Jiaquan; Xu, Meirong; Fox, Eduardo G P; Beattie, G Andrew C; Holford, Paul; Cen, Yijing; Deng, Xiaoling

    2018-05-03

    Diaphorina citri is a vector of "Candidatus Liberibacter asiaticus" (CLas) associated with citrus Huanglongbing. In this study, the infection and titers of CLas in the psyllid, were monitored for life cycle stage, sex, host-plant CLas titer, host-plant genotype, and ambient temperature. Acquisition efficiency of CLas by D. citri was highest in nymphs reared at 25 °C on a host plant with high CLas titers but was independent of the host genotypes assessed and of vector sex. We further observed that D. citri nymphs acquired CLas more rapidly than adults based on acquisition access periods (AAPs). CLas did not multiply in the alimentary canal, hemolymph, and salivary glands of adults for 18 d after a 3-day AAP as adult. However, CLas multiplication was detected in hemolymph and salivary gland of adults after the bacterium was acquired by nymphs. Eighty percent of salivary glands of adults contained CLas 18 d after a 3-day AAP as nymph compared to 10% 18 d after a 3-day AAP as adults. Different factors tested herein influenced CLas acquisition efficiency of D. citri, CLas multiplication and spread inside the psyllid. These observations serve to better understand mechanisms of CLas infection in D. citri. This article is protected by copyright. All rights reserved.

  8. Allopatric integrations selectively change host transcriptomes, leading to varied expression efficiencies of exotic genes in Myxococcus xanthus.

    Science.gov (United States)

    Zhu, Li-Ping; Yue, Xin-Jing; Han, Kui; Li, Zhi-Feng; Zheng, Lian-Shuai; Yi, Xiu-Nan; Wang, Hai-Long; Zhang, You-Ming; Li, Yue-Zhong

    2015-07-22

    Exotic genes, especially clustered multiple-genes for a complex pathway, are normally integrated into chromosome for heterologous expression. The influences of insertion sites on heterologous expression and allotropic expressions of exotic genes on host remain mostly unclear. We compared the integration and expression efficiencies of single and multiple exotic genes that were inserted into Myxococcus xanthus genome by transposition and attB-site-directed recombination. While the site-directed integration had a rather stable chloramphenicol acetyl transferase (CAT) activity, the transposition produced varied CAT enzyme activities. We attempted to integrate the 56-kb gene cluster for the biosynthesis of antitumor polyketides epothilones into M. xanthus genome by site-direction but failed, which was determined to be due to the insertion size limitation at the attB site. The transposition technique produced many recombinants with varied production capabilities of epothilones, which, however, were not paralleled to the transcriptional characteristics of the local sites where the genes were integrated. Comparative transcriptomics analysis demonstrated that the allopatric integrations caused selective changes of host transcriptomes, leading to varied expressions of epothilone genes in different mutants. With the increase of insertion fragment size, transposition is a more practicable integration method for the expression of exotic genes. Allopatric integrations selectively change host transcriptomes, which lead to varied expression efficiencies of exotic genes.

  9. Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease.

    Directory of Open Access Journals (Sweden)

    Shigeo Hanada

    Full Text Available Invasive pneumococcal disease (IPD causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.In a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.Overall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7-12.8, p < .001; age ≥80 years (OR, 6.5; 95% CI, 2.0-21.6, p = .002; serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5-8.1, p < .001; underlying liver disease (OR, 3.5; 95% CI, 1.6-7.8, p = .002; mechanical ventilation (OR, 3.0; 95% CI, 1.7-5.6, p < .001; and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4-4.0, p = .001. Pneumococcal serotype and drug resistance were not associated with poor outcomes.Host factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.

  10. Impact of sex on prognostic host factors in surgical patients with lung cancer.

    Science.gov (United States)

    Wainer, Zoe; Wright, Gavin M; Gough, Karla; Daniels, Marissa G; Choong, Peter; Conron, Matthew; Russell, Prudence A; Alam, Naveed Z; Ball, David; Solomon, Benjamin

    2017-12-01

    Lung cancer has markedly poorer survival in men. Recognized important prognostic factors are divided into host, tumour and environmental factors. Traditional staging systems that use only tumour factors to predict prognosis are of limited accuracy. By examining sex-based patterns of disease-specific survival in non-small cell lung cancer patients, we determined the effect of sex on the prognostic value of additional host factors. Two cohorts of patients treated surgically with curative intent between 2000 and 2009 were utilized. The primary cohort was from Melbourne, Australia, with an independent validation set from the American Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate analyses of validated host-related prognostic factors were performed in both cohorts to investigate the differences in survival between men and women. The Melbourne cohort had 605 patients (61% men) and SEER cohort comprised 55 681 patients (51% men). Disease-specific 5-year survival showed men had statistically significant poorer survival in both cohorts (P < 0.001); Melbourne men at 53.2% compared with women at 68.3%, and SEER 53.3% men and 62.0% women were alive at 5 years. Being male was independently prognostic for disease-specific mortality in the Melbourne cohort after adjustment for ethnicity, smoking history, performance status, age, pathological stage and histology (hazard ratio = 1.54, 95% confidence interval: 1.10-2.16, P = 0.012). Sex differences in non-small cell lung cancer are important irrespective of age, ethnicity, smoking, performance status and tumour, node and metastasis stage. Epidemiological findings such as these should be translated into research and clinical paradigms to determine the factors that influence the survival disadvantage experienced by men. © 2016 Royal Australasian College of Surgeons.

  11. Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication

    Directory of Open Access Journals (Sweden)

    Julianna Han

    2018-04-01

    Full Text Available Summary: The emergence of influenza A viruses (IAVs from zoonotic reservoirs poses a great threat to human health. As seasonal vaccines are ineffective against zoonotic strains, and newly transmitted viruses can quickly acquire drug resistance, there remains a need for host-directed therapeutics against IAVs. Here, we performed a genome-scale CRISPR/Cas9 knockout screen in human lung epithelial cells with a human isolate of an avian H5N1 strain. Several genes involved in sialic acid biosynthesis and related glycosylation pathways were highly enriched post-H5N1 selection, including SLC35A1, a sialic acid transporter essential for IAV receptor expression and thus viral entry. Importantly, we have identified capicua (CIC as a negative regulator of cell-intrinsic immunity, as loss of CIC resulted in heightened antiviral responses and restricted replication of multiple viruses. Therefore, our study demonstrates that the CRISPR/Cas9 system can be utilized for the discovery of host factors critical for the replication of intracellular pathogens. : Using a genome-wide CRISPR/Cas9 screen, Han et al. demonstrate that the major hit, the sialic acid transporter SLC35A1, is an essential host factor for IAV entry. In addition, they identify the DNA-binding transcriptional repressor CIC as a negative regulator of cell-intrinsic immunity. Keywords: CRISPR/Cas9 screen, GeCKO, influenza virus, host factors, sialic acid pathway, SLC35A1, Capicua, CIC, cell-intrinsic immunity, H5N1

  12. Risk Factors in Host and Environment for Cervicitis Among Commercial Sex Workers

    OpenAIRE

    Saputra, Nazarwin; Widjanarko, Bagoes; Setyawan, Henry

    2016-01-01

    sexually transmitted infection (STI) remains a major health problem in some parts of the world. This study aimed to determine the host and environmental factors the effect on the incidence of cervicitis on sex workers. The study was observational case-control design with consecutive sampling technique. Risk factor for cervicitis is a history of sexually transmitted infections (p=0,0001), have couple (boy friend) different gender (p=0,014, OR=4,4; CI95%=1,3-14,3), history of oral sex/cunniling...

  13. Energy transfer between a nanosystem and its host fluid: A multiscale factorization approach

    Science.gov (United States)

    Sereda, Yuriy V.; Espinosa-Duran, John M.; Ortoleva, Peter J.

    2014-02-01

    Energy transfer between a macromolecule or supramolecular assembly and a host medium is considered from the perspective of Newton's equations and Lie-Trotter factorization. The development starts by demonstrating that the energy of the molecule evolves slowly relative to the time scale of atomic collisions-vibrations. The energy is envisioned to be a coarse-grained variable that coevolves with the rapidly fluctuating atomistic degrees of freedom. Lie-Trotter factorization is shown to be a natural framework for expressing this coevolution. A mathematical formalism and workflow for efficient multiscale simulation of energy transfer is presented. Lactoferrin and human papilloma virus capsid-like structure are used for validation.

  14. Energy transfer between a nanosystem and its host fluid: A multiscale factorization approach

    International Nuclear Information System (INIS)

    Sereda, Yuriy V.; Espinosa-Duran, John M.; Ortoleva, Peter J.

    2014-01-01

    Energy transfer between a macromolecule or supramolecular assembly and a host medium is considered from the perspective of Newton's equations and Lie-Trotter factorization. The development starts by demonstrating that the energy of the molecule evolves slowly relative to the time scale of atomic collisions-vibrations. The energy is envisioned to be a coarse-grained variable that coevolves with the rapidly fluctuating atomistic degrees of freedom. Lie-Trotter factorization is shown to be a natural framework for expressing this coevolution. A mathematical formalism and workflow for efficient multiscale simulation of energy transfer is presented. Lactoferrin and human papilloma virus capsid-like structure are used for validation

  15. CD151, a novel host factor of nuclear export signaling in influenza virus infection.

    Science.gov (United States)

    Qiao, Yongkang; Yan, Yan; Tan, Kai Sen; Tan, Sheryl S L; Seet, Ju Ee; Arumugam, Thiruma Valavan; Chow, Vincent T K; Wang, De Yun; Tran, Thai

    2018-05-01

    Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains. We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro-differentiated human nasal epithelial cells cultured at air-liquid interface. As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly. Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Time resolved bovine host reponse to virulence factors mapped in milk by selected reaction monitoring

    DEFF Research Database (Denmark)

    Bislev, Stine Lønnerup; Kusebauch, Ulrike; Codrea, Marius Cosmin

    . In this study, we present a sensitive selected reaction monitoring (SRM) proteomics approach, targeting proteins suggested to play key roles in the bovine host response to mastitis. 17 biomarker candidates related to inflammatory response and mastitis were selected. The 17 candidate proteins were quantified......TIME RESOLVED BOVINE HOST RESPONSE TO VIRULENCE FACTORS, MAPPED IN MILK BY SELECTED REACTION MONITORING S.L. Bislev1, U. Kusebauch2, M.C. Codrea1, R. Moritz2, C.M. Røntved1, E. Bendixen1 1 Department of Animal Science, Faculty of Science and Technology, Aarhus University, Tjele, Denmark; 2...... Institute for Systems Biology, Seattle, Washington, USA Mastitis is beyond doubt the largest health problem in modern milk production. Many different pathogens can cause infections in the mammary gland, and give rise to severe toll on animal welfare, economic gain as well as on excessive use of antibiotics...

  17. Panethnicity and Ethnic Resources in Residential Integration: A Comparative Study of Two Host Societies

    Directory of Open Access Journals (Sweden)

    Kim, Ann H.

    2005-01-01

    Full Text Available EnglishThe racial and ethnic structure of a host society as well as itsinstitutional andideological context of integration shape the ethnic integration process. Toexamine these forces for residential integration, this study compares threepanethnic groups in Canada and the United States using tabular data from the2001 Canadian and the 2000 US censuses. Two ways in which the social contextis important are identified. First, the social context affects how groups aredistributed across urban neighbourhoods. As expected, being a Black ethnicgroup meant being less segregated in Canada than in the US but Asian groupswere more segregated, controlling for group characteristics and the urban andregional context. White ethnic groups in both countries were similarlysegregated. Second, the social context influences the process of incorporationitself. The effect of ethnic resources, in terms of acculturation and socioeconomicstatus, was dependent on the group and host society. The resultsdemonstrate that the national context plays a significant role in the waypanethnic group membership influences the spatial processes of ethnic groups inthe urban neighbourhoods of the two host societies.FrenchLa structure raciale et ethnique d’une société d’accueil et son contexteinstitutionnel et idéologique d’intégration forment le processus d’intégrationethnique. Dans le but d’examiner l’impact de ces éléments dans l’intégrationrésidentielle, cette étude compare trois groupes panethniques au Canada et auxÉtats-Unis en s’appuyant sur les données tabulaires du recensement canadien de2001 et du recensement américain de 2000. L’importance du contexte social aété mesurée de deux façons : D’abord, le contexte social affecte la distributiondes groupes dans les quartiers urbains. Comme on pouvait s’y attendre,appartenir à un groupe ethnique noir se traduit par une ségrégation moindre auCanada qu’aux États-Unis mais pas pour les groupes

  18. Factors affecting patterns of Amblyomma triste (Acari: Ixodidae) parasitism in a rodent host.

    Science.gov (United States)

    Colombo, Valeria C; Nava, Santiago; Antoniazzi, Leandro R; Monje, Lucas D; Racca, Andrea L; Guglielmone, Alberto A; Beldomenico, Pablo M

    2015-07-30

    Here we offer a multivariable analysis that explores associations of different factors (i.e., environmental, host parameters, presence of other ectoparasites) with the interaction of Amblyomma triste immature stages and one of its main hosts in Argentina, the rodent Akodon azarae. Monthly and for two years, we captured and sampled rodents at 16 points located at 4 different sites in the Parana River Delta region. The analyses were conducted with Generalized Linear Mixed Models with a negative binomial response (counts of larvae or nymphs). The independent variables assessed were: (a) environmental: trapping year, season, presence of cattle; type of vegetation (natural grassland or implanted forest); rodent abundance; (b) host parameters: body length; sex; body condition; blood cell counts; natural antibody titres; and (c) co-infestation with other ectoparasites: other stage of A. triste; Ixodes loricatus; lice; mites; and fleas. Two-way interaction terms deemed a priori as relevant were also included in the analysis. Larvae were affected by all environmental variables assessed and by the presence of other ectoparasites (lice, fleas and other tick species). Host factors significantly associated with larval count were sex and levels of natural antibodies. Nymphs were associated with season, presence of cattle, body condition, body length and with burdens of I. loricatus. In most cases, the direction and magnitude of the associations were context-dependent (many interaction terms were significant). The findings of greater significance and implications of our study are two. Firstly, as burdens of A. triste larvae and nymphs were greater where cattle were present, and larval tick burdens were higher in implanted forests, silvopastoral practices developing in the region may affect the population dynamics of A. triste, and consequently the eco-epidemiology of Rickettsia parkeri. Secondly, strong associations and numerous interactions with other ectoparasites suggest that

  19. Host-Country Related Risk Factors in International Construction: Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Güzin AYDOGAN

    2014-09-01

    Full Text Available Internationalization has been on the agenda of construction firms as a strategic option in global competition. Due to globalization every sector including the construction industry has faced with high levels of competitiveness, uncertainty, and risk. International construction involves common risks to domestic construction, as well as risks that are related to the host country. These risks have serious effects on the performance of international projects. Since the sustainable competitiveness of international contractors depends largely on the effective management of these risks, their assessment becomes vital for the success of international contractors. The main aim of this study is to analyse the risks for international construction projects that are related to the host country. Meta-analysis technique is used in order to determine these risks. This paper, therefore, reviews the literature that has been published in four most respected construction and management journals, these being; Journal of Construction Engineering and Management, Journal of Management in Engineering, Construction Management and Economics, and International Journal of Project Management for the period of 2000-2010. International construction risk assessment models are also reviewed within the context of this study, since host country related risk factors were found to have serious effects on the profitability of international contractors due to literature review. As a result; political stability, law and regulations, exchange rate risk, cultural differences, inflation, expropriation, tax discrimination, language barrier, bribery and corruption, force majeure, and societal conflicts in the host country are found to be the most important risk factors in international construction. Findings of this study can be used in risk assessment models for international construction projects.

  20. Maintenance of host DNA integrity in field-preserved mosquito (Diptera: Culicidae) blood meals for identification by DNA barcoding.

    Science.gov (United States)

    Reeves, Lawrence E; Holderman, Chris J; Gillett-Kaufman, Jennifer L; Kawahara, Akito Y; Kaufman, Phillip E

    2016-09-15

    Determination of the interactions between hematophagous arthropods and their hosts is a necessary component to understanding the transmission dynamics of arthropod-vectored pathogens. Current molecular methods to identify hosts of blood-fed arthropods require the preservation of host DNA to serve as an amplification template. During transportation to the laboratory and storage prior to molecular analysis, genetic samples need to be protected from nucleases, and the degradation effects of hydrolysis, oxidation and radiation. Preservation of host DNA contained in field-collected blood-fed specimens has an additional caveat: suspension of the degradative effects of arthropod digestion on host DNA. Unless effective preservation methods are implemented promptly after blood-fed specimens are collected, host DNA will continue to degrade. Preservation methods vary in their efficacy, and need to be selected based on the logistical constraints of the research program. We compared four preservation methods (cold storage at -20 °C, desiccation, ethanol storage of intact mosquito specimens and crushed specimens on filter paper) for field storage of host DNA from blood-fed mosquitoes across a range of storage and post-feeding time periods. The efficacy of these techniques in maintaining host DNA integrity was evaluated using a polymerase chain reaction (PCR) to detect the presence of a sufficient concentration of intact host DNA templates for blood meal analysis. We applied a logistic regression model to assess the effects of preservation method, storage time and post-feeding time on the binomial response variable, amplification success. Preservation method, storage time and post-feeding time all significantly impacted PCR amplification success. Filter papers and, to a lesser extent, 95 % ethanol, were the most effective methods for the maintenance of host DNA templates. Amplification success of host DNA preserved in cold storage at -20 °C and desiccation was poor. Our data

  1. Implications for risk assessment of host factors causing large pharmacokinetic variations

    Energy Technology Data Exchange (ETDEWEB)

    Vesell, E.S.

    1985-12-01

    Normal human subjects vary widely in their capacity to eliminate many drugs and environmental chemicals. These variations range in magnitude from fourfold to fortyfold depending on the drug and the population studied. Pharmacogenetics deals with only one of many host factors responsible for these large pharmacokinetic differences. Age, sex, diet and exposure to other drugs and chemicals, including oral contraceptives, ethanol and cigarette smoking, can alter the genetically determined rate at which a particular subject eliminates drugs and environmental chemicals. These elimination rates, therefore, are dynamic and change even in the same subject with time and condition. Regulatory legislation has only recently begun to recognize this very broad spectrum of human susceptibility and the existence of multiple special subgroups of particularly sensitive subjects. In setting standards for environmental chemicals, EPA and NIOSH have attempted to protect the most sensitive humans and should be encouraged to continue this policy. For some drugs and environmental chemicals, the commonly used safety factor of 100 may be too low; for these chemicals large, interindividual pharmacokinetic variations produced by pharmacogenetic and other host factors may make a safety factor of 400 or 500 more adequate.

  2. Social Hackers: Integration in the Host Chemical Recognition System by a Paper Wasp Social Parasite

    Science.gov (United States)

    Turillazzi, S.; Sledge, M. F.; Dani, F. R.; Cervo, R.; Massolo, A.; Fondelli, L.

    Obligate social parasites in the social insects have lost the worker caste and the ability to establish nests. As a result, parasites must usurp a host nest, overcome the host recognition system, and depend on the host workers to rear their offspring. We analysed cuticular hydrocarbon profiles of live parasite females of the paper wasp social parasite Polistes sulcifer before and after usurpation of host nests, using the non-destructive technique of solid-phase micro-extraction. Our results reveal that hydrocarbon profiles of parasites change after usurpation of host nests to match the cuticular profile of the host species. Chemical evidence further shows that the parasite queen changes the odour of the nest by the addition of a parasite-specific hydrocarbon. We discuss the possible role of this in the recognition and acceptance of the parasite and its offspring in the host colony.

  3. Integrative analyses unveil speciation linked to host plant shift in Spialia butterflies.

    Science.gov (United States)

    Hernández-Roldán, Juan L; Dapporto, Leonardo; Dincă, Vlad; Vicente, Juan C; Hornett, Emily A; Šíchová, Jindra; Lukhtanov, Vladimir A; Talavera, Gerard; Vila, Roger

    2016-09-01

    Discovering cryptic species in well-studied areas and taxonomic groups can have profound implications in understanding eco-evolutionary processes and in nature conservation because such groups often involve research models and act as flagship taxa for nature management. In this study, we use an array of techniques to study the butterflies in the Spialia sertorius species group (Lepidoptera, Hesperiidae). The integration of genetic, chemical, cytogenetic, morphological, ecological and microbiological data indicates that the sertorius species complex includes at least five species that differentiated during the last three million years. As a result, we propose the restitution of the species status for two taxa often treated as subspecies, Spialia ali (Oberthür, 1881) stat. rest. and Spialia therapne (Rambur, 1832) stat. rest., and describe a new cryptic species Spialia rosae Hernández-Roldán, Dapporto, Dincă, Vicente & Vila sp. nov. Spialia sertorius (Hoffmannsegg, 1804) and S. rosae are sympatric and synmorphic, but show constant differences in mitochondrial DNA, chemical profiles and ecology, suggesting that S. rosae represents a case of ecological speciation involving larval host plant and altitudinal shift, and apparently associated with Wolbachia infection. This study exemplifies how a multidisciplinary approach can reveal elusive cases of hidden diversity. © 2016 John Wiley & Sons Ltd.

  4. Host DNA synthesis-suppressing factor in culture fluid of tissue cultures infected with measles virus

    International Nuclear Information System (INIS)

    Minagawa, T.; Nakaya, C.; Iida, H.

    1974-01-01

    Host DNA synthesis is suppressed by the culture fluid of cell cultures infected with measles virus. This activity in the culture fluid is initiated somewhat later than the growth of infectious virus. Ninety percent of host DNA synthesis in HeLa cells is inhibited by culture fluid of 3-day-old cell cultures of Vero or HeLa cells infected with measles virus. This suppressing activity is not a property of the virion, but is due to nonvirion-associated componentnent which shows none of the activities of measles virus such as hemagglutination, hemolysis, or cell fusion nor does it have the antigenicity of measles virus as tested by complement-fixation or hemagglutination-inhibiting antibody blocking tests. Neutralization of the activity of this component is not attained with the pooled sera of convalescent measles patients. This component has molecular weights of about 45,000, 20,000, and 3,000 and appears to be a heat-stable protein. The production of host DNA suppressing factor (DSF) is blocked by cycloheximide. Neither uv-inactivated nor antiserum-neutralized measles virus produce DSF. Furthermore, such activity of nonvirion-associated component is not detected in the culture fluid of cultures infected with other RNA viruses such as poliovirus, vesicular stomatitis virus, or Sindbis virus. (auth)

  5. Yersinia virulence factors - a sophisticated arsenal for combating host defences [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Steve Atkinson

    2016-06-01

    Full Text Available The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six ‘effector’ proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen.

  6. Integrated approaches to spatiotemporally directing angiogenesis in host and engineered tissues.

    Science.gov (United States)

    Kant, Rajeev J; Coulombe, Kareen L K

    2018-03-15

    The field of tissue engineering has turned towards biomimicry to solve the problem of tissue oxygenation and nutrient/waste exchange through the development of vasculature. Induction of angiogenesis and subsequent development of a vascular bed in engineered tissues is actively being pursued through combinations of physical and chemical cues, notably through the presentation of topographies and growth factors. Presenting angiogenic signals in a spatiotemporal fashion is beginning to generate improved vascular networks, which will allow for the creation of large and dense engineered tissues. This review provides a brief background on the cells, mechanisms, and molecules driving vascular development (including angiogenesis), followed by how biomaterials and growth factors can be used to direct vessel formation and maturation. Techniques to accomplish spatiotemporal control of vascularization include incorporation or encapsulation of growth factors, topographical engineering, and 3D bioprinting. The vascularization of engineered tissues and their application in angiogenic therapy in vivo is reviewed herein with an emphasis on the most densely vascularized tissue of the human body - the heart. Vascularization is vital to wound healing and tissue regeneration, and development of hierarchical networks enables efficient nutrient transfer. In tissue engineering, vascularization is necessary to support physiologically dense engineered tissues, and thus the field seeks to induce vascular formation using biomaterials and chemical signals to provide appropriate, pro-angiogenic signals for cells. This review critically examines the materials and techniques used to generate scaffolds with spatiotemporal cues to direct vascularization in engineered and host tissues in vitro and in vivo. Assessment of the field's progress is intended to inspire vascular applications across all forms of tissue engineering with a specific focus on highlighting the nuances of cardiac tissue

  7. The Impact of Host Metabolic Factors on Treatment Outcome in Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Savvidou Savvoula

    2012-01-01

    Full Text Available Background. Recent data suggest that chronic hepatitis C has to be considered a metabolic disease further to a viral infection. The aim of this study was to elaborate on the complex interactions between hepatitis C virus, host metabolic factors, and treatment response. Methods. Demographic, virological, and histological data from 356 consecutive patients were analyzed retrospectively. Hepatic steatosis, obesity, and insulin resistance were examined in relation to their impact on treatment outcome. Comparison between genotype 1 and 3 patients was performed to identify differences in the determinants of hepatic steatosis. Results. Histological evidence of hepatic steatosis was found in 113 patients, distributed in 20.3%, 9.0%, and 2.5% for grades I, II, and III, respectively. Hepatic steatosis was associated with past alcohol abuse (P=0.003 and histological evidence of advanced fibrosis (P<0.001. Older age (OR 2.51, P=0.002, genotype (OR 3.28, P<0.001, cirrhosis (OR 4.23, P=0.005, and hepatic steatosis (OR 2.48, P=0.001 were independent predictors for nonresponse. Correlations of hepatic steatosis with alcohol, insulin resistance, and fibrosis stage were found similar for both genotypes 1 and 3. Conclusions. Host metabolic factors may predict treatment outcome, and this impact remains significant even in genotype 3, where steatosis has been believed to be exclusively virus related.

  8. Dietary Factors Modulate Colonic Tumorigenesis Through the Interaction of Gut Microbiota and Host Chloride Channels.

    Science.gov (United States)

    Zhang, Yong; Kang, Chao; Wang, Xiao-Lan; Zhou, Min; Chen, Meng-Ting; Zhu, Xiao-Hui; Liu, Kai; Wang, Bin; Zhang, Qian-Yong; Zhu, Jun-Dong; Mi, Man-Tian

    2018-03-01

    In recent decades, the association among diet, gut microbiota, and the risk of colorectal cancer (CRC) has been established. Gut microbiota and associated metabolites, such as bile acids and butyrate, are now known to play a key role in CRC development. The aim of this study is to identify that the progression to CRC is influenced by cholic acid, sodium butyrate, a high-fat diet, or different dose of dihydromyricetin (DMY) interacted with gut microbiota. An AOM/DSS (azoxymethan/dextran sodium sulfate) model is established to study the gut microbiota compsition before and after tumor formation during colitis-induced tumorigenesis. All above dietary factors profoundly influence the composition of gut microbiota and host colonic tumorigenesis. In addition, mice with DMY-modified initial microbiota display different degrees of chemically induced tumorigenesis. Mechanism analysis reveals that gut microbiota-associated chloride channels participated in colon tumorigenesis. Gut microbiota changes occur in the hyperproliferative stage before tumor formation. Gut microbiota and host chloride channels, both of which are regulated by dietary factors, are associated with CRC development. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Lipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria

    Directory of Open Access Journals (Sweden)

    Wood Robin

    2012-02-01

    Full Text Available Abstract Background Detection of lipoarabinomannan (LAM, a Mycobacterium tuberculosis (Mtb cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection. Methods LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP and urines were tested for mycobacteriuria by Xpert® MTB/RIF assay. Results 32/199 (16.1% of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200, 100-199, 50-99, and Conclusions Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection.

  10. Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration.

    Directory of Open Access Journals (Sweden)

    Irena Zurnic

    2016-08-01

    Full Text Available Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H screen with prototype FV (PFV Gag protein as bait we identified human polo-like kinase 2 (hPLK2, a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells.

  11. Energy transfer between a nanosystem and its host fluid: A multiscale factorization approach

    Energy Technology Data Exchange (ETDEWEB)

    Sereda, Yuriy V.; Espinosa-Duran, John M.; Ortoleva, Peter J., E-mail: ortoleva@indiana.edu [Center for Cell and Virus Theory, Department of Chemistry, Indiana University, 800 E. Kirkwood Ave, Bloomington, Indiana 47405 (United States)

    2014-02-21

    Energy transfer between a macromolecule or supramolecular assembly and a host medium is considered from the perspective of Newton's equations and Lie-Trotter factorization. The development starts by demonstrating that the energy of the molecule evolves slowly relative to the time scale of atomic collisions-vibrations. The energy is envisioned to be a coarse-grained variable that coevolves with the rapidly fluctuating atomistic degrees of freedom. Lie-Trotter factorization is shown to be a natural framework for expressing this coevolution. A mathematical formalism and workflow for efficient multiscale simulation of energy transfer is presented. Lactoferrin and human papilloma virus capsid-like structure are used for validation.

  12. Relevance of genetically determined host factors to the prognosis of meningococcal disease.

    Science.gov (United States)

    Domingo, P; Muñiz-Diaz, E; Baraldès, M A; Arilla, M; Barquet, N; Pericas, R; Juárez, C; Madoz, P; Vázquez, G

    2004-08-01

    To assess the relevance of genetically determined host factors for the prognosis of meningococcal disease, Fc gamma receptor IIA (FcgammaRIIA), the tumor necrosis factor alpha (TNF-alpha) gene promoter region, and plasminogen-activator-inhibitor-1 (PAI-1) gene polymorphisms were studied in 145 patients with meningococcal disease and in 290 healthy controls matched by sex. Distribution of FcgammaRIIA, TNF-alpha, and PAI-1 alleles was not significantly different between patients and controls. Patients with the FcgammaRIIA-R/R 131 allotype scored > or =1 point in the Barcelona prognostic system more frequently than patients with other allotypes (odds ratio, 18.6; 95% confidence interval, 7.1-49.0, PFc gamma receptor IIA polymorphism was associated with markers of disease severity, but TNF-alpha and PAI-1 polymorphisms were not.

  13. Repair of oxidative DNA base damage in the host genome influences the HIV integration site sequence preference.

    Directory of Open Access Journals (Sweden)

    Geoffrey R Bennett

    Full Text Available Host base excision repair (BER proteins that repair oxidative damage enhance HIV infection. These proteins include the oxidative DNA damage glycosylases 8-oxo-guanine DNA glycosylase (OGG1 and mutY homolog (MYH as well as DNA polymerase beta (Polβ. While deletion of oxidative BER genes leads to decreased HIV infection and integration efficiency, the mechanism remains unknown. One hypothesis is that BER proteins repair the DNA gapped integration intermediate. An alternative hypothesis considers that the most common oxidative DNA base damages occur on guanines. The subtle consensus sequence preference at HIV integration sites includes multiple G:C base pairs surrounding the points of joining. These observations suggest a role for oxidative BER during integration targeting at the nucleotide level. We examined the hypothesis that BER repairs a gapped integration intermediate by measuring HIV infection efficiency in Polβ null cell lines complemented with active site point mutants of Polβ. A DNA synthesis defective mutant, but not a 5'dRP lyase mutant, rescued HIV infection efficiency to wild type levels; this suggested Polβ DNA synthesis activity is not necessary while 5'dRP lyase activity is required for efficient HIV infection. An alternate hypothesis that BER events in the host genome influence HIV integration site selection was examined by sequencing integration sites in OGG1 and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases the chromatin elements of HIV integration site selection remain the same as in wild type cells. However, the HIV integration site sequence preference at G:C base pairs is altered at several positions in OGG1 and MYH null cells. Inefficient HIV infection in the absence of oxidative BER proteins does not appear related to repair of the gapped integration intermediate; instead oxidative damage repair may participate in HIV integration site preference at the sequence level.

  14. Identifying influential factors on integrated marketing planning using information technology

    Directory of Open Access Journals (Sweden)

    Karim Hamdi

    2014-07-01

    Full Text Available This paper presents an empirical investigation to identify important factors influencing integrated marketing planning using information technology. The proposed study designs a questionnaire for measuring integrated marketing planning, which consists of three categories of structural factors, behavioral factors and background factors. There are 40 questions associated with the proposed study in Likert scale. Cronbach alphas have been calculated for structural factors, behavioral factors and background factors as 0.89, 0.86 and 0.83, respectively. Using some statistical test, the study has confirmed the effects of three factors on integrated marketing. In addition, the implementation of Freedman test has revealed that structural factors were the most important factor followed by background factors and behavioral factors.

  15. Posthodiplostomum cuticola (Digenea: Diplostomatidae) in intermediate fish hosts: factors contributing to the parasite infection and prey selection by the definitive bird host

    Czech Academy of Sciences Publication Activity Database

    Ondračková, Markéta; Šimková, A.; Gelnar, M.; Jurajda, Pavel

    2004-01-01

    Roč. 129, č. 6 (2004), s. 761-770 ISSN 0031-1820 R&D Projects: GA ČR GA524/02/0924; GA ČR GP524/03/P108 Institutional research plan: CEZ:AV0Z6093917 Keywords : fish assemblages * intermediate host * complex life-cycle Subject RIV: EG - Zoology Impact factor: 1.685, year: 2004

  16. Museum specimens reveal loss of pollen host plants as key factor driving wild bee decline in The Netherlands

    Science.gov (United States)

    Scheper, Jeroen; Reemer, Menno; van Kats, Ruud; Ozinga, Wim A.; van der Linden, Giel T. J.; Schaminée, Joop H. J.; Siepel, Henk; Kleijn, David

    2014-01-01

    Evidence for declining populations of both wild and managed bees has raised concern about a potential global pollination crisis. Strategies to mitigate bee loss generally aim to enhance floral resources. However, we do not really know whether loss of preferred floral resources is the key driver of bee decline because accurate assessment of host plant preferences is difficult, particularly for species that have become rare. Here we examine whether population trends of wild bees in The Netherlands can be explained by trends in host plants, and how this relates to other factors such as climate change. We determined host plant preference of bee species using pollen loads on specimens in entomological collections that were collected before the onset of their decline, and used atlas data to quantify population trends of bee species and their host plants. We show that decline of preferred host plant species was one of two main factors associated with bee decline. Bee body size, the other main factor, was negatively related to population trend, which, because larger bee species have larger pollen requirements than smaller species, may also point toward food limitation as a key factor driving wild bee loss. Diet breadth and other potential factors such as length of flight period or climate change sensitivity were not important in explaining twentieth century bee population trends. These results highlight the species-specific nature of wild bee decline and indicate that mitigation strategies will only be effective if they target the specific host plants of declining species. PMID:25422416

  17. Factors influencing implementation of integrated management of ...

    African Journals Online (AJOL)

    intern

    implementation of health facility based Integrated Management of Childhood Illness ... community-owned resource persons (CORPs) to provide health education to care ... differing coverage of basic essential services such safe water supply, ...

  18. Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.

    Directory of Open Access Journals (Sweden)

    Eric Baranowski

    Full Text Available Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i the development of a specific antibody response and (ii dynamic changes in expression of M. agalactiae surface variable proteins (Vpma, with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.

  19. Intermediate hosts of the trematode Collyriclum faba (Plagiochiida: Collyriclidae) identified by an integrated morphological and genetic approach

    Czech Academy of Sciences Publication Activity Database

    Heneberg, P.; Faltýnková, Anna; Bizos, J.; Mala, M.; Žiak, J.; Literák, I.

    2015-01-01

    Roč. 8, FEB 8 2015 (2015), s. 85 ISSN 1756-3305 Institutional support: RVO:60077344 Keywords : cercariae * DNA analysis * fluke * host -parasite interaction * Hydrobiidae * life cycle * Littorinimorpha Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 3.234, year: 2015

  20. The roles of actors in the host society in the integration of inmigrants associations: a social networks analysis approach

    Directory of Open Access Journals (Sweden)

    José Manuel Gaete Fiscella

    2016-06-01

    Full Text Available This article explores the stages of integration of immigrant associations in Spain according to stock of social capital, specifically, given the relationships established with actors in the environment, and consequently this role is derived for each type of counterpart. The data are drawn from a representative sample consisting of 225 immigrant associations around the country. The results suggest that immigrant associations play cohesive and specific roles with their peers, even achieve certain asymmetries in their favor with certain actors in the host society. On the other hand, native actors host society are distributed in a continuum ranging from the development of specific roles to other multiple, and even contradictory, which, as a whole, ends up drawing a map of complex and diverse opportunities for integration of associations.

  1. Uveal melanoma in relation to ultraviolet light exposure and host factors.

    Science.gov (United States)

    Holly, E A; Aston, D A; Char, D H; Kristiansen, J J; Ahn, D K

    1990-09-15

    We conducted a case-control interview study among 1277 subjects (407 patients, 870 controls selected by using random digit dial) in 11 western United States to determine whether uveal melanoma and cutaneous melanoma shared common risk factors. After adjustment for other factors, the risk of uveal melanoma was increased for those with green, gray, or hazel eyes [relative risk (RR) = 2.5, P less than 0.001] or blue eyes (RR = 2.2, P less than 0.001) when compared to brown. A tendency to sunburn after 0.5 h midday summer sun exposure increased risk for uveal melanoma (burn with tanning RR = 1.5, P = 0.02; burn with little tanning RR = 1.8, P less than 0.001; burn with no tanning RR = 1.7, P = 0.002); as did exposure to UV or black lights (RR = 3.7, P = 0.003); and welding burn, sunburn of the eye, or snow blindness (RR = 7.2, P less than 0.001). An association with uveal melanoma was also noted with an increasing number of large nevi (P = 0.04 for trend), although the individual risk estimates were not remarkable. These data suggest that host factors and exposure to UV light are risk factors for uveal melanoma.

  2. No Major Host Genetic Risk Factor Contributed to A(H1N12009 Influenza Severity.

    Directory of Open Access Journals (Sweden)

    Koldo Garcia-Etxebarria

    Full Text Available While most patients affected by the influenza A(H1N1 pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

  3. Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors

    Energy Technology Data Exchange (ETDEWEB)

    Lammerts van Bueren,A.; Higgins, M.; Wang, D.; Burke, R.; Boraston, A.

    2007-01-01

    The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basis for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.

  4. A loss of function analysis of host factors influencing Vaccinia virus replication by RNA interference.

    Directory of Open Access Journals (Sweden)

    Philippa M Beard

    Full Text Available Vaccinia virus (VACV is a large, cytoplasmic, double-stranded DNA virus that requires complex interactions with host proteins in order to replicate. To explore these interactions a functional high throughput small interfering RNA (siRNA screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF influencing the replication and spread of an eGFP-tagged VACV. The experimental design incorporated a low multiplicity of infection, thereby enhancing detection of cellular proteins involved in cell-to-cell spread of VACV. The screen revealed 153 pro- and 149 anti-viral HFs that strongly influenced VACV replication. These HFs were investigated further by comparisons with transcriptional profiling data sets and HFs identified in RNAi screens of other viruses. In addition, functional and pathway analysis of the entire screen was carried out to highlight cellular mechanisms involved in VACV replication. This revealed, as anticipated, that many pro-viral HFs are involved in translation of mRNA and, unexpectedly, suggested that a range of proteins involved in cellular transcriptional processes and several DNA repair pathways possess anti-viral activity. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. This advancement in our understanding of the VACV life cycle provides a reliable knowledge base for the improvement of poxvirus-based vaccine vectors and development of anti-viral theraputics.

  5. Macrophage Migration Inhibitory Factor Contributes to Host Defense against Acute Trypanosoma cruzi Infection

    Science.gov (United States)

    Reyes, José L.; Terrazas, Luis I.; Espinoza, Bertha; Cruz-Robles, David; Soto, Virgilia; Rivera-Montoya, Irma; Gómez-García, Lorena; Snider, Heidi; Satoskar, Abhay R.; Rodríguez-Sosa, Miriam

    2006-01-01

    Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is involved in the host defense against several pathogens. Here we used MIF−/− mice to determine the role of endogenous MIF in the regulation of the host immune response against Trypanosoma cruzi infection. MIF−/− mice displayed high levels of blood and tissue parasitemia, developed severe heart and skeletal muscle immunopathology, and succumbed to T. cruzi infection faster than MIF+/+ mice. The enhanced susceptibility of MIF−/− mice to T. cruzi was associated with reduced levels of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-12 (IL-12), IL-18, gamma interferon (IFN-γ), and IL-1β, in their sera and reduced production of IL-12, IFN-γ, and IL-4 by spleen cells during the early phase of infection. At all time points, antigen-stimulated splenocytes from MIF+/+ and MIF−/− mice produced comparable levels of IL-10. MIF−/− mice also produced significantly less Th1-associated antigen-specific immunoglobulin G2a (IgG2a) throughout the infection, but both groups produced comparable levels of Th2-associated IgG1. Lastly, inflamed hearts from T. cruzi-infected MIF−/− mice expressed increased transcripts for IFN-γ, but fewer for IL-12 p35, IL-12 p40, IL-23, and inducible nitric oxide synthase, compared to MIF+/+ mice. Taken together, our findings show that MIF plays a role in controlling acute T. cruzi infection. PMID:16714544

  6. Highlights Regarding Host Predisposing Factors to Recurrent Vulvovaginal Candidiasis: Chronic Stress and Reduced Antioxidant Capacity.

    Science.gov (United States)

    Akimoto-Gunther, Luciene; Bonfim-Mendonça, Patrícia de Souza; Takahachi, Gisele; Irie, Mary Mayumi T; Miyamoto, Sônia; Consolaro, Márcia Edilaine Lopes; Svidzinsk, Terezinha I Estivalet

    2016-01-01

    We studied host factors that could predispose women to develop recurrent vulvovaginal candidiasis (RVVC), including glycemia, insulin resistance, chronic stress, antioxidant capacity, overall immune status, local inflammation and vaginal microbiota. The presence of yeasts in vaginal culture was screened in 277 women, with or without signs and symptoms of VVC and RVVC. The presence of an inflammatory process and microbiota were analyzed through vaginal bacterioscopy and cervical-vaginal cytology, respectively. Fasting-blood samples were collected by standard venipuncture for biochemical analyses. Flow cytometry was employed to obtain the T helper/T cytotoxic lymphocyte ratio, and insulin resistance was assessed by the HOMA index (HI). Yeasts were isolated from 71 (26%) women: 23 (32.4%) with a positive culture but without symptoms (COL), 22 (31%) in an acute episode (VVC), and 26 (36.6%) with RVVC. C. albicans was the main yeast isolated in all clinical profiles. The control group (negative culture) comprised 206 women. Diabetes mellitus and insulin resistance were more associated with the positive-culture groups (COL, VVC and RVVC) than with negative ones. The RVVC group showed lower mean levels of cortisol than the control group and lower antioxidant capacity than all other groups. The T Helper/T cytotoxic lymphocyte ratio was similar in all groups. The RVVC group showed a similar level of vaginal inflammation to the control group, and lower than in the COL and VVC groups. Only the CVV group showed a reduction in vaginal lactobacillus microbiota. Our data suggest that both chronic stress (decreased early-morning cortisol levels) and reduced antioxidant capacity can be host predisposing factors to RVVC.

  7. Highlights Regarding Host Predisposing Factors to Recurrent Vulvovaginal Candidiasis: Chronic Stress and Reduced Antioxidant Capacity.

    Directory of Open Access Journals (Sweden)

    Luciene Akimoto-Gunther

    Full Text Available We studied host factors that could predispose women to develop recurrent vulvovaginal candidiasis (RVVC, including glycemia, insulin resistance, chronic stress, antioxidant capacity, overall immune status, local inflammation and vaginal microbiota. The presence of yeasts in vaginal culture was screened in 277 women, with or without signs and symptoms of VVC and RVVC. The presence of an inflammatory process and microbiota were analyzed through vaginal bacterioscopy and cervical-vaginal cytology, respectively. Fasting-blood samples were collected by standard venipuncture for biochemical analyses. Flow cytometry was employed to obtain the T helper/T cytotoxic lymphocyte ratio, and insulin resistance was assessed by the HOMA index (HI. Yeasts were isolated from 71 (26% women: 23 (32.4% with a positive culture but without symptoms (COL, 22 (31% in an acute episode (VVC, and 26 (36.6% with RVVC. C. albicans was the main yeast isolated in all clinical profiles. The control group (negative culture comprised 206 women. Diabetes mellitus and insulin resistance were more associated with the positive-culture groups (COL, VVC and RVVC than with negative ones. The RVVC group showed lower mean levels of cortisol than the control group and lower antioxidant capacity than all other groups. The T Helper/T cytotoxic lymphocyte ratio was similar in all groups. The RVVC group showed a similar level of vaginal inflammation to the control group, and lower than in the COL and VVC groups. Only the CVV group showed a reduction in vaginal lactobacillus microbiota. Our data suggest that both chronic stress (decreased early-morning cortisol levels and reduced antioxidant capacity can be host predisposing factors to RVVC.

  8. Free amino acids exhibit anthozoan "host factor" activity: they induce the release of photosynthate from symbiotic dinoflagellates in vitro.

    Science.gov (United States)

    Gates, R D; Hoegh-Guldberg, O; McFall-Ngai, M J; Bil, K Y; Muscatine, L

    1995-08-01

    Reef-building corals and other tropical anthozoans harbor endosymbiotic dinoflagellates. It is now recognized that the dinoflagellates are fundamental to the biology of their hosts, and their carbon and nitrogen metabolisms are linked in important ways. Unlike free living species, growth of symbiotic dinoflagellates is unbalanced and a substantial fraction of the carbon fixed daily by symbiont photosynthesis is released and used by the host for respiration and growth. Release of fixed carbon as low molecular weight compounds by freshly isolated symbiotic dinoflagellates is evoked by a factor (i.e., a chemical agent) present in a homogenate of host tissue. We have identified this "host factor" in the Hawaiian coral Pocillopora damicornis as a set of free amino acids. Synthetic amino acid mixtures, based on the measured free amino acid pools of P. damicornis tissues, not only elicit the selective release of 14C-labeled photosynthetic products from isolated symbiotic dinoflagellates but also enhance total 14CO2 fixation.

  9. KAP1 Is a Host Restriction Factor That Promotes Human Adenovirus E1B-55K SUMO Modification

    DEFF Research Database (Denmark)

    Bürck, Carolin; Mund, Andreas; Berscheminski, Julia

    2016-01-01

    Once transported to the replication sites, HAdVs need to assure decondensation and transcriptional activation of their viral genomes to synthesize viral proteins and initiate steps to reprogram the host cell for viral replication. These early stages during adenoviral infection are poorly characte......Once transported to the replication sites, HAdVs need to assure decondensation and transcriptional activation of their viral genomes to synthesize viral proteins and initiate steps to reprogram the host cell for viral replication. These early stages during adenoviral infection are poorly...... characterized, but represent a decisive moment in establishing a productive infection. Here, we identify a novel host viral restriction factor, KAP1. This heterochromatin associated transcription factor regulates the dynamic organization of host chromatin structure via its ability to influence epigenetic marks...

  10. Integrating human factors into process hazard analysis

    International Nuclear Information System (INIS)

    Kariuki, S.G.; Loewe, K.

    2007-01-01

    A comprehensive process hazard analysis (PHA) needs to address human factors. This paper describes an approach that systematically identifies human error in process design and the human factors that influence its production and propagation. It is deductive in nature and therefore considers human error as a top event. The combinations of different factors that may lead to this top event are analysed. It is qualitative in nature and is used in combination with other PHA methods. The method has an advantage because it does not look at the operator error as the sole contributor to the human failure within a system but a combination of all underlying factors

  11. Differential expression and interaction of host factors augment HIV-1 gene expression in neonatal mononuclear cells

    International Nuclear Information System (INIS)

    Sundaravaradan, Vasudha; Mehta, Roshni; Harris, David T.; Zack, Jerome A.; Ahmad, Nafees

    2010-01-01

    We have previously shown a higher level of HIV-1 replication and gene expression in neonatal (cord) blood mononuclear cells (CBMC) compared with adult blood cells (PBMC), which could be due to differential expression of host factors. We performed the gene expression profile of CBMC and PBMC and found that 8013 genes were expressed at higher levels in CBMC than PBMC and 8028 genes in PBMC than CBMC, including 1181 and 1414 genes upregulated after HIV-1 infection in CBMC and PBMC, respectively. Several transcription factors (NF-κB, E2F, HAT-1, TFIIE, Cdk9, Cyclin T1), signal transducers (STAT3, STAT5A) and cytokines (IL-1β, IL-6, IL-10) were upregulated in CBMC than PBMC, which are known to influence HIV-1 replication. In addition, a repressor of HIV-1 transcription, YY1, was down regulated in CBMC than PBMC and several matrix metalloproteinase (MMP-7, -12, -14) were significantly upregulated in HIV-1 infected CBMC than PBMC. Furthermore, we show that CBMC nuclear extracts interacted with a higher extent to HIV-1 LTR cis-acting sequences, including NF-κB, NFAT, AP1 and NF-IL6 compared with PBMC nuclear extracts and retroviral based short hairpin RNA (shRNA) for STAT3 and IL-6 down regulated their own and HIV-1 gene expression, signifying that these factors influenced differential HIV-1 gene expression in CBMC than PBMC.

  12. Risk Factors in Host and Environment for Cervicitis Among Commercial Sex Workers

    Directory of Open Access Journals (Sweden)

    Nazarwin Saputra

    2017-09-01

    Full Text Available sexually transmitted infection (STI remains a major health problem in some parts of the world. This study aimed to determine the host and environmental factors the effect on the incidence of cervicitis on sex workers. The study was observational case-control design with consecutive sampling technique. Risk factor for cervicitis is a history of sexually transmitted infections (p=0,0001, have couple (boy friend different gender (p=0,014, OR=4,4; CI95%=1,3-14,3, history of oral sex/cunnilingus (p=0,003, OR=6,8;CI95%=1,9-24,8, smokers (p=0,0001, CI95%=5,6; CI95%=2,4-13,1. Condom use last sex behavior is a protective factor affecting the incidence of cervicitis (p=0,0001, OR= 0,198; CI95 %=0,07- 0,5. The conclusion of this study is to prevent servisitis at-risk groups of commercial sex workers it should avoid from exposure of agents that cause sexually transmitted infections, does not have a spouse who is not authorized (girlfriend that leads to sex behavior, avoid behaviors oral sex / cunnilingus, no smoke. At-risk behavior should use condoms for prevention servisitis

  13. Genome-Wide Search for Host Association Factors during Ovine Progressive Pneumonia Virus Infection.

    Directory of Open Access Journals (Sweden)

    Jesse Thompson

    Full Text Available Ovine progressive pneumonia virus (OPPV is an important virus that causes serious diseases in sheep and goats with a prevalence of 36% in the USA. Although OPPV was discovered more than half of a century ago, little is known about the infection and pathogenesis of this virus. In this report, we used RNA-seq technology to conduct a genome-wide probe for cellular factors that are associated with OPPV infection. A total of approximately 22,000 goat host genes were detected of which 657 were found to have been significantly up-regulated and 889 down-regulated at 12 hours post-infection. In addition to previously known restriction factors from other viral infections, a number of factors which may be specific for OPPV infection were uncovered. The data from this RNA-seq study will be helpful in our understanding of OPPV infection, and also for further study in the prevention and intervention of this viral disease.

  14. Prevalence of inter-appointment endodontic flare-ups and host-related factors.

    Science.gov (United States)

    Azim, Adham A; Azim, Katharina A; Abbott, Paul V

    2017-04-01

    The aims of this study were to report the prevalence of inter-appointment flare-ups following adequate root canal disinfection and to investigate the host factors contributing to its occurrence. One thousand five hundred patient records were reviewed and the prevalence of flare-up was recorded. Patients' root canal space status (vital, non-vital or retreatment), medical condition and demographics (age, gender, tooth type and position) were recorded from their dental records. Statistical analyses were performed to determine the impact of the recorded factors on flare-up occurrence. Nine hundred fifty-one patient records met the inclusion criteria. The prevalence of flare-up was 2.3 %. There was a correlation between the canal space status and patient's age with flare-up development (P flare-up occurrence and tooth type, location, gender or medical condition (P > 0.5). The root canal space status was the primary factor affecting flare-up occurrence. Patients >50 years had the highest risk in developing flare-ups. This article provides evidence that patients suffering from inflamed pulp will not develop flare-up if adequate cleaning and shaping of the root canal space was performed. It also shows that patients above the age of 50 are a high-risk group that is prone to flare-up development.

  15. Factors influencing implementation of integrated management of ...

    African Journals Online (AJOL)

    Background: Save the Children Tanzania has been supporting several projects in Lindi Region including implementation of health facility based Integrated Management of Childhood Illness (IMCI) services in Kilwa, Ruangwa and Lindi rural districts. The objective of this study was to assess the IMCI services in a sample of ...

  16. Chlamydia infection across host species boundaries promotes distinct sets of transcribed anti-apoptotic factors.

    Directory of Open Access Journals (Sweden)

    Joshua eMessinger

    2015-12-01

    Full Text Available Chlamydiae, obligate intracellular bacteria, cause significant human and veterinary associated diseases. Having emerged an estimated 700-million years ago, these bacteria have twice adapted to humans as a host species, causing sexually transmitted infection (C. trachomatis and respiratory associated disease (C. pneumoniae. The principle mechanism of host cell defense against these intracellular bacteria is the induction of cell death via apoptosis. However, in the arms race of co-evolution, Chlamydiae have developed mechanisms to promote cell viability and inhibit cell death. Herein we examine the impact of Chlamydiae infection across multiple host species on transcription of anti-apoptotic genes. We found mostly distinct patterns of gene expression (Mcl1 and cIAPs elicited by each pathogen-host pair indicating Chlamydiae infection across host species boundaries does not induce a universally shared host response. Understanding species specific host-pathogen interactions is paramount to deciphering how potential pathogens become emerging diseases.

  17. Host-specific interactions with environmental factors shape the distribution of symbiodinium across the Great Barrier Reef.

    Directory of Open Access Journals (Sweden)

    Linda Tonk

    Full Text Available The endosymbiotic dinoflagellates (genus Symbiodinium within coral reef invertebrates are critical to the survival of the holobiont. The genetic variability of Symbiodinium may contribute to the tolerance of the symbiotic association to elevated sea surface temperatures (SST. To assess the importance of factors such as the local environment, host identity and biogeography in driving Symbiodinium distributions on reef-wide scales, data from studies on reef invertebrate-Symbiodinium associations from the Great Barrier Reef (GBR were compiled.The resulting database consisted of 3717 entries from 26 studies. It was used to explore ecological patterns such as host-specificity and environmental drivers structuring community complexity using a multi-scalar approach. The data was analyzed in several ways: (i frequently sampled host species were analyzed independently to investigate the influence of the environment on symbiont distributions, thereby excluding the influence of host specificity, (ii host species distributions across sites were added as an environmental variable to determine the contribution of host identity on symbiont distribution, and (iii data were pooled based on clade (broad genetic groups dividing the genus Symbiodinium to investigate factors driving Symbiodinium distributions using lower taxonomic resolution. The results indicated that host species identity plays a dominant role in determining the distribution of Symbiodinium and environmental variables shape distributions on a host species-specific level. SST derived variables (especially SSTstdev most often contributed to the selection of the best model. Clade level comparisons decreased the power of the predictive model indicating that it fails to incorporate the main drivers behind Symbiodinium distributions.Including the influence of different host species on Symbiodinium distributional patterns improves our understanding of the drivers behind the complexity of Symbiodinium

  18. Systems integration of biodefense omics data for analysis of pathogen-host interactions and identification of potential targets.

    Directory of Open Access Journals (Sweden)

    Peter B McGarvey

    2009-09-01

    Full Text Available The NIAID (National Institute for Allergy and Infectious Diseases Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1 The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells infected by different bacterial (Bacillus anthracis and Salmonella typhimurium and viral (orthopox pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2 The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3 Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and

  19. Female genital tract graft-versus-host disease: incidence, risk factors and recommendations for management.

    Science.gov (United States)

    Zantomio, D; Grigg, A P; MacGregor, L; Panek-Hudson, Y; Szer, J; Ayton, R

    2006-10-01

    Female genital tract graft-versus-host disease (GVHD) is an under-recognized complication of allogeneic stem cell transplantation impacting on quality of life. We describe a prospective surveillance programme for female genital GVHD to better characterize incidence, risk factors and clinical features and the impact of a structured intervention policy. A retrospective audit was conducted on the medical records of all female transplant recipients surviving at least 6 months at a single centre over a 5-year period. Patients commenced topical vaginal oestrogen early post transplant with hormone replacement as appropriate for age, prior menopausal status and co-morbidities. A genital tract management programme included regular gynaecological review and self-maintenance of vaginal capacity by dilator or intercourse. The incidence of genital GVHD was 35% (95% confidence interval (CI) (25, 50%)) at 1 year and 49% (95% CI (36, 63%)) at 2 years. Topical therapy was effective in most cases; no patient required surgical intervention to divide vaginal adhesions. The main risk factor was stem cell source with peripheral blood progenitor cells posing a higher risk than marrow (hazard ratio=3.07 (1.22, 7.73), P=0.017). Extensive GVHD in other organs was a common association. We conclude that female genital GVHD is common, and early detection and commencement of topical immunosuppression with dilator use appears to be highly effective at preventing progression.

  20. Host genetic risk factors for West Nile virus infection and disease progression.

    Directory of Open Access Journals (Sweden)

    Abigail W Bigham

    Full Text Available West Nile virus (WNV, a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035 and MX1, (OR 0.19, p = 0.014 were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003 was associated with increased risk for West Nile encephalitis and paralysis (WNE/P. Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.

  1. A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors

    Directory of Open Access Journals (Sweden)

    Mohamed Lamine Hafirassou

    2017-12-01

    Full Text Available Dengue virus (DENV infections cause the most prevalent mosquito-borne viral disease worldwide, for which no therapies are available. DENV encodes seven non-structural (NS proteins that co-assemble and recruit poorly characterized host factors to form the DENV replication complex essential for viral infection. Here, we provide a global proteomic analysis of the human host factors that interact with the DENV NS1 protein. Combined with a functional RNAi screen, this study reveals a comprehensive network of host cellular processes involved in DENV infection and identifies DENV host restriction and dependency factors. We highlight an important role of RACK1 and the chaperonin TRiC (CCT and oligosaccharyltransferase (OST complexes during DENV replication. We further show that the OST complex mediates NS1 and NS4B glycosylation, and pharmacological inhibition of its N-glycosylation function strongly impairs DENV infection. In conclusion, our study provides a global interactome of the DENV NS1 and identifies host factors targetable for antiviral therapies.

  2. Assuring virtual network function image integrity and host sealing in telco cloud

    NARCIS (Netherlands)

    Lal, S.; Ravidas, S.; Oliver, I.; Taleb, T.

    In Telco cloud environment, virtual network func- tions (VNFs) can be shipped in the form of virtual machine images and hosted over commodity hardware. It is likely that these VNF images will contain highly sensitive data and mission critical network operations. For this reason, these VNF images are

  3. Rare earth doped nanoparticles in organic and inorganic host materials for application in integrated optics

    NARCIS (Netherlands)

    Dekker, R.; Hilderink, L.T.H.; Diemeer, Mart; Stouwdam, J.W.; Sudarsan, V; van Veggel, F.C.J.M.; Driessen, A.; Worhoff, Kerstin; Misra, D; Masscher, P.; Sundaram, K.; Yen, W.M.; Capobianco, J.

    2006-01-01

    The preparation and the optical properties of lanthanum fluoride (LaF3) nanoparticles doped with erbium and neodymium will be discussed. Organic and inorganic materials in the form of polymers and sol-gels were used to serve as the hosts for the inorganic nanoparticles, respectively. The organic

  4. An Integrated Omics Analysis: Impact of Microgravity on Host Response to Lipopolysaccharide in vitro

    Science.gov (United States)

    2014-08-07

    on host response to lipopolysaccharide in vitro 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Nabarun Chakraborty...49. Mateescu B, Batista L, Cardon M, Gruosso T, de Feraudy Y, Mariani O, Nicolas A, Meyniel JP, Cottu P, Sastre Garau X, Mechta Grigoriou F: miR 141

  5. Analysis of the Pantoea ananatis pan-genome reveals factors underlying its ability to colonize and interact with plant, insect and vertebrate hosts.

    Science.gov (United States)

    De Maayer, Pieter; Chan, Wai Yin; Rubagotti, Enrico; Venter, Stephanus N; Toth, Ian K; Birch, Paul R J; Coutinho, Teresa A

    2014-05-27

    Pantoea ananatis is found in a wide range of natural environments, including water, soil, as part of the epi- and endophytic flora of various plant hosts, and in the insect gut. Some strains have proven effective as biological control agents and plant-growth promoters, while other strains have been implicated in diseases of a broad range of plant hosts and humans. By analysing the pan-genome of eight sequenced P. ananatis strains isolated from different sources we identified factors potentially underlying its ability to colonize and interact with hosts in both the plant and animal Kingdoms. The pan-genome of the eight compared P. ananatis strains consisted of a core genome comprised of 3,876 protein coding sequences (CDSs) and a sizeable accessory genome consisting of 1,690 CDSs. We estimate that ~106 unique CDSs would be added to the pan-genome with each additional P. ananatis genome sequenced in the future. The accessory fraction is derived mainly from integrated prophages and codes mostly for proteins of unknown function. Comparison of the translated CDSs on the P. ananatis pan-genome with the proteins encoded on all sequenced bacterial genomes currently available revealed that P. ananatis carries a number of CDSs with orthologs restricted to bacteria associated with distinct hosts, namely plant-, animal- and insect-associated bacteria. These CDSs encode proteins with putative roles in transport and metabolism of carbohydrate and amino acid substrates, adherence to host tissues, protection against plant and animal defense mechanisms and the biosynthesis of potential pathogenicity determinants including insecticidal peptides, phytotoxins and type VI secretion system effectors. P. ananatis has an 'open' pan-genome typical of bacterial species that colonize several different environments. The pan-genome incorporates a large number of genes encoding proteins that may enable P. ananatis to colonize, persist in and potentially cause disease symptoms in a wide range of

  6. A novel role of the ferric reductase Cfl1 in cell wall integrity, mitochondrial function, and invasion to host cells in Candida albicans.

    Science.gov (United States)

    Yu, Qilin; Dong, Yijie; Xu, Ning; Qian, Kefan; Chen, Yulu; Zhang, Biao; Xing, Laijun; Li, Mingchun

    2014-11-01

    Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases. Iron acquisition is an important factor for pathogen-host interaction and also a significant element for the pathogenicity of this organism. Ferric reductases, which convert ferric iron into ferrous iron, are important components of the high-affinity iron uptake system. Sequence analyses have identified at least 17 putative ferric reductase genes in C. albicans genome. CFL1 was the first ferric reductase identified in C. albicans. However, little is known about its roles in C. albicans physiology and pathogenicity. In this study, we found that disruption of CFL1 led to hypersensitivity to chemical and physical cell wall stresses, activation of the cell wall integrity (CWI) pathway, abnormal cell wall composition, and enhanced secretion, indicating a defect in CWI in this mutant. Moreover, this mutant showed abnormal mitochondrial activity and morphology, suggesting a link between ferric reductases and mitochondrial function. In addition, this mutant displayed decreased ability of adhesion to both the polystyrene microplates and buccal epithelial cells and invasion of host epithelial cells. These findings revealed a novel role of C. albicans Cfl1 in maintenance of CWI, mitochondrial function, and interaction between this pathogen and the host. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  7. A Note on the First Integrals of Vector Fields with Integrating Factors and Normalizers

    Directory of Open Access Journals (Sweden)

    Jaume Llibre

    2012-06-01

    Full Text Available We prove a sufficient condition for the existence of explicit first integrals for vector fields which admit an integrating factor. This theorem recovers and extends previous results in the literature on the integrability of vector fields which are volume preserving and possess nontrivial normalizers. Our approach is geometric and coordinate-free and hence it works on any smooth orientable manifold.

  8. H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes.

    OpenAIRE

    Koichi Higashi; Toru Tobe; Akinori Kanai; Ebru Uyar; Shu Ishikawa; Yutaka Suzuki; Naotake Ogasawara; Ken Kurokawa; Taku Oshima

    2016-01-01

    Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investiga...

  9. Responses of wild small mammals to a pollution gradient: Host factors influence metal and metallothionein levels

    International Nuclear Information System (INIS)

    Fritsch, Clementine; Cosson, Richard P.; Coeurdassier, Michael; Raoul, Francis; Giraudoux, Patrick; Crini, Nadia; Vaufleury, Annette de; Scheifler, Renaud

    2010-01-01

    We investigated how host factors (species, age, gender) modulated Cd, Pb, Zn, and Cu concentrations, metallothionein levels (MTs) and their relationships in 7 sympatric small mammal species along a pollution gradient. Cd concentrations in liver and kidneys increased with age in all species. Age effect on other metals and MTs differs among species. Gender did not influence metal and MT levels except in the bank vole. Three patterns linking internal metal concentrations and MTs were observed along the gradient: a low metal accumulation with a (i) high (wood mouse) or (ii) low (bank vole) level of MTs accompanied by a slight or no increase of MTs with Cd accumulation; (iii) an elevated metal accumulation with a sharp increase of MTs (common and pygmy shrews). In risk assessment and biomonitoring perspectives, we conclude that measurements of MTs and metals might be associated because they cannot be interpreted properly when considered separately. - Age more than gender and species more than trophic group influence metallic trace element and metallothionein levels and their relationships in wild small mammals exposed to metals.

  10. Factors That Influence Technology Integration in the Classroom

    Science.gov (United States)

    Montgomery, Maureen C.

    2017-01-01

    Education is one area where the use of technology has had great impact on student learning. The integration of technology in teaching and learning can significantly influence the outcome of education in the classroom. However, there are a myriad of factors that influence technology integration in the classroom. The purpose of this study was to…

  11. Biotic mortality factors affecting emerald ash borer (Agrilus planipennis) are highly dependent on life stage and host tree crown condition.

    Science.gov (United States)

    Jennings, D E; Duan, J J; Shrewsbury, P M

    2015-10-01

    Emerald ash borer (EAB), Agrilus planipennis, is a serious invasive forest pest in North America responsible for killing tens to hundreds of millions of ash trees since it was accidentally introduced in the 1990 s. Although host-plant resistance and natural enemies are known to be important sources of mortality for EAB in Asia, less is known about the importance of different sources of mortality at recently colonized sites in the invaded range of EAB, and how these relate to host tree crown condition. To further our understanding of EAB population dynamics, we used a large-scale field experiment and life-table analyses to quantify the fates of EAB larvae and the relative importance of different biotic mortality factors at 12 recently colonized sites in Maryland. We found that the fates of larvae were highly dependent on EAB life stage and host tree crown condition. In relatively healthy trees (i.e., with a low EAB infestation) and for early instars, host tree resistance was the most important mortality factor. Conversely, in more unhealthy trees (i.e., with a moderate to high EAB infestation) and for later instars, parasitism and predation were the major sources of mortality. Life-table analyses also indicated how the lack of sufficient levels of host tree resistance and natural enemies contribute to rapid population growth of EAB at recently colonized sites. Our findings provide further evidence of the mechanisms by which EAB has been able to successfully establish and spread in North America.

  12. Genetic Factors in Rhizobium Affecting the Symbiotic Carbon Costs of N2 Fixation and Host Plant Biomass Production

    DEFF Research Database (Denmark)

    Skøt, L.; Hirsch, P. R.; Witty, J. F.

    1986-01-01

    The effect of genetic factors in Rhizobium on host plant biomass production and on the carbon costs of N2 fixation in pea root nodules was studied. Nine strains of Rhizobium leguminosarum were constructed, each containing one of three symbiotic plasmids in combination with one of three different ...

  13. The role of host genetic factors in respiratory tract infectious diseases: systematic review, meta-analyses and field synopsis

    NARCIS (Netherlands)

    Patarčić, Inga; Gelemanović, Andrea; Kirin, Mirna; Kolčić, Ivana; Theodoratou, Evropi; Baillie, Kenneth J.; de Jong, Menno D.; Rudan, Igor; Campbell, Harry; Polašek, Ozren

    2015-01-01

    Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of

  14. Biology of teeth and implants: Host factors - pathology, regeneration, and the role of stem cells.

    Science.gov (United States)

    Eggert, F-Michael; Levin, Liran

    2018-01-01

    In chronic periodontitis and peri-implantitis, cells of the innate and adaptive immune systems are involved directly in the lesions within the tissues of the patient. Absence of a periodontal ligament around implants does not prevent a biologic process similar to that of periodontitis from affecting osseointegration. Our first focus is on factors in the biology of individuals that are responsible for the susceptibility of such individuals to chronic periodontitis and to peri-implantitis. Genetic factors are of significant importance in susceptibility to these diseases. Genetic factors of the host affect the composition of the oral microbiome in the same manner that they influence other microbiomes, such as those of the intestines and of the lungs. Our second focus is on the central role of stem cells in tissue regeneration, in the functioning of innate and adaptive immune systems, and in metabolism of bone. Epithelial cell rests of Malassez (ERM) are stem cells of epithelial origin that maintain the periodontal ligament as well as the cementum and alveolar bone associated with the ligament. The tissue niche within which ERM are found extends into the supracrestal areas of collagen fiber-containing tissues of the gingivae above the bony alveolar crest. Maintenance and regeneration of all periodontal tissues involves the activity of a variety of stem cells. The success of dental implants indicates that important groups of stem cells in the periodontium are active to enable that biologic success. Successful replantation of avulsed teeth and auto-transplantation of teeth is comparable to placing dental implants, and so must also involve periodontal stem cells. Biology of teeth and biology of implants represents the biology of the various stem cells that inhabit specialized niches within the periodontal tissues. Diverse biologic processes must function together successfully to maintain periodontal health. Osseointegration of dental implants does not involve formation of

  15. The Host Plant Metabolite Glucose Is the Precursor of Diffusible Signal Factor (DSF) Family Signals in Xanthomonas campestris

    OpenAIRE

    Deng, Yinyue; Liu, Xiaoling; Wu, Ji'en; Lee, Jasmine; Chen, Shaohua; Cheng, Yingying; Zhang, Chunyan; Zhang, Lian-Hui

    2015-01-01

    Plant pathogen Xanthomonas campestris pv. campestris produces cis-11-methyl-2-dodecenoic acid (diffusible signal factor [DSF]) as a cell-cell communication signal to regulate biofilm dispersal and virulence factor production. Previous studies have demonstrated that DSF biosynthesis is dependent on the presence of RpfF, an enoyl-coenzyme A (CoA) hydratase, but the DSF synthetic mechanism and the influence of the host plant on DSF biosynthesis are still not clear. We show here that exogenous ad...

  16. Novel Burkholderia mallei Virulence Factors Linked to Specific Host-Pathogen Protein Interactions

    Science.gov (United States)

    2013-06-23

    equine hosts. Thus, the genes retained in B. mallei share a high sequence similarity to genes common to B. pseudomallei (3), and many virulence...oppor- tunistic infections in mammalian hosts. Even for the equine - adapted and, thus, more genetically constrained, B. mallei pathogen, we cannot...BioDrugs: Clin. Immunotherapeut., Biopharmaceut. Gene Therapy 17, 413–424 88. Anderson, D. M., and Frank, D. W. (2012) Five mechanisms of manipula

  17. Ecological and genetic factors influencing the transition between host-use strategies in sympatric Heliconius butterflies.

    Science.gov (United States)

    Merrill, R M; Naisbit, R E; Mallet, J; Jiggins, C D

    2013-09-01

    Shifts in host-plant use by phytophagous insects have played a central role in their diversification. Evolving host-use strategies will reflect a trade-off between selection pressures. The ecological niche of herbivorous insects is partitioned along several dimensions, and if populations remain in contact, recombination will break down associations between relevant loci. As such, genetic architecture can profoundly affect the coordinated divergence of traits and subsequently the ability to exploit novel habitats. The closely related species Heliconius cydno and H. melpomene differ in mimetic colour pattern, habitat and host-plant use. We investigate the selection pressures and genetic basis underlying host-use differences in these two species. Host-plant surveys reveal that H. melpomene specializes on a single species of Passiflora. This is also true for the majority of other Heliconius species in secondary growth forest at our study site, as expected under a model of interspecific competition. In contrast, H. cydno, which uses closed-forest habitats where both Heliconius and Passiflora are less common, appears not to be restricted by competition and uses a broad selection of the available Passiflora. However, other selection pressures are likely involved, and field experiments reveal that early larval survival of both butterfly species is highest on Passiflora menispermifolia, but most markedly so for H. melpomene, the specialist on that host. Finally, we demonstrate an association between host-plant acceptance and colour pattern amongst interspecific hybrids, suggesting that major loci underlying these important ecological traits are physically linked in the genome. Together, our results reveal ecological and genetic associations between shifts in habitat, host use and mimetic colour pattern that have likely facilitated both speciation and coexistence. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

  18. Genetic Factors and Host Traits Predict Spore Morphology for a Butterfly Pathogen

    Directory of Open Access Journals (Sweden)

    Jacobus C. de Roode

    2013-08-01

    Full Text Available Monarch butterflies (Danaus plexippus throughout the world are commonly infected by the specialist pathogen Ophryocystis elektroscirrha (OE. This protozoan is transmitted when larvae ingest infectious stages (spores scattered onto host plant leaves by infected adults. Parasites replicate internally during larval and pupal stages, and adult monarchs emerge covered with millions of dormant spores on the outsides of their bodies. Across multiple monarch populations, OE varies in prevalence and virulence. Here, we examined geographic and genetic variation in OE spore morphology using clonal parasite lineages derived from each of four host populations (eastern and western North America, South Florida and Hawaii. Spores were harvested from experimentally inoculated, captive-reared adult monarchs. Using light microscopy and digital image analysis, we measured the size, shape and color of 30 replicate spores per host. Analyses examined predictors of spore morphology, including parasite source population and clone, parasite load, and the following host traits: family line, sex, wing area, and wing color (orange and black pigmentation. Results showed significant differences in spore size and shape among parasite clones, suggesting genetic determinants of morphological variation. Spore size also increased with monarch wing size, and monarchs with larger and darker orange wings tended to have darker colored spores, consistent with the idea that parasite development depends on variation in host quality and resources. We found no evidence for effects of source population on variation in spore morphology. Collectively, these results provide support for heritable variation in spore morphology and a role for host traits in affecting parasite development.

  19. Radiation and host factors in human thyroid tumors following thymus irradiation

    International Nuclear Information System (INIS)

    Shore, R.E.; Pasternack, B.S.; Woodard, E.D.; Hempelmann, L.H.

    1980-01-01

    Thyroid tumor data from the 1971 survey of the Rochester, New York thymus irradiated population are further analyzed to study radiobiological and host factors. The analyses were based on the approx. 2650 irradiated subjects and 4800 sibling controls who had 5 or more years of follow-up. Twenty-four thyroid cancers and 52 thyroid adenomas were found in the irradiated group, and O thyroid cancers and 6 adenomas among the controls. The overall risk estimates were 3.8 thyroid cancers/10 6 persons/yr/rad and 4.5 thyroid adenomas/10 6 persons/yr/rad. The dose-response data (thyroid dose range of 5 to > 1000 rad) for thyroid cancer indicate both a linear and a dose-squared component, but no dose-squared component is evident for thyroid adenomas. At lower total doses (< 400 rad) there was a suggestion that dose fractionation diminished the thyroid cancer response, but a similar fractionation effect was not found for thyroid adenomas. The temporal pattern of tumors suggested an extended plateau of excess tumor production, rather than a wavelike temporal pattern. There was no evidence for an inverse relationship between thyroid radiation dose and thyroid cancer latency. Female and Jewish subjects had a higher risk of radiation-induced thyroid cancer than did their respective counterparts. The additive and multiplicative models of radiation effects were compared with respect to sex differences; neither model provided a superior fit to the data. The tentative nature of the conclusions is stressed because of the relatively small number of thyroid cancers. (author)

  20. Induction of MAP Kinase Homologues during Growth and Morphogenetic Development of Karnal Bunt (Tilletia indica) under the Influence of Host Factor(s) from Wheat Spikes

    Science.gov (United States)

    Gupta, Atul K.; Seneviratne, J. M.; Joshi, G. K.; Kumar, Anil

    2012-01-01

    Signaling pathways that activate different mitogen-activated protein kinases (MAPKs) in response to certain environmental conditions, play important role in mating type switching (Fus3) and pathogenicity (Pmk1) in many fungi. In order to determine the roles of such regulatory genes in Tilletia indica, the causal pathogen of Karnal bunt (KB) of wheat, semi-quantitative and quantitative RT-PCR was carried out to isolate and determine the expression of MAP kinase homologues during fungal growth and development under in vitro culture. Maximum expression of TiFus3 and TiPmk1 genes were observed at 14th and 21st days of culture and decreased thereafter. To investigate whether the fungus alters the expression levels of same kinases upon interaction with plants, cultures were treated with 1% of host factors (extracted from S-2 stage of wheat spikes). Such treatment induced the expression of MAPks in time dependent manner compared to the absence of host factors. These results suggest that host factor(s) provide certain signal(s) which activate TiFus3 and TiPmk1 during morphogenetic development of T. indica. The results also provides a clue about the role of host factors in enhancing the disease potential due to induction of MAP kinases involved in fungal development and pathogenecity. PMID:22547988

  1. The integration of multiple OS-9 stations with a VAX/VMS host via Ethernet

    International Nuclear Information System (INIS)

    Charity, T.

    1989-01-01

    In this paper a method for providing embedded microprocessors with virtual disk storage capacity and remote terminal access from a VAX/VMS host via Ethernet is described. The underlying Ethernet driver permits different network protocols to be co-resident in the microprocessors. The system described is in use in many experiments at CERN and elsewhere, and provides a cheap and effective method for sharing data and programs between microprocessors and VAX/VMS systems. Existing approaches to these problems required sole use of a dedicated intelligent network interface, and were biased towards VMEbus systems. One of the goals of the design was to provide a highly transparent and easy-to-use development environment such that users would appear to be working on dedicated microprocessor workstations, unaware of the underlying network connections

  2. Microscopy-based Assays for High-throughput Screening of Host Factors Involved in Brucella Infection of Hela Cells.

    Science.gov (United States)

    Casanova, Alain; Low, Shyan H; Emmenlauer, Mario; Conde-Alvarez, Raquel; Salcedo, Suzana P; Gorvel, Jean-Pierre; Dehio, Christoph

    2016-08-05

    Brucella species are facultative intracellular pathogens that infect animals as their natural hosts. Transmission to humans is most commonly caused by direct contact with infected animals or by ingestion of contaminated food and can lead to severe chronic infections. Brucella can invade professional and non-professional phagocytic cells and replicates within endoplasmic reticulum (ER)-derived vacuoles. The host factors required for Brucella entry into host cells, avoidance of lysosomal degradation, and replication in the ER-like compartment remain largely unknown. Here we describe two assays to identify host factors involved in Brucella entry and replication in HeLa cells. The protocols describe the use of RNA interference, while alternative screening methods could be applied. The assays are based on the detection of fluorescently labeled bacteria in fluorescently labeled host cells using automated wide-field microscopy. The fluorescent images are analyzed using a standardized image analysis pipeline in CellProfiler which allows single cell-based infection scoring. In the endpoint assay, intracellular replication is measured two days after infection. This allows bacteria to traffic to their replicative niche where proliferation is initiated around 12 hr after bacterial entry. Brucella which have successfully established an intracellular niche will thus have strongly proliferated inside host cells. Since intracellular bacteria will greatly outnumber individual extracellular or intracellular non-replicative bacteria, a strain constitutively expressing GFP can be used. The strong GFP signal is then used to identify infected cells. In contrast, for the entry assay it is essential to differentiate between intracellular and extracellular bacteria. Here, a strain encoding for a tetracycline-inducible GFP is used. Induction of GFP with simultaneous inactivation of extracellular bacteria by gentamicin enables the differentiation between intracellular and extracellular

  3. Multiple factors and processes involved in host cell killing by bacteriophage Mu: characterization and mapping.

    Science.gov (United States)

    Waggoner, B T; Marrs, C F; Howe, M M; Pato, M L

    1984-07-15

    The regions of bacteriophage Mu involved in host cell killing were determined by infection of a lambda-immune host with 12 lambda pMu-transducing phages carrying different amounts of Mu DNA beginning at the left end. Infecting lambda pMu phages containing 5.0 (+/- 0.2) kb or less of the left end of Mu DNA did not kill the lambda-immune host, whereas lambda pMu containing 5.1 kb did kill, thus locating the right end of the kil gene between approximately 5.0 and 5.1 kb. For the Kil+ phages the extent of killing increased as the multiplicity of infection (m.o.i.) increased. In addition, killing was also affected by the presence of at least two other regions of Mu DNA: one, located between 5.1 and 5.8 kb, decreased the extent of killing; the other, located between 6.3 and 7.9 kb, greatly increased host cell killing. Killing was also assayed after lambda pMu infection of a lambda-immune host carrying a mini-Mu deleted for most of the B gene and the middle region of Mu DNA. Complementation of mini-Mu replication by infecting B+ lambda pMu phages resulted in killing of the lambda-immune, mini-Mu-containing host, regardless of the presence or absence of the Mu kil gene. The extent of host cell killing increased as the m.o.i. of the infecting lambda pMu increased, and was further enhanced by both the presence of the kil gene and the region located between 6.3 and 7.9 kb. These distinct processes of kil-mediated killing in the absence of replication and non-kil-mediated killing in the presence of replication were also observed after induction of replication-deficient and kil mutant prophages, respectively.

  4. Viral and Host Factors Required for Avian H5N1 Influenza A Virus Replication in Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    2013-06-01

    Full Text Available Following the initial and sporadic emergence into humans of highly pathogenic avian H5N1 influenza A viruses in Hong Kong in 1997, we have come to realize the potential for avian influenza A viruses to be transmitted directly from birds to humans. Understanding the basic viral and cellular mechanisms that contribute to infection of mammalian species with avian influenza viruses is essential for developing prevention and control measures against possible future human pandemics. Multiple physical and functional cellular barriers can restrict influenza A virus infection in a new host species, including the cell membrane, the nuclear envelope, the nuclear environment, and innate antiviral responses. In this review, we summarize current knowledge on viral and host factors required for avian H5N1 influenza A viruses to successfully establish infections in mammalian cells. We focus on the molecular mechanisms underpinning mammalian host restrictions, as well as the adaptive mutations that are necessary for an avian influenza virus to overcome them. It is likely that many more viral and host determinants remain to be discovered, and future research in this area should provide novel and translational insights into the biology of influenza virus-host interactions.

  5. Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements.

    Directory of Open Access Journals (Sweden)

    Olga V Viktorovskaya

    2016-08-01

    Full Text Available There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses replication.Seventy-nine novel RNA binding proteins for dengue virus (DENV were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated.The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps

  6. Host molecular factors and viral genotypes in the mother-to-child HIV-1 transmission in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Linda Chapdeleine M. Mouafo

    2017-07-01

    Full Text Available Maternal viral load and immune status, timing and route of delivery, viral subtype, and host genetics are known to influence the transmission, acquisition and disease progression of human immunodeficiency virus-1 (HIV-1 infection. This review summarizes the findings from published works on host molecular factors and virus genotypes affecting mother to child transmission (MTCT in Africa and identifies the gaps that need to be addressed in future research. Articles in PubMed, Google and AIDSearch and relevant conference abstracts publications were searched. Accessible articles on host factors and viral genetics impacting the MTCT of HIV, done on African populations till 2015 were downloaded. Forty-six articles were found and accessed; 70% described host genes impacting the transmission. The most studied gene was the CCR5 promoter, followed by the CCR2-64I found to reduce MTCT; then SDF1-3’A shown to have no effect on MTCT and others like the DC-SIGNR, CD4, CCL3 and IP- 10. The HLA class I was most studied and was generally linked to the protective effect on MTCT. Breast milk constituents were associated to protection against MTCT. However, existing studies in Sub Saharan Africa were done just in few countries and some done without control groups. Contradictory results obtained may be due to different genetic background, type of controls, different socio-cultural and economic environment and population size. More studies are thus needed to better understand the mechanism of transmission or prevention.

  7. Adaptation to toxic hosts as a factor in the evolution of insecticide resistance.

    Science.gov (United States)

    Alyokhin, Andrei; Chen, Yolanda H

    2017-06-01

    Insecticide resistance is a serious economic problem that jeopardizes sustainability of chemical control of herbivorous insects and related arthropods. It can be viewed as a specific case of adaptation to toxic chemicals, which has been driven in large part, but not exclusively, by the necessity for insect pests to tolerate defensive compounds produced by their host plants. Synthetic insecticides may simply change expression of specific sets of detoxification genes that have evolved due to ancestral associations with host plants. Feeding on host plants with more abundant or novel secondary metabolites has even been shown to prime insect herbivores to tolerate pesticides. Clear understanding of basic evolutionary processes is important for achieving lasting success in managing herbivorous arthropods. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. HSPA5 is an essential host factor for Ebola virus infection.

    Science.gov (United States)

    Reid, St Patrick; Shurtleff, Amy C; Costantino, Julie A; Tritsch, Sarah R; Retterer, Cary; Spurgers, Kevin B; Bavari, Sina

    2014-09-01

    Development of novel strategies targeting the highly virulent ebolaviruses is urgently required. A proteomic study identified the ER chaperone HSPA5 as an ebolavirus-associated host protein. Here, we show using the HSPA5 inhibitor (-)- epigallocatechin gallate (EGCG) that the chaperone is essential for virus infection, thereby demonstrating a functional significance for the association. Furthermore, in vitro and in vivo gene targeting impaired viral replication and protected animals in a lethal infection model. These findings demonstrate that HSPA5 is vital for replication and can serve as a viable target for the design of host-based countermeasures. Published by Elsevier B.V.

  9. Key factors of successful JIT integration with IBS - An overview

    Science.gov (United States)

    Asri, Mohammad Azwanie Naim Mohammad; Nawi, Mohd Nasrun Mohd; Nadarajan, Santhirasegaran

    2016-08-01

    The Just-In-Time (JIT) philosophy has been used for many decades to increase productivity through waste elimination process. The purpose of this paper is to contribute to the knowledge by addressing the transportation and material delivery activities in Industrialized Building System (IBS) and integrating JIT to improve the performance of those activities. The literature review has been conducted through relevant database. It was found that there is a need for more holistic approach to be adopted to integrate JIT in IBS project. This paper discusses the key success factors for effective integration between JIT and IBS in the context of transportation and material delivery activities.

  10. Master integrals for the four-loop Sudakov form factor

    Directory of Open Access Journals (Sweden)

    Rutger H. Boels

    2016-01-01

    Full Text Available The light-like cusp anomalous dimension is a universal function in the analysis of infrared divergences. In maximally (N=4 supersymmetric Yang–Mills theory (SYM in the planar limit, it is known, in principle, to all loop orders. The non-planar corrections are not known in any theory, with the first appearing at the four-loop order. The simplest quantity which contains this correction is the four-loop two-point form factor of the stress tensor multiplet. This form factor was largely obtained in integrand form in a previous work for N=4 SYM, up to a free parameter. In this work, a reduction of the appearing integrals obtained by solving integration-by-parts (IBP identities using a modified version of Reduze is reported. The form factor is shown to be independent of the remaining parameter at integrand level due to an intricate pattern of cancellations after IBP reduction. Moreover, two of the integral topologies vanish after reduction. The appearing master integrals are cross-checked using independent algebraic-geometry techniques explored in the Mint package. The latter results provide the basis of master integrals applicable to generic form factors, including those in Quantum Chromodynamics. Discrepancies between explicitly solving the IBP relations and the MINT approach are highlighted. Remaining bottlenecks to completing the computation of the four-loop non-planar cusp anomalous dimension in N=4 SYM and beyond are identified.

  11. Yeast casein kinase 2 governs morphology, biofilm formation, cell wall integrity, and host cell damage of Candida albicans.

    Science.gov (United States)

    Jung, Sook-In; Rodriguez, Natalie; Irrizary, Jihyun; Liboro, Karl; Bogarin, Thania; Macias, Marlene; Eivers, Edward; Porter, Edith; Filler, Scott G; Park, Hyunsook

    2017-01-01

    The regulatory networks governing morphogenesis of a pleomorphic fungus, Candida albicans are extremely complex and remain to be completely elucidated. This study investigated the function of C. albicans yeast casein kinase 2 (CaYck2p). The yck2Δ/yck2Δ strain displayed constitutive pseudohyphae in both yeast and hyphal growth conditions, and formed enhanced biofilm under non-biofilm inducing condition. This finding was further supported by gene expression analysis of the yck2Δ/yck2Δ strain which showed significant upregulation of UME6, a key transcriptional regulator of hyphal transition and biofilm formation, and cell wall protein genes ALS3, HWP1, and SUN41, all of which are associated with morphogenesis and biofilm architecture. The yck2Δ/yck2Δ strain was hypersensitive to cell wall damaging agents and had increased compensatory chitin deposition in the cell wall accompanied by an upregulation of the expression of the chitin synthase genes, CHS2, CHS3, and CHS8. Absence of CaYck2p also affected fungal-host interaction; the yck2Δ/yck2Δ strain had significantly reduced ability to damage host cells. However, the yck2Δ/yck2Δ strain had wild-type susceptibility to cyclosporine and FK506, suggesting that CaYck2p functions independently from the Ca+/calcineurin pathway. Thus, in C. albicans, Yck2p is a multifunctional kinase that governs morphogenesis, biofilm formation, cell wall integrity, and host cell interactions.

  12. Conservation Physiology and Conservation Pathogens: White-Nose Syndrome and Integrative Biology for Host-Pathogen Systems.

    Science.gov (United States)

    Willis, Craig K R

    2015-10-01

    Conservation physiology aims to apply an understanding of physiological mechanisms to management of imperiled species, populations, or ecosystems. One challenge for physiologists hoping to apply their expertise to conservation is connecting the mechanisms we study, often in the laboratory, with the vital rates of populations in the wild. There is growing appreciation that infectious pathogens can threaten populations and species, and represent an important issue for conservation. Conservation physiology has much to offer in terms of addressing the threat posed to some host species by infectious pathogens. At the same time, the well-developed theoretical framework of disease ecology could provide a model to help advance the application of physiology to a range of other conservation issues. Here, I use white-nose syndrome (WNS) in hibernating North American bats as an example of a conservation problem for which integrative physiological research has been a critical part of research and management. The response to WNS highlights the importance of a well-developed theoretical framework for the application of conservation physiology to a particular threat. I review what is known about physiological mechanisms associated with mortality from WNS and emphasize the value of combining a strong theoretical background with integrative physiological studies in order to connect physiological mechanisms with population processes and thereby maximize the potential benefits of conservation physiology. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  13. Energy integration: Regional economic integration lever and possible insertion factor in the global economy

    International Nuclear Information System (INIS)

    Lokolo, M.C.

    2001-01-01

    In the 1920s, just after the War, an idea began taking root in the Old Continent, to build what could be described as the United States of Europe. Thirty years later, in 1951, a new source of energy, coal, paved the way for the economic integration of Europe. It culminated into monetary integration in January 2002. Economic integration makes sense in the context of the relatively small size of some national economies and markets, and the judicious utilization of rare resources and their unequal distribution. In this document, the author elaborated on the principles at play in economic integration and argued that the integration of the national energy markets could be the lever for economic integration through the gradual elimination of the various obstacles to trade. The author first presented a brief historical overview of economic integration from the perspective of global economic relationships, covering the period between the two world wars to the General Agreement on Tariffs and Trade (GATT) to the World Trade Organization (WTO). The concept and the forms of economic integration were reviewed. Energy integration as a lever of regional economic integration and as a factor in global economic insertion were discussed. Energy integration is a tool for the improvement of the human condition. 15 refs

  14. Factors affecting virus dynamics and microbial host-virus interactions in marine environments

    NARCIS (Netherlands)

    Mojica, K.D.A.; Brussaard, C.P.D.

    2014-01-01

    Marine microorganisms constitute the largest percentage of living biomass and serve as the major driving force behind nutrient and energy cycles. While viruses only comprise a small percentage of this biomass (i.e., 5%), they dominate in numerical abundance and genetic diversity. Through host

  15. H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes.

    Directory of Open Access Journals (Sweden)

    Koichi Higashi

    2016-01-01

    Full Text Available Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investigated whether and how H-NS contributes to this optimization process. A comparison of H-NS binding profiles on common chromosomal segments of three E. coli strains belonging to different phylogenetic groups indicated that the positions of H-NS-bound regions have been conserved in E. coli strains. The sequences of the H-NS-bound regions appear to have diverged more so than H-NS-unbound regions only when H-NS-bound regions are located upstream or in coding regions of genes. Because these regions generally contain regulatory elements for gene expression, sequence divergence in these regions may be associated with alteration of gene expression. Indeed, nucleotide substitutions in H-NS-bound regions of the ybdO promoter and coding regions have diversified the potential for H-NS-independent negative regulation among E. coli strains. The ybdO expression in these strains was still negatively regulated by H-NS, which reduced the effect of H-NS-independent regulation under normal growth conditions. Hence, we propose that, during E. coli evolution, the conservation of H-NS binding sites resulted in the diversification of the regulation of horizontally transferred genes, which may have facilitated E. coli adaptation to new ecological niches.

  16. H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes.

    Science.gov (United States)

    Higashi, Koichi; Tobe, Toru; Kanai, Akinori; Uyar, Ebru; Ishikawa, Shu; Suzuki, Yutaka; Ogasawara, Naotake; Kurokawa, Ken; Oshima, Taku

    2016-01-01

    Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investigated whether and how H-NS contributes to this optimization process. A comparison of H-NS binding profiles on common chromosomal segments of three E. coli strains belonging to different phylogenetic groups indicated that the positions of H-NS-bound regions have been conserved in E. coli strains. The sequences of the H-NS-bound regions appear to have diverged more so than H-NS-unbound regions only when H-NS-bound regions are located upstream or in coding regions of genes. Because these regions generally contain regulatory elements for gene expression, sequence divergence in these regions may be associated with alteration of gene expression. Indeed, nucleotide substitutions in H-NS-bound regions of the ybdO promoter and coding regions have diversified the potential for H-NS-independent negative regulation among E. coli strains. The ybdO expression in these strains was still negatively regulated by H-NS, which reduced the effect of H-NS-independent regulation under normal growth conditions. Hence, we propose that, during E. coli evolution, the conservation of H-NS binding sites resulted in the diversification of the regulation of horizontally transferred genes, which may have facilitated E. coli adaptation to new ecological niches.

  17. Development of integrated evaluation information system for sandstone-hosted uranium deposits based on ComGIS

    International Nuclear Information System (INIS)

    Ke Dan; Han Shaoyang; Hou Huiqun; Hu Shuiqing

    2006-01-01

    Component GIS owns many merits such as flexible function and easy to be used, which makes it very suitable for the development of professional GIS application system in geoscience field. During the process of exploration and evaluation for uranium resources, computer application system has been a powerful tool owning to the following functions: professional processing, management and storage of data, spatial analysis, visualization and mapping, etc. In this paper technological routine is presented for the development of integrated evaluation information system for sandstone-hosted uranium deposits based on ArcGIS Engine. General GIS functions can be realized with ArcGIS Engine easily and quickly, the developers could concentrate their attentions on developing professional functions, which will shorten the developing period and make the system more efficient. It is showed that the system developed on ArcGIS Engine platform is stable in operation, flexible in functions and professional in application. (authors)

  18. Simultaneous Identification of Potential Pathogenicity Factors of Mycoplasma agalactiae in the Natural Ovine Host by Negative Selection

    OpenAIRE

    Hegde, Shivanand; Hegde, Shrilakshmi; Zimmermann, Martina; Flöck, Martina; Spergser, Joachim; Rosengarten, Renate; Chopra-Dewasthaly, Rohini

    2015-01-01

    Mycoplasmas possess complex pathogenicity determinants that are largely unknown at the molecular level. Mycoplasma agalactiae serves as a useful model to study the molecular basis of mycoplasma pathogenicity. The generation and in vivo screening of a transposon mutant library of M. agalactiae were employed to unravel its host colonization factors. Tn4001mod mutants were sequenced using a novel sequencing method, and functionally heterogeneous pools containing 15 to 19 selected mutants were sc...

  19. Integrative analyses unveil speciation linked to host plant shift in Spialia butterflies

    Czech Academy of Sciences Publication Activity Database

    Hernández-Roldán, J. L.; Dapporto, L.; Dincă, V.; Vicente, J. C.; Hornett, E. A.; Šíchová, Jindra; Lukhtanov, V. A.; Talavera, G.; Vila, R.

    2016-01-01

    Roč. 25, č. 17 (2016), s. 4267-4284 ISSN 0962-1083 R&D Projects: GA ČR(CZ) GA14-22765S Institutional support: RVO:60077344 Keywords : biogeography * butterflies * Lepidoptera Subject RIV: EG - Zoology Impact factor: 6.086, year: 2016 http://onlinelibrary.wiley.com/doi/10.1111/mec.13756/abstract

  20. The influence of "host release factor" on carbon release by zooxanthellae isolated from fed and starved Aiptasia pallida (Verrill).

    Science.gov (United States)

    Davy, S K; Cook, C B

    2001-06-01

    Symbiotic dinoflagellates (zooxanthellae) typically respond to extracts of host tissue with enhanced release of short-term photosynthetic products. We examined this "host release factor" (HRF) response using freshly isolated zooxanthellae of differing nutritional status. The nutritional status was manipulated by either feeding or starving the sea anemone Aiptasia pallida (Verrill). The release of fixed carbon from isolated zooxanthellae was measured using 14C in 30 min experiments. Zooxanthellae in filtered seawater alone released approximately 5% of photosynthate irrespective of host feeding history. When we used a 10-kDa ultrafiltrate of A. pallida host tissue as a source of HRF, approximately 14% of photosynthate was released to the medium. This increased to over 25% for zooxanthellae from anemones starved for 29 days or more. The cell-specific photosynthetic rate declined with starvation in these filtrate experiments, but the decline was offset by the increased percentage release. Indeed, the total amount of released photosynthate remained unchanged, or even increased, as zooxanthellae became more nutrient deficient. Similar trends were also observed when zooxanthellae from A. pallida were incubated in a 3-kDa ultrafiltrate of the coral Montastraea annularis, suggesting that HRF in the different filtrates operated in a similar manner. Our results support the suggestion that HRF diverts surplus carbon away from storage compounds to translocated compounds such as glycerol.

  1. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

    Science.gov (United States)

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-07-29

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens.

  2. Transformative Learning Factors to Enhance Integral Healthy Organizations

    Science.gov (United States)

    Thavinpipatkul, Chanchai; Ratana-Ubol, Archanya; Charungkaittikul, Suwithida

    2016-01-01

    This article focuses on how organizations search for the key factors to develop integral changes and determine broader and higher transcendental learning skills in order to achieve healthy and sustainable organizational growth more effectively and efficiently. This study employed qualitative approaches. The research method used is an in-depth…

  3. Master integrals for the four-loop Sudakov form factor

    International Nuclear Information System (INIS)

    Boels, Rutger; Kniehl, Bernd A.; Yang, Gang; Chinese Academy of Sciences, Beijing

    2015-08-01

    The light-like cusp anomalous dimension is a universal function in the analysis of infrared divergences. In maximally (N=4) supersymmetric Yang-Mills theory (SYM) in the planar limit, it is known, in principle, to all loop orders. The non-planar corrections are not known in any theory, with the first appearing at the four-loop order. Probably the simplest quantity which contains this correction is the four-loop two-point form factor of the stress tensor multiplet. This form factor was obtained in integrand form in a previous work for N=4 SYM, up to a single parameter. In this work, a reduction of the appearing integrals obtained by solving integration-by-parts (IBP) identities using (a tweaked version of) Reduze is reported. The form factor is shown to be independent of the remaining parameter at integrand level due to an intricate pattern of cancellations after IBP reduction. The appearing master integrals are cross-checked using algebraic techniques explored in the Mint package. The latter results provide the basis of master integrals applicable to generic form factors, including those in Quantum Chromodynamics. Remaining bottlenecks to completing the computation of the four-loop non-planar cusp anomalous dimension in N=4 SYM and beyond are identified.

  4. Conformal anomaly of generalized form factors and finite loop integrals

    CERN Document Server

    Chicherin, Dmitry

    2017-01-01

    We reveal a new mechanism of conformal symmetry breaking at Born level. It occurs in generalized form factors with several local operators and an on-shell state of massless particles. The effect is due to hidden singularities on collinear configurations of the momenta. This conformal anomaly is different from the holomorphic anomaly of amplitudes. We present a number of examples in four and six dimensions. We find an application of the new conformal anomaly to finite loop momentum integrals with one or more massless legs. The collinear region around a massless leg creates a contact anomaly, made visible by the loop integration. The anomalous conformal Ward identity for an $\\ell-$loop integral is a 2nd-order differential equation whose right-hand side is an $(\\ell-1)-$loop integral. We show several examples, in particular the four-dimensional scalar double box.

  5. Helminth burden and ecological factors associated with alterations in wild host gastrointestinal microbiota

    DEFF Research Database (Denmark)

    Newbold, Lindsay K.; Burthe, Sarah J.; Oliver, Anna E.

    2017-01-01

    Infection by gastrointestinal helminths of humans, livestock and wild animals is common, but the impact of such endoparasites on wild hosts and their gut microbiota represents an important overlooked component of population dynamics. Wild host gut microbiota and endoparasites occupy the same...... to quantify helminth infection in situ. Microbiota from the significantly distinct proventriculus (site of infection), cloacal and faecal gastrointestinal tract microbiomes were characterised using 16S rRNA gene-targeted high-throughput sequencing. We found increasingly strong associations between helminth...... infection and microbiota composition progressing away from the site of infection, observing a pronounced dysbiosis in microbiota when samples were partitioned into high- and low-burden groups. We posit this dysbiosis is predominately explained by helminths inducing an anti-inflammatory environment...

  6. Lentivector Integration Sites in Ependymal Cells From a Model of Metachromatic Leukodystrophy: Non-B DNA as a New Factor Influencing Integration

    Science.gov (United States)

    McAllister, Robert G; Liu, Jiahui; Woods, Matthew W; Tom, Sean K; Rupar, C Anthony; Barr, Stephen D

    2014-01-01

    The blood–brain barrier controls the passage of molecules from the blood into the central nervous system (CNS) and is a major challenge for treatment of neurological diseases. Metachromatic leukodystrophy is a neurodegenerative lysosomal storage disease caused by loss of arylsulfatase A (ARSA) activity. Gene therapy via intraventricular injection of a lentiviral vector is a potential approach to rapidly and permanently deliver therapeutic levels of ARSA to the CNS. We present the distribution of integration sites of a lentiviral vector encoding human ARSA (LV-ARSA) in murine brain choroid plexus and ependymal cells, administered via a single intracranial injection into the CNS. LV-ARSA did not exhibit a strong preference for integration in or near actively transcribed genes, but exhibited a strong preference for integration in or near satellite DNA. We identified several genomic hotspots for LV-ARSA integration and identified a consensus target site sequence characterized by two G-quadruplex-forming motifs flanking the integration site. In addition, our analysis identified several other non-B DNA motifs as new factors that potentially influence lentivirus integration, including human immunodeficiency virus type-1 in human cells. Together, our data demonstrate a clinically favorable integration site profile in the murine brain and identify non-B DNA as a potential new host factor that influences lentiviral integration in murine and human cells. PMID:25158091

  7. Optimal control issues in plant disease with host demographic factor and botanical fungicides

    Science.gov (United States)

    Anggriani, N.; Mardiyah, M.; Istifadah, N.; Supriatna, A. K.

    2018-03-01

    In this paper, we discuss a mathematical model of plant disease with the effect of fungicide. We assume that the fungicide is given as a preventive treatment to infectious plants. The model is constructed based on the development of the disease in which the monomolecular is monocyclic. We show the value of the Basic Reproduction Number (BRN) ℛ0 of the plant disease transmission. The BRN is computed from the largest eigenvalue of the next generation matrix of the model. The result shows that in the region where ℛ0 greater than one there is a single stable endemic equilibrium. However, in the region where ℛ0 less than one this endemic equilibrium becomes unstable. The dynamics of the model is highly sensitive to changes in contact rate and infectious period. We also discuss the optimal control of the infected plant host by considering a preventive treatment aimed at reducing the infected host plant. The obtaining optimal control shows that it can reduce the number of infected hosts compared to that without control. Some numerical simulations are also given to illustrate our analytical results.

  8. The design of the frame structure used in integral hosting of the nuclear island steel lining cylinder module and problems analysis

    International Nuclear Information System (INIS)

    Yu Xinian; Liu Xiao; Wang Jianguo

    2011-01-01

    The use of the steel frame in the integral hosting of nuclear island steel lining cylinder module made a breakthrough in China's nuclear power construction. The deformation of the cylinder wall is the key issue in the integral lifting process of the nuclear island steel lining. Using the frame in lifting large and thin steel cylinder, the form of frame structure and its deformation will directly affect the radial deformation of the lifted cylinder, the buckling deformation of the distal cylinder, and the cylinder's deformation surround the penetrations. The diameter of nuclear island steel liner is 44 meters. The wall of the cylinder is thin, and the total weight of the cylinder itself and its attached penetrations, walkways and lifting tools, etc. is up to 120 tons, which not only increase the difficulty of lifting, but also have some risks. To ensure the cylinder deformation within the limits, this thesis establishes the parameter structure for the lifting frame, calculates the displacement and analyzes the axial stresses, based on the ANSYS finite element analysis software. The results showed that the models and parameters for integral hosting of the steel lining cylinder modular frame structure is reasonable and feasible, and analyzing the hosting-frame data is necessary, which lay the foundation for the design of the hosting frame and the eventual implementation of the integral hosting scheme of the steel lining cylinder module. (authors)

  9. Validation-based insertional mutagenesis for identification of Nup214 as a host factor for EV71 replication in RD cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bei; Zhang, XiaoYu; Zhao, Zhendong, E-mail: timjszzd@163.com

    2013-08-02

    Highlights: •We introduced a new mutagenesis strategy named VBIM to the viral research. •This method can identify either host factors or host restriction factors. •Using VBIM system, we identified Nup214 as a host factor for EV71 replication in RD cells. -- Abstract: Lentiviral validation-based insertional mutagenesis (VBIM) is a sophisticated, forward genetic approach that is used for the investigation of signal transduction in mammalian cells. Using VBIM, we conducted function-based genetic screening for host genes that affect enterovirus 71 (EV71) viral replication. This included host factors that are required for the life cycle of EV71 and host restriction factors that inhibit EV71 replication. Several cell clones, resistant to EV71, were produced using EV71 infection as a selection pressure and the nuclear pore protein 214 (Nup214) was identified as a host factor required for EV71 replication. In SD2-2, the corresponding VBIM lentivirus transformed clone, the expression of endogenous Nup214 was significantly down-regulated by the reverse inserted VBIM promoter. After Cre recombinase-mediated excision of the VBIM promoter, the expression of Nup214 recovered and the clone regained sensitivity to the EV71 infection. Furthermore, over-expression of Nup214 in the cells suggested that Nup214 was promoting EV71 replication. Results of this study indicate that a successful mutagenesis strategy has been established for screening host genes related to viral replication.

  10. Validation-based insertional mutagenesis for identification of Nup214 as a host factor for EV71 replication in RD cells

    International Nuclear Information System (INIS)

    Wang, Bei; Zhang, XiaoYu; Zhao, Zhendong

    2013-01-01

    Highlights: •We introduced a new mutagenesis strategy named VBIM to the viral research. •This method can identify either host factors or host restriction factors. •Using VBIM system, we identified Nup214 as a host factor for EV71 replication in RD cells. -- Abstract: Lentiviral validation-based insertional mutagenesis (VBIM) is a sophisticated, forward genetic approach that is used for the investigation of signal transduction in mammalian cells. Using VBIM, we conducted function-based genetic screening for host genes that affect enterovirus 71 (EV71) viral replication. This included host factors that are required for the life cycle of EV71 and host restriction factors that inhibit EV71 replication. Several cell clones, resistant to EV71, were produced using EV71 infection as a selection pressure and the nuclear pore protein 214 (Nup214) was identified as a host factor required for EV71 replication. In SD2-2, the corresponding VBIM lentivirus transformed clone, the expression of endogenous Nup214 was significantly down-regulated by the reverse inserted VBIM promoter. After Cre recombinase-mediated excision of the VBIM promoter, the expression of Nup214 recovered and the clone regained sensitivity to the EV71 infection. Furthermore, over-expression of Nup214 in the cells suggested that Nup214 was promoting EV71 replication. Results of this study indicate that a successful mutagenesis strategy has been established for screening host genes related to viral replication

  11. THE BIOTIC FACTOR OF TREMATOD OPISTHORHIS FELINEUS INVASION INFLUENCE ON HOST IMMUNE STATUS AND SOMATIC CELLS PROLIFERATIVE ACTIVITY

    Directory of Open Access Journals (Sweden)

    A. G. Rybka

    2016-01-01

    Full Text Available The paper confirms long-time opisthorhis invasion role as a risk factor of host immune system reconstitution as well as an important factor in holangiocarcinomas development. It was shown that opisthorhosis invasion primal stage induce host immune system reconstitution. Host immune B-cells system is activated by metacercaria antigens, while the same antigens inhibits T-cells activity. Opisthorhis metabolites stimulate proliferative mithogen-induced T-cells acti vity. Chronic opisthorchis invasion leads to immune system disbalance. It means: decrease of specific and non-speci fic natural killers activity, number of high proliferative activity T-lymphocytes and the shift of regulatory T-cells subset to suppressors prevalence. At the same time specific as well as non-specific T-suppressors functional ability is very low. It was shown T-cells helper-amplifier activation. Despite of circulating B-cells decrease the antibody produced cells number is spleen increases significantly at the same time with circulating immune complexes accumulation. Even 3–6 month after dehelmintisation the immune system disbalance decreases but lefts. In addition, chronic opisthorhis invasion leads to the proliferative processes activation in ductal epithelium, liver, lymph nodes and in other organs which leads to cancer proliferation. According to the results obtained the opisthorhis infected patients needs to be immunocorrected before as well as after dehelmintisation for holangiocancerogenesis profylaxis.

  12. Conformal anomaly of generalized form factors and finite loop integrals

    Science.gov (United States)

    Chicherin, Dmitry; Sokatchev, Emery

    2018-04-01

    We reveal a new mechanism of conformal symmetry breaking at Born level. It occurs in generalized form factors with several local operators and an on-shell state of massless particles. The effect is due to hidden singularities on collinear configurations of the momenta. This conformal anomaly is different from the holomorphic anomaly of amplitudes. We present a number of examples in four and six dimensions. We find an application of the new conformal anomaly to finite loop momentum integrals with one or more massless legs. The collinear region around a massless leg creates a contact anomaly, made visible by the loop integration. The anomalous conformal Ward identity for an ℓ-loop integral is a 2nd-order differential equation whose right-hand side is an (ℓ - 1)-loop integral. It could serve as a new useful tool to find/test analytic expressions for conformal integrals. We illustrate this point with several examples of known integrals. We propose a new differential equation for the four-dimensional scalar double box.

  13. Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

    Science.gov (United States)

    Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

    2007-04-01

    Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

  14. Inhibition of Avian Influenza A Virus Replication in Human Cells by Host Restriction Factor TUFM Is Correlated with Autophagy.

    Science.gov (United States)

    Kuo, Shu-Ming; Chen, Chi-Jene; Chang, Shih-Cheng; Liu, Tzu-Jou; Chen, Yi-Hsiang; Huang, Sheng-Yu; Shih, Shin-Ru

    2017-06-13

    Avian influenza A viruses generally do not replicate efficiently in human cells, but substitution of glutamic acid (Glu, E) for lysine (Lys, K) at residue 627 of avian influenza virus polymerase basic protein 2 (PB2) can serve to overcome host restriction and facilitate human infectivity. Although PB2 residue 627 is regarded as a species-specific signature of influenza A viruses, host restriction factors associated with PB2 627 E have yet to be fully investigated. We conducted immunoprecipitation, followed by differential proteomic analysis, to identify proteins associating with PB2 627 K (human signature) and PB2 627 E (avian signature) of influenza A/WSN/1933(H1N1) virus, and the results indicated that Tu elongation factor, mitochondrial (TUFM), had a higher binding affinity for PB2 627 E than PB2 627 K in transfected human cells. Stronger binding of TUFM to avian-signature PB2 590 G/ 591 Q and PB2 627 E in the 2009 swine-origin pandemic H1N1 and 2013 avian-origin H7N9 influenza A viruses was similarly observed. Viruses carrying avian-signature PB2 627 E demonstrated increased replication in TUFM-deficient cells, but viral replication decreased in cells overexpressing TUFM. Interestingly, the presence of TUFM specifically inhibited the replication of PB2 627 E viruses, but not PB2 627 K viruses. In addition, enhanced levels of interaction between TUFM and PB2 627 E were noted in the mitochondrial fraction of infected cells. Furthermore, TUFM-dependent autophagy was reduced in TUFM-deficient cells infected with PB2 627 E virus; however, autophagy remained consistent in PB2 627 K virus-infected cells. The results suggest that TUFM acts as a host restriction factor that impedes avian-signature influenza A virus replication in human cells in a manner that correlates with autophagy. IMPORTANCE An understanding of the mechanisms that influenza A viruses utilize to shift host tropism and the identification of host restriction factors that can limit infection are both

  15. Finite volume form factors in the presence of integrable defects

    International Nuclear Information System (INIS)

    Bajnok, Z.; Buccheri, F.; Hollo, L.; Konczer, J.; Takacs, G.

    2014-01-01

    We developed the theory of finite volume form factors in the presence of integrable defects. These finite volume form factors are expressed in terms of the infinite volume form factors and the finite volume density of states and incorporate all polynomial corrections in the inverse of the volume. We tested our results, in the defect Lee–Yang model, against numerical data obtained by truncated conformal space approach (TCSA), which we improved by renormalization group methods adopted to the defect case. To perform these checks we determined the infinite volume defect form factors in the Lee–Yang model exactly, including their vacuum expectation values. We used these data to calculate the two point functions, which we compared, at short distance, to defect CFT. We also derived explicit expressions for the exact finite volume one point functions, which we checked numerically. In all of these comparisons excellent agreement was found

  16. Route assessment using comparative risk factors integrated through a GIS

    International Nuclear Information System (INIS)

    Toth, D.M.; O'Connell, W.J.

    1996-01-01

    The assessment of potential alternative routes for the shipment of spent nuclear fuel was simplified through the use of comparative risk factors evaluated using detailed route and environmental attributes. The route characteristics, integrated into risk measures, vary strongly with location and were developed from national, state, and local sources. The route data and evaluation were managed using a geographic information system (GIS). An assessment of four real North Florida routes was performed and an interstate highway route exhibited the lowest risk based on the application of the risk factors

  17. The host plant metabolite glucose is the precursor of diffusible signal factor (DSF) family signals in Xanthomonas campestris.

    Science.gov (United States)

    Deng, Yinyue; Liu, Xiaoling; Wu, Ji'en; Lee, Jasmine; Chen, Shaohua; Cheng, Yingying; Zhang, Chunyan; Zhang, Lian-Hui

    2015-04-01

    Plant pathogen Xanthomonas campestris pv. campestris produces cis-11-methyl-2-dodecenoic acid (diffusible signal factor [DSF]) as a cell-cell communication signal to regulate biofilm dispersal and virulence factor production. Previous studies have demonstrated that DSF biosynthesis is dependent on the presence of RpfF, an enoyl-coenzyme A (CoA) hydratase, but the DSF synthetic mechanism and the influence of the host plant on DSF biosynthesis are still not clear. We show here that exogenous addition of host plant juice or ethanol extract to the growth medium of X. campestris pv. campestris could significantly boost DSF family signal production. It was subsequently revealed that X. campestris pv. campestris produces not only DSF but also BDSF (cis-2-dodecenoic acid) and another novel DSF family signal, which was designated DSF-II. BDSF was originally identified in Burkholderia cenocepacia to be involved in regulation of motility, biofilm formation, and virulence in B. cenocepacia. Functional analysis suggested that DSF-II plays a role equal to that of DSF in regulation of biofilm dispersion and virulence factor production in X. campestris pv. campestris. Furthermore, chromatographic separation led to identification of glucose as a specific molecule stimulating DSF family signal biosynthesis in X. campestris pv. campestris. (13)C-labeling experiments demonstrated that glucose acts as a substrate to provide a carbon element for DSF biosynthesis. The results of this study indicate that X. campestris pv. campestris could utilize a common metabolite of the host plant to enhance DSF family signal synthesis and therefore promote virulence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Gisela Canedo-Marroquín

    2017-08-01

    Full Text Available The Human Respiratory Syncytial Virus (hRSV is a major cause of acute lower respiratory tract infections (ARTIs and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F, the Glycoprotein (G, and the Small Hydrophobic (SH protein, which are located on the virus surface. In addition, the Nucleoprotein (N, Phosphoprotein (P large polymerase protein (L part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2. HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

  19. Factors Hindering the Integration of CALL in a Tertiary Institution

    Directory of Open Access Journals (Sweden)

    Izaham Shah Ismail

    2008-12-01

    Full Text Available The field of Computer Assisted Language Learning (CALL is a field that is constantly evolving as it is very much dependent on the advancement of computer technologies. With new technologies being invented almost every day, experts in the field are looking for ways to apply these new technologies in the language classroom. Despite that, teachers are said to be slow at adopting technology in their classrooms and language teachers, whether at schools or tertiary institutions, are no exception. This study attempts to investigate the factors that hinder ESL instructors at an institution of higher learning from integrating CALL in their lessons. Interviews were conducted with five ESL instructors and results revealed that factors which hinder them from integrating CALL in their teaching are universal factors such as knowledge in technology and pedagogy, computer facilities and resources, absence of exemplary integration of CALL, personal beliefs on language teaching, views on the role of a computers as teacher, and evaluation of learning outcomes.

  20. Variations on the larval incubation of Anodontites trapesialis (Unionoida, Mycetopodidae: Synergetic effect of the environmental factors and host availability

    Directory of Open Access Journals (Sweden)

    CT. Callil

    Full Text Available The unionid Anodontites trapesilais (Lamarck, 1819 like most freshwater mussels is a parasite of fish. So it is trivial to assume that the availability of hosts is an important factor for the maintenance of unionoid populations. What seems obvious is not always so easy to demonstrate. This study proposes to investigate the effects of abiotic and biotic variables related to the incubation of larvae in A. trapesialis. For this, we estimate different biological indexes and try to capture the dimensionality of the fish, along with the temporal variation of environmental variables. From the application of a CCA, it was demonstrated that there was a synchronicity among the factors and variables proposed here, and we infer that the flood pulse acts as a synergistic factor in this process.

  1. Dual RNA-sequencing of Eucalyptus nitens during Phytophthora cinnamomi challenge reveals pathogen and host factors influencing compatibility

    Directory of Open Access Journals (Sweden)

    Febe Elizabeth Meyer

    2016-03-01

    Full Text Available Damage caused by Phytophthora cinnamomi Rands remains an important concern on forest tree species. The pathogen causes root and collar rot, stem cankers and dieback of various economically important Eucalyptus spp. In South Africa, susceptible cold tolerant Eucalyptus plantations have been affected by various Phytophthora spp. with P. cinnamomi considered one of the most virulent. The molecular basis of this compatible interaction is poorly understood. In this study, susceptible Eucalyptus nitens plants were stem inoculated with P. cinnamomi and tissue was harvested five days post inoculation. Dual RNA-sequencing, a technique which allows the concurrent detection of both pathogen and host transcripts during infection, was performed. Approximately 1% of the reads mapped to the draft genome of P. cinnamomi while 78% of the reads mapped to the Eucalyptus grandis genome. The highest expressed P. cinnamomi gene in planta was a putative crinkler effector (CRN1. Phylogenetic analysis indicated the high similarity of this P. cinnamomi CRN1 to that of Phytophthora infestans. Some CRN effectors are known to target host nuclei to suppress defense. In the host, over 1400 genes were significantly differentially expressed in comparison to mock inoculated trees, including suites of pathogenesis related (PR genes. In particular, a PR-9 peroxidase gene with a high similarity to a Carica papaya PR-9 ortholog previously shown to be suppressed upon infection by Phytophthora palmivora was down-regulated two-fold. This PR-9 gene may represent a cross-species effector target during P. cinnamomi infection. This study identified pathogenicity factors, potential manipulation targets and attempted host defense mechanisms activated by E. nitens that contributed to the susceptible outcome of the interaction.

  2. Coagulation factor XI improves host defence during murine pneumonia-derived sepsis independent of factor XII activation

    NARCIS (Netherlands)

    Stroo, Ingrid; Zeerleder, Sacha; Ding, Chao; Luken, Brenda M.; Roelofs, Joris J. T. H.; de Boer, Onno J.; Meijers, Joost C. M.; Castellino, Francis J.; van 't Veer, Cornelis; van der Poll, Tom

    2017-01-01

    Bacterial pneumonia, the most common cause of sepsis, is associated with activation of coagulation. Factor XI (FXI), the key component of the intrinsic pathway, can be activated via factor XII (FXII), part of the contact system, or via thrombin. To determine whether intrinsic coagulation is involved

  3. Serratia marcescens Suppresses Host Cellular Immunity via the Production of an Adhesion-inhibitory Factor against Immunosurveillance Cells*

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-01-01

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis. PMID:24398686

  4. Serratia marcescens suppresses host cellular immunity via the production of an adhesion-inhibitory factor against immunosurveillance cells.

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-02-28

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis.

  5. Factors Relevant to Utility Integration of Intermittent Renewable Technologies

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Y.; Parsons, B.

    1993-08-24

    This study assesses factors that utilities must address when they integrate intermittent renewable technologies into their power-supply systems; it also reviews the literature in this area and has a bibliography containing more than 350 listings. Three topics are covered: (1) interface (hardware and design-related interconnection), (2) operability/stability, and (3) planning. This study finds that several commonly held perceptions regarding integration of intermittent renewable energy technologies are not valid. Among fmdings of the study are the following: (1) hardware and system design advances have eliminated most concerns about interface, (2) cost penalties have not occurred at low to moderate penetration levels (and high levels am feasible); and (3) intermittent renewable energy technologies can have capacity values. Obstacles still interfering with intermittent renewable technologies are also indentified.

  6. Factors relevant to utility integration of intermittent renewable technologies

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Yih-huei; Parsons, B.K.

    1993-08-01

    This study assesses factors that utilities must address when they integrate intermittent renewable technologies into their power-supply systems; it also reviews the literature in this area and has a bibliography containing more than 350 listings. Three topics are covered: (1) interface (hardware and design-related interconnection), (2) operability/stability, and (3) planning. This study finds that several commonly held perceptions regarding integration of intermittent renewable energy technologies are not valid. Among findings of the study are the following: (1) hardware and system design advances have eliminated most concerns about interface; (2) cost penalties have not occurred at low to moderate penetration levels (and high levels are feasible); and (3) intermittent renewable energy technologies can have capacity values. Obstacles still interfering with intermittent renewable technologies are also identified.

  7. Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host.

    Science.gov (United States)

    Pila, Emmanuel A; Gordy, Michelle A; Phillips, Valerie K; Kabore, Alethe L; Rudko, Sydney P; Hanington, Patrick C

    2016-05-10

    Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection.

  8. A Factor Analysis of Trade Integration: The Case of Asian and Oceanic Economies

    OpenAIRE

    Yin-Wong Cheung; Matthew S. Yiu; Kenneth K. Chow

    2009-01-01

    We study trade integration among 15 selected Asian and Oceanic economies using factor models. The principal component approach is employed to extract the common factor that drives trade integration from bilateral trade integration series. It is found that the estimated common trade integration factor has strong seasonal and deterministic components. In accordance with theory, the common trade integration factor is significantly associated with the economic growth and the trade barriers of the...

  9. Factors Influencing Learning Environments in an Integrated Experiential Program

    Science.gov (United States)

    Koci, Peter

    The research conducted for this dissertation examined the learning environment of a specific high school program that delivered the explicit curriculum through an integrated experiential manner, which utilized field and outdoor experiences. The program ran over one semester (five months) and it integrated the grade 10 British Columbian curriculum in five subjects. A mixed methods approach was employed to identify the students' perceptions and provide richer descriptions of their experiences related to their unique learning environment. Quantitative instruments were used to assess changes in students' perspectives of their learning environment, as well as other supporting factors including students' mindfulness, and behaviours towards the environment. Qualitative data collection included observations, open-ended questions, and impromptu interviews with the teacher. The qualitative data describe the factors and processes that influenced the learning environment and give a richer, deeper interpretation which complements the quantitative findings. The research results showed positive scores on all the quantitative measures conducted, and the qualitative data provided further insight into descriptions of learning environment constructs that the students perceived as most important. A major finding was that the group cohesion measure was perceived by students as the most important attribute of their preferred learning environment. A flow chart was developed to help the researcher conceptualize how the learning environment, learning process, and outcomes relate to one another in the studied program. This research attempts to explain through the consideration of this case study: how learning environments can influence behavioural change and how an interconnectedness among several factors in the learning process is influenced by the type of learning environment facilitated. Considerably more research is needed in this area to understand fully the complexity learning

  10. Pediatric acute respiratory distress syndrome: Host factors in Down syndrome and the general population

    NARCIS (Netherlands)

    Bruijn, M.

    2013-01-01

    We find that Down syndrome is an important risk factor for developing acute respiratory distress syndrome (ARDS) in children, but the reason why remains to be elucidated. In addition, we find several differences between adult and pediatric ARDS. The association between C-reactive protein (CRP)

  11. Setting and solving several factorization problems for integral operators

    International Nuclear Information System (INIS)

    Engibaryan, N B

    2000-01-01

    The problem of factorization I-K=(I-U - )(I-U + ), is considered. Here I is the identity operator, K is a fixed integral operator of Fredholm type: (Kf)(x)=∫ a b k(x,t)f(t)dt, -∞≤a ± are unknown upper and lower Volterra operators. Classes of generalized Volterra operators U ± are introduced such that I-U ± are not necessarily invertible operators in the spaces of functions on (a,b) under consideration. A combination of the method of non-linear factorization equations and a priori estimates brings forth new results on the existence and properties of the solution to this problem for k≥0, both in the subcritical case μ + and U - vanish on some parts S - and S + of the domain S=(a,b) 2 such that S + union S - =S

  12. Factors associated with clinical inertia: an integrative review

    Science.gov (United States)

    Aujoulat, Isabelle; Jacquemin, Patricia; Rietzschel, Ernst; Scheen, André; Tréfois, Patrick; Wens, Johan; Darras, Elisabeth; Hermans, Michel P

    2014-01-01

    Failure to initiate or intensify therapy according to evidence-based guidelines is increasingly being acknowledged as a phenomenon that contributes to inadequate management of chronic conditions, and is referred to as clinical inertia. However, the number and complexity of factors associated with the clinical reasoning that underlies the decision-making processes in medicine calls for a critical examination of the consistency of the concept. Indeed, in the absence of information on and justification of treatment decisions that were made, clinical inertia may be only apparent, and actually reflect good clinical practice. This integrative review seeks to address the factors generally associated with clinical inaction, in order to better delineate the concept of true clinical inertia. PMID:24868181

  13. The relationship between host factors of allergic nature and respiratory symptoms.

    Science.gov (United States)

    Gepts, L; Minette, A

    1977-01-01

    Respiratory symptoms and personal history of allergy were examined in 1659 children, including the entire elementary school population of four villages of the Belgian Ardennes. Levels of atmospheric pollution were monitored during the survey and proved to be very low. It is suggested that socio-economic factors produce a small increase in respiratory symptoms, particularly in cough symptoms. A personal history of eczema and of hay fever was highly associated with dyspnea and wheezing.

  14. No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.

    Science.gov (United States)

    Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

    2015-01-01

    While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

  15. Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Costa Luciano Bello

    2002-01-01

    Full Text Available There is increasing interest in the identification of factors associated with liver disease progression in patients infected with hepatitis C virus (HCV. We assessed host-related factors associated with a histologically advanced stage of this disease and determined the rate of liver fibrosis progression in HCV-infected patients. We included patients submitted to liver biopsy, who were anti-HCV and HCV RNA positive, who showed a parenteral risk factor (blood transfusion or intravenous drug use, and who gave information about alcohol consumption.Patients were divided into two groups for analysis: group 1 - grades 0 to 2; group 2 - grades 3 to 4. The groups were compared in terms of sex, age at the time of infection, estimated duration of infection and alcoholism. The rate of fibrosis progression (index of fibrosis was determined based on the relationship between disease stage and duration of infection (years. Logistic regression analysis revealed that age at the time of infection (P or = 40 years (median = 0.47. The main factors associated with a more rapid fibrosis progression were age at the time of infection and the estimated duration of infection. Patients who acquired HCV after 40 years of age showed a higher rate of fibrosis progression.

  16. Screening and identification of host factors interacting with UL14 of herpes simplex virus 1.

    Science.gov (United States)

    Wu, Fuqing; Xing, Junji; Wang, Shuai; Li, Meili; Zheng, Chunfu

    2011-08-01

    The UL14 protein of herpes simplex virus type 1 (HSV-1) is highly conserved in herpesvirus family. However, its exact function during the HSV-1 replication cycle is little known. In the present study, a high throughput yeast two-hybrid system was employed to screen the cellular factors interacting with UL14, and five target candidates were yielded: (1) TSC22 domain family protein 3 (TSC22D3); (2) Mediator of RNA polymerase II transcription subunit 8 isoform 1(MED8); (3) Runt-related transcription factor 3 (RUNX3); (4) Arrestin beta-2 (ARRB2); (5) Cereblon (CRBN). Indirect immunofluorescent assay showed that both TSC22D3 and MED8 co-localized with UL14. Co-immunoprecipitation assay demonstrated that UL14 could be immunoprecipitated by TSC22D3, suggesting that UL14 interacted with TSC22D3 under physiological condition. In summary, this study opened up new avenues toward delineating the function and physiological significance of UL14 during the HSV-1 replication cycle.

  17. C-terminal peptides of tissue factor pathway inhibitor are novel host defense molecules.

    Science.gov (United States)

    Papareddy, Praveen; Kalle, Martina; Kasetty, Gopinath; Mörgelin, Matthias; Rydengård, Victoria; Albiger, Barbara; Lundqvist, Katarina; Malmsten, Martin; Schmidtchen, Artur

    2010-09-03

    Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C terminus, also modulate cell surface, heparin, and lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the "classic" human antimicrobial peptide LL-37. The killing of E. coli, but not P. aeruginosa, by the C-terminal peptide GGLIKTKRKRKKQRVKIAYEEIFVKNM (GGL27), was enhanced in human plasma and largely abolished in heat-inactivated plasma, a phenomenon linked to generation of antimicrobial C3a and activation of the classic pathway of complement activation. Furthermore, GGL27 displayed anti-endotoxic effects in vitro and in vivo in a mouse model of LPS shock. Importantly, TFPI was found to be expressed in the basal layers of normal epidermis, and was markedly up-regulated in acute skin wounds as well as wound edges of chronic leg ulcers. Furthermore, C-terminal fragments of TFPI were associated with bacteria present in human chronic leg ulcers. These findings suggest a new role for TFPI in cutaneous defense against infections.

  18. Identification of host factors potentially involved in RTM-mediated resistance during potyvirus long distance movement.

    Science.gov (United States)

    Sofer, Luc; Cabanillas, Daniel Garcia; Gayral, Mathieu; Téplier, Rachèle; Pouzoulet, Jérôme; Ducousso, Marie; Dufin, Laurène; Bréhélin, Claire; Ziegler-Graff, Véronique; Brault, Véronique; Revers, Frédéric

    2017-07-01

    The long distance movement of potyviruses is a poorly understood step of the viral cycle. Only factors inhibiting this process, referred to as "Restricted TEV Movement" (RTM), have been identified in Arabidopsis thaliana. On the virus side, the potyvirus coat protein (CP) displays determinants required for long-distance movement and for RTM-based resistance breaking. However, the potyvirus CP was previously shown not to interact with the RTM proteins. We undertook the identification of Arabidopsis factors which directly interact with either the RTM proteins or the CP of lettuce mosaic virus (LMV). An Arabidopsis cDNA library generated from companion cells was screened with LMV CP and RTM proteins using the yeast two-hybrid system. Fourteen interacting proteins were identified. Two of them were shown to interact with CP and the RTM proteins suggesting that a multiprotein complex could be formed between the RTM proteins and virions or viral ribonucleoprotein complexes. Co-localization experiments in Nicotiana benthamiana showed that most of the viral and cellular protein pairs co-localized at the periphery of chloroplasts which suggests a putative role for plastids in this process.

  19. Orchestrating the Selection and Packaging of Genomic RNA by Retroviruses: An Ensemble of Viral and Host Factors

    Science.gov (United States)

    Kaddis Maldonado, Rebecca J.; Parent, Leslie J.

    2016-01-01

    Infectious retrovirus particles contain two copies of unspliced viral RNA that serve as the viral genome. Unspliced retroviral RNA is transcribed in the nucleus by the host RNA polymerase II and has three potential fates: (1) it can be spliced into subgenomic messenger RNAs (mRNAs) for the translation of viral proteins; or it can remain unspliced to serve as either (2) the mRNA for the translation of Gag and Gag–Pol; or (3) the genomic RNA (gRNA) that is packaged into virions. The Gag structural protein recognizes and binds the unspliced viral RNA to select it as a genome, which is selected in preference to spliced viral RNAs and cellular RNAs. In this review, we summarize the current state of understanding about how retroviral packaging is orchestrated within the cell and explore potential new mechanisms based on recent discoveries in the field. We discuss the cis-acting elements in the unspliced viral RNA and the properties of the Gag protein that are required for their interaction. In addition, we discuss the role of host factors in influencing the fate of the newly transcribed viral RNA, current models for how retroviruses distinguish unspliced viral mRNA from viral genomic RNA, and the possible subcellular sites of genomic RNA dimerization and selection by Gag. Although this review centers primarily on the wealth of data available for the alpharetrovirus Rous sarcoma virus, in which a discrete RNA packaging sequence has been identified, we have also summarized the cis- and trans-acting factors as well as the mechanisms governing gRNA packaging of other retroviruses for comparison. PMID:27657110

  20. [Validation of the modified algorithm for predicting host susceptibility to viruses taking into account susceptibility parameters of primary target cell cultures and natural immunity factors].

    Science.gov (United States)

    Zhukov, V A; Shishkina, L N; Safatov, A S; Sergeev, A A; P'iankov, O V; Petrishchenko, V A; Zaĭtsev, B N; Toporkov, V S; Sergeev, A N; Nesvizhskiĭ, Iu V; Vorob'ev, A A

    2010-01-01

    The paper presents results of testing a modified algorithm for predicting virus ID50 values in a host of interest by extrapolation from a model host taking into account immune neutralizing factors and thermal inactivation of the virus. The method was tested for A/Aichi/2/68 influenza virus in SPF Wistar rats, SPF CD-1 mice and conventional ICR mice. Each species was used as a host of interest while the other two served as model hosts. Primary lung and trachea cells and secretory factors of the rats' airway epithelium were used to measure parameters needed for the purpose of prediction. Predicted ID50 values were not significantly different (p = 0.05) from those experimentally measured in vivo. The study was supported by ISTC/DARPA Agreement 450p.

  1. Improving Aspergillus niger as a production host through manipulation of pH responding transcription factors

    DEFF Research Database (Denmark)

    Poulsen, Lars; Bruno, K.S.; Thykær, Jette

    for gene knockout. The resulting mutants were first exposed to screening experiments including morphological studies and investigation of acid profile and protease activity. Among others an interesting finding was that one mutant had an oxalic acid overproducing phenotype (OOP). In the screening...... experiments the OOP mutant showed a 30 % (± 5%) increase in oxalic acid titer. The OOP mutant was further characterized in 2L scale bioreactors, and a 90 % (±30%) increase of the overall yield coefficient of oxalic acid on glucose was seen. Further data on the OOP mutant will be presented and results from......). In the present study the effect of modulation of transcription factors in Aspergillus niger, which is an industrially important micro-organism used in various processes including organic acid and enzyme production, was investigated. The strategy described in this work focuses on regulation connected to p...

  2. Identification of Burkholderia cenocepacia strain H111 virulence factors using nonmammalian infection hosts

    DEFF Research Database (Denmark)

    Schwager, Stephan; Agnoli, Kirsty; Köthe, Manuela

    2013-01-01

    Burkholderia cenocepacia H111, a strain isolated from a cystic fibrosis patient, has been shown to effectively kill the nematode Caenorhabditis elegans. We used the C. elegans model of infection to screen a mini-Tn5 mutant library of B. cenocepacia H111 for attenuated virulence....... Of the approximately 5,500 B. cenocepacia H111 random mini-Tn5 insertion mutants that were screened, 22 showed attenuated virulence in C. elegans. Except for the quorum-sensing regulator cepR, none of the mutated genes coded for the biosynthesis of classical virulence factors such as extracellular proteases...... or siderophores. Instead, the mutants contained insertions in metabolic and regulatory genes. Mutants attenuated in virulence in the C. elegans infection model were also tested in the Drosophila melanogaster pricking model, and those also attenuated in this model were further tested in Galleria mellonella. Six...

  3. Critical factors in the implementation process of integrated management systems

    Directory of Open Access Journals (Sweden)

    Ademir Antonio Ferreira

    2015-09-01

    Full Text Available This study is the result of research whose purpose was to study the implementation process of integrated management systems, called ERP Enterprise Resource Planning in the business environment. This study, more specifically, tried to identify the variables in this process and that, somehow, made it easy or caused some type of difficulty implementing the system. Based on the mixed method approach (Creswell, 2003, the study was performed by means of the content analysis of technical and scientific publications about this theme and by means of a field research for data collection from primary sources. The content analysis was based on the per mile procedure by Bardin (1977, making it possible to identify critical factors that may be found in the implementation of ERP system projects. Primary data was collected from structured interviews with the managers in charge of the implementation of the system, in each of the 12 companies in different sectors of the economy and based in Brazil. Based on this information, it was possible to test the factors extracted from the content analysis and then develop a list of factors that may effectively influence the implementation process of the system. In order to recognize the possible relations between the selected factors, the Spearman (rsp correlation coefficient was applied and the multiple regression analysis was performed by means of the stepwise procedure. The purpose of the regression analysis was to determine the relation of the “Assessment of the Implementation” dependent variable with other dependent variables in the selected categories. The results of these analyses showed that the support of the top management, the communication process for the clear evidence of this support, the technical support of the ERP program provider together with the project team expertise, training and qualification processes of the team in the system operation are significantly correlated and relevant factors for a

  4. Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

    Science.gov (United States)

    Nuss, Jonathan E; Kehn-Hall, Kylene; Benedict, Ashwini; Costantino, Julie; Ward, Michael; Peyser, Brian D; Retterer, Cary J; Tressler, Lyal E; Wanner, Laura M; McGovern, Hugh F; Zaidi, Anum; Anthony, Scott M; Kota, Krishna P; Bavari, Sina; Hakami, Ramin M

    2014-01-01

    Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV). Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry) with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90), as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.

  5. Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

    Directory of Open Access Journals (Sweden)

    Jonathan E Nuss

    Full Text Available Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV. Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90, as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.

  6. Characterisation of mouse mammary tumour virus and host related regulatory factors

    International Nuclear Information System (INIS)

    Müllner, M.

    2012-01-01

    , respectively. Thus, a region located at the 5’ end of the env coding region was demonstrated to be involved in the Rem/RmRE-independent RNA export. Deletion of this region led to a complete loss of single-spliced env mRNA export. Cloning of this 5’ transport element (5’TE) into the heterologous HIV-1 gag RNA reporter construct revealed that the 5’TE-mediated nuclear export is independent of a virally encoded accessory protein. Additional results have shown that the MMTV env mRNA nucleo-cytoplasmic transport is dependent on the cellular factor Tap. Together, the results presented in this work clearly demonstrate that MMTV exploits different strategies to export various viral RNA messages from the nucleus. On the one hand, transport of full length genomic RNA is mediated by the Rem/RmRE interaction which then allows binding of the nuclear export factor CRM1. On the other hand, single-spliced env mRNA makes use of a cis-acting transport element located at the 5’ end of the subgenomic RNA. Export via this structure is dependent on the cellular Tap nuclear export factor. However, molecular details about the MMTV export strategies still have to be determined.(author) [de

  7. Host- and microbe-related risk factors for and pathophysiology of fatal Rickettsia conorii infection in Portuguese patients.

    Science.gov (United States)

    Sousa, Rita de; França, Ana; Dória Nòbrega, Sónia; Belo, Adelaide; Amaro, Mario; Abreu, Tiago; Poças, José; Proença, Paula; Vaz, José; Torgal, Jorge; Bacellar, Fátima; Ismail, Nahed; Walker, David H

    2008-08-15

    The pathophysiologic mechanisms that determine the severity of Mediterranean spotted fever (MSF) and the host-related and microbe-related risk factors for a fatal outcome are incompletely understood. This prospective study used univariate and multivariate analyses to determine the risk factors for a fatal outcome for 140 patients with Rickettsia conorii infection admitted to 13 Portuguese hospitals during 1994-2006 with documented identification of the rickettsial strain causing their infection. A total of 71 patients (51%) were infected with the Malish strain of Rickettsia conorii, and 69 (49%) were infected with the Israeli spotted fever (ISF) strain. Patients were admitted to the intensive care unit (40 [29%]), hospitalized as routine inpatients (95[67%]), or managed as outpatients (5[4%]). Death occurred in 29 adults (21%). A fatal outcome was significantly more likely for patients infected with the ISF strain, and alcoholism was a risk factor. The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, obtundation and/or confusion, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated levels of hepatic enzymes and creatine kinase. Some, but not all, of these findings were observed more often in ISF strain-infected patients. Although fatalities and similar clinical manifestations occurred among both groups of patients, the ISF strain was more virulent than the Malish strain. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strongly associated with a fatal outcome.

  8. Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.

    Directory of Open Access Journals (Sweden)

    Sophie Joly

    Full Text Available Interferon Regulatory Factor (IRF 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Toll-like receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrow-derived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.

  9. A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication.

    Science.gov (United States)

    Griffiths, Samantha J; Koegl, Manfred; Boutell, Chris; Zenner, Helen L; Crump, Colin M; Pica, Francesca; Gonzalez, Orland; Friedel, Caroline C; Barry, Gerald; Martin, Kim; Craigon, Marie H; Chen, Rui; Kaza, Lakshmi N; Fossum, Even; Fazakerley, John K; Efstathiou, Stacey; Volpi, Antonio; Zimmer, Ralf; Ghazal, Peter; Haas, Jürgen

    2013-01-01

    Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to

  10. A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication.

    Directory of Open Access Journals (Sweden)

    Samantha J Griffiths

    Full Text Available Herpes simplex virus type 1 (HSV-1 is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi screen with a druggable genome small interfering RNA (siRNA library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome

  11. Butterfly Larval Host Plant use in a Tropical Urban Context: Life History Associations, Herbivory, and Landscape Factors

    Science.gov (United States)

    Tiple, Ashish D.; Khurad, Arun M.; Dennis, Roger L. H.

    2011-01-01

    This study examines butterfly larval host plants, herbivory and related life history attributes within Nagpur City, India. The larval host plants of 120 butterfly species are identified and their host specificity, life form, biotope, abundance and perennation recorded; of the 126 larval host plants, most are trees (49), with fewer herbs (43), shrubs (22), climbers (7) and stem parasites (2). They include 89 wild, 23 cultivated, 11 wild/cultivated and 3 exotic plant species; 78 are perennials, 43 annuals and 5 biannuals. Plants belonging to Poaceae and Fabaceae are most widely used by butterfly larvae. In addition to distinctions in host plant family affiliation, a number of significant differences between butterfly families have been identified in host use patterns: for life forms, biotopes, landforms, perennation, host specificity, egg batch size and ant associations. These differences arising from the development of a butterfly resource database have important implications for conserving butterfly species within the city area. Differences in overall butterfly population sizes within the city relate mainly to the number of host plants used, but other influences, including egg batch size and host specificity are identified. Much of the variation in population size is unaccounted for and points to the need to investigate larval host plant life history and strategies as population size is not simply dependent on host plant abundance. PMID:21864159

  12. Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors.

    Science.gov (United States)

    Holtan, Shernan G; Khera, Nandita; Levine, John E; Chai, Xiaoyu; Storer, Barry; Liu, Hien D; Inamoto, Yoshihiro; Chen, George L; Mayer, Sebastian; Arora, Mukta; Palmer, Jeanne; Flowers, Mary E D; Cutler, Corey S; Lukez, Alexander; Arai, Sally; Lazaryan, Aleksandr; Newell, Laura F; Krupski, Christa; Jagasia, Madan H; Pusic, Iskra; Wood, William; Renteria, Anne S; Yanik, Gregory; Hogan, William J; Hexner, Elizabeth; Ayuk, Francis; Holler, Ernst; Watanaboonyongcharoen, Phandee; Efebera, Yvonne A; Ferrara, James L M; Panoskaltsis-Mortari, Angela; Weisdorf, Daniel; Lee, Stephanie J; Pidala, Joseph

    2016-11-10

    Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring >100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n = 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n = 55) and controls (n = 50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic GVHD. © 2016 by The American Society of Hematology.

  13. Interaction of MYC with host cell factor-1 is mediated by the evolutionarily conserved Myc box IV motif.

    Science.gov (United States)

    Thomas, L R; Foshage, A M; Weissmiller, A M; Popay, T M; Grieb, B C; Qualls, S J; Ng, V; Carboneau, B; Lorey, S; Eischen, C M; Tansey, W P

    2016-07-07

    The MYC family of oncogenes encodes a set of three related transcription factors that are overexpressed in many human tumors and contribute to the cancer-related deaths of more than 70,000 Americans every year. MYC proteins drive tumorigenesis by interacting with co-factors that enable them to regulate the expression of thousands of genes linked to cell growth, proliferation, metabolism and genome stability. One effective way to identify critical co-factors required for MYC function has been to focus on sequence motifs within MYC that are conserved throughout evolution, on the assumption that their conservation is driven by protein-protein interactions that are vital for MYC activity. In addition to their DNA-binding domains, MYC proteins carry five regions of high sequence conservation known as Myc boxes (Mb). To date, four of the Mb motifs (MbI, MbII, MbIIIa and MbIIIb) have had a molecular function assigned to them, but the precise role of the remaining Mb, MbIV, and the reason for its preservation in vertebrate Myc proteins, is unknown. Here, we show that MbIV is required for the association of MYC with the abundant transcriptional coregulator host cell factor-1 (HCF-1). We show that the invariant core of MbIV resembles the tetrapeptide HCF-binding motif (HBM) found in many HCF-interaction partners, and demonstrate that MYC interacts with HCF-1 in a manner indistinguishable from the prototypical HBM-containing protein VP16. Finally, we show that rationalized point mutations in MYC that disrupt interaction with HCF-1 attenuate the ability of MYC to drive tumorigenesis in mice. Together, these data expose a molecular function for MbIV and indicate that HCF-1 is an important co-factor for MYC.

  14. The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

    Science.gov (United States)

    de Chassey, Benoît; Aublin-Gex, Anne; Ruggieri, Alessia; Meyniel-Schicklin, Laurène; Pradezynski, Fabrine; Davoust, Nathalie; Chantier, Thibault; Tafforeau, Lionel; Mangeot, Philippe-Emmanuel; Ciancia, Claire; Perrin-Cocon, Laure; Bartenschlager, Ralf; André, Patrice; Lotteau, Vincent

    2013-01-01

    Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

  15. The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

    Directory of Open Access Journals (Sweden)

    Benoît de Chassey

    Full Text Available Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1 appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

  16. Integrated Human Factors Design Guidelines for Sound Interface

    International Nuclear Information System (INIS)

    Lee, Jung Woon; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul; Cha, Woo Chang

    2004-05-01

    Digital MMI, such as CRT, LCD etc., has been used increasingly in the design of main control room of the Korean standard nuclear power plants following the YGN units 3 and 4. The utilization of digital MMI may introduce various kind of sound interface into the control room design. In this project, for five top-level guideline items, including Sound Formats, Alarms, Sound Controls, Communications, and Environments, a total of 147 detail guidelines were developed and a database system for these guidelines was developed. The integrated human factors design guidelines for sound interface and the database system developed in this project will be useful for the design of sound interface of digital MMI in Korean NPPs

  17. Integrated Human Factors Design Guidelines for Sound Interface

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul [KAERI, Daejeon (Korea, Republic of); Cha, Woo Chang [Kumoh National Univ. of Technology, Gumi (Korea, Republic of)

    2004-05-15

    Digital MMI, such as CRT, LCD etc., has been used increasingly in the design of main control room of the Korean standard nuclear power plants following the YGN units 3 and 4. The utilization of digital MMI may introduce various kind of sound interface into the control room design. In this project, for five top-level guideline items, including Sound Formats, Alarms, Sound Controls, Communications, and Environments, a total of 147 detail guidelines were developed and a database system for these guidelines was developed. The integrated human factors design guidelines for sound interface and the database system developed in this project will be useful for the design of sound interface of digital MMI in Korean NPPs.

  18. Factors affecting rural volunteering in palliative care - an integrated review.

    Science.gov (United States)

    Whittall, Dawn; Lee, Susan; O'Connor, Margaret

    2016-12-01

    To review factors shaping volunteering in palliative care in Australian rural communities using Australian and International literature. Identify gaps in the palliative care literature and make recommendations for future research. A comprehensive literature search was conducted using Proquest, Scopus, Sage Premier, Wiley online, Ovid, Cochran, Google Scholar, CINAHL and Informit Health Collection. The literature was synthesised and presented in an integrated thematic narrative. Australian Rural communities. While Australia, Canada, the United States (US) and the United Kingdom (UK) are leaders in palliative care volunteer research, limited research specifically focuses on volunteers in rural communities with the least occurring in Australia. Several interrelated factors influence rural palliative care provision, in particular an increasingly ageing population which includes an ageing volunteer and health professional workforce. Also current and models of palliative care practice fail to recognise the innumerable variables between and within rural communities such as distance, isolation, lack of privacy, limited health care services and infrastructure, and workforce shortages. These issues impact palliative care provision and are significant for health professionals, volunteers, patients and caregivers. The three key themes of this integrated review include: (i) Geography, ageing rural populations in palliative care practice, (ii) Psychosocial impact of end-end-of life care in rural communities and (iii) Palliative care models of practice and volunteering in rural communities. The invisibility of volunteers in rural palliative care research is a concern in understanding the issues affecting the sustainability of quality palliative care provision in rural communities. Recommendations for future Australian research includes examination of the suitability of current models of palliative care practice in addressing the needs of rural communities; the recruitment

  19. Recurrent invasive pneumococcal disease in children--host factors and vaccination response.

    Science.gov (United States)

    Ingels, Helene Andrea Sinclair

    2015-07-01

    Streptococcus pneumoniae is still a leading cause of septicaemia, pneumonia and meningitis in young children world-wide with over half a million children dying annually from pneumococcal disease.  Some children are prone to repeated episodes of invasive pneumococcal disease (IPD) because of an underlying predisposing disease. Recurrent IPD (rIPD) is a rarity and published reports on rIPD are limited by having few children included, selected groups of patients or short follow-up periods. Deficiencies in the innate or adaptive immune system have been described in children with rIPD, but the frequency of immunodeficiency among such patients is unknown. The aim of this PhD thesis was to examine paediatric cases of laboratory-confirmed rIPD, over a 33-year period in Denmark, to determine risk factors and study aspects of the immunological background for this problem in children. In October 2007, a seven-valent pneumococcal conjugate vaccine (PCV7) was implemented in the Danish infant immunization programme. An additional aim of the thesis was to examine the impact of vaccination on a population level, following the first three years of general PCV7 vaccination in Denmark. The thesis consists of three papers, which are all directly or indirectly based on data retrieved from the National Streptococcus Pneumoniae Registry. This registry is nationwide and dates back to 1938. The registry contains data from all laboratory-confirmed cases of IPD in Denmark and is continually updated for national surveillance. In Paper 1, we conducted a 33-year retrospective nationwide study of paediatric rIPD. By using data from the National Streptococcus Pneumoniae Registry combined with clinical data from hospital records, we could describe one of the largest known cohorts of children (n:59) with rIPD . We covered epidemiological, microbiological, and clinical features of this clinical entity. Of all children experiencing rIPD, 47% had a known predisposing underlying disease at the time of

  20. Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors.

    Science.gov (United States)

    Hauser, Kurt F; Knapp, Pamela E

    2014-01-01

    Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individuals to HIV and to drug abuse can vary tremendously. Host-genetic variability is important in determining viral tropism, neuropathogenesis, drug responses, and addictive behavior. However, genetic differences alone cannot account for individual variability in the brain "connectome." Environment and experience are critical determinants in the evolution of synaptic circuitry throughout life. Neurons and glia both exercise control over determinants of synaptic plasticity that are disrupted by HIV and drug abuse. Perivascular macrophages, microglia, and to a lesser extent astroglia can harbor the infection. Uninfected bystanders, especially astroglia, propagate and amplify inflammatory signals. Drug abuse by itself derails neuronal and glial function, and the outcome of chronic exposure is maladaptive plasticity. The negative consequences of coexposure to HIV and drug abuse are determined by numerous factors including genetics, sex, age, and multidrug exposure. Glia and some neurons are generated throughout life, and their progenitors appear to be targets of HIV and opiates/psychostimulants. The chronic nature of HIV and drug abuse appears to result in sustained alterations in the maturation and fate of neural progenitors, which may affect the balance of glial populations within multiple brain regions. © 2014 Elsevier Inc. All rights reserved.

  1. The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

    Science.gov (United States)

    Sun, Xingmin; Hirota, Simon A.

    2014-01-01

    Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

  2. Tumor Necrosis Factor-α Is Required for Mast Cell-Mediated Host Immunity Against Cutaneous Staphylococcus aureus Infection.

    Science.gov (United States)

    Liu, Chao; Ouyang, Wei; Xia, Jingyan; Sun, Xiaoru; Zhao, Liying; Xu, Feng

    2018-05-08

    Mast cells (MCs) play a key role in immune process response to invading pathogens. This study assessed the involvement of MCs in controlling Staphylococcus aureus infection in a cutaneous infection model of MC-deficient (KitW-sh/W-sh) mice. KitW-sh/W-sh mice developed significantly larger skin lesions after the cutaneous S. aureus challenge, when compared to wild-type (WT) mice, while MC dysfunction reduced the inflammation response to S. aureus. The levels of tumor necrosis factor (TNF)-α in skin tissues were significantly decreased in KitW-sh/W-sh mice upon infection. Moreover, the exogenous administration of MCs or recombinant TNF-α effectively restored the immune response against S. aureus in KitW-sh/W-sh mice via the recruitment of neutrophils to the infected site. These results indicate that the effects of MC deficiency are largely attributed to the decrease in production of TNF-α in cutaneous S. aureus infection. In addition, S. aureus-induced MC activation was dependent on the c-kit receptor-activated phosphoinositide 3-kinase (PI3K)/AKT/P65-nuclear factor (NF-κB) pathway, which was confirmed by treatment with Masitinib (a c-kit receptor inhibitor), Wortmannin (a PI3K inhibitor), and pyrrolidine dithiocarbamate (a NF-κB inhibitor), respectively. The present study identifies the critical role of MCs in the host defense against S. aureus infection.

  3. Radiation-induced mouse chimeras: a cellular analysis of the major lymphoid compartments, factors affecting lethal graft versus host disease and host-tumor interactions

    International Nuclear Information System (INIS)

    Almaraz, R.

    1981-01-01

    The major lymphoid compartments of allogeneic bone marrow chimeras were evaluated for the extent of cell chimerism and distribution of Thy 1 and la bearing cells. These chimeras contained lymphoid cell primarily of donor origin. The bone marrow compartment was a mixture of host and donor origin cells. The distribution of Thy 1 and la bearing cells was similar as in normal mice. The effect of adult thymectomy alone or followed by whole-body irradiation and bone marrow reconstitution on the distribution of the Thy 1 positive cells was also investigated. Thymectomy with or without WBI and bone marrow reconstitution significantly lowered the number of Thy 1 bearing cells in the blood and spleen. The number of la bearing cells did not appear to be affected by thymectomy. The role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation induced fully allogeneic mouse chimeras was studied. Mice reconstituted with allogeneic bone marrow from bled donors had a statistically lower incidence of GVHD than those reconstituted with bone marrow from unbled donors. Addition of mature peripheral lymphocytes from blood to the reconstituting bone marrow cells from bled donors reduplicated the high incidence of lethal GVHD. It was demonstrated that the bone marrow of mice not exsanguinated prior to harvesting of bone marrow contained significant numbers of peripheral contaminating cells in the harvested bone marrow. The role of suppressor cell elimination in resisting tumor growth was investigated using radiation induced mouse chimeras. Local effects of irradiation alone at the site of tumor inoculation could account for this lack of growth

  4. Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach

    Science.gov (United States)

    Ye, Yusen; Gao, Lin; Zhang, Shihua

    2017-01-01

    Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions. PMID:29033978

  5. Integrated traffic conflict model for estimating crash modification factors.

    Science.gov (United States)

    Shahdah, Usama; Saccomanno, Frank; Persaud, Bhagwant

    2014-10-01

    Crash modification factors (CMFs) for road safety treatments are usually obtained through observational models based on reported crashes. Observational Bayesian before-and-after methods have been applied to obtain more precise estimates of CMFs by accounting for the regression-to-the-mean bias inherent in naive methods. However, sufficient crash data reported over an extended period of time are needed to provide reliable estimates of treatment effects, a requirement that can be a challenge for certain types of treatment. In addition, these studies require that sites analyzed actually receive the treatment to which the CMF pertains. Another key issue with observational approaches is that they are not causal in nature, and as such, cannot provide a sound "behavioral" rationale for the treatment effect. Surrogate safety measures based on high risk vehicle interactions and traffic conflicts have been proposed to address this issue by providing a more "causal perspective" on lack of safety for different road and traffic conditions. The traffic conflict approach has been criticized, however, for lacking a formal link to observed and verified crashes, a difficulty that this paper attempts to resolve by presenting and investigating an alternative approach for estimating CMFs using simulated conflicts that are linked formally to observed crashes. The integrated CMF estimates are compared to estimates from an empirical Bayes (EB) crash-based before-and-after analysis for the same sample of treatment sites. The treatment considered involves changing left turn signal priority at Toronto signalized intersections from permissive to protected-permissive. The results are promising in that the proposed integrated method yields CMFs that closely match those obtained from the crash-based EB before-and-after analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Epidermal Growth Factor Improves Intestinal Integrity and Survival in Murine Sepsis Following Chronic Alcohol Ingestion.

    Science.gov (United States)

    Klingensmith, Nathan J; Yoseph, Benyam P; Liang, Zhe; Lyons, John D; Burd, Eileen M; Margoles, Lindsay M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

    2017-02-01

    Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness. We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. Six-week-old FVB/N mice were randomized to receive 20% alcohol or water for 12 weeks. All mice then underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive either intraperitoneal injection of EGF (150 μg/kg/day) or normal saline. Water-fed mice given EGF had decreased 7-day mortality compared with water-fed mice (18% vs. 55%). Alcohol-fed mice given EGF also had decreased 7-day mortality compared with alcohol-fed mice (48% vs. 79%). Notably, while systemic EGF improved absolute survival to a similar degree in both water-fed and alcohol-fed mice, mortality was significantly higher in alcohol+EGF mice compared with water+EGF mice. Compared with water-fed septic mice, alcohol-fed septic mice had worsened intestinal integrity with intestinal hyperpermeability, increased intestinal epithelial apoptosis, decreased proliferation and shorter villus length. Systemic administration of EGF to septic alcohol-fed mice decreased intestinal permeability compared with septic alcohol-fed mice given vehicle, with increased levels of the tight junction mediators claudin-5 and JAM-A. Systemic administration of EGF to septic alcohol-fed mice also decreased intestinal apoptosis with an improvement in the Bax/Bcl-2 ratio. EGF also improved both crypt proliferation and villus length in septic alcohol-fed mice. EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore

  7. Identification of the key weather factors affecting overwintering success of Apolygus lucorum eggs in dead host tree branches.

    Directory of Open Access Journals (Sweden)

    Hongsheng Pan

    Full Text Available Understanding the effects of weather on insect population dynamics is crucial to simulate and forecast pest outbreaks, which is becoming increasingly important with the effects of climate change. The mirid bug Apolygus lucorum is an important pest on cotton, fruit trees and other crops in China, and primarily lays its eggs on dead parts of tree branches in the fall for subsequent overwintering. As such, the eggs that hatch the following spring are most strongly affected by ambient weather factors, rather than by host plant biology. In this study, we investigated the effects of three major weather factors: temperature, relative humidity and rainfall, on the hatching rate of A. lucorum eggs overwintering on dead branches of Chinese date tree (Ziziphus jujuba. Under laboratory conditions, rainfall (simulated via soaking was necessary for the hatching of overwintering A. lucorum eggs. In the absence of rainfall (unsoaked branches, very few nymphs successfully emerged under any of the tested combinations of temperature and relative humidity. In contrast, following simulated rainfall, the hatching rate of the overwintering eggs increased dramatically. Hatching rate and developmental rate were positively correlated with relative humidity and temperature, respectively. Under field conditions, the abundance of nymphs derived from overwintering eggs was positively correlated with rainfall amount during the spring seasons of 2009-2013, while the same was not true for temperature and relative humidity. Overall, our findings indicate that rainfall is the most important factor affecting the hatching rate of overwintering A. lucorum eggs on dead plant parts and nymph population levels during the spring season. It provides the basic information for precisely forecasting the emergence of A. lucorum and subsequently timely managing its population in spring, which will make it possible to regional control of this insect pest widely occurring in multiple crops in

  8. Identification of the key weather factors affecting overwintering success of Apolygus lucorum eggs in dead host tree branches.

    Science.gov (United States)

    Pan, Hongsheng; Liu, Bing; Lu, Yanhui; Desneux, Nicolas

    2014-01-01

    Understanding the effects of weather on insect population dynamics is crucial to simulate and forecast pest outbreaks, which is becoming increasingly important with the effects of climate change. The mirid bug Apolygus lucorum is an important pest on cotton, fruit trees and other crops in China, and primarily lays its eggs on dead parts of tree branches in the fall for subsequent overwintering. As such, the eggs that hatch the following spring are most strongly affected by ambient weather factors, rather than by host plant biology. In this study, we investigated the effects of three major weather factors: temperature, relative humidity and rainfall, on the hatching rate of A. lucorum eggs overwintering on dead branches of Chinese date tree (Ziziphus jujuba). Under laboratory conditions, rainfall (simulated via soaking) was necessary for the hatching of overwintering A. lucorum eggs. In the absence of rainfall (unsoaked branches), very few nymphs successfully emerged under any of the tested combinations of temperature and relative humidity. In contrast, following simulated rainfall, the hatching rate of the overwintering eggs increased dramatically. Hatching rate and developmental rate were positively correlated with relative humidity and temperature, respectively. Under field conditions, the abundance of nymphs derived from overwintering eggs was positively correlated with rainfall amount during the spring seasons of 2009-2013, while the same was not true for temperature and relative humidity. Overall, our findings indicate that rainfall is the most important factor affecting the hatching rate of overwintering A. lucorum eggs on dead plant parts and nymph population levels during the spring season. It provides the basic information for precisely forecasting the emergence of A. lucorum and subsequently timely managing its population in spring, which will make it possible to regional control of this insect pest widely occurring in multiple crops in summer.

  9. Symmetric integrable-polynomial factorization for symplectic one-turn-map tracking

    International Nuclear Information System (INIS)

    Shi, Jicong

    1993-01-01

    It was found that any homogeneous polynomial can be written as a sum of integrable polynomials of the same degree which Lie transformations can be evaluated exactly. By utilizing symplectic integrators, an integrable-polynomial factorization is developed to convert a symplectic map in the form of Dragt-Finn factorization into a product of Lie transformations associated with integrable polynomials. A small number of factorization bases of integrable polynomials enable one to use high order symplectic integrators so that the high-order spurious terms can be greatly suppressed. A symplectic map can thus be evaluated with desired accuracy

  10. Predictors of School Garden Integration: Factors Critical to Gardening Success in New York City.

    Science.gov (United States)

    Burt, Kate Gardner; Burgermaster, Marissa; Jacquez, Raquel

    2018-03-01

    The purpose of this study was to determine the level of integration of school gardens and identify factors that predict integration. 211 New York City schools completed a survey that collected demographic information and utilized the School Garden Integration Scale. A mean garden integration score was calculated, and multiple regression analysis was conducted to determine independent predictors of integration and assess relationships between individual integration characteristics and budget. The average integration score was 34.1 (of 57 points) and ranged from 8 to 53. Operating budget had significant influence on integration score, controlling for all other factors ( p integrated, as budget is a modifiable factor. When adequate funding is secured, a well-integrated garden may be established with proper planning and sound implementation.

  11. Factors controlling nanoparticle pharmacokinetics: an integrated analysis and perspective.

    Science.gov (United States)

    Moghimi, S M; Hunter, A C; Andresen, T L

    2012-01-01

    Intravenously injected nanoparticulate drug carriers provide a wide range of unique opportunities for site-specific targeting of therapeutic agents to many areas within the vasculature and beyond. Pharmacokinetics and biodistribution of these carriers are controlled by a complex array of interrelated core and interfacial physicochemical and biological factors. Pertinent to realizing therapeutic goals, definitive maps that establish the interdependency of nanoparticle size, shape, and surface characteristics in relation to interfacial forces, biodistribution, controlled drug release, excretion, and adverse effects must be outlined. These concepts are critically evaluated and an integrated perspective is provided on the basis of the recent application of nanoscience approaches to nanocarrier design and engineering. The future of this exciting field is bright; some regulatory-approved products are already on the market and many are in late-phase clinical trials. With concomitant advances in extensive computational knowledge of the genomics and epigenomics of interindividual variations in drug responses, the boundaries toward development of personalized nanomedicines can be pushed further.

  12. Simultaneous Identification of Potential Pathogenicity Factors of Mycoplasma agalactiae in the Natural Ovine Host by Negative Selection.

    Science.gov (United States)

    Hegde, Shivanand; Hegde, Shrilakshmi; Zimmermann, Martina; Flöck, Martina; Spergser, Joachim; Rosengarten, Renate; Chopra-Dewasthaly, Rohini

    2015-07-01

    Mycoplasmas possess complex pathogenicity determinants that are largely unknown at the molecular level. Mycoplasma agalactiae serves as a useful model to study the molecular basis of mycoplasma pathogenicity. The generation and in vivo screening of a transposon mutant library of M. agalactiae were employed to unravel its host colonization factors. Tn4001mod mutants were sequenced using a novel sequencing method, and functionally heterogeneous pools containing 15 to 19 selected mutants were screened simultaneously through two successive cycles of sheep intramammary infections. A PCR-based negative selection method was employed to identify mutants that failed to colonize the udders and draining lymph nodes in the animals. A total of 14 different mutants found to be absent from ≥ 95% of samples were identified and subsequently verified via a second round of stringent confirmatory screening where 100% absence was considered attenuation. Using this criterion, seven mutants with insertions in genes MAG1050, MAG2540, MAG3390, uhpT, eutD, adhT, and MAG4460 were not recovered from any of the infected animals. Among the attenuated mutants, many contain disruptions in hypothetical genes, implying their previously unknown role in M. agalactiae pathogenicity. These data indicate the putative role of functionally different genes, including hypothetical ones, in the pathogenesis of M. agalactiae. Defining the precise functions of the identified genes is anticipated to increase our understanding of M. agalactiae infections and to develop successful intervention strategies against it. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Manipulation of host factors optimizes the pathogenesis of western equine encephalitis virus infections in mice for antiviral drug development

    Science.gov (United States)

    Blakely, Pennelope K.; Delekta, Phillip C.; Miller, David J.; Irani, David N.

    2014-01-01

    While alphaviruses spread naturally via mosquito vectors, some can also be transmitted as aerosols making them potential bioterrorism agents. One such pathogen, western equine encephalitis virus (WEEV), causes fatal human encephalitis via multiple routes of infection and thus presumably via multiple mechanisms. Although WEEV also produces acute encephalitis in non-human primates, a small animal model that recapitulates features of human disease would be useful for both pathogenesis studies and to evaluate candidate antiviral therapies. We have optimized conditions to infect mice with a low passage isolate of WEEV, thereby allowing detailed investigation of virus tropism, replication, neuroinvasion, and neurovirulence. We find that host factors strongly influence disease outcome, and in particular that age, gender and genetic background all have significant effects on disease susceptibility independent of virus tropism or replication within the central nervous system. Our data show that experimental variables can be adjusted in mice to recapitulate disease features known to occur in both non-human primates and humans, thus aiding further study of WEEV pathogenesis and providing a realistic therapeutic window for antiviral drug delivery. PMID:25361697

  14. Host-defense and trefoil factor family peptides in skin secretions of the Mawa clawed frog Xenopus boumbaensis (Pipidae).

    Science.gov (United States)

    Conlon, J Michael; Mechkarska, Milena; Kolodziejek, Jolanta; Leprince, Jérôme; Coquet, Laurent; Jouenne, Thierry; Vaudry, Hubert; Nowotny, Norbert; King, Jay D

    2015-10-01

    Peptidomic analysis of norepinephrine-stimulated skin secretions from the octoploid Mawa clawed frog Xenopus boumbaensis Loumont, 1983 led to the identification and characterization of 15 host-defense peptides belonging to the magainin (two peptides), peptide glycine-leucine-amide (PGLa; three peptides), xenopsin precursor fragment (XPF; three peptides), caerulein precursor fragment (CPF; two peptides), and caerulein precursor fragment-related peptide (CPF-RP; five peptides) families. In addition, caerulein and three peptides with structural similarity to the trefoil factor family (TFF) peptides, xP2 and xP4 from Xenopus laevis were also present in the secretions. Consistent with data from comparisons of the nucleotides sequence of mitochondrial and nuclear genes, the primary structures of the peptides suggest a close phylogenetic relationship between X. boumbaensis and the octoploid frogs Xenopus amieti and Xenopus andrei. As the three species occupy disjunct ranges within Cameroon, it is suggested that they diverged from a common ancestor by allopatric speciation. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of studies conducted in an endemic area of Brazil

    Directory of Open Access Journals (Sweden)

    Léa Cristina Castellucci

    2014-06-01

    Full Text Available American cutaneous leishmaniasis (ACL is a vector-transmitted infectious disease with an estimated 1.5 million new cases per year. In Brazil, ACL represents a significant public health problem, with approximately 30,000 new reported cases annually, representing an incidence of 18.5 cases per 100,000 inhabitants. Corte de Pedra is in a region endemic for ACL in the state of Bahia (BA, northeastern Brazil, with 500-1,300 patients treated annually. Over the last decade, population and family-based candidate gene studies were conducted in Corte de Pedra, founded on previous knowledge from studies on mice and humans. Notwithstanding limitations related to sample size and power, these studies contribute important genetic biomarkers that identify novel pathways of disease pathogenesis and possible new therapeutic targets. The present paper is a narrative review about ACL immunogenetics in BA, highlighting in particular the interacting roles of the wound healing gene FLI1 with interleukin-6 and genes SMAD2 and SMAD3 of the transforming growth factor beta signalling pathway. This research highlights the need for well-powered genetic and functional studies on Leishmania braziliensis infection as essential to define and validate the role of host genes in determining resistance/susceptibility regarding this disease.

  16. Improvement of macrophage dysfunction by administration of anti-transforming growth factor-beta antibody in EL4-bearing hosts.

    Science.gov (United States)

    Maeda, H; Tsuru, S; Shiraishi, A

    1994-11-01

    An experimental therapy for improvement of macrophage dysfunction caused by transforming growth factor-beta (TGF-beta) was tried in EL4 tumor-bearing mice. TGF-beta was detected in cell-free ascitic fluid from EL4-bearers, but not in that from normal mice, by western blot analysis. The ascites also showed growth-suppressive activity against Mv1Lu cells, and the suppressive activity was potentiated by transient acidification. To investigate whether the functions of peritoneal macrophages were suppressed in EL4-bearers, the abilities to produce nitric oxide and tumor necrosis factor-alpha (TNF-alpha) upon lipopolysaccharide (LPS) stimulation were measured. Both abilities of macrophages in EL4-bearing mice were suppressed remarkably on day 9, and decreased further by day 14, compared with non-tumor-bearing controls. TGF-beta activity was abrogated by administration of anti-TGF-beta antibody to EL4-bearing mice. While a large amount of TGF-beta was detected in ascitic fluid from control EL4-bearers, little TGF-beta was detectable in ascites from EL4-bearers given anti-TGF-beta antibody. Furthermore, while control macrophages exhibited little or no production of nitric oxide and TNF-alpha on LPS stimulation in vitro, macrophages from EL4-bearers administered with anti-TGF-beta antibody showed the same ability as normal macrophages. These results clearly indicate that TGF-beta contributes to macrophage dysfunction and that the administration of specific antibody for TGF-beta reverses macrophage dysfunction in EL4-bearing hosts.

  17. Anticoagulant factor V: factors affecting the integration of novel scientific discoveries into the broader framework.

    Science.gov (United States)

    LaBonte, Michelle L

    2014-09-01

    Since its initial discovery in the 1940s, factor V has long been viewed as an important procoagulant protein in the coagulation cascade. However, in the later part of the 20th century, two different scientists proposed novel anticoagulant roles for factor V. Philip Majerus proposed the first anticoagulant function for factor V in 1983, yet ultimately it was not widely accepted by the broader scientific community. In contrast, Björn Dahlbäck proposed a different anticoagulant role for factor V in 1994. While this role was initially contested, it was ultimately accepted and integrated into the scientific framework. In this paper, I present a detailed historical account of these two anticoagulant discoveries and propose three key reasons why Dahlbäck's anticoagulant role for factor V was accepted whereas Majerus' proposed role was largely overlooked. Perhaps most importantly, Dahlbäck's proposed anticoagulant role was of great clinical interest because the discovery involved the study of an important subset of patients with thrombophilia. Soon after Dahlbäck's 1994 work, this patient population was shown to possess the factor V Leiden mutation. Also key in the ultimate acceptance of the second proposed anticoagulant role was the persistence of the scientist who made the discovery and the interest in and ability of others to replicate and reinforce this work. This analysis of two different yet similar discoveries sheds light on factors that play an important role in how new discoveries are incorporated into the existing scientific framework. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  18. Integrating high-content imaging and chemical genetics to probe host cellular pathways critical for Yersinia pestis infection.

    Directory of Open Access Journals (Sweden)

    Krishna P Kota

    Full Text Available The molecular machinery that regulates the entry and survival of Yersinia pestis in host macrophages is poorly understood. Here, we report the development of automated high-content imaging assays to quantitate the internalization of virulent Y. pestis CO92 by macrophages and the subsequent activation of host NF-κB. Implementation of these assays in a focused chemical screen identified kinase inhibitors that inhibited both of these processes. Rac-2-ethoxy-3 octadecanamido-1-propylphosphocholine (a protein Kinase C inhibitor, wortmannin (a PI3K inhibitor, and parthenolide (an IκB kinase inhibitor, inhibited pathogen-induced NF-κB activation and reduced bacterial entry and survival within macrophages. Parthenolide inhibited NF-κB activation in response to stimulation with Pam3CSK4 (a TLR2 agonist, E. coli LPS (a TLR4 agonist or Y. pestis infection, while the PI3K and PKC inhibitors were selective only for Y. pestis infection. Together, our results suggest that phagocytosis is the major stimulus for NF-κB activation in response to Y. pestis infection, and that Y. pestis entry into macrophages may involve the participation of protein kinases such as PI3K and PKC. More importantly, the automated image-based screening platform described here can be applied to the study of other bacteria in general and, in combination with chemical genetic screening, can be used to identify host cell functions facilitating the identification of novel antibacterial therapeutics.

  19. Suppressor T-cell factor(s) display an altered pattern of Igh (immunoglobulin heavy chain locus) genetic restriction when developed in an Igh-congeneic host

    International Nuclear Information System (INIS)

    HayGlass, K.T.; Naides, S.J.; Benacerraf, B.; Sy, M.S.

    1985-01-01

    Suppressor T cell factor(s) (TsF 1 ) inhibit the in vivo priming of azobenzenearsonate-specific cytotoxic T-cell responses. The activity of TsF 1 is restricted by genes linked to Igh-1 allotypic markers. TsF 1 obtained from B6.Igh-1/sup n/ mice was unable to suppress the immune response in B6.Igh-1/sup b/ mice and vice versa. However, TsF 1 prepared from B6.Igh-1/sup n/ T cells parked in an Igh-congeneic B6.Igh-1/sup b/ environment displays an additional restriction specificity of the host. Thus, TsF 1 prepared from these Igh-chimeric mice suppressed immune responses in both B6.Igh-1/sup n/ (donor) and B6.Igh-1/sup b/ (recipient) mice but not in mice of the unrelated strain BALB/c.Igh-1/sup a/. The results indicate that the establishment of the suppressor T-cell repertoire is dependent not only upon the genetic background of the individual T cell but also upon the influence of Igh-linked determinants present when T-cell clones are selected during the response

  20. Transplantation of germ cells from glial cell line-derived neurotrophic factor-overexpressing mice to host testes depleted of endogenous spermatogenesis by fractionated irradiation

    NARCIS (Netherlands)

    Creemers, L. B.; Meng, X.; den Ouden, K.; van Pelt, A. M. M.; Izadyar, F.; Santoro, M.; Sariola, H.; de rooij, D. G.

    2002-01-01

    With a novel method of eliminating spermatogenesis in host animals, male germ cells isolated from mice with targeted overexpression of glial cell line-derived neurotrophic factor (GDNF) were transplanted to evaluate their ability to reproduce the phenotype previously found in the transgenic animals.

  1. Coxsackievirus mutants that can bypass host factor PI4KIIIbeta and the need for high levels of PI4P lipids for replication

    NARCIS (Netherlands)

    van der Schaar, H.M.; van der Linden, L.; Lanke, K.H.W.; Strating, J.R.P.M.; Purstinger, G.; Vries, E. De; de Haan, C.A.; Neyts, J.; Kuppeveld, F.J.M. van

    2012-01-01

    RNA viruses can rapidly mutate and acquire resistance to drugs that directly target viral enzymes, which poses serious problems in a clinical context. Therefore, there is a growing interest in the development of antiviral drugs that target host factors critical for viral replication, since they are

  2. On the importance of macroeconomic factors for the foreign student’s decision to stay in the host country

    DEFF Research Database (Denmark)

    Vasiljeva, Kristine

    The paper tests empirically whether the macroeconomic variables suggested by migration theories have a significant impact on the foreign student’s decision to stay in their host country. The analysis is based on the combination of country level variables and individual register data. The mean...... labour income difference between the home and the host countries significantly negatively affects the student’s probability of staying in the host country. The differences in the unemployment rates, welfare benefits, business cycles do not affect the probability of staying. The more hierarchical society...

  3. Myxoma virus M064 is a novel member of the poxvirus C7L superfamily of host range factors that controls the kinetics of myxomatosis in European rabbits.

    Science.gov (United States)

    Liu, Jia; Wennier, Sonia; Moussatche, Nissin; Reinhard, Mary; Condit, Richard; McFadden, Grant

    2012-05-01

    The myxoma virus (MYXV) carries three tandem C7L-like host range genes (M062R, M063R, and M064R). However, despite the fact that the sequences of these three genes are similar, they possess very distinctive functions in vivo. The role of M064 in MYXV pathogenesis was investigated and compared to the roles of M062 and M063. We report that M064 is a virulence factor that contributes to MYXV pathogenesis but lacks the host range properties associated with M062 and M063.

  4. The case of a city where 1 in 6 residents is a refugee: ecological factors and host community adaptation in successful resettlement.

    Science.gov (United States)

    Smith, R Scott

    2008-12-01

    The notable success of an upstate New York community in resettling refugees raises the question of whether multiple waves of resettlement over a 15-year period have resulted in greater accommodation to refugees. Structured interviews based on transactional models of acculturation were used along with archival data to explore ecological factors supporting a host community's behavioral flexibility and perseverance in response to the influx of refugees. Evidence suggests that socioeconomic climate, historical background/social norms, and the organizational structure of agencies involved in resettlement moderate successful inclusion of refugees into a host community in a bidirectional process.

  5. A Novel, Broad-Spectrum Inhibitor of Enterovirus Replication That Targets Host Cell Factor Phosphatidylinositol 4-Kinase IIIβ

    Science.gov (United States)

    van der Schaar, Hilde M.; Leyssen, Pieter; Thibaut, Hendrik J.; de Palma, Armando; van der Linden, Lonneke; Lanke, Kjerstin H. W.; Lacroix, Céline; Verbeken, Erik; Conrath, Katja; MacLeod, Angus M.; Mitchell, Dale R.; Palmer, Nicholas J.; van de Poël, Hervé; Andrews, Martin

    2013-01-01

    Despite their high clinical and socioeconomic impacts, there is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections. Here we report on a novel inhibitor of enterovirus replication, compound 1, 2-fluoro-4-(2-methyl-8-(3-(methylsulfonyl)benzylamino)imidazo[1,2-a]pyrazin-3-yl)phenol. This compound exhibited a broad spectrum of antiviral activity, as it inhibited all tested species of enteroviruses and rhinoviruses, with 50% effective concentrations ranging between 4 and 71 nM. After a lengthy resistance selection process, coxsackievirus mutants resistant to compound 1 were isolated that carried substitutions in their 3A protein. Remarkably, the same substitutions were recently shown to provide resistance to inhibitors of phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ), a lipid kinase that is essential for enterovirus replication, suggesting that compound 1 may also target this host factor. Accordingly, compound 1 directly inhibited PI4KIIIβ in an in vitro kinase activity assay. Furthermore, the compound strongly reduced the PI 4-phosphate levels of the Golgi complex in cells. Rescue of coxsackievirus replication in the presence of compound 1 by a mutant PI4KIIIβ carrying a substitution in its ATP-binding pocket revealed that the compound directly binds the kinase at this site. Finally, we determined that an analogue of compound 1, 3-(3-fluoro-4-methoxyphenyl)-2-methyl-N-(pyridin-4-ylmethyl)imidazo[1,2-a]pyrazin-8-amine, is well tolerated in mice and has a dose-dependent protective activity in a coxsackievirus serotype B4-induced pancreatitis model. PMID:23896472

  6. Air Force Host and Tenant Agreements Between the 50th Space Wing, the Joint National Integration Center, and Tenants

    National Research Council Canada - National Science Library

    2007-01-01

    .... The 50th Space Wing makes available by permit two buildings on the base's real property records, 720 and 730, to the Joint National Integration Center, a Component of the Missile Defense Agency...

  7. Global genetic differentiation in a cosmopolitan pest of stored beans: effects of geography, host-plant usage and anthropogenic factors.

    Science.gov (United States)

    Tuda, Midori; Kagoshima, Kumiko; Toquenaga, Yukihiko; Arnqvist, Göran

    2014-01-01

    Genetic differentiation can be promoted allopatrically by geographic isolation of populations due to limited dispersal ability and diversification over time or sympatrically through, for example, host-race formation. In crop pests, the trading of crops across the world can lead to intermixing of genetically distinct pest populations. However, our understanding of the importance of allopatric and sympatric genetic differentiation in the face of anthropogenic genetic intermixing is limited. Here, we examined global sequence variation in two mitochondrial and one nuclear genes in the seed beetle Callosobruchus maculatus that uses different legumes as hosts. We analyzed 180 samples from 42 populations of this stored bean pest from tropical and subtropical continents and archipelagos: Africa, the Middle East, South and Southeast Asia, Oceania and South America. For the mitochondrial genes, there was weak but significant genetic differentiation across continents/archipelagos. Further, we found pronounced differentiation among subregions within continents/archipelagos both globally and within Africa but not within Asia. We suggest that multiple introductions into Asia and subsequent intermixing within Asia have generated this pattern. The isolation by distance hypothesis was supported globally (with or without continents controlled) but not when host species was restricted to cowpeas Vigna unguiculata, the ancestral host of C. maculatus. We also document significant among-host differentiation both globally and within Asia, but not within Africa. We failed to reject a scenario of a constant population size in the recent past combined with selective neutrality for the mitochondrial genes. We conclude that mitochondrial DNA differentiation is primarily due to geographic isolation within Africa and to multiple invasions by different alleles, followed by host shifts, within Asia. The weak inter-continental differentiation is most likely due to frequent inter-continental gene

  8. Host factors that interact with the pestivirus N-terminal protease, Npro, are components of the ribonucleoprotein complex.

    Science.gov (United States)

    Jefferson, Matthew; Donaszi-Ivanov, Andras; Pollen, Sean; Dalmay, Tamas; Saalbach, Gerhard; Powell, Penny P

    2014-09-01

    The viral N-terminal protease N(pro) of pestiviruses counteracts cellular antiviral defenses through inhibition of IRF3. Here we used mass spectrometry to identify a new role for N(pro) through its interaction with over 55 associated proteins, mainly ribosomal proteins and ribonucleoproteins, including RNA helicase A (DHX9), Y-box binding protein (YBX1), DDX3, DDX5, eIF3, IGF2BP1, multiple myeloma tumor protein 2, interleukin enhancer binding factor 3 (IEBP3), guanine nucleotide binding protein 3, and polyadenylate-binding protein 1 (PABP-1). These are components of the translation machinery, ribonucleoprotein particles (RNPs), and stress granules. Significantly, we found that stress granule formation was inhibited in MDBK cells infected with a noncytopathic bovine viral diarrhea virus (BVDV) strain, Kyle. However, ribonucleoproteins binding to N(pro) did not inhibit these proteins from aggregating into stress granules. N(pro) interacted with YBX1 though its TRASH domain, since the mutant C112R protein with an inactive TRASH domain no longer redistributed to stress granules. Interestingly, RNA helicase A and La autoantigen relocated from a nuclear location to form cytoplasmic granules with N(pro). To address a proviral role for N(pro) in RNP granules, we investigated whether N(pro) affected RNA interference (RNAi), since interacting proteins are involved in RISC function during RNA silencing. Using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) silencing with small interfering RNAs (siRNAs) followed by Northern blotting of GAPDH, expression of N(pro) had no effect on RNAi silencing activity, contrasting with other viral suppressors of interferon. We propose that N(pro) is involved with virus RNA translation in the cytoplasm for virus particle production, and when translation is inhibited following stress, it redistributes to the replication complex. Although the pestivirus N-terminal protease, N(pro), has been shown to have an important role in degrading IRF3 to

  9. The Factors Influencing Young Children's Social Interaction in Technology Integration

    Science.gov (United States)

    Lim, Eun Mee

    2015-01-01

    When technology integration is accomplished successfully in early childhood education settings, children tend to interact more with one another and exchange information related to computer tasks as well as the overall classroom on-going curriculum themes. Therefore, to explore how young children are interacting in computer areas when using…

  10. Intraspecific variation in host susceptibility and climatic factors mediate epidemics of sudden oak death in western US forests

    Science.gov (United States)

    D. Huberli; K.J. Hayden; M. Calver; M. Garbelotto

    2011-01-01

    Umbellularia californica is one of the key infectious hosts of the exotic Phytophthora ramorum, which causes sudden oak death (SOD) in California and Oregon forests. This study provides a comprehensive analysis of the epidemiologically relevant parameters for SOD in California and southern Oregon, including potential differences between the two...

  11. Cell-mediated immunity to histocompatibility antigens : controlling factors, with emphasis on Graft-versus-host reactions in mice

    NARCIS (Netherlands)

    H. Bril (Herman)

    1984-01-01

    textabstractGraft-versus-Host (GvH) disease is characterized by weight loss, diarrhea, skin lesions, hypofunction of the immune system with concomitant infections, etc. This syndrome is potentially lethal. GvH reactions, which underly this disease, may occur when immunocompetent T lymphocytes are

  12. Interaction of CSFV E2 protein with swine host factors as detected by yeast two-hybrid system.

    Directory of Open Access Journals (Sweden)

    Douglas P Gladue

    Full Text Available E2 is one of the envelope glycoproteins of pestiviruses, including classical swine fever virus (CSFV and bovine viral diarrhea virus (BVDV. E2 is involved in several critical functions, including virus entry into target cells, induction of a protective immune response and virulence in swine. However, there is no information regarding any host binding partners for the E2 proteins. Here, we utilized the yeast two-hybrid system and identified fifty-seven host proteins as positive binding partners which bound E2 from both CSFV and BVDV with the exception of two proteins that were found to be positive for binding only to CSFV E2. Alanine scanning of CSFV E2 demonstrated that the binding sites for these cellular proteins on E2 are likely non-linear binding sites. The possible roles of the identified host proteins are discussed as the results presented here will be important for future studies to elucidate mechanisms of host protein-virus interactions during pestivirus infection. However, due to the limitations of the yeast two hybrid system, the proteins identified is not exhaustive and each interaction identified needs to be confirmed by independent experimental approaches in the context of virus-infected cells before any definitive conclusion can be drawn on relevance for the virus life cycle.

  13. New host, geographical records, and factors affecting the prevalence of helminths infection from synanthropic rodents in Yucatán, Mexico

    OpenAIRE

    Panti-May J. A.; Palomo-Arjona E.; Gurubel-González Y.; Torres-Castro M. A.; Vidal-Martínez V. M.; Machain-Williams C.; Hernández-Betancourt S. F.; Del Rosario Robles M.

    2017-01-01

    The aim of this paper was to study the occurrence of helminths in Mus musculus and Rattus rattus from urban, suburban and rural settlements in Yucatán, Mexico; and to analyse the host factors (e.g. sex) related to helminths’ distribution. Helminths in a total of 279 rodents were surveyed by visual examination of the liver for metacestodes and faecal examination for helminth eggs using the formalin-ethyl acetate sedimentation technique. The cestodes Hydatigera taeniaeformis (metacestodes detec...

  14. Host Factors Influencing the Retrohoming Pathway of Group II Intron RmInt1, Which Has an Intron-Encoded Protein Naturally Devoid of Endonuclease Activity.

    Directory of Open Access Journals (Sweden)

    Rafael Nisa-Martínez

    Full Text Available Bacterial group II introns are self-splicing catalytic RNAs and mobile retroelements that have an open reading frame encoding an intron-encoded protein (IEP with reverse transcriptase (RT and RNA splicing or maturase activity. Some IEPs carry a DNA endonuclease (En domain, which is required to cleave the bottom strand downstream from the intron-insertion site for target DNA-primed reverse transcription (TPRT of the inserted intron RNA. Host factors complete the insertion of the intron. By contrast, the major retrohoming pathway of introns with IEPs naturally lacking endonuclease activity, like the Sinorhizobium meliloti intron RmInt1, is thought to involve insertion of the intron RNA into the template for lagging strand DNA synthesis ahead of the replication fork, with possible use of the nascent strand to prime reverse transcription of the intron RNA. The host factors influencing the retrohoming pathway of such introns have not yet been described. Here, we identify key candidates likely to be involved in early and late steps of RmInt1 retrohoming. Some of these host factors are common to En+ group II intron retrohoming, but some have different functions. Our results also suggest that the retrohoming process of RmInt1 may be less dependent on the intracellular free Mg2+ concentration than those of other group II introns.

  15. Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors

    OpenAIRE

    Hauser, Kurt F.; Knapp, Pamela E.

    2014-01-01

    Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome (neuroAIDS) and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individua...

  16. Factors that influence the acceptance of integrated community energy systems

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, A. S.; Tschanz, J. F.; Mosena, D.; Erley, D.; Gil, E.; Slovak, P.; Lenth, C. S.

    1977-01-01

    This report is part of a series of studies designed to analyze the commercialization potential of various concepts of community-scale energy systems that have been termed Integrated Community Energy Systems (ICES). The study reported here concerns ways that affected individuals and organizations will respond to proposed ICES development projects. The intent is an initial examination of several institutional sectors that will: (1) anticipate responses that could impede ICES proposals and (2) provide an information base from which strategies to address adverse responses can be formulated.

  17. A conserved helicase processivity factor is needed for conjugation and replication of an integrative and conjugative element.

    Directory of Open Access Journals (Sweden)

    Jacob Thomas

    Full Text Available Integrative and conjugative elements (ICEs are agents of horizontal gene transfer and have major roles in evolution and acquisition of new traits, including antibiotic resistances. ICEs are found integrated in a host chromosome and can excise and transfer to recipient bacteria via conjugation. Conjugation involves nicking of the ICE origin of transfer (oriT by the ICE-encoded relaxase and transfer of the nicked single strand of ICE DNA. For ICEBs1 of Bacillus subtilis, nicking of oriT by the ICEBs1 relaxase NicK also initiates rolling circle replication. This autonomous replication of ICEBs1 is critical for stability of the excised element in growing cells. We found a conserved and previously uncharacterized ICE gene that is required for conjugation and replication of ICEBs1. Our results indicate that this gene, helP (formerly ydcP, encodes a helicase processivity factor that enables the host-encoded helicase PcrA to unwind the double-stranded ICEBs1 DNA. HelP was required for both conjugation and replication of ICEBs1, and HelP and NicK were the only ICEBs1 proteins needed for replication from ICEBs1 oriT. Using chromatin immunoprecipitation, we measured association of HelP, NicK, PcrA, and the host-encoded single-strand DNA binding protein Ssb with ICEBs1. We found that NicK was required for association of HelP and PcrA with ICEBs1 DNA. HelP was required for association of PcrA and Ssb with ICEBs1 regions distal, but not proximal, to oriT, indicating that PcrA needs HelP to progress beyond nicked oriT and unwind ICEBs1. In vitro, HelP directly stimulated the helicase activity of the PcrA homologue UvrD. Our findings demonstrate that HelP is a helicase processivity factor needed for efficient unwinding of ICEBs1 for conjugation and replication. Homologues of HelP and PcrA-type helicases are encoded on many known and putative ICEs. We propose that these factors are essential for ICE conjugation, replication, and genetic stability.

  18. Surgical Technology Integration with Tools for Cognitive Human Factors (STITCH)

    Science.gov (United States)

    2010-10-01

    Measurement Tool We conducted another round of data collection using the daVinci Surgical System at the University of Kentucky Hospital in May. In this...9 3. Tools and Display Technology...considering cognitive and environmental factors such as mental workload, stress, situation awareness, and level of comfort with complex tools . To

  19. Positive semidefinite integrated covariance estimation, factorizations and asynchronicity

    DEFF Research Database (Denmark)

    Boudt, Kris; Laurent, Sébastien; Lunde, Asger

    2017-01-01

    An estimator of the ex-post covariation of log-prices under asynchronicity and microstructure noise is proposed. It uses the Cholesky factorization of the covariance matrix in order to exploit the heterogeneity in trading intensities to estimate the different parameters sequentially with as many...

  20. Positive Semidefinite Integrated Covariance Estimation, Factorizations and Asynchronicity

    DEFF Research Database (Denmark)

    Boudt, Kris; Laurent, Sébastien; Lunde, Asger

    An estimator of the ex-post covariation of log-prices under asynchronicity and microstructure noise is proposed. It uses the Cholesky factorization on the correlation matrix in order to exploit the heterogeneity in trading intensity to estimate the different parameters sequentially with as many...

  1. Distribution of intermediate host snails of schistosomiasis and fascioliasis in relation to environmental factors during the dry season in the Tchologo region, Côte d'Ivoire

    Science.gov (United States)

    Krauth, Stefanie J.; Wandel, Nathalie; Traoré, Seïdinan I.; Vounatsou, Penelope; Hattendorf, Jan; Achi, Louise Y.; McNeill, Kristopher; N'Goran, Eliézer K.; Utzinger, Jürg

    2017-10-01

    Snail-borne trematodiases, such as fascioliasis and schistosomiasis, belong to the neglected tropical diseases; yet, millions of people and livestock are affected. The spatial and temporal distribution of intermediate host snails plays an important role in the epidemiology and control of trematodiases. Snail distribution is influenced by numerous environmental and anthropomorphic factors. The aim of this study was to assess the distribution and constitution of the snail fauna during the dry season in constructed and natural water bodies in the Tchologo region, northern Côte d'Ivoire, and to relate these findings to environmental factors and human infections. Snails were collected using standard procedures and environmental parameters were assessed from a total of 50 water bodies in and around 30 randomly selected villages. A canonical correspondence analysis was performed to establish the relationship between snail occurrence and environmental factors. Furthermore, a total of 743 people from the same 30 villages and nearby settlements were invited for stool and urine examination for the diagnosis of Fasciola spp., Schistosoma haematobium and Schistosoma mansoni. Snails of medical importance of the genera Biomphalaria, Bulinus, Lymnaea and Physa were found. Differences in snail occurrence from sites sampled in December 2014 and snails sampled in February 2015, as well as between the northern and southern part of the study area, were revealed. Various environmental factors, such as temperature and human activities, were related to the occurrence of intermediate host snail species in the region. Only 2.3% of human participants tested positive for schistosomiasis, while no Fasciola eggs were found in stool samples. We conclude that intermediate host snails of Fasciola and Schistosoma co-occur in water bodies in the Tchologo region and that the distribution of these snails correlates not only with environmental factors, but also with the presence of humans and animals

  2. Risk factors associated with mental health issues in adolescents: a integrative review

    Directory of Open Access Journals (Sweden)

    Agnes Caroline Souza Pinto

    2014-06-01

    Full Text Available Objective: To identify the risk factors associated with mental health issues in adolescents. Method: An integrative review was conducted in four databases with publications from 2007 to 2013. The terms Adolescent and Mental Health were used to search adequate articles as DeCs/MeSH bases. Results: Publications were found in different journals in different fields of knowledge and the quantitative research was the most frequent. The mental health issues were categorized as individual factors; drug related factors, school factors, family factors, social factors and STDs/Aids related factors. The most addressed category was individual factors, with 23 publications. Conclusion: The integrative review allowed to point important questions to be addressed in preventive actions by the health professional, including the nurse, to create a space that works with risk conditioning factors in adolescents for mental health aggravation.

  3. Initial Gut Microbial Composition as a Key Factor Driving Host Response to Antibiotic Treatment, as Exemplified by the Presence or Absence of Commensal Escherichia coli.

    Science.gov (United States)

    Ju, Tingting; Shoblak, Yasmeen; Gao, Yanhua; Yang, Kaiyuan; Fouhse, Janelle; Finlay, B Brett; So, Yee Wing; Stothard, Paul; Willing, Benjamin P

    2017-09-01

    Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3β (Reg3β) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3β and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies. IMPORTANCE This work provides an understanding of variability in studies where

  4. An Integrated View of the Effects of Wine Polyphenols and Their Relevant Metabolites on Gut and Host Health

    Directory of Open Access Journals (Sweden)

    Carolina Cueva

    2017-01-01

    Full Text Available Over the last few decades, polyphenols, and flavonoids in particular, have attracted the interest of researchers, as they have been associated with the health-promoting effects derived from diets rich in vegetables and fruits, including moderate wine consumption. Recent scientific evidence suggests that wine polyphenols exert their effects through interactions with the gut microbiota, as they seem to modulate microbiota and, at the same time, are metabolized by intestinal bacteria into specific bioavailable metabolites. Microbial metabolites are better absorbed than their precursors and may be responsible for positive health activities in the digestive system (local effects and, after being absorbed, in tissues and organs (systemic effects. Differences in gut microbiota composition and functionality among individuals can affect polyphenol activity and, therefore, their health effects. The aim of this review is to integrate the understanding of the metabolism and mechanisms of action of wine polyphenols at both local and systemic levels, underlining their impact on the gut microbiome and the inter-individual variability associated with polyphenols’ metabolism and further physiological effects. The advent of promising dietary approaches linked to wine polyphenols beyond the gut microbiota community and metabolism are also discussed.

  5. Volume integral equation for electromagnetic scattering: Rigorous derivation and analysis for a set of multilayered particles with piecewise-smooth boundaries in a passive host medium

    Science.gov (United States)

    Yurkin, Maxim A.; Mishchenko, Michael I.

    2018-04-01

    We present a general derivation of the frequency-domain volume integral equation (VIE) for the electric field inside a nonmagnetic scattering object from the differential Maxwell equations, transmission boundary conditions, radiation condition at infinity, and locally-finite-energy condition. The derivation applies to an arbitrary spatially finite group of particles made of isotropic materials and embedded in a passive host medium, including those with edges, corners, and intersecting internal interfaces. This is a substantially more general type of scatterer than in all previous derivations. We explicitly treat the strong singularity of the integral kernel, but keep the entire discussion accessible to the applied scattering community. We also consider the known results on the existence and uniqueness of VIE solution and conjecture a general sufficient condition for that. Finally, we discuss an alternative way of deriving the VIE for an arbitrary object by means of a continuous transformation of the everywhere smooth refractive-index function into a discontinuous one. Overall, the paper examines and pushes forward the state-of-the-art understanding of various analytical aspects of the VIE.

  6. Spatial and Temporal Epidemiology of Nephropathia Epidemica Incidence and Hantavirus Seroprevalence in Rodent Hosts: Identification of the Main Environmental Factors in Europe.

    Science.gov (United States)

    Monchatre-Leroy, E; Crespin, L; Boué, F; Marianneau, P; Calavas, D; Hénaux, V

    2017-08-01

    In Europe, the increasing number of nephropathia epidemica (NE) infections in humans, caused by Puumala virus carried by bank voles (Myodes glareolus), has triggered studies of environmental factors driving these infections. NE infections have been shown to occur in specific geographical areas characterized by environmental factors that influence the distribution and dynamics of host populations and virus persistence in the soil. Here, we review the influence of environmental conditions (including climate factors, food availability and habitat conditions) with respect to incidence in humans and seroprevalence in rodents, considering both direct and indirect transmission pathways. For each type of environmental factor, results and discrepancies between studies are presented and examined in the light of biological hypotheses. Overall, food availability and temperature appear to be the main drivers of host seroprevalence and NE incidence, but data quality and statistical approaches varied greatly among studies. We highlight the issues that now need to be addressed and suggest improvements for study design in regard to the current knowledge on hantavirus epidemiology. © 2016 Blackwell Verlag GmbH.

  7. Factorization, reduction and embedding in integrable cellular automata

    International Nuclear Information System (INIS)

    Kuniba, Atsuo; Takagi, Taichiro; Takenouchi, Akira

    2004-01-01

    Factorized dynamics in soliton cellular automata with quantum group symmetry is identified with a motion of particles and anti-particles exhibiting pair creation and annihilation. An embedding scheme is presented showing that the D (1) n -automaton contains, as certain subsectors, the box-ball systems and all the other automata associated with the crystal bases of non-exceptional affine Lie algebras. The results extend the earlier ones to higher representations by a certain reduction and to a wider class of boundary conditions

  8. Integrals of random fields treated by the model correction factor method

    DEFF Research Database (Denmark)

    Franchin, P.; Ditlevsen, Ove Dalager; Kiureghian, Armen Der

    2002-01-01

    The model correction factor method (MCFM) is used in conjunction with the first-order reliability method (FORM) to solve structural reliability problems involving integrals of non-Gaussian random fields. The approach replaces the limit-state function with an idealized one, in which the integrals ...

  9. Model correction factor method for reliability problems involving integrals of non-Gaussian random fields

    DEFF Research Database (Denmark)

    Franchin, P.; Ditlevsen, Ove Dalager; Kiureghian, Armen Der

    2002-01-01

    The model correction factor method (MCFM) is used in conjunction with the first-order reliability method (FORM) to solve structural reliability problems involving integrals of non-Gaussian random fields. The approach replaces the limit-state function with an idealized one, in which the integrals ...

  10. Extending "the Rubber Rope": Convergent Series, Divergent Series and the Integrating Factor

    Science.gov (United States)

    McCartney, Mark

    2013-01-01

    A well-known mathematical puzzle regarding a worm crawling along an elastic rope is considered. The resulting generalizations provide examples for use in a teaching context including applications of series summation, the use of the integrating factor for the solution of differential equations, and the evaluation of definite integrals. A number of…

  11. Factors Influencing the Integration of Technology by Community College Adjunct Faculty

    Science.gov (United States)

    Paver, Jonathan David

    2012-01-01

    This research examined the factors that predict intention to integrate technology into instruction by community college adjunct faculty. For this study the integration of technology was defined as beyond simple occasional use, within the next academic year. The decomposed theory of planned behavior was tested for its predictive ability with this…

  12. Design and management of production systems: Integration of human factors and ergonomics

    DEFF Research Database (Denmark)

    Jensen, Per Langå; Broberg, Ole; Hasle, Peter

    2006-01-01

    Integration of ergonomics, human factors and occupational health and safety into design and management of pro-duction systems has for years been the major strategy for professional within the field. The traditional approach based on establishing ergonomic criteria’s to be integrated into other...

  13. Host phylogeny determines viral persistence and replication in novel hosts.

    Directory of Open Access Journals (Sweden)

    Ben Longdon

    2011-09-01

    Full Text Available Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

  14. Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

    Science.gov (United States)

    Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

    2011-01-01

    Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

  15. Hα Intensity Map of the Repeating Fast Radio Burst FRB 121102 Host Galaxy from Subaru/Kyoto 3DII AO-assisted Optical Integral-field Spectroscopy

    Science.gov (United States)

    Kokubo, Mitsuru; Mitsuda, Kazuma; Sugai, Hajime; Ozaki, Shinobu; Minowa, Yosuke; Hattori, Takashi; Hayano, Yutaka; Matsubayashi, Kazuya; Shimono, Atsushi; Sako, Shigeyuki; Doi, Mamoru

    2017-08-01

    We present the Hα intensity map of the host galaxy of the repeating fast radio burst FRB 121102 at a redshift of z = 0.193 obtained with the AO-assisted Kyoto 3DII optical integral-field unit mounted on the 8.2 m Subaru Telescope. We detected a compact Hα-emitting (I.e., star-forming) region in the galaxy, which has a much smaller angular size (GMOS z\\prime -band image (≃ 1\\buildrel{\\prime\\prime}\\over{.} 4 (4.6 kpc) at FWHM with ellipticity b/a=0.45). The spatial offset between the centroid of the Hα emission region and the position of the radio bursts is 0\\buildrel{\\prime\\prime}\\over{.} 08+/- 0\\buildrel{\\prime\\prime}\\over{.} 02 (0.26 ± 0.07 kpc), indicating that FRB 121102 is located within the star-forming region. This close spatial association of FRB 121102 with the star-forming region is consistent with expectations from young pulsar/magnetar models for FRB 121102, and it also suggests that the observed Hα emission region can make a major dispersion measure (DM) contribution to the host galaxy DM component of FRB 121102. Nevertheless, the largest possible value of the DM contribution from the Hα emission region inferred from our observations still requires a significant amount of ionized baryons in intergalactic medium (IGM; the so-called “missing” baryons) as the DM source of FRB 121102, and we obtain a 90% confidence level lower limit on the cosmic baryon density in the IGM in the low-redshift universe as {{{Ω }}}{IGM}> 0.012. Based on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan.

  16. Loss of elongation factor P disrupts bacterial outer membrane integrity

    DEFF Research Database (Denmark)

    Zou, S Betty; Hersch, Steven J; Roy, Hervé

    2012-01-01

    background ameliorates the detergent, antibiotic, and osmosensitivity phenotypes and restores wild-type permeability to NPN. Our data support a role for EF-P in the translational regulation of a limited number of proteins that, when perturbed, renders the cell susceptible to stress by the adventitious......Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established the importance of this modification in Salmonella stress resistance. Here we report that, like poxA and yjeK mutants......, Salmonella strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, and detergents and enhanced resistance to the compound S-nitrosoglutathione. The susceptibility phenotypes are largely explained by the enhanced membrane permeability of the efp mutant, which exhibits...

  17. Factors influencing groundwater quality: towards an integrated management approach.

    Science.gov (United States)

    De Giglio, O; Quaranta, A; Barbuti, G; Napoli, C; Caggiano, G; Montagna, M T

    2015-01-01

    The safety of groundwater resources is a serious issue, particularly when these resources are the main source of water for drinking, irrigation and industrial use in coastal areas. In Italy, 85% of the water used by the public is of underground origin. The aim of this report is to analyze the main factors that make groundwater vulnerable. Soil characteristics and filtration capacity can promote or hinder the diffusion of environmental contaminants. Global climate change influences the prevalence and degree of groundwater contamination. Anthropic pressure causes considerable exploitation of water resources, leading to reduced water availability and the progressive deterioration of water quality. Management of water quality will require a multidisciplinary, dynamic and practical approach focused on identifying the measures necessary to reduce contamination and mitigate the risks associated with the use of contaminated water resources.

  18. Factors Controlling Nanoparticle Pharmacokinetics: An Integrated Analysis and Perspective

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moien; Hunter, A.C.; Andresen, T.L.

    2012-01-01

    of interrelated core and interfacial physicochemical and biological factors. Pertinent to realizing therapeutic goals, definitive maps that establish the interdependency of nanoparticle size, shape, and surface characteristics in relation to interfacial forces, biodistribution, controlled drug release, excretion......Intravenously injected nanoparticulate drug carriers provide a wide range of unique opportunities for site-specific targeting of therapeutic agents to many areas within the vasculature and beyond. Pharmacokinetics and biodistribution of these carriers are controlled by a complex array...... are already on the market and many are in late-phase clinical trials. With concomitant advances in extensive computational knowledge of the genomics and epigenomics of interindividual variations in drug responses, the boundaries toward development of personalized nanomedicines can be pushed further....

  19. Survival and evolution of a large multidrug resistance plasmid in new clinical bacterial hosts

    DEFF Research Database (Denmark)

    Porse, Andreas; Schønning, Kristian; Munck, Christian

    2016-01-01

    sequencing to show that the long-term persistence and molecular integrity of the plasmid is highly influenced by multiple factors within a 25 kb plasmid region constituting a host-dependent burden. In the E. coli hosts investigated here, improved plasmid stability readily evolves via IS26 mediated deletions...... consistently followed by all evolved E. coli lineages exposes a trade-off between horizontal and vertical transmission that may ultimately limit the dissemination potential of clinical multidrug resistance plasmids in these hosts....

  20. Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut.

    Directory of Open Access Journals (Sweden)

    Vincent Raquin

    2017-12-01

    Full Text Available Dengue virus (DENV causes more human infections than any other mosquito-borne virus. The current lack of antiviral strategies has prompted genome-wide screens for host genes that are required for DENV infectivity. Earlier transcriptomic studies that identified DENV host factors in the primary vector Aedes aegypti used inbred laboratory colonies and/or pools of mosquitoes that erase individual variation. Here, we performed transcriptome sequencing on individual midguts in a field-derived Ae. aegypti population to identify new candidate host factors modulating DENV replication. We analyzed the transcriptomic data using an approach that accounts for individual co-variation between viral RNA load and gene expression. This approach generates a prediction about the agonist or antagonist effect of candidate genes on DENV replication based on the sign of the correlation between gene expression and viral RNA load. Using this method, we identified 39 candidate genes that went undetected by conventional pairwise comparison of gene expression levels between DENV-infected midguts and uninfected controls. Only four candidate genes were detected by both methods, emphasizing their complementarity. We demonstrated the value of our approach by functional validation of a candidate agonist gene encoding a sterol regulatory element-binding protein (SREBP, which was identified by correlation analysis but not by pairwise comparison. We confirmed that SREBP promotes DENV infection in the midgut by RNAi-mediated gene knockdown in vivo. We suggest that our approach for transcriptomic analysis can empower genome-wide screens for potential agonist or antagonist factors by leveraging inter-individual variation in gene expression. More generally, this method is applicable to a wide range of phenotypic traits displaying inter-individual variation.

  1. Phenological patterns of Spodoptera Guenée, 1852 (Lepidoptera: Noctuidae) is more affected by ENSO than seasonal factors and host plant availability in a Brazilian Savanna

    Science.gov (United States)

    Piovesan, Mônica; Specht, Alexandre; Carneiro, Eduardo; Paula-Moraes, Silvana Vieira; Casagrande, Mirna Martins

    2018-03-01

    The identification of factors responsible for the population dynamics is fundamental for pest management, since losses can reach 18% of annual production. Besides regular seasonal environmental factors and crop managements, additional supra-annual meteorological phenomena can also affect population dynamics, although its relevance has been rarely investigated. Among crop pests, Spodoptera stands out due to its worldwide distribution, high degree of polyphagy, thus causing damages in several crops in the world. Aiming to distinguish the relevance of different factors shaping population dynamics of Spodoptera in an ecosystem constituted of dry and rainy seasons, the current study used circular statistics to identify phenological patterns and test if its population fluctuation is driven by El Niño-Southern Oscillation (ENSO) effect, seasonal meteorological parameters, and/or host plant availability. Samplings were done in an intercropping system, in the Brazilian Savanna, during the new moon cycles between July/2013 and June/2016. Species were recorded all year round, but demonstrated differently non-uniform distribution, being concentrated in different seasons of the year. Population fluctuations were mostly affected by the ENSO intensity, despite the contrasting seasonal meteorological variation or host plant availability in a 400-m radius. Studies involving the observation of supra-annual phenomena, although rare, reach similar conclusions in relation to Neotropical insect fauna. Therefore, it is paramount to have long-term sampling studies to obtain a more precise response of the pest populations towards the agroecosystem conditions.

  2. Angiogenic Type I Collagen Extracellular Matrix Integrated with Recombinant Bacteriophages Displaying Vascular Endothelial Growth Factors.

    Science.gov (United States)

    Yoon, Junghyo; Korkmaz Zirpel, Nuriye; Park, Hyun-Ji; Han, Sewoon; Hwang, Kyung Hoon; Shin, Jisoo; Cho, Seung-Woo; Nam, Chang-Hoon; Chung, Seok

    2016-01-21

    Here, a growth-factor-integrated natural extracellular matrix of type I collagen is presented that induces angiogenesis. The developed matrix adapts type I collagen nanofibers integrated with synthetic colloidal particles of recombinant bacteriophages that display vascular endothelial growth factor (VEGF). The integration is achieved during or after gelation of the type I collagen and the matrix enables spatial delivery of VEGF into a desired region. Endothelial cells that contact the VEGF are found to invade into the matrix to form tube-like structures both in vitro and in vivo, proving the angiogenic potential of the matrix. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Factor analysis of geochemical data from ore and host rocks of the uranium mineralization at Mika, N. E. Nigeria

    International Nuclear Information System (INIS)

    Funtua, I. I.

    1997-01-01

    The Mika uranium occurrence is located in one of a series of NW-NE trending shear zones which host uraniferous Jurassic rhyolitic dykes located in Pan-African brecciated granites within peraluminous granite complex of NE Nigeria. The bodies of mineralization are about 100 metres long and up to 4 metres thick. The U mineralization associated with the rhyolite dykes contains predominantly meta-autunite and apatite, while that of the brecciated granites displays variable mineralogy with meta-autunite, one or two generations of coffinite and colloformic, pitch blend in open veins. The mineralization is thought to be related to bimodel magmatism of the Burashika group and the reactivation of regional structures. Multivariate statistical evaluation of geochemical data of 28 elements/oxides in 296 host rock and mineralized samples from the surface and drill cores display a coherent association of [(U, Pb, Zn, Cu, P 2 O 5 , Fe 2 O 3 ) + Mo], [(CaO, Zr, Sr) +(Y, Mo, V, As)] and [(MgO, K 2 O) + (TiO 2 , Rb)] in the mineralized rocks; reflecting the presence of hamatized phosphate bearing ores in association with sulphide minerals and apatite in the granite rhyolites. A link of the mineralizing fluids with the emplacement of the rhyolites is implied from the striking resemblance between the above element association in mineralized rocks to those of the unmineralized rhyolites. A source of ore fluids over saturated in uranium and silica emanating from crystallizing rhyolitic melts which were expelled into faults and/or shear zones in the surrounding country rock is inferred

  4. Relevant Factors in The Post-Merger Systems Integration and Information Technology in Brazilian Banks

    Directory of Open Access Journals (Sweden)

    Marcel Ginotti Pires

    2017-01-01

    Full Text Available This article discusses the factors present in post-merger integration of Systems and Information Technology (SIT that lead to positive and negative results in mergers and acquisitions (M & A. The research comprised three of the largest acquiring banks in Brazil. We adopted two methods of research, qualitative, to operationalize the theoretical concepts and quantitative, to test the hypotheses. We interviewed six executives of banks that held relevant experience in M & A processes. Subsequently, we applied questionnaires to IT professionals who were involved in the SIT integration processes. The results showed that the quality and expertise of the integration teams and managing the integration were the most relevant factors in the processes, with positive results for increased efficiency and the increased capacity of SIT. Negative results were due to failures in exploiting learning opportunities, the loss of employees and the inexpressive record of integration procedures.

  5. Ranking of integration factors within supply chains of forward and backward types - recommendations from researches

    Directory of Open Access Journals (Sweden)

    Bernd Hentschel

    2015-06-01

    Full Text Available Background: Integration trends are one of main determinants of the development of modern logistics. After the period of interest focused mainly on supply chains realizing one-way flows only, at present there is a time for supply chains characterized by two-way flows, realizing at the same time both forward and backward flows. The possibility of various configurations of such chains requires identification of integration factors and determination of their influence on the results of the whole supply chain. Experiences of the science as well as the practice of supply chains show the urgent need of learning of reasons of the integration within supply chains of the two-way type.  Material and methods: The researches on modeling and simulation of integration processes within supply chains of forward and backward type were carried out in the environment of iGrafx Process 2013 for Six Sigma. The empirical material obtained in these researches was put to the statistical analysis by the used of Minitab 17. The identification of the significance of differences was made with the help of analysis of variance ANOVA. Additionally the analysis of differences in form of absolute averages was made.  The following measures are main ones for the evaluation of the integration of a supply chain of forward and backward types: cashflow, profitability, service level.  Results: 8 192 simulation experiments were made for 6 integration factors: accessibility of recycled materials, production planning, stock management, integration of transport, unification of packing materials and optimization of the material flow. Based on the analysis of the significance and values of differences, the results of the influence of each integration factor on global results of supply chains of forward and backward type were obtained. They were used to prepare the ranking of integration factors. The main factors, forming the integration shape of two-way supply chains were: stock

  6. The Potential Role of Recombinant Hematopoietic Colony-Stimulating Factors in Preventing Infections in the Immunocompromised Host

    Directory of Open Access Journals (Sweden)

    James Rusthoven

    1991-01-01

    Full Text Available Hematopoietic colony-stimulating factors coordinate the proliferation and maturation of bone marrow and peripheral blood cells during normal hematopoiesis. Most of these factors are now available as recombinant human colony-stimulating factors, and preclinical and clinical testing is proceeding rapidly. Granulocyte and granulocyte/macrophage colony-stimulating factors have been the most extensively studied to date. In human clinical trials, granulocyte colony-stimulating factor improves neutrophil counts and function, reduces episodes of febrile neutropenia, improves neutrophil recovery after disease- or treatment-induced myelosuppression, and reduces the number of serious infections in several neutropenic disease states. Granulocyte/macrophage colony-stimulating factor has similar biological properties but may also improve eosinophil proliferation and function, and platelet cell recovery after myelotoxic bone marrow injury, Interleukin-1 boosts the effects of granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor, but also may promote the resolution of established infections in conjunction with antibiotics. The therapeutic realities and future therapeutic implications of these agents for the therapy of infections, cancer and hemopoietic disorders are discussed.

  7. Pediatric spinal epidural abscess in an immunocompetent host without risk factors: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Alessandra Vergori

    2015-01-01

    The rarity and the possible differential diagnosis can lead to underestimate SEA occurrence in children without risk factors. It seems therefore essential to maintain a high attention to pediatric SEAs. A prompt diagnosis and adequate therapy are essential prognostic factors for remission.

  8. Form factors in quantum integrable models with GL(3)-invariant R-matrix

    Energy Technology Data Exchange (ETDEWEB)

    Pakuliak, S., E-mail: pakuliak@theor.jinr.ru [Laboratory of Theoretical Physics, JINR, 141980 Dubna, Moscow Reg. (Russian Federation); Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Moscow Reg. (Russian Federation); Institute of Theoretical and Experimental Physics, 117259 Moscow (Russian Federation); Ragoucy, E., E-mail: eric.ragoucy@lapth.cnrs.fr [Laboratoire de Physique Théorique LAPTH, CNRS and Université de Savoie, BP 110, 74941 Annecy-le-Vieux Cedex (France); Slavnov, N.A., E-mail: nslavnov@mi.ras.ru [Steklov Mathematical Institute, Moscow (Russian Federation)

    2014-04-15

    We study integrable models solvable by the nested algebraic Bethe ansatz and possessing GL(3)-invariant R-matrix. We obtain determinant representations for form factors of off-diagonal entries of the monodromy matrix. These representations can be used for the calculation of form factors and correlation functions of the XXX SU(3)-invariant Heisenberg chain.

  9. An Investigation of Relationships between Internal and External Factors Affecting Technology Integration in Classrooms

    Science.gov (United States)

    Hur, Jung Won; Shannon, David; Wolf, Sara

    2016-01-01

    Various factors affecting technology integration have been identified, but little research has examined the relationships between factors, especially internal and external ones, and whether they directly or indirectly influenced each other. To fill this research gap, this study examined the significance and relationships of five factors…

  10. Heartland virus NSs protein disrupts host defenses by blocking the TBK1 kinase-IRF3 transcription factor interaction and signaling required for interferon induction.

    Science.gov (United States)

    Ning, Yun-Jia; Feng, Kuan; Min, Yuan-Qin; Deng, Fei; Hu, Zhihong; Wang, Hualin

    2017-10-06

    Heartland virus (HRTV) is a pathogenic phlebovirus related to the severe fever with thrombocytopenia syndrome virus (SFTSV), another phlebovirus causing life-threatening disease in humans. Previous findings have suggested that SFTSV can antagonize the host interferon (IFN) system via viral nonstructural protein (NSs)-mediated sequestration of antiviral signaling proteins into NSs-induced inclusion bodies. However, whether and how HRTV counteracts the host innate immunity is unknown. Here, we report that HRTV NSs (HNSs) also antagonizes IFN and cytokine induction and bolsters viral replication, although no noticeable inclusion body formation was observed in HNSs-expressing cells. Furthermore, HNSs inhibited the virus-triggered activation of IFN-β promoter by specifically targeting the IFN-stimulated response element but not the NF-κB response element. Consistently, HNSs blocked the phosphorylation and nuclear translocation of IFN regulatory factor 3 (IRF3, an IFN-stimulated response element-activating transcription factor). Reporter gene assays next showed that HNSs blockades the antiviral signaling mediated by RIG-I-like receptors likely at the level of TANK-binding kinase 1 (TBK1). Indeed, HNSs strongly interacts with TBK1 as indicated by confocal microscopy and pulldown analyses, and we also noted that the scaffold dimerization domain of TBK1 is required for the TBK1-HNSs interaction. Finally, pulldown assays demonstrated that HNSs expression dose-dependently diminishes a TBK1-IRF3 interaction, further explaining the mechanism for HNSs function. Collectively, these data suggest that HNSs, an antagonist of host innate immunity, interacts with TBK1 and thereby hinders the association of TBK1 with its substrate IRF3, thus blocking IRF3 activation and transcriptional induction of the cellular antiviral responses. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. C7L family of poxvirus host range genes inhibits antiviral activities induced by type I interferons and interferon regulatory factor 1.

    Science.gov (United States)

    Meng, Xiangzhi; Schoggins, John; Rose, Lloyd; Cao, Jingxin; Ploss, Alexander; Rice, Charles M; Xiang, Yan

    2012-04-01

    Vaccinia virus (VACV) K1L and C7L function equivalently in many mammalian cells to support VACV replication and antagonize antiviral activities induced by type I interferons (IFNs). While K1L is limited to orthopoxviruses, genes that are homologous to C7L are found in diverse mammalian poxviruses. In this study, we showed that the C7L homologues from sheeppox virus and swinepox virus could rescue the replication defect of a VACV mutant deleted of both K1L and C7L (vK1L(-)C7L(-)). Interestingly, the sheeppox virus C7L homologue could rescue the replication of vK1L(-)C7L(-) in human HeLa cells but not in murine 3T3 and LA-4 cells, in contrast to all other C7L homologues. Replacing amino acids 134 and 135 of the sheeppox virus C7L homologue, however, made it functional in the two murine cell lines, suggesting that these two residues are critical for antagonizing a putative host restriction factor which has some subtle sequence variation in human and murine cells. Furthermore, the C7L family of host range genes from diverse mammalian poxviruses were all capable of antagonizing type I IFN-induced antiviral activities against VACV. Screening of a library of more than 350 IFN-stimulated genes (ISGs) identified interferon-regulated factor 1 (IRF1) as an inhibitor of vK1L(-)C7L(-) but not wild-type VACV. Expression of either K1L or C7L, however, rendered vK1L(-)C7L(-) resistant to IRF1-induced antiviral activities. Altogether, our data show that K1L and C7L antagonize IRF1-induced antiviral activities and that the host modulation function of C7L is evolutionally conserved in all poxviruses that can readily replicate in tissue-cultured mammalian cells.

  12. Host transcription factor Speckled 110 kDa (Sp110), a nuclear body protein, is hijacked by hepatitis B virus protein X for viral persistence.

    Science.gov (United States)

    Sengupta, Isha; Das, Dipanwita; Singh, Shivaram Prasad; Chakravarty, Runu; Das, Chandrima

    2017-12-15

    Promyelocytic leukemia nuclear bodies (PML-NB) are sub-nuclear organelles that are the hub of numerous proteins. DNA/RNA viruses often hijack the cellular factors resident in PML-NBs to promote their proliferation in host cells. Hepatitis B virus (HBV), belonging to Hepadnaviridae family, remains undetected in early infection as it does not induce the innate immune response and is known to be the cause of several hepatic diseases leading to cirrhosis and hepatocellular carcinoma. The association of PML-NB proteins and HBV is being addressed in a number of recent studies. Here, we report that the PML-NB protein Speckled 110 kDa (Sp110) is SUMO1-modified and undergoes a deSUMOylation-driven release from the PML-NB in the presence of HBV. Intriguingly, Sp110 knockdown significantly reduced viral DNA load in the culture supernatant by activation of the type I interferon-response pathway. Furthermore, we found that Sp110 differentially regulates several direct target genes of hepatitis B virus protein X (HBx), a viral co-factor. Subsequently, we identified Sp110 as a novel interactor of HBx and found this association to be essential for the exit of Sp110 from the PML-NB during HBV infection and HBx recruitment on the promoter of these genes. HBx, in turn, modulates the recruitment of its associated transcription cofactors p300/HDAC1 to these co-regulated genes, thereby altering the host gene expression program in favor of viral persistence. Thus, we report a mechanism by which HBV can evade host immune response by hijacking the PML-NB protein Sp110, and therefore, we propose it to be a novel target for antiviral therapy. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Market and organizational factors associated with hospital vertical integration into sub-acute care.

    Science.gov (United States)

    Hogan, Tory H; Lemak, Christy Harris; Hearld, Larry R; Sen, Bisakha P; Wheeler, Jack R C; Menachemi, Nir

    2018-04-11

    Changes in payment models incentivize hospitals to vertically integrate into sub-acute care (SAC) services. Through vertical integration into SAC, hospitals have the potential to reduce the transaction costs associated with moving patients throughout the care continuum and reduce the likelihood that patients will be readmitted. The purpose of this study is to examine the correlates of hospital vertical integration into SAC. Using panel data of U.S. acute care hospitals (2008-2012), we conducted logit regression models to examine environmental and organizational factors associated with hospital vertical integration. Results are reported as average marginal effects. Among 3,775 unique hospitals (16,269 hospital-year observations), 25.7% vertically integrated into skilled nursing facilities during at least 1 year of the study period. One measure of complexity, the availability of skilled nursing facilities in a county (ME = -1.780, p integration into SAC. Measures of munificence, percentage of the county population eligible for Medicare (ME = 0.018, p integration into SAC. Dynamism, when measured as the change county population between 2008 and 2011 (ME = 1.19e-06, p integration into SAC. Organizational resources, when measured as swing beds (ME = 0.069, p integration into SAC. Organizational resources, when measured as investor owned (ME = -0.052, p integration into SAC. Hospital adaption to the changing health care landscape through vertical integration varies across market and organizational conditions. Current Centers for Medicare and Medicaid reimbursement programs do not take these factors into consideration. Vertical integration strategy into SAC may be more appropriate under certain market conditions. Hospital leaders may consider how to best align their organization's SAC strategy with their operating environment.

  14. Deterministic factor analysis: methods of integro-differentiation of non-integral order

    Directory of Open Access Journals (Sweden)

    Valentina V. Tarasova

    2016-12-01

    Full Text Available Objective to summarize the methods of deterministic factor economic analysis namely the differential calculus and the integral method. nbsp Methods mathematical methods for integrodifferentiation of nonintegral order the theory of derivatives and integrals of fractional nonintegral order. Results the basic concepts are formulated and the new methods are developed that take into account the memory and nonlocality effects in the quantitative description of the influence of individual factors on the change in the effective economic indicator. Two methods are proposed for integrodifferentiation of nonintegral order for the deterministic factor analysis of economic processes with memory and nonlocality. It is shown that the method of integrodifferentiation of nonintegral order can give more accurate results compared with standard methods method of differentiation using the first order derivatives and the integral method using the integration of the first order for a wide class of functions describing effective economic indicators. Scientific novelty the new methods of deterministic factor analysis are proposed the method of differential calculus of nonintegral order and the integral method of nonintegral order. Practical significance the basic concepts and formulas of the article can be used in scientific and analytical activity for factor analysis of economic processes. The proposed method for integrodifferentiation of nonintegral order extends the capabilities of the determined factorial economic analysis. The new quantitative method of deterministic factor analysis may become the beginning of quantitative studies of economic agents behavior with memory hereditarity and spatial nonlocality. The proposed methods of deterministic factor analysis can be used in the study of economic processes which follow the exponential law in which the indicators endogenous variables are power functions of the factors exogenous variables including the processes

  15. All-MXene-Based Integrated Electrode Constructed by Ti3C2 Nanoribbon Framework Host and Nanosheet Interlayer for High-Energy-Density Li-S Batteries.

    Science.gov (United States)

    Dong, Yanfeng; Zheng, Shuanghao; Qin, Jieqiong; Zhao, Xuejun; Shi, Haodong; Wang, Xiaohui; Chen, Jian; Wu, Zhong-Shuai

    2018-03-27

    High-energy-density lithium-sulfur (Li-S) batteries hold promise for next-generation portable electronic devices, but are facing great challenges in rational construction of high-performance flexible electrodes and innovative cell configurations for actual applications. Here we demonstrated an all-MXene-based flexible and integrated sulfur cathode, enabled by three-dimensional alkalized Ti 3 C 2 MXene nanoribbon (a-Ti 3 C 2 MNR) frameworks as a S/polysulfides host (a-Ti 3 C 2 -S) and two-dimensional delaminated Ti 3 C 2 MXene (d-Ti 3 C 2 ) nanosheets as interlayer on a polypropylene (PP) separator, for high-energy and long-cycle Li-S batteries. Notably, an a-Ti 3 C 2 MNR framework with open interconnected macropores and an exposed surface area guarantees high S loading and fast ionic diffusion for prompt lithiation/delithiation kinetics, and the 2D d-Ti 3 C 2 MXene interlayer remarkably prevents the shuttle effect of lithium polysulfides via both chemical absorption and physical blocking. As a result, the integrated a-Ti 3 C 2 -S/d-Ti 3 C 2 /PP electrode was directly used for Li-S batteries, without the requirement of a metal current collector, and exhibited a high reversible capacity of 1062 mAh g -1 at 0.2 C and enhanced capacity of 632 mAh g -1 after 50 cycles at 0.5 C, outperforming the a-Ti 3 C 2 -S/PP electrode (547 mAh g -1 ) and conventional a-Ti 3 C 2 -S on an Al current collector (a-Ti 3 C 2 -S/Al) (597 mAh g -1 ). Furthermore, the all-MXene-based integrated cathode displayed outstanding rate capacity of 288 mAh g -1 at 10 C and long-life cyclability. Therefore, this proposed strategy of constructing an all-MXene-based cathode can be readily extended to assemble a large number of MXene-derived materials, from a group of 60+ MAX phases, for applications such as various batteries and supercapacitors.

  16. Low rank factorization of the Coulomb integrals for periodic coupled cluster theory.

    Science.gov (United States)

    Hummel, Felix; Tsatsoulis, Theodoros; Grüneis, Andreas

    2017-03-28

    We study a tensor hypercontraction decomposition of the Coulomb integrals of periodic systems where the integrals are factorized into a contraction of six matrices of which only two are distinct. We find that the Coulomb integrals can be well approximated in this form already with small matrices compared to the number of real space grid points. The cost of computing the matrices scales as O(N 4 ) using a regularized form of the alternating least squares algorithm. The studied factorization of the Coulomb integrals can be exploited to reduce the scaling of the computational cost of expensive tensor contractions appearing in the amplitude equations of coupled cluster methods with respect to system size. We apply the developed methodologies to calculate the adsorption energy of a single water molecule on a hexagonal boron nitride monolayer in a plane wave basis set and periodic boundary conditions.

  17. Host state screening process: Regional management plan: [Final report

    International Nuclear Information System (INIS)

    Drobny, N.L.

    1986-01-01

    This report discusses the procedure and cirteria that the Commission selected for designating a host state, should a state not volunteer for this role. Section 2 describes the wide range of approaches considered. Advantages and disadvantages of each are reviewed briefly, and the overall timetable established by the Commission for host state selection is presented. Section 3 describes the selected process for host state designation which involves emphasis on waste quantities generated and transportation factors. Section 4 presents relevant data on characteristics of wastes presently generated and presents estimates for future waste generation to Year 2015. Section 5 presents the results of transportation analyses considering the distance over which waste would be transported and safety (accident) statistics for waste transport routes. Section 6 integrates the conclusions from the analysis of waste volumes generated and transportation factors and suggests how these results might be used to designate a host state. 11 refs., 6 figs., 9 tabs

  18. INTER, ENDF/B Thermal Cross-Sections, Resonance Integrals, G-Factors Calculation

    International Nuclear Information System (INIS)

    Dunford, Charles L.

    2007-01-01

    1 - Description of program or function: INTER calculates thermal cross sections, g-factors, resonance integrals, fission spectrum averaged cross sections and 14.0 MeV (or other energy) cross sections for major reactions in an ENDF-6 or ENDF-5 format data file. Version 7.01 (Jan 2005): set success flag after return from beginning. 2 - Method of solution: INTER performs integrations by using the trapezoidal rule

  19. Same host, same lagoon, different transmission pathways: effects of exogenous factors on larval emergence in two marine digenean parasites

    Czech Academy of Sciences Publication Activity Database

    Born-Torrijos, A.; Raga, J. A.; Holzer, Astrid S.; Kostadinova, Aneta

    2014-01-01

    Roč. 113, č. 2 (2014), s. 545-554 ISSN 0932-0113 R&D Projects: GA ČR GAP505/10/1562 Institutional support: RVO:60077344 Keywords : patterns * water * life-cycles Subject RIV: EH - Ecology, Behaviour Impact factor: 2.098, year: 2014

  20. Yip1A, a Novel Host Factor for the Activation of the IRE1 Pathway of the Unfolded Protein Response during Brucella Infection

    Science.gov (United States)

    Taguchi, Yuki; Imaoka, Koichi; Kataoka, Michiyo; Uda, Akihiko; Nakatsu, Daiki; Horii-Okazaki, Sakuya; Kunishige, Rina; Kano, Fumi; Murata, Masayuki

    2015-01-01

    Brucella species replicate within host cells in the form of endoplasmic reticulum (ER)-derived vacuoles. The mechanisms by which the bacteria are sequestered into such vacuoles and obtain a continuous membrane supply for their replication remain to be elucidated. In the present study, we provided several lines of evidence that demonstrate the mechanism by which B. abortus acquires the ER-derived membrane. First, during Brucella infection, the IRE1 pathway, but not the PERK and ATF6 pathways, of the unfolded protein response (UPR) was activated in a time-dependent manner, and the COPII vesicle components Sar1, Sec23, and Sec24D were upregulated. Second, a marked accretion of ER-derived vacuoles was observed around replicating bacteria using fluorescent microscopy and electron microscopy. Third, we identified a novel host factor, Yip1A, for the activation of the IRE1 pathway in response to both tunicamycin treatment and infection with B. abortus. We found that Yip1A is responsible for the phosphorylation of IRE1 through high-order assembly of Ire1 molecules at ER exit sites (ERES) under the UPR conditions. In Yip1A-knockdown cells, B. abortus failed to generate the ER-derived vacuoles, and remained in endosomal/lysosomal compartments. These results indicate that the activation of the IRE1 pathway and the subsequent formation of ER-derived vacuoles are critical for B. abortus to establish a safe replication niche, and that Yip1A is indispensable for these processes. Furthermore, we showed that the autophagy-related proteins Atg9 and WIPI1, but not DFCP1, were required for the biogenesis of the ER-derived membrane compartments.  On the basis of our findings, we propose a model for intracellular Brucella replication that exploits the host UPR and ER-derived vacuole formation machineries, both of which depend on Yip1A-mediated IRE1 activation. PMID:25742138

  1. Genesis of diamond inclusions: An integrated cathodoluminescence (CL) and Electron backscatter diffraction (EBSD) study on eclogitic and peridotitic inclusions and their diamond host.

    Science.gov (United States)

    van den Heuvel, Quint; Matveev, Sergei; Drury, Martyn; Gress, Michael; Chinn, Ingrid; Davies, Gareth

    2017-04-01

    Diamond inclusions are potentially fundamental to understanding the formation conditions of diamond and the volatile cycles in the deep mantle. In order to fully understand the implications of the compositional information recorded by inclusions it is vital to know whether the inclusions are proto-, syn-, or epigenetic and the extent to which they have equilibrated with diamond forming fluids. In previous studies, the widespread assumption was made that the majority of diamond inclusions are syngenetic, based upon observation of cubo-octahedral morphology imposed on the inclusions. Recent work has reported the crystallographic relationship between inclusions and the host diamond to be highly complex and the lack of crystallographic relationships between inclusions and diamonds has led some to question the significance of imposed cubo-octahedral morphology. This study presents an integrated EBSD and CL study of 9 diamonds containing 20 pyropes, 2 diopsides, 1 forsterite and 1 rutile from the Jwaneng and Letlhakane kimberlite clusters, Botswana. A new method was developed to analyze the crystallographic orientation of the host diamond and the inclusions with EBSD. Diamonds plates were sequentially polished to expose inclusions at different levels in the diamond. CL imaging at different depths was performed in order to produce a 3D view of diamond growth zones around the inclusions. Standard diamond polishing techniques proved too aggressive for silicate inclusions as they were damaged to such a degree that EBSD measurements on the inclusions were impossible. The inclusions were milled with a Ga+ focused ion beam (FIB) at a 12° angle to clean the surface for EBSD measurements. Of the 24 inclusions, 9 have an imposed cubo-octahedral morphology. Of these inclusions, 6 have faces orientated parallel to diamond growth zones and/or appear to have nucleated on a diamond growth surface, implying syngenesis. In contrast, other diamonds record resorption events such that

  2. Design for human factors (DfHF): a grounded theory for integrating human factors into production design processes.

    Science.gov (United States)

    Village, Judy; Searcy, Cory; Salustri, Filipo; Patrick Neumann, W

    2015-01-01

    The 'design for human factors' grounded theory explains 'how' human factors (HF) went from a reactive, after-injury programme in safety, to being proactively integrated into each step of the production design process. In this longitudinal case study collaboration with engineers and HF Specialists in a large electronics manufacturer, qualitative data (e.g. meetings, interviews, observations and reflections) were analysed using a grounded theory methodology. The central tenet in the theory is that when HF Specialists acclimated to the engineering process, language and tools, and strategically aligned HF to the design and business goals of the organisation, HF became a means to improve business performance. This led to engineers 'pulling' HF Specialists onto their team. HF targets were adopted into engineering tools to communicate HF concerns quantitatively, drive continuous improvement, visibly demonstrate change and lead to benchmarking. Senior management held engineers accountable for HF as a key performance indicator, thus integrating HF into the production design process. Practitioner Summary: Research and practice lack explanations about how HF can be integrated early in design of production systems. This three-year case study and the theory derived demonstrate how ergonomists changed their focus to align with design and business goals to integrate HF into the design process.

  3. Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice

    Directory of Open Access Journals (Sweden)

    Allison R. Rogala

    2018-02-01

    Full Text Available Crohn's disease (CD represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M (IRGM is an established risk allele in CD. We have shown previously that conventionally raised (CV mice lacking the IRGM ortholog, Irgm1 exhibit abnormal Paneth cells (PCs and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD. To accomplish this, wild-type and Irgm1−/− mice were rederived into specific pathogen-free (SPF and germ-free (GF conditions. We next assessed how these differential housing environments influenced intestinal injury patterns, and epithelial cell morphology and function in wild-type and Irgm1−/− mice. Remarkably, in contrast to CV mice, SPF Irgm1−/− mice showed only a slight increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF Irgm1−/− mice also displayed minimal abnormalities in PC number and morphology, and in antimicrobial peptide expression. Goblet cell numbers and epithelial proliferation were also unaffected by Irgm1 in SPF conditions. No microbial differences were observed between wild-type and Irgm1−/− mice, but gut bacterial communities differed profoundly between CV and SPF mice. Specifically, Helicobacter sequences were significantly increased in CV mice; however, inoculating SPF Irgm1−/− mice with Helicobacter hepaticus was not sufficient to transmit a pro-inflammatory phenotype. In summary, our findings suggest the impact of Irgm1-deficiency on susceptibility to intestinal inflammation and epithelial function is critically dependent on environmental influences. This work establishes the importance of Irgm1−/− mice as a model to elucidate host

  4. Analytic results for planar three-loop integrals for massive form factors

    Energy Technology Data Exchange (ETDEWEB)

    Henn, Johannes M. [PRISMA Cluster of Excellence, Johannes Gutenberg Universität Mainz,55099 Mainz (Germany); Kavli Institute for Theoretical Physics, UC Santa Barbara,Santa Barbara (United States); Smirnov, Alexander V. [Research Computing Center, Moscow State University,119992 Moscow (Russian Federation); Smirnov, Vladimir A. [Skobeltsyn Institute of Nuclear Physics of Moscow State University,119992 Moscow (Russian Federation); Institut für Theoretische Teilchenphysik, Karlsruhe Institute of Technology (KIT),76128 Karlsruhe (Germany)

    2016-12-28

    We use the method of differential equations to analytically evaluate all planar three-loop Feynman integrals relevant for form factor calculations involving massive particles. Our results for ninety master integrals at general q{sup 2} are expressed in terms of multiple polylogarithms, and results for fiftyone master integrals at the threshold q{sup 2}=4m{sup 2} are expressed in terms of multiple polylogarithms of argument one, with indices equal to zero or to a sixth root of unity.

  5. Integrable dissipative nonlinear second order differential equations via factorizations and Abel equations

    Energy Technology Data Exchange (ETDEWEB)

    Mancas, Stefan C. [Department of Mathematics, Embry–Riddle Aeronautical University, Daytona Beach, FL 32114-3900 (United States); Rosu, Haret C., E-mail: hcr@ipicyt.edu.mx [IPICYT, Instituto Potosino de Investigacion Cientifica y Tecnologica, Apdo Postal 3-74 Tangamanga, 78231 San Luis Potosí, SLP (Mexico)

    2013-09-02

    We emphasize two connections, one well known and another less known, between the dissipative nonlinear second order differential equations and the Abel equations which in their first-kind form have only cubic and quadratic terms. Then, employing an old integrability criterion due to Chiellini, we introduce the corresponding integrable dissipative equations. For illustration, we present the cases of some integrable dissipative Fisher, nonlinear pendulum, and Burgers–Huxley type equations which are obtained in this way and can be of interest in applications. We also show how to obtain Abel solutions directly from the factorization of second order nonlinear equations.

  6. An efficient viral vector for functional genomic studies of Prunus fruit trees and its induced resistance to Plum pox virus via silencing of a host factor gene.

    Science.gov (United States)

    Cui, Hongguang; Wang, Aiming

    2017-03-01

    RNA silencing is a powerful technology for molecular characterization of gene functions in plants. A commonly used approach to the induction of RNA silencing is through genetic transformation. A potent alternative is to use a modified viral vector for virus-induced gene silencing (VIGS) to degrade RNA molecules sharing similar nucleotide sequence. Unfortunately, genomic studies in many allogamous woody perennials such as peach are severely hindered because they have a long juvenile period and are recalcitrant to genetic transformation. Here, we report the development of a viral vector derived from Prunus necrotic ringspot virus (PNRSV), a widespread fruit tree virus that is endemic in all Prunus fruit production countries and regions in the world. We show that the modified PNRSV vector, harbouring the sense-orientated target gene sequence of 100-200 bp in length in genomic RNA3, could efficiently trigger the silencing of a transgene or an endogenous gene in the model plant Nicotiana benthamiana. We further demonstrate that the PNRSV-based vector could be manipulated to silence endogenous genes in peach such as eukaryotic translation initiation factor 4E isoform (eIF(iso)4E), a host factor of many potyviruses including Plum pox virus (PPV). Moreover, the eIF(iso)4E-knocked down peach plants were resistant to PPV. This work opens a potential avenue for the control of virus diseases in perennial trees via viral vector-mediated silencing of host factors, and the PNRSV vector may serve as a powerful molecular tool for functional genomic studies of Prunus fruit trees. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  7. Factores, grupos de riesgo y atención integral a la conducta violenta Factors, risk groups and integral care to violent behavior

    Directory of Open Access Journals (Sweden)

    Anais Marta Valladares González

    2010-09-01

    Full Text Available La violencia es la acción ejercida por una o varias personas, en la que se somete de manera intencional al maltrato, presión, sufrimiento, manipulación u otra acción que atente contra la integridad física, psicológica y moral de cualquier persona o grupo de personas. Los factores de riesgo de la conducta violenta se pueden agrupar en macrosociales, microsociales e individuales. El enfoque integral de intervención hacia la conducta violenta, debe tener en cuenta, no solo los componentes biológicos, psicológicos y sociales, sino también las peculiaridades sociales, grupales e individuales de su determinación.Violence is the action exerted by one or a certain number of persons practicing in an intentional way the ill-treatment, the pressure, suffering, manipulation or another action attempting on physical, psychological or moral integrity of any person of group of persons. The risk factors of violent behavior may be grouped into macrosocial, microsocial and individual. The integral approach of the intervention to violent behavior must to be into account not only the biological, psychological and social components but also the social, group and individual particular features of its determination.

  8. An integrated graphic–taxonomic–associative approach to analyze human factors in aviation accidents

    Directory of Open Access Journals (Sweden)

    Gong Lei

    2014-04-01

    Full Text Available Human factors are critical causes of modern aviation accidents. However, existing accident analysis methods encounter limitations in addressing aviation human factors, especially in complex accident scenarios. The existing graphic approaches are effective for describing accident mechanisms within various categories of human factors, but cannot simultaneously describe inadequate human–aircraft–environment interactions and organizational deficiencies effectively, and highly depend on analysts’ skills and experiences. Moreover, the existing methods do not emphasize latent unsafe factors outside accidents. This paper focuses on the above three limitations and proposes an integrated graphic–taxonomic–associative approach. A new graphic model named accident tree (AcciTree, with a two-mode structure and a reaction-based concept, is developed for accident modeling and safety defense identification. The AcciTree model is then integrated with the well-established human factors analysis and classification system (HFACS to enhance both reliability of the graphic part and logicality of the taxonomic part for improving completeness of analysis. An associative hazard analysis technique is further put forward to extend analysis to factors outside accidents, to form extended safety requirements for proactive accident prevention. Two crash examples, a research flight demonstrator by our team and an industrial unmanned aircraft, illustrate that the integrated approach is effective for identifying more unsafe factors and safety requirements.

  9. Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection.

    Science.gov (United States)

    Zeng, Xiang; Qiu, Xue-Cheng; Ma, Yuan-Huan; Duan, Jing-Jing; Chen, Yuan-Feng; Gu, Huai-Yu; Wang, Jun-Mei; Ling, Eng-Ang; Wu, Jin-Lang; Wu, Wutian; Zeng, Yuan-Shan

    2015-06-01

    Functional deficits following spinal cord injury (SCI) primarily attribute to loss of neural connectivity. We therefore tested if novel tissue engineering approaches could enable neural network repair that facilitates functional recovery after spinal cord transection (SCT). Rat bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress TrkC, receptor of neurotrophin-3 (NT-3), were pre-differentiated into cells carrying neuronal features via co-culture with NT-3 overproducing Schwann cells in 3-dimensional gelatin sponge (GS) scaffold for 14 days in vitro. Intra-GS formation of MSC assemblies emulating neural network (MSC-GS) were verified morphologically via electron microscopy (EM) and functionally by whole-cell patch clamp recording of spontaneous post-synaptic currents. The differentiated MSCs still partially maintained prototypic property with the expression of some mesodermal cytokines. MSC-GS or GS was then grafted acutely into a 2 mm-wide transection gap in the T9-T10 spinal cord segments of adult rats. Eight weeks later, hindlimb function of the MSC-GS-treated SCT rats was significantly improved relative to controls receiving the GS or lesion only as indicated by BBB score. The MSC-GS transplantation also significantly recovered cortical motor evoked potential (CMEP). Histologically, MSC-derived neuron-like cells maintained their synapse-like structures in vivo; they additionally formed similar connections with host neurites (i.e., mostly serotonergic fibers plus a few corticospinal axons; validated by double-labeled immuno-EM). Moreover, motor cortex electrical stimulation triggered c-fos expression in the grafted and lumbar spinal cord cells of the treated rats only. Our data suggest that MSC-derived neuron-like cells resulting from NT-3-TrkC-induced differentiation can partially integrate into transected spinal cord and this strategy should be further investigated for reconstructing disrupted neural circuits. Copyright

  10. Structure factors for tunneling ionization rates of molecules: General Hartree-Fock-based integral representation

    Science.gov (United States)

    Madsen, Lars Bojer; Jensen, Frank; Dnestryan, Andrey I.; Tolstikhin, Oleg I.

    2017-07-01

    In the leading-order approximation of the weak-field asymptotic theory (WFAT), the dependence of the tunneling ionization rate of a molecule in an electric field on its orientation with respect to the field is determined by the structure factor of the ionizing molecular orbital. The WFAT yields an expression for the structure factor in terms of a local property of the orbital in the asymptotic region. However, in general quantum chemistry approaches molecular orbitals are expanded in a Gaussian basis which does not reproduce their asymptotic behavior correctly. This hinders the application of the WFAT to polyatomic molecules, which are attracting increasing interest in strong-field physics. Recently, an integral-equation approach to the WFAT for tunneling ionization of one electron from an arbitrary potential has been developed. The structure factor is expressed in an integral form as a matrix element involving the ionizing orbital. The integral is not sensitive to the asymptotic behavior of the orbital, which resolves the difficulty mentioned above. Here, we extend the integral representation for the structure factor to many-electron systems treated within the Hartree-Fock method and show how it can be implemented on the basis of standard quantum chemistry software packages. We validate the methodology by considering noble-gas atoms and the CO molecule, for which accurate structure factors exist in the literature. We also present benchmark results for CO2 and for NH3 in the pyramidal and planar geometries.

  11. Identification and functional characterization of Rca1, a transcription factor involved in both antifungal susceptibility and host response in Candida albicans.

    Science.gov (United States)

    Vandeputte, Patrick; Pradervand, Sylvain; Ischer, Françoise; Coste, Alix T; Ferrari, Sélène; Harshman, Keith; Sanglard, Dominique

    2012-07-01

    The identification of novel transcription factors associated with antifungal response may allow the discovery of fungus-specific targets for new therapeutic strategies. A collection of 241 Candida albicans transcriptional regulator mutants was screened for altered susceptibility to fluconazole, caspofungin, amphotericin B, and 5-fluorocytosine. Thirteen of these mutants not yet identified in terms of their role in antifungal response were further investigated, and the function of one of them, a mutant of orf19.6102 (RCA1), was characterized by transcriptome analysis. Strand-specific RNA sequencing and phenotypic tests assigned Rca1 as the regulator of hyphal formation through the cyclic AMP/protein kinase A (cAMP/PKA) signaling pathway and the transcription factor Efg1, but also probably through its interaction with a transcriptional repressor, most likely Tup1. The mechanisms responsible for the high level of resistance to caspofungin and fluconazole observed resulting from RCA1 deletion were investigated. From our observations, we propose that caspofungin resistance was the consequence of the deregulation of cell wall gene expression and that fluconazole resistance was linked to the modulation of the cAMP/PKA signaling pathway activity. In conclusion, our large-scale screening of a C. albicans transcription factor mutant collection allowed the identification of new effectors of the response to antifungals. The functional characterization of Rca1 assigned this transcription factor and its downstream targets as promising candidates for the development of new therapeutic strategies, as Rca1 influences host sensing, hyphal development, and antifungal response.

  12. Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Emily F A van 't Wout

    2015-06-01

    Full Text Available Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA. Efficient functioning of the endoplasmic reticulum (ER is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR. Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host.

  13. Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells

    Science.gov (United States)

    van ‘t Wout, Emily F. A.; van Schadewijk, Annemarie; van Boxtel, Ria; Dalton, Lucy E.; Clarke, Hanna J.; Tommassen, Jan; Marciniak, Stefan J.; Hiemstra, Pieter S.

    2015-01-01

    Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA). Efficient functioning of the endoplasmic reticulum (ER) is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to “ER stress” and activation of the “unfolded protein response” (UPR). Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR) which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host. PMID:26083346

  14. Nature of parent rocks, mineralization styles and ore genesis of regolith-hosted REE deposits in South China: An integrated genetic model

    Science.gov (United States)

    Li, Yan Hei Martin; Zhao, Wen Winston; Zhou, Mei-Fu

    2017-10-01

    -illuviation dynamics is the main mechanism for REE accumulation in weathering crusts. Favorable exogenetic factors facilitate the accumulation of REE in regolith and preservation of the ore bodies. These include quasi-equilibrium between denudation and exhumation at regional scales, local geomorphology dominated by low-lying gentle slopes, adequate rainfall, and favorable groundwater conditions. Continuous operation of such a dynamic weathering system is essential in the formation of regolith-hosted REE deposits.

  15. Factor Structure and Market Integration under Two-Factor Monopolistic Competition Model

    Directory of Open Access Journals (Sweden)

    Evgeny Vladimirovich Zhelobodko

    2013-09-01

    Full Text Available The authors study the impact of trade liberalization on the market of a differentiated good and consumers’ welfare. The economy involves two factors of production: labor and capital. The researchers find that consumers always gain from trade liberalization. The article also establishes that the behavior of equilibrium price is independent of factor endowments’ structure in the countries involved into trade. The equilibrium price decreases (increases, remains unchanged under trade liberalization if and only if the inverse demand elasticity is increasing (decreasing, constant with respect to the individual consumption level. Furthermore, firms’ size which are measured as output increases (decreases when autarky changes to free trade if and only if the country is relatively richer (poorer in capital than its trading partner, regardless of the demand-side properties of the economy. Finally, the behavior of capital price (which equals firms’ profits in equilibrium is more complicated in the general case, but can be fully characterized for two limiting cases: (i when the structure of factor endowments in both countries is the same, and (ii when the Foreign country is a periphery country, i.e. it has zero endowment of capital

  16. Population differences in host immune factors may influence survival of Gunnison's prairie dogs (Cynomys Gunnisoni) during plague outbreaks

    Science.gov (United States)

    Busch, Joseph D.; Van Andel, Roger; Cordova, Jennifer; Colman, Rebecca E.; Keim, Paul; Rocke, Tonie E.; Leid, Jeff G.; Van Pelt, William E.; Wagner, David M.

    2011-01-01

    Over the past 40 yr, epizootics of plague (Yersinia pestis) in northern Arizona have reduced populations of the Gunnison’s prairie dog (Cynomys gunnisoni), with the exception of a large population found in the Aubrey Valley (AV). To examine potential mechanisms accounting for their survival, we collected prairie dog serum samples in 2005–2006 from AV and a neighboring population near Seligman (SE), Arizona. We quantified gene expression at 58 diverse immune proteins using a multiplexed enzyme-linked immunosorbent assay panel. We found a subset of proteins important in coagulation and inflammation (tissue factor [TF], calbindin [Cal], and thrombopoietin [TPO]) and T-cell responses (CD40L and CD40) that were present in AV at levels two to eight times greater than SE. These results suggest that AV and SE animals might differ in their ability to mount an immune response.

  17. The B-domain of factor VIII reduces cell membrane attachement to host cells in serum free conditions

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Flintegaard, Thomas Veje

    2010-01-01

    engineered extensively throughout the years to increase the low production yields that initially were obtained from mammalian cell cultures. The scope of this work was to investigate the interaction of rFVIII with the cell membrane surface of the producing cells in serum free medium. We wondered whether...... binding of rFVIII to the cell membrane could be a factor diminishing the production yield. We studied the contribution of the rFVIII B-domain to membrane attachment by transfecting several constructs containing increasing lengths of the B-domain into cells under serum free conditions. We found that 90......% of rFVIII is attached to the cell membrane of the producing cell when the rFVIII variant contains a short B-domain (21 aa). By increasing the length of the B-domain the membrane attached fraction can be reduced to 50% of the total expressed rFVIII. Further, our studies show that the N...

  18. Factors Influencing Teachers' Attitudes toward Mobile Technology Integration in K-12

    Science.gov (United States)

    Khlaif, Zuheir N.

    2018-01-01

    The purpose of the present study was to explore, in depth, the factors influencing teachers' attitudes towards the integration of tablets into their classroom for teaching purposes. In order to achieve the purpose of the study, semi-structured interviews were conducted with 15 teachers from five rural middle schools in Palestine. A thematic…

  19. Pedagogical Factors Affecting Integration of Computers in Mathematics Instruction in Secondary Schools in Kenya

    Science.gov (United States)

    Wanjala, Martin M. S.; Aurah, Catherine M.; Symon, Koros C.

    2015-01-01

    The paper reports findings of a study which sought to examine the pedagogical factors that affect the integration of computers in mathematics instruction as perceived by teachers in secondary schools in Kenya. This study was based on the Technology Acceptance Model (TAM). A descriptive survey design was used for this study. Stratified and simple…

  20. The Views of Mathematics Teachers on the Factors Affecting the Integration of Technology in Mathematics Courses

    Science.gov (United States)

    Kaleli-Yilmaz, Gül

    2015-01-01

    The aim of this study was to determine the views of mathematics teachers on the factors that affect the integration of technology in mathematic courses. It is a qualitative case study. The sample size of the study is 10 teachers who are receiving postgraduate education in a university in Turkey. The current study was conducted in three stages. At…

  1. Alternate Solution to Generalized Bernoulli Equations via an Integrating Factor: An Exact Differential Equation Approach

    Science.gov (United States)

    Tisdell, C. C.

    2017-01-01

    Solution methods to exact differential equations via integrating factors have a rich history dating back to Euler (1740) and the ideas enjoy applications to thermodynamics and electromagnetism. Recently, Azevedo and Valentino presented an analysis of the generalized Bernoulli equation, constructing a general solution by linearizing the problem…

  2. Fusion integral experiments and analysis and the determination of design safety factors - I: Methodology

    International Nuclear Information System (INIS)

    Youssef, M.Z.; Kumar, A.; Abdou, M.A.; Oyama, Y.; Maekawa, H.

    1995-01-01

    The role of the neutronics experimentation and analysis in fusion neutronics research and development programs is discussed. A new methodology was developed to arrive at estimates to design safety factors based on the experimental and analytical results from design-oriented integral experiments. In this methodology, and for a particular nuclear response, R, a normalized density function (NDF) is constructed from the prediction uncertainties, and their associated standard deviations, as found in the various integral experiments where that response, R, is measured. Important statistical parameters are derived from the NDF, such as the global mean prediction uncertainty, and the possible spread around it. The method of deriving safety factors from many possible NDFs based on various calculational and measuring methods (among other variants) is also described. Associated with each safety factor is a confidence level, designers may choose to have, that the calculated response, R, will not exceed (or will not fall below) the actual measured value. An illustrative example is given on how to construct the NDFs. The methodology is applied in two areas, namely the line-integrated tritium production rate and bulk shielding integral experiments. Conditions under which these factors could be derived and the validity of the method are discussed. 72 refs., 17 figs., 4 tabs

  3. Factors for Effective E-learning Integration in Higher Education in ...

    African Journals Online (AJOL)

    This article discusses factors that contribute to effective e-learning integration in higher education in the context of Sub-Sahara Africa. It involved retrieving articles using key words such as e-learning, perceptions, knowledge, skills, implementation, facilities, access, support, learning management system and higher ...

  4. Integrating human factors and artificial intelligence in the development of human-machine cooperation

    NARCIS (Netherlands)

    Maanen, P.P. van; Lindenberg, J.; Neericx, M.A.

    2005-01-01

    Increasing machine intelligence leads to a shift from a mere interactive to a much more complex cooperative human-machine relation requiring a multidisciplinary development approach. This paper presents a generic multidisciplinary cognitive engineering method CE+ for the integration of human factors

  5. Risk factors for unstable blood glucose level: integrative review of the risk factors related to the nursing diagnosis

    Directory of Open Access Journals (Sweden)

    Andressa Magalhães Teixeira

    Full Text Available ABSTRACT Objective: to identify evidence in the literature on the possible risk factors for the risk of unstable blood glucose diagnosis in individuals with type 2 diabetes mellitus, and to compare them with the risk factors described by NANDA International. Method: an integrative literature review guided by the question: what are the risk factors for unstable blood glucose level in people with type 2 diabetes mellitus? Primary studies were included whose outcomes were variations in glycemic levels, published in English, Portuguese or Spanish, in PubMed or CINAHL between 2010 and 2015. Results: altered levels of glycated hemoglobin, body mass index>31 kg/m2, previous history of hypoglycemia, cognitive deficit/dementia, autonomic cardiovascular neuropathy, comorbidities and weight loss corresponded to risk factors described in NANDA International. Other risk factors identified were: advanced age, black skin color, longer length of diabetes diagnosis, daytime sleepiness, macroalbuminuria, genetic polymorphisms, insulin therapy, use of oral antidiabetics, and use of metoclopramide, inadequate physical activity and low fasting glycemia. Conclusions: risk factors for the diagnosis, risk for unstable blood glucose level, for persons with type 2 diabetes mellitus were identified, and 42% of them corresponded to those of NANDA International. These findings may contribute to the practice of clinical nurses in preventing the deleterious effects of glycemic variation.

  6. Determinant factors in the integration of information and communication technologies in teaching

    Directory of Open Access Journals (Sweden)

    Eric A. Bordios

    2016-12-01

    Full Text Available Binary Logistic Regression and Exploratory Factor Analysis (EFA were employed to determine factors that can influence teachers’ decision whether or not to integrate Information and communication technology (ICT in teaching and also to uncover ABC (Attitudes, Beliefs, Confidence as the factors to be considered which subsequently came out as predictors of the study along with age and grade level taught. Results implied that along with the efforts of the government to provide physical resources to implement the Department of Education Computerization Program, teachers as the main drivers of this initiative must be engaged in conceptual change regarding their ABC toward ICTintegration.

  7. Influence of Mortality Factors and Host Resistance on the Population Dynamics of Emerald Ash Borer (Coleoptera: Buprestidae) in Urban Forests.

    Science.gov (United States)

    Macquarrie, Chris J K; Scharbach, Roger

    2015-02-01

    The success of emerald ash borer (Agrilus planipennis Fairmaire) in North America is hypothesized to be due to both the lack of significant natural enemies permitting easy establishment and a population of trees that lack the ability to defend themselves, which allows populations to grow unchecked. Since its discovery in 2002, a number of studies have examined mortality factors of the insect in forests, but none have examined the role of natural enemies and other mortality agents in the urban forest. This is significant because it is in the urban forest where the emerald ash borer has had the most significant economic impacts. We studied populations in urban forests in three municipalities in Ontario, Canada, between 2010 and 2012 using life tables and stage-specific survivorship to analyze data from a split-rearing manipulative experiment. We found that there was little overall mortality caused by natural enemies; most mortality we did observe was caused by disease. Stage-specific survivorship was lowest in small and large larvae, supporting previous observations of high mortality in these two stages. We also used our data to test the hypothesis that mortality and density in emerald ash borer are linked. Our results support the prediction of a negative relationship between mortality and density. However, the relationship varies between insects developing in the crown and those in the trunk of the tree. This relationship was significant because when incorporated with previous findings, it suggests a mechanism and hypothesis to explain the outbreak dynamics of the emerald ash borer. © The Author 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Determination of the Main Influencing Factors on Road Fatalities Using an Integrated Neuro-Fuzzy Algorithm

    Directory of Open Access Journals (Sweden)

    Amir Masoud Rahimi

    Full Text Available Abstract This paper proposed an integrated algorithm of neuro-fuzzy techniques to examine the complex impact of socio-technical influencing factors on road fatalities. The proposed algorithm could handle complexity, non-linearity and fuzziness in the modeling environment due to its mechanism. The Neuro-fuzzy algorithm for determination of the potential influencing factors on road fatalities consisted of two phases. In the first phase, intelligent techniques are compared for their improved accuracy in predicting fatality rate with respect to some socio-technical influencing factors. Then in the second phase, sensitivity analysis is performed to calculate the pure effect on fatality rate of the potential influencing factors. The applicability and usefulness of the proposed algorithm is illustrated using the data in Iran provincial road transportation systems in the time period 2012-2014. Results show that road design improvement, number of trips, and number of passengers are the most influencing factors on provincial road fatality rate.

  9. Integrated application of human factors to a power plant control room information system

    International Nuclear Information System (INIS)

    Fish, H.C. Jr.; Gutierrez, R.

    1988-01-01

    The human factors plan was developed as a methodology to apply human factors from the conceptual design of the EPIC system to the functional verification conducted at the plant. An integral part of the Human Factors Plan was the Functional Verification Plan. Developed in parallel, this second plan and its resultant programs verified functional appropriateness of the SPDS display, NSSS displays, EOP displays, man-machine interfaces (MMI), and workstation designs. The functional verification process was performed at the hardware/software developer's factory and at the JAFNPP, following installation of the EPIC system. Because the EPIC system replaces existing control room equipment, it is important that human factors be applied in a systematic manner consistent with other control room displays and controls. To ensure that this goal was met, a human factors plan was developed

  10. Temporal activation of anti- and pro-apoptotic factors in human gingival fibroblasts infected with the periodontal pathogen, Porphyromonas gingivalis: potential role of bacterial proteases in host signalling

    Directory of Open Access Journals (Sweden)

    Takehara Tadamichi

    2006-03-01

    Full Text Available Abstract Background Porphyromonas gingivalis is the foremost oral pathogen of adult periodontitis in humans. However, the mechanisms of bacterial invasion and the resultant destruction of the gingival tissue remain largely undefined. Results We report host-P. gingivalis interactions in primary human gingival fibroblast (HGF cells. Quantitative immunostaining revealed the need for a high multiplicity of infection for optimal infection. Early in infection (2–12 h, P. gingivalis activated the proinflammatory transcription factor NF-kappa B, partly via the PI3 kinase/AKT pathway. This was accompanied by the induction of cellular anti-apoptotic genes, including Bfl-1, Boo, Bcl-XL, Bcl2, Mcl-1, Bcl-w and Survivin. Late in infection (24–36 h the anti-apoptotic genes largely shut down and the pro-apoptotic genes, including Nip3, Hrk, Bak, Bik, Bok, Bax, Bad, Bim and Moap-1, were activated. Apoptosis was characterized by nuclear DNA degradation and activation of caspases-3, -6, -7 and -9 via the intrinsic mitochondrial pathway. Use of inhibitors revealed an anti-apoptotic function of NF-kappa B and PI3 kinase in P. gingivalis-infected HGF cells. Use of a triple protease mutant P. gingivalis lacking three major gingipains (rgpA rgpB kgp suggested a role of some or all these proteases in myriad aspects of bacteria-gingival interaction. Conclusion The pathology of the gingival fibroblast in P. gingivalis infection is affected by a temporal shift from cellular survival response to apoptosis, regulated by a number of anti- and pro-apoptotic molecules. The gingipain group of proteases affects bacteria-host interactions and may directly promote apoptosis by intracellular proteolytic activation of caspase-3.

  11. Polynomial inverse integrating factors of quadratic differential systems and other results

    OpenAIRE

    Ferragut i Amengual, Antoni

    2006-01-01

    Consultable des del TDX Títol obtingut de la portada digitalitzada Aquesta tesi està dividida en dues parts diferents. En la primera, estudiam els sistemes quadràtics (sistemes polinomials de grau dos) que tenen un invers de factor integrant polinomial. En la segona, estudiam tres problemes diferents referits als sistemes diferencials polinomials. La primera part En l'estudi dels sistemes diferencials plans el coneixement d'una integral primera és molt important. Els seus conjunts de ni...

  12. arXiv Conformal anomaly of generalized form factors and finite loop integrals

    CERN Document Server

    Chicherin, Dmitry

    2018-04-16

    We reveal a new mechanism of conformal symmetry breaking at Born level. It occurs in generalized form factors with several local operators and an on-shell state of massless particles. The effect is due to hidden singularities on collinear configurations of the momenta. This conformal anomaly is different from the holomorphic anomaly of amplitudes. We present a number of examples in four and six dimensions. We find an application of the new conformal anomaly to finite loop momentum integrals with one or more massless legs. The collinear region around a massless leg creates a contact anomaly, made visible by the loop integration. The anomalous conformal Ward identity for an ℓ−loop integral is a 2nd-order differential equation whose right-hand side is an (ℓ − 1)−loop integral. It could serve as a new useful tool to find/test analytic expressions for conformal integrals. We illustrate this point with several examples of known integrals. We propose a new differential equation for the four-dimensional sca...

  13. Aedes aegypti Molecular Responses to Zika Virus: Modulation of Infection by the Toll and Jak/Stat Immune Pathways and Virus Host Factors

    Directory of Open Access Journals (Sweden)

    Yesseinia I. Angleró-Rodríguez

    2017-10-01

    Full Text Available Zika (ZIKV and dengue virus (DENV are transmitted to humans by Aedes mosquitoes. However, the molecular interactions between the vector and ZIKV remain largely unexplored. In this work, we further investigated the tropism of ZIKV in two different Aedes aegypti strains and show that the virus infection kinetics, tissue migration, and susceptibility to infection differ between mosquito strains. We also compare the vector transcriptome changes upon ZIKV or DENV infection demonstrating that 40% of the mosquito’s midgut infection-responsive transcriptome is virus-specific at 7 days after virus ingestion. Regulated genes included key factors of the mosquito’s anti-viral immunity. Comparison of the ZIKV and DENV infection-responsive transcriptome data to those available for yellow fever virus and West Nile virus identified 26 genes likely to play key roles in virus infection of Aedes mosquitoes. Through reverse genetic analyses, we show that the Toll and the Jak/Stat innate immune pathways mediate increased resistance to ZIKV infection, and the conserved DENV host factors vATPase and inosine-5′-monophosphate dehydrogenase are also utilized for ZIKV infection.

  14. HTLV-1 Tax mediated downregulation of miRNAs associated with chromatin remodeling factors in T cells with stably integrated viral promoter.

    Directory of Open Access Journals (Sweden)

    Saifur Rahman

    Full Text Available RNA interference (RNAi is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1 transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR using a CD4(+ T-cell line, Jurkat. Transcription factor profiling of the HTLV-1 LTR stably integrated T-cell clone transfected with Tax demonstrates increased activation of substrates and factors associated with chromatin remodeling complexes. Using a miRNA microarray and bioinformatics experimental approach, Tax was also shown to downregulate the expression of miRNAs associated with the translational regulation of factors required for chromatin remodeling. These observations were validated with selected miRNAs and an HTLV-1 infected T cells line, MT-2. miR-149 and miR-873 were found to be capable of directly targeting p300 and p/CAF, chromatin remodeling factors known to play critical role in HTLV-1 pathogenesis. Overall, these results are first in line establishing HTLV-1/Tax-miRNA-chromatin concept and open new avenues toward understanding retroviral latency and/or replication in a given cell type.

  15. Integrating the ICF with positive psychology: Factors predicting role participation for mothers with multiple sclerosis.

    Science.gov (United States)

    Farber, Ruth S; Kern, Margaret L; Brusilovsky, Eugene

    2015-05-01

    Being a mother has become a realizable life role for women with disabilities and chronic illnesses, including multiple sclerosis (MS). Identifying psychosocial factors that facilitate participation in important life roles-including motherhood-is essential to help women have fuller lives despite the challenge of their illness. By integrating the International Classification of Functioning, Disability, and Health (ICF) and a positive psychology perspective, this study examined how environmental social factors and positive personal factors contribute to daily role participation and satisfaction with parental participation. One hundred and 11 community-dwelling mothers with MS completed Ryff's Psychological Well-Being Scales, the Medical Outcome Study Social Support Survey, the Short Form-36, and the Parental Participation Scale. Hierarchical regression analyses examined associations between social support and positive personal factors (environmental mastery, self-acceptance, purpose in life) with daily role participation (physical and emotional) and satisfaction with parental participation. One-way ANOVAs tested synergistic combinations of social support and positive personal factors. Social support predicted daily role participation (fewer limitations) and greater satisfaction with parental participation. Positive personal factors contributed additional unique variance. Positive personal factors and social support synergistically predicted better function and greater satisfaction than either alone. Integrating components of the ICF and positive psychology provides a useful model for understanding how mothers with MS can thrive despite challenge or impairment. Both positive personal factors and environmental social factors were important contributors to positive role functioning. Incorporating these paradigms into treatment may help mothers with MS participate more fully in meaningful life roles. (c) 2015 APA, all rights reserved).

  16. Host apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide-like 3G is an innate defensive factor and drug target against hepatitis C virus.

    Science.gov (United States)

    Peng, Zong-Gen; Zhao, Zhi-Yun; Li, Yan-Ping; Wang, Yu-Ping; Hao, Lan-Hu; Fan, Bo; Li, Yu-Huan; Wang, Yue-Ming; Shan, Yong-Qiang; Han, Yan-Xing; Zhu, Yan-Ping; Li, Jian-Rui; You, Xue-Fu; Li, Zhuo-Rong; Jiang, Jian-Dong

    2011-04-01

    Host cellular factor apolipoprotein B messenger RNA (mRNA)-editing enzyme catalytic polypeptide-like 3G (hA3G) is a cytidine deaminase that inhibits a group of viruses including human immunodeficiency virus-1 (HIV-1). In the continuation of our research on hA3G, we found that hA3G stabilizing compounds significantly inhibited hepatitis C virus (HCV) replication. Therefore, this study investigated the role of hA3G in HCV replication. Introduction of external hA3G into HCV-infected Huh7.5 human hepatocytes inhibited HCV replication; knockdown of endogenous hA3G enhanced HCV replication. Exogenous HIV-1 virion infectivity factor (Vif) decreased intracellular hA3G and therefore enhanced HCV proliferation, suggesting that the presence of Vif might be an explanation for the HIV-1/HCV coinfection often observed in HIV-1(+) individuals. Treatment of the HCV-infected Huh7.5 cells with RN-5 or IMB-26, two known hA3G stabilizing compounds, increased intracellular hA3G and accordingly inhibited HCV replication. The compounds inhibit HCV through increasing the level of hA3G incorporated into HCV particles, but not through inhibiting HCV enzymes. However, G/A hypermutation in the HCV genome were not detected, suggesting a new antiviral mechanism of hA3G in HCV, different from that in HIV-1. Stabilization of hA3G by RN-5 was safe in vivo. hA3G appears to be a cellular restrict factor against HCV and could be a potential target for drug discovery. 2011 American Association for the Study of Liver Diseases.

  17. Factors Influencing Registered Nurses' Perceptions of Their Professional Identity: An Integrative Literature Review.

    Science.gov (United States)

    Rasmussen, Philippa; Henderson, Ann; Andrew, Nicky; Conroy, Tiffany

    2018-05-01

    This review synthesizes contemporary research investigating the factors influencing RNs' perceptions of their professional identity. The method used was an integrative literature review. Factors influencing RNs' perceptions of their professional identity were synthesized into three categories: the self, the role, and the context. The self is the nurse who enacts the role in practice, and the context is the practice setting. Poor alignment of these categories leads to stress, tension, and uncertainty affecting work-force retention. Strong alignment leads to satisfaction with the nursing role, increased staff retention, and improved quality of care and patient outcomes. These three categories should be considered when planning nursing professional development activities. This integrative review identified a lack of research addressing how nurses' perceptions of their professional identity change over time. A deeper understanding of their perspective is needed to establish whether career longevity and continued professional development are influences. J Contin Educ Nurs. 2018;49(5):225-232. Copyright 2018, SLACK Incorporated.

  18. The contribution of perceptual factors and training on varying audiovisual integration capacity.

    Science.gov (United States)

    Wilbiks, Jonathan M P; Dyson, Benjamin J

    2018-06-01

    The suggestion that the capacity of audiovisual integration has an upper limit of 1 was challenged in 4 experiments using perceptual factors and training to enhance the binding of auditory and visual information. Participants were required to note a number of specific visual dot locations that changed in polarity when a critical auditory stimulus was presented, under relatively fast (200-ms stimulus onset asynchrony [SOA]) and slow (700-ms SOA) rates of presentation. In Experiment 1, transient cross-modal congruency between the brightness of polarity change and pitch of the auditory tone was manipulated. In Experiment 2, sustained chunking was enabled on certain trials by connecting varying dot locations with vertices. In Experiment 3, training was employed to determine if capacity would increase through repeated experience with an intermediate presentation rate (450 ms). Estimates of audiovisual integration capacity (K) were larger than 1 during cross-modal congruency at slow presentation rates (Experiment 1), during perceptual chunking at slow and fast presentation rates (Experiment 2), and, during an intermediate presentation rate posttraining (Experiment 3). Finally, Experiment 4 showed a linear increase in K using SOAs ranging from 100 to 600 ms, suggestive of quantitative rather than qualitative changes in the mechanisms in audiovisual integration as a function of presentation rate. The data compromise the suggestion that the capacity of audiovisual integration is limited to 1 and suggest that the ability to bind sounds to sights is contingent on individual and environmental factors. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  19. ANALYSIS OF INFLUENCE FACTORS OF ECONOMIC EFFICIENCY ON THE ECONOMY OF THE INTEGRATED STRUCTURES

    Directory of Open Access Journals (Sweden)

    I. P. Bogomolova

    2014-01-01

    Full Text Available Currently in Russia, special attention is paid to the food industry, providing a key influence on the state's economy and food security of the country. The food industry not only creates substantial part of the gross domestic product, which is one of the main sources of fillings budgets of all levels, and contributes to the strengthening of the state in world markets. These circum-stances make it necessary to increase the efficiency of industrial structures by mobilizing factors affecting the economy of enterprises, including by shifting emphasis on the integration of food industry enterprises in General competitiveness of the goods produced, the stability of the entire industry, its leading industries and organizations. The article substantiates the expediency of application of integrated structures, discusses the methods and tools of analysis of influence factors of economic efficiency on the economy of inte-grated structures. Evaluation is recommended in two key areas: assessment of the financial condition and evaluation of training and development of staff, taking into account the strategic objectives of integrated structures. The analysis makes it possible to correctly allocate financial resources and to achieve balanced economic performance management through more effective use of credit re-sources, the rational management of economic parameters optimization of the number of employees and production capacity.

  20. On the factorization of integral operators on spaces of summable functions

    International Nuclear Information System (INIS)

    Engibaryan, Norayr B

    2009-01-01

    We consider the factorization I-K=(I-U + )(I-U - ), where I is the identity operator, K is an integral operator acting on some Banach space of functions summable with respect to a measure μ on (a,b) subset of (-∞,+∞) continuous relative to the Lebesgue measure, (Kf)(x)=∫ a b k(x,t)f(t)μ(dt), x element of (a,b), and U ± are the desired Volterra operators. A necessary and sufficient condition is found for the existence of this factorization for a rather wide class of operators K with positive kernels and for Hilbert-Schmidt operators.

  1. Manpower systems integration factors for frigate design in the Turkish Navy

    OpenAIRE

    Kilicaslan, Ismail

    2016-01-01

    Approved for public release; distribution is unlimited This research examines the manpower systems integration factors for frigate design in the Turkish Navy. The qualitative and quantitative analyses of the correlation between ship design specifications and manpower requirements play a pivotal role in this research. Information about 45 frigate classes from 29 countries is collected from the Information Handling Services Jane's Fighting Ships database and varying approaches of different n...

  2. Modularity, Integration and IT Personnel Skills Factors in Linking ERP to SCM Systems

    OpenAIRE

    Chung, Sock H; Tang, Hung-Lian; Ahmad, Imtiaz

    2011-01-01

    This study investigates some underlying technological factors for linking enterprise resource planning (ERP) to supply chain management (SCM) systems. ERP systems serve technological requirements across functional areas within a corporate boundary while SCM systems focus on collaborative relationships with partners in the supply chain, emphasizing business process integration and information sharing through IT. In order to facilitate SCM operations for business planning and decision making, a...

  3. Noncognitive Factors in an Elementary School-Wide Arts Integrated Model

    OpenAIRE

    Simpson Steele, Jamie

    2016-01-01

    Pomaika‘i Elementary School has answered a call to improve education by providing content instruction through the arts. How does school wide arts integration in an elementary setting support students as they transition to middle school? This bounded case study examines the experiences of eight families through a series of interviews with students, parents, and teachers. It describes and explains learning through the arts within three overarching noncognitive factors: a) academic mindsets, or ...

  4. Psychosocial Factors, Maladaptive Cognitive Schemas, and Depression in Young Adults: An Integration

    OpenAIRE

    Cankaya, Banu

    2002-01-01

    The present study examined a psychosocial-cognitive model that integrates recent findings on the independent effects of early maladaptive cognitive schemas (EMSs; Young, 1994) and psychosocial factors/stressors; viz., social support, expressed emotion, stressful life events and daily hassles, on level of depressive symptoms in young adults. Consistent with Beck's theory of depression, the expectation was that individuals with the EMSs would be more likely to respond to psychosocial stressors...

  5. ARF6, PI3-kinase and host cell actin cytoskeleton in Toxoplasma gondii cell invasion

    International Nuclear Information System (INIS)

    Vieira da Silva, Claudio; Alves da Silva, Erika; Costa Cruz, Mario; Chavrier, Philippe; Arruda Mortara, Renato

    2009-01-01

    Toxoplasma gondii infects a variety of different cell types in a range of different hosts. Host cell invasion by T. gondii occurs by active penetration of the host cell, a process previously described as independent of host actin polymerization. Also, the parasitophorous vacuole has been shown to resist fusion with endocytic and exocytic pathways of the host cell. ADP-ribosylation factor-6 (ARF6) belongs to the ARF family of small GTP-binding proteins. ARF6 regulates membrane trafficking and actin cytoskeleton rearrangements at the plasma membrane. Here, we have observed that ARF6 is recruited to the parasitophorous vacuole of tachyzoites of T. gondii RH strain and it also plays an important role in the parasite cell invasion with activation of PI3-kinase and recruitment of PIP 2 and PIP 3 to the parasitophorous vacuole of invading parasites. Moreover, it was verified that maintenance of host cell actin cytoskeleton integrity is important to parasite invasion.

  6. Resistance to Plum pox virus strain C in Arabidopsis thaliana and Chenopodium foetidum involves genome-linked viral protein and other viral determinants and might depend on compatibility with host translation initiation factors.

    Science.gov (United States)

    Calvo, María; Martínez-Turiño, Sandra; García, Juan Antonio

    2014-11-01

    Research performed on model herbaceous hosts has been useful to unravel the molecular mechanisms that control viral infections. The most common Plum pox virus (PPV) strains are able to infect Nicotiana species as well as Chenopodium and Arabidopsis species. However, isolates belonging to strain C (PPV-C) that have been adapted to Nicotiana spp. are not infectious either in Chenopodium foetidum or in Arabidopsis thaliana. In order to determine the mechanism underlying this interesting host-specific behavior, we have constructed chimerical clones derived from Nicotiana-adapted PPV isolates from the D and C strains, which differ in their capacity to infect A. thaliana and C. foetidum. With this approach, we have identified the nuclear inclusion a protein (VPg+Pro) as the major pathogenicity determinant that conditions resistance in the presence of additional secondary determinants, different for each host. Genome-linked viral protein (VPg) mutations similar to those involved in the breakdown of eIF4E-mediated resistance to other potyviruses allow some PPV chimeras to infect A. thaliana. These results point to defective interactions between a translation initiation factor and the viral VPg as the most probable cause of host-specific incompatibility, in which other viral factors also participate, and suggest that complex interactions between multiple viral proteins and translation initiation factors not only define resistance to potyviruses in particular varieties of susceptible hosts but also contribute to establish nonhost resistance.

  7. An ergonomics action research demonstration: integrating human factors into assembly design processes.

    Science.gov (United States)

    Village, J; Greig, M; Salustri, F; Zolfaghari, S; Neumann, W P

    2014-01-01

    In action research (AR), the researcher participates 'in' the actions in an organisation, while simultaneously reflecting 'on' the actions to promote learning for both the organisation and the researchers. This paper demonstrates a longitudinal AR collaboration with an electronics manufacturing firm where the goal was to improve the organisation's ability to integrate human factors (HF) proactively into their design processes. During the three-year collaboration, all meetings, workshops, interviews and reflections were digitally recorded and qualitatively analysed to inform new 'actions'. By the end of the collaboration, HF tools with targets and sign-off by the HF specialist were integrated into several stages of the design process, and engineers were held accountable for meeting the HF targets. We conclude that the AR approach combined with targeting multiple initiatives at different stages of the design process helped the organisation find ways to integrate HF into their processes in a sustainable way. Researchers acted as a catalyst to help integrate HF into the engineering design process in a sustainable way. This paper demonstrates how an AR approach can help achieve HF integration, the benefits of using a reflective stance and one method for reporting an AR study.

  8. New host, geographical records, and factors affecting the prevalence of helminths infection from synanthropic rodents in Yucatán, Mexico

    Directory of Open Access Journals (Sweden)

    Panti-May J. A.

    2017-09-01

    Full Text Available The aim of this paper was to study the occurrence of helminths in Mus musculus and Rattus rattus from urban, suburban and rural settlements in Yucatán, Mexico; and to analyse the host factors (e.g. sex related to helminths’ distribution. Helminths in a total of 279 rodents were surveyed by visual examination of the liver for metacestodes and faecal examination for helminth eggs using the formalin-ethyl acetate sedimentation technique. The cestodes Hydatigera taeniaeformis (metacestodes detected in the liver and Hymenolepis diminuta, and the nematodes Aspiculuris sp., Nippostrongylus brasiliensis, Syphacia muris, Syphacia obvelata, and Trichuris muris were identified. In M. musculus, the prevalence of infection with T. muris and H. taeniaeformis was higher in the rural village compared to those in the suburban neighbourhood. For R. rattus, a higher prevalence of infection with H. diminuta was found in the urban site compared to that in the suburban site. This study reports the occurrence of H. diminuta among rodents living in close proximity to humans, representing a potential public health risk. In addition, this survey increases our understanding of dynamic transmission among intestinal helminths recorded in Yucatán, Mexico.

  9. Proportional-Integral-Derivative (PID) Control of Secreted Factors for Blood Stem Cell Culture.

    Science.gov (United States)

    Caldwell, Julia; Wang, Weijia; Zandstra, Peter W

    2015-01-01

    Clinical use of umbilical cord blood has typically been limited by the need to expand hematopoietic stem and progenitor cells (HSPC) ex vivo. This expansion is challenging due to the accumulation of secreted signaling factors in the culture that have a negative regulatory effect on HSPC output. Strategies for global regulation of these factors through dilution have been developed, but do not accommodate the dynamic nature or inherent variability of hematopoietic cell culture. We have developed a mathematical model to simulate the impact of feedback control on in vitro hematopoiesis, and used it to design a proportional-integral-derivative (PID) control algorithm. This algorithm was implemented with a fed-batch bioreactor to regulate the concentrations of secreted factors. Controlling the concentration of a key target factor, TGF-β1, through dilution limited the negative effect it had on HSPCs, and allowed global control of other similarly-produced inhibitory endogenous factors. The PID control algorithm effectively maintained the target soluble factor at the target concentration. We show that feedback controlled dilution is predicted to be a more cost effective dilution strategy compared to other open-loop strategies, and can enhance HSPC expansion in short term culture. This study demonstrates the utility of secreted factor process control strategies to optimize stem cell culture systems, and motivates the development of multi-analyte protein sensors to automate the manufacturing of cell therapies.

  10. MIGRATION INTEGRATION AS A FACTOR OF ECONOMIC AND REGIONAL DEVELOPMENT IN THE EUROPEAN UNION

    Directory of Open Access Journals (Sweden)

    Petronela Daniela FERARU

    2015-10-01

    Full Text Available International migration, together with economic and financial crisis or the different socio-economic development of Member States, is a serious threat to security in Europe. Population migration as a threatening factor, places the European Union in the face of a decision to establish clear policies for the establishment of a climate of external security, both for the migrant population and for the rest of the population. All in all, this study will centre on the following hypothesis: the better we know the challenges of international migration in the European Union and its Member States the more the European policies to mitigate negative effects of the world will be diminished. The aim is to highlight aspects pertaining to migration integration as a factor of economic, social and regional development in the European Union, and less as a factor of destabilization and insecurity. In other words, a good knowledge of the phenomenon leads to drawing up effective policies to reduce hazards, risks, threats and negative effects that happen today due to the increasing number of immigrants. Finally, the study will present a series of conclusions, including on the work hypothesis verification and some proposals related to migration integration efficiency as a factor of regional and economic development in the European Union.

  11. Technical factors that affect anastomotic integrity following esophagectomy: systematic review and meta-analysis.

    Science.gov (United States)

    Markar, Sheraz R; Arya, Shobhit; Karthikesalingam, Alan; Hanna, George B

    2013-12-01

    Due to the significant contribution of anastomotic leak, with its disastrous consequences to patient morbidity and mortality, multiple parameters have been proposed and individually meta-analyzed for the formation of the ideal esophagogastric anastomosis following cancer resection. The purpose of this pooled analysis was to examine the main technical parameters that impact on anastomotic integrity. Medline, Embase, trial registries, and conference proceedings were searched. Technical factors evaluated included hand-sewn versus stapled esophagogastric anastomosis (EGA), cervical versus thoracic EGA, minimally invasive versus open esophagectomy, anterior versus posterior route of reconstruction and ischemic conditioning of the gastric conduit. The outcome of interest was the incidence of anastomotic leak, for which pooled odds ratios were calculated for each technical factor. No significant difference in the incidence of anastomotic leak was demonstrated for the following technical factors: hand-sewn versus stapled EGA, minimally invasive versus open esophagectomy, anterior versus posterior route of reconstruction and ischemic conditioning of the gastric conduit. Four randomized, controlled trials comprising 298 patients were included that compared cervical and thoracic EGA. Anastomotic leak was seen more commonly in the cervical group (13.64 %) than in the thoracic group (2.96 %). Pooled analysis demonstrated a significantly increased incidence of anastomotic leak in the cervical group (pooled odds ratio = 4.73; 95 % CI 1.61-13.9; P = 0.005). A tailored surgical approach to the patient's physiology and esophageal cancer stage is the most important factor that influences anastomotic integrity after esophagectomy.

  12. Baseline prediction of combination therapy outcome in hepatitis C virus 1b infected patients by discriminant analysis using viral and host factors.

    Science.gov (United States)

    Saludes, Verónica; Bracho, Maria Alma; Valero, Oliver; Ardèvol, Mercè; Planas, Ramón; González-Candelas, Fernando; Ausina, Vicente; Martró, Elisa

    2010-11-30

    Current treatment of chronic hepatitis C virus (HCV) infection has limited efficacy -especially among genotype 1 infected patients-, is costly, and involves severe side effects. Thus, predicting non-response is of major interest for both patient wellbeing and health care expense. At present, treatment cannot be individualized on the basis of any baseline predictor of response. We aimed to identify pre-treatment clinical and virological parameters associated with treatment failure, as well as to assess whether therapy outcome could be predicted at baseline. Forty-three HCV subtype 1b (HCV-1b) chronically infected patients treated with pegylated-interferon alpha plus ribavirin were retrospectively studied (21 responders and 22 non-responders). Host (gender, age, weight, transaminase levels, fibrosis stage, and source of infection) and viral-related factors (viral load, and genetic variability in the E1-E2 and Core regions) were assessed. Logistic regression and discriminant analyses were used to develop predictive models. A "leave-one-out" cross-validation method was used to assess the reliability of the discriminant models. Lower alanine transaminase levels (ALT, p=0.009), a higher number of quasispecies variants in the E1-E2 region (number of haplotypes, nHap_E1-E2) (p=0.003), and the absence of both amino acid arginine at position 70 and leucine at position 91 in the Core region (p=0.039) were significantly associated with treatment failure. Therapy outcome was most accurately predicted by discriminant analysis (90.5% sensitivity and 95.5% specificity, 85.7% sensitivity and 81.8% specificity after cross-validation); the most significant variables included in the predictive model were the Core amino acid pattern, the nHap_E1-E2, and gamma-glutamyl transferase and ALT levels. Discriminant analysis has been shown as a useful tool to predict treatment outcome using baseline HCV genetic variability and host characteristics. The discriminant models obtained in this

  13. Age as a factor in sensory integration function in Taiwanese children

    Directory of Open Access Journals (Sweden)

    Lin CK

    2013-07-01

    Full Text Available Chin-Kai Lin,1 Huey-Min Wu,2 Hsin-Yi Wang,3 Mei-Hui Tseng,4,5 Chung-Hui Lin61Department of Early Childhood Education, National Taichung University of Education, Taichung, Taiwan; 2Research Center for Testing and Assessment, National Academy for Educational Research, New Taipei, Taiwan; 3Department of Special Education, National Taichung University of Education, Taichung, Taiwan; 4School of Occupational Therapy, College of Medicine, National Taiwan University, Taipei, Taiwan; 5Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan; 6School of Occupational Therapy, College of Medical Science and Technology, Chung Shan Medical University, Taichung, TaiwanObjective: Sensory integration progresses along a normal developmental sequence. However, few studies have explored how age difference affects the way sensory integration functions in Taiwanese children as they develop. Therefore, this study aims to pinpoint the role of age in sensory integration.Method: A purposive sampling plan was employed. The study population comprised 1,000 Chinese children aged 36 to 131 months (mean = 74.48 months, standard deviation = 25.69 months. Subjects were scored on seven subsets of the Test of Sensory Integration Function (TSIF. An analysis of variance (ANOVA was used to identify differences between four age groups (ages 3−4, 5−6, 7−8, and 9−10 years, in the categories of the TSIF.Results: ANOVA revealed that age is a significant factor in each of the seven tasks of sensory integration associated with various stages of development. The effect of age was significant in all four groups for the subscale of Bilateral Integration Sequences. The function of sensory integration for the children aged 5−8 years did not produce statistically significant results for the subscale of Postural Movement, Sensory Discrimination, Sensory Seeking, or Attention and Activity. For the subscale of Sensory Modulation and Emotional

  14. Integration

    DEFF Research Database (Denmark)

    Emerek, Ruth

    2004-01-01

    Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration......Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration...

  15. Field configurations for small deviations of the integral filling factors in IQHE

    International Nuclear Information System (INIS)

    Cabo, A.; Castineiras, J.; Gonzalez, R.; Penaranda, S.

    1990-07-01

    A numerical solution of the effective Maxwell equations of the IQHE is presented. It corresponds to inhomogeneous electromagnetic field distributions appearing after a small constant magnetic field is added to a 2D-electron gas sheet when the density exactly fills an integral number of Landau levels. It follows that the Chern-Simons terms of the Maxwell equation transform the applied magnetic field into an equivalent homogeneous charge density. The numerical value of this density is exactly the one which is needed to furnish complete filling at the new value of the total magnetic field. The system then reacts tending to screen the effective charge density by removing charge from the sample edges. It is interesting that for the selected parameter values here, reflecting the current experimental situations, the system response is able to approximately establish an integral filling factor in the central portion of the sheet. Then, at least a small plateau is predicted to occur in pure samples at zero temperature. It also follows that the current distribution is unsymmetric under the inversion, as opposed to the configuration associated to a flow of a net Hall current at integral filling factors. (author). 8 refs, 4 figs

  16. Network analysis of epidermal growth factor signaling using integrated genomic, proteomic and phosphorylation data.

    Directory of Open Access Journals (Sweden)

    Katrina M Waters

    Full Text Available To understand how integration of multiple data types can help decipher cellular responses at the systems level, we analyzed the mitogenic response of human mammary epithelial cells to epidermal growth factor (EGF using whole genome microarrays, mass spectrometry-based proteomics and large-scale western blots with over 1000 antibodies. A time course analysis revealed significant differences in the expression of 3172 genes and 596 proteins, including protein phosphorylation changes measured by western blot. Integration of these disparate data types showed that each contributed qualitatively different components to the observed cell response to EGF and that varying degrees of concordance in gene expression and protein abundance measurements could be linked to specific biological processes. Networks inferred from individual data types were relatively limited, whereas networks derived from the integrated data recapitulated the known major cellular responses to EGF and exhibited more highly connected signaling nodes than networks derived from any individual dataset. While cell cycle regulatory pathways were altered as anticipated, we found the most robust response to mitogenic concentrations of EGF was induction of matrix metalloprotease cascades, highlighting the importance of the EGFR system as a regulator of the extracellular environment. These results demonstrate the value of integrating multiple levels of biological information to more accurately reconstruct networks of cellular response.

  17. Network Analysis of Epidermal Growth Factor Signaling using Integrated Genomic, Proteomic and Phosphorylation Data

    Energy Technology Data Exchange (ETDEWEB)

    Waters, Katrina M.; Liu, Tao; Quesenberry, Ryan D.; Willse, Alan R.; Bandyopadhyay, Somnath; Kathmann, Loel E.; Weber, Thomas J.; Smith, Richard D.; Wiley, H. S.; Thrall, Brian D.

    2012-03-29

    To understand how integration of multiple data types can help decipher cellular responses at the systems level, we analyzed the mitogenic response of human mammary epithelial cells to epidermal growth factor (EGF) using whole genome microarrays, mass spectrometry-based proteomics and large-scale western blots with over 1000 antibodies. A time course analysis revealed significant differences in the expression of 3172 genes and 596 proteins, including protein phosphorylation changes measured by western blot. Integration of these disparate data types showed that each contributed qualitatively different components to the observed cell response to EGF and that varying degrees of concordance in gene expression and protein abundance measurements could be linked to specific biological processes. Networks inferred from individual data types were relatively limited, whereas networks derived from the integrated data recapitulated the known major cellular responses to EGF and exhibited more highly connected signaling nodes than networks derived from any individual dataset. While cell cycle regulatory pathways were altered as anticipated, we found the most robust response to mitogenic concentrations of EGF was induction of matrix metalloprotease cascades, highlighting the importance of the EGFR system as a regulator of the extracellular environment. These results demonstrate the value of integrating multiple levels of biological information to more accurately reconstruct networks of cellular response.

  18. Transcriptional and Bioinformatic Analysis Provide a Relationship between Host Response Changes to Marek’s Disease Viruses Infection and an Integrated Long Terminal Repeat

    Directory of Open Access Journals (Sweden)

    Ning eCui

    2016-04-01

    Full Text Available GX0101, Marek’s disease virus (MDV strain with a long terminal repeat (LTR insert of reticuloendotheliosis virus (REV, was isolated from CVI988/Rispens vaccinated birds showing tumors. We have constructed a LTR deleted strain GX0101∆LTR in our previous study. To compare the host responses to GX0101 and GX0101∆LTR, chicken embryo fibroblasts (CEF cells were infected with two MDV strains and a gene-chip containing chicken genome was employed to examine gene transcription changes in host cells in the present study. Of the 42 368 chicken transcripts on the chip, there were 2199 genes that differentially expressed in CEF infected with GX0101 compared to GX0101∆LTR significantly. Differentially expressed genes were distributed to 25 possible gene networks according to their intermolecular connections and were annotated to 56 pathways. The insertion of REV LTR showed the greatest influence on cancer formation and metastasis, followed with immune changes, atherosclerosis and nervous system disorders in MDV-infected CEF cells. Based on these bio functions, GX0101 infection was predicated with a greater growth and survival inhibition but lower oncogenicity in chickens than GX0101∆LTR, at least in the acute phase of infection. In summary, the insertion of REV LTR altered the expression of host genes in response to MDV infection, possibly resulting in novel phenotypic properties in chickens. Our study has provided the evidence of retroviral insertional changes of host responses to herpesvirus infection for the first time, which will promote to elucidation of the possible relationship between the LTR insertion and the observed phenotypes.

  19. Ebola virus host cell entry.

    Science.gov (United States)

    Sakurai, Yasuteru

    2015-01-01

    Ebola virus is an enveloped virus with filamentous structure and causes a severe hemorrhagic fever in human and nonhuman primates. Host cell entry is the first essential step in the viral life cycle, which has been extensively studied as one of the therapeutic targets. A virus factor of cell entry is a surface glycoprotein (GP), which is an only essential viral protein in the step, as well as the unique particle structure. The virus also interacts with a lot of host factors to successfully enter host cells. Ebola virus at first binds to cell surface proteins and internalizes into cells, followed by trafficking through endosomal vesicles to intracellular acidic compartments. There, host proteases process GPs, which can interact with an intracellular receptor. Then, under an appropriate circumstance, viral and endosomal membranes are fused, which is enhanced by major structural changes of GPs, to complete host cell entry. Recently the basic research of Ebola virus infection mechanism has markedly progressed, largely contributed by identification of host factors and detailed structural analyses of GPs. This article highlights the mechanism of Ebola virus host cell entry, including recent findings.

  20. [Integrated Management Area of Vascular Risk: A new organisational model for global control of risk factors].

    Science.gov (United States)

    Armario, P; Jericó, C; Vila, L; Freixa, R; Martin-Castillejos, C; Rotllan, M

    Cardiovascular disease (CVD), is a major cause of morbidity and mortality that increases the cost of care. Currently there is a low degree of control of the main cardiovascular risk factors, although we have a good therapeutic arsenal. To achieve the improvement of this reality, a good coordination and multidisciplinary participation are essential. The development of new organizational models such as the Integrated Management Area of Vascular Risk can facilitate the therapeutic harmonization and unification of the health messages offered by different levels of care, based on clinical practice guidelines, in order to provide patient-centred integrated care. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Organizational factors and collaboration and integration activities in criminal justice and drug abuse treatment agencies.

    Science.gov (United States)

    Lehman, Wayne E K; Fletcher, Bennett W; Wexler, Harry K; Melnick, Gerald

    2009-08-01

    Despite strong interest in improving collaborations between correctional and substance abuse treatment organizations, there is a lack of empirical data describing the existing practices. The current study used a national survey of correctional administrators to examine organizational factors related to cross-agency collaboration and integration activities between corrections and substance abuse treatment organizations. Using a measure of collaboration that scaled cross-agency activities from less structured, informal networking and coordination to more structured and formalized levels of cooperation and collaboration, we found that different correctional settings (e.g., community corrections, jails, prisons) differed significantly in terms of their collaborative activities with substance abuse treatment agencies. We also found that the organizational characteristics that were associated with different levels of collaboration and integration differed across the correctional settings. Further research is needed to better understand how and why correctional agencies decide to formalize collaborative arrangements with treatment agencies and whether these efforts lead to more favorable outcomes.

  2. Stakeholder consultations and opportunities for integrating socio-behavioural factors into the pesticide risk analysis process.

    Science.gov (United States)

    Calliera, Maura; Marchis, Alex; Sacchettini, Gabriele; Capri, Ettore

    2016-02-01

    The pesticide risk analysis process is well regulated in the EU, especially in relation to placing on the market authorisation procedures, but in order to avoid risks for human health and environment in the use phase, information on how these substances are employed and on socio-behavioural factors that can influence the exposure have to be taken into account. To better explore reasons about the gap between risk assessment and risk management, within the EU FP7 Health and Environmental Risks: Organisation, Integration and Cross-fertilisation of Scientific Knowledge (HEROIC) project, a stepwise stakeholder's consultation process was developed using a mixed approach in two different phases (survey and roundtable). We elicited stakeholder views regarding factors that could limit the pesticide risk assessment phase linked on how the knowledge is produced and the way the data are used in risk management and in risk communication, also taking into account qualitative factors such as responsibility, trust and behaviours, which could have impact on risk assessment policies. Activities deployed indicate that some changes and interaction are needed to better define the problems at the formulation stage, and the type of information risk assessor has to provide, to better inform risk manager in addressing different societal needs, to strengthen the credibility of the process of risk assessment and improve the effectiveness of policies. Integrations between disciplines may initially increase the complexity but in turn will provide a better and more useful estimation of the risk, reinforce transparency and drive a more efficient use of risk management resources.

  3. Factors of Resilience in Informal Caregivers of People with Dementia from Integrative International Data Analysis.

    Science.gov (United States)

    Joling, Karlijn J; Windle, Gill; Dröes, Rose-Marie; Meiland, Franka; van Hout, Hein P J; MacNeil Vroomen, Janet; van de Ven, Peter M; Moniz-Cook, Esmé; Woods, Bob

    2016-01-01

    Although caring for a person with dementia can be stressful, some caregivers appear to experience few negative consequences to their well-being. This study aimed to examine what proportion of caregivers demonstrates resilience under different challenging circumstances and to identify factors related to their resilience. Baseline data from 4 studies from the Netherlands and UK among informal caregivers of people with dementia were harmonized and integrated. Caregiver resilience was defined as high levels of psychological well-being despite different types of high caregiving demands. Multivariate regression analyses identified factors significantly related to caregiver resilience. The integrated data set included 15 harmonized variables with data from 1,048 caregivers facing a high care demand. The prevalence of resilience varied between 35 and 43%, depending on the demand for high care. Being a male caregiver, caring for a female, living apart from your relative, and low caregiver burden were positively related to caregiver resilience. Caregivers have the capacity to demonstrate resilience despite significant challenges. This study demonstrates how harmonization of data from multiple existing studies can be used to increase power and explore the consistency of findings. This contributes to a better understanding of which factors are likely to facilitate caregiver resilience and offers insights for developing services. © 2016 The Author(s) Published by S. Karger AG, Basel.

  4. Adaptive Multiview Nonnegative Matrix Factorization Algorithm for Integration of Multimodal Biomedical Data

    Directory of Open Access Journals (Sweden)

    Bisakha Ray

    2017-08-01

    Full Text Available The amounts and types of available multimodal tumor data are rapidly increasing, and their integration is critical for fully understanding the underlying cancer biology and personalizing treatment. However, the development of methods for effectively integrating multimodal data in a principled manner is lagging behind our ability to generate the data. In this article, we introduce an extension to a multiview nonnegative matrix factorization algorithm (NNMF for dimensionality reduction and integration of heterogeneous data types and compare the predictive modeling performance of the method on unimodal and multimodal data. We also present a comparative evaluation of our novel multiview approach and current data integration methods. Our work provides an efficient method to extend an existing dimensionality reduction method. We report rigorous evaluation of the method on large-scale quantitative protein and phosphoprotein tumor data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC acquired using state-of-the-art liquid chromatography mass spectrometry. Exome sequencing and RNA-Seq data were also available from The Cancer Genome Atlas for the same tumors. For unimodal data, in case of breast cancer, transcript levels were most predictive of estrogen and progesterone receptor status and copy number variation of human epidermal growth factor receptor 2 status. For ovarian and colon cancers, phosphoprotein and protein levels were most predictive of tumor grade and stage and residual tumor, respectively. When multiview NNMF was applied to multimodal data to predict outcomes, the improvement in performance is not overall statistically significant beyond unimodal data, suggesting that proteomics data may contain more predictive information regarding tumor phenotypes than transcript levels, probably due to the fact that proteins are the functional gene products and therefore a more direct measurement of the functional state of the tumor. Here, we

  5. Sparse multivariate factor analysis regression models and its applications to integrative genomics analysis.

    Science.gov (United States)

    Zhou, Yan; Wang, Pei; Wang, Xianlong; Zhu, Ji; Song, Peter X-K

    2017-01-01

    The multivariate regression model is a useful tool to explore complex associations between two kinds of molecular markers, which enables the understanding of the biological pathways underlying disease etiology. For a set of correlated response variables, accounting for such dependency can increase statistical power. Motivated by integrative genomic data analyses, we propose a new methodology-sparse multivariate factor analysis regression model (smFARM), in which correlations of response variables are assumed to follow a factor analysis model with latent factors. This proposed method not only allows us to address the challenge that the number of association parameters is larger than the sample size, but also to adjust for unobserved genetic and/or nongenetic factors that potentially conceal the underlying response-predictor associations. The proposed smFARM is implemented by the EM algorithm and the blockwise coordinate descent algorithm. The proposed methodology is evaluated and compared to the existing methods through extensive simulation studies. Our results show that accounting for latent factors through the proposed smFARM can improve sensitivity of signal detection and accuracy of sparse association map estimation. We illustrate smFARM by two integrative genomics analysis examples, a breast cancer dataset, and an ovarian cancer dataset, to assess the relationship between DNA copy numbers and gene expression arrays to understand genetic regulatory patterns relevant to the disease. We identify two trans-hub regions: one in cytoband 17q12 whose amplification influences the RNA expression levels of important breast cancer genes, and the other in cytoband 9q21.32-33, which is associated with chemoresistance in ovarian cancer. © 2016 WILEY PERIODICALS, INC.

  6. Human factors analysis and design methods for nuclear waste retrieval systems. Human factors design methodology and integration plan

    Energy Technology Data Exchange (ETDEWEB)

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed.

  7. Human factors analysis and design methods for nuclear waste retrieval systems. Human factors design methodology and integration plan

    International Nuclear Information System (INIS)

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed

  8. Secretion of human epidermal growth factor (EGF) in autotrophic culture by a recombinant hydrogen-utilizing bacterium, Pseudomonas pseudoflava, carrying broad-host-range EGF secretion vector pKSEGF2.

    OpenAIRE

    Hayase, N; Ishiyama, A; Niwano, M

    1994-01-01

    We constructed the broad-host-range human epidermal growth factor (EGF) secretion plasmid pKSEGF2 by inserting the Escherichia coli tac promoter, the signal sequence of Pseudomonas stutzeri amylase, and the synthesized EGF gene into the broad-host-range vector pKT230. E. coli JM109 carrying pKSEGF2 secreted EGF into the periplasm and the culture medium under the control of the tac promoter. Pseudomonas aeruginosa PAO1161 carrying pKSEGF2 and Pseudomonas putida AC10 carrying pKSEGF2 secreted E...

  9. Integration of developmental and environmental signals via a polyadenylation factor in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Man Liu

    Full Text Available The ability to integrate environmental and developmental signals with physiological responses is critical for plant survival. How this integration is done, particularly through posttranscriptional control of gene expression, is poorly understood. Previously, it was found that the 30 kD subunit of Arabidopsis cleavage and polyadenylation specificity factor (AtCPSF30 is a calmodulin-regulated RNA-binding protein. Here we demonstrated that mutant plants (oxt6 deficient in AtCPSF30 possess a novel range of phenotypes--reduced fertility, reduced lateral root formation, and altered sensitivities to oxidative stress and a number of plant hormones (auxin, cytokinin, gibberellic acid, and ACC. While the wild-type AtCPSF30 (C30G was able to restore normal growth and responses, a mutant AtCPSF30 protein incapable of interacting with calmodulin (C30GM could only restore wild-type fertility and responses to oxidative stress and ACC. Thus, the interaction with calmodulin is important for part of AtCPSF30 functions in the plant. Global poly(A site analysis showed that the C30G and C30GM proteins can restore wild-type poly(A site choice to the oxt6 mutant. Genes associated with hormone metabolism and auxin responses are also affected by the oxt6 mutation. Moreover, 19 genes that are linked with calmodulin-dependent CPSF30 functions, were identified through genome-wide expression analysis. These data, in conjunction with previous results from the analysis of the oxt6 mutant, indicate that the polyadenylation factor AtCPSF30 is a regulatory hub where different signaling cues are transduced, presumably via differential mRNA 3' end formation or alternative polyadenylation, into specified phenotypic outcomes. Our results suggest a novel function of a polyadenylation factor in environmental and developmental signal integration.

  10. Probing Genomic Aspects of the Multi-Host Pathogen Clostridium perfringens Reveals Significant Pangenome Diversity, and a Diverse Array of Virulence Factors

    Directory of Open Access Journals (Sweden)

    Raymond Kiu

    2017-12-01

    Full Text Available Clostridium perfringens is an important cause of animal and human infections, however information about the genetic makeup of this pathogenic bacterium is currently limited. In this study, we sought to understand and characterise the genomic variation, pangenomic diversity, and key virulence traits of 56 C. perfringens strains which included 51 public, and 5 newly sequenced and annotated genomes using Whole Genome Sequencing. Our investigation revealed that C. perfringens has an “open” pangenome comprising 11667 genes and 12.6% of core genes, identified as the most divergent single-species Gram-positive bacterial pangenome currently reported. Our computational analyses also defined C. perfringens phylogeny (16S rRNA gene in relation to some 25 Clostridium species, with C. baratii and C. sardiniense determined to be the closest relatives. Profiling virulence-associated factors confirmed presence of well-characterised C. perfringens-associated exotoxins genes including α-toxin (plc, enterotoxin (cpe, and Perfringolysin O (pfo or pfoA, although interestingly there did not appear to be a close correlation with encoded toxin type and disease phenotype. Furthermore, genomic analysis indicated significant horizontal gene transfer events as defined by presence of prophage genomes, and notably absence of CRISPR defence systems in >70% (40/56 of the strains. In relation to antimicrobial resistance mechanisms, tetracycline resistance genes (tet and anti-defensins genes (mprF were consistently detected in silico (tet: 75%; mprF: 100%. However, pre-antibiotic era strain genomes did not encode for tet, thus implying antimicrobial selective pressures in C. perfringens evolutionary history over the past 80 years. This study provides new genomic understanding of this genetically divergent multi-host bacterium, and further expands our knowledge on this medically and veterinary important pathogen.

  11. Probing Genomic Aspects of the Multi-Host Pathogen Clostridium perfringens Reveals Significant Pangenome Diversity, and a Diverse Array of Virulence Factors.

    Science.gov (United States)

    Kiu, Raymond; Caim, Shabhonam; Alexander, Sarah; Pachori, Purnima; Hall, Lindsay J

    2017-01-01

    Clostridium perfringens is an important cause of animal and human infections, however information about the genetic makeup of this pathogenic bacterium is currently limited. In this study, we sought to understand and characterise the genomic variation, pangenomic diversity, and key virulence traits of 56 C. perfringens strains which included 51 public, and 5 newly sequenced and annotated genomes using Whole Genome Sequencing. Our investigation revealed that C. perfringens has an "open" pangenome comprising 11667 genes and 12.6% of core genes, identified as the most divergent single-species Gram-positive bacterial pangenome currently reported. Our computational analyses also defined C. perfringens phylogeny (16S rRNA gene) in relation to some 25 Clostridium species, with C. baratii and C. sardiniense determined to be the closest relatives. Profiling virulence-associated factors confirmed presence of well-characterised C. perfringens -associated exotoxins genes including α-toxin ( plc ), enterotoxin ( cpe ), and Perfringolysin O ( pfo or pfoA ), although interestingly there did not appear to be a close correlation with encoded toxin type and disease phenotype. Furthermore, genomic analysis indicated significant horizontal gene transfer events as defined by presence of prophage genomes, and notably absence of CRISPR defence systems in >70% (40/56) of the strains. In relation to antimicrobial resistance mechanisms, tetracycline resistance genes ( tet ) and anti-defensins genes ( mprF ) were consistently detected in silico ( tet : 75%; mprF : 100%). However, pre-antibiotic era strain genomes did not encode for tet , thus implying antimicrobial selective pressures in C. perfringens evolutionary history over the past 80 years. This study provides new genomic understanding of this genetically divergent multi-host bacterium, and further expands our knowledge on this medically and veterinary important pathogen.

  12. Limited agreement of independent RNAi screens for virus-required host genes owes more to false-negative than false-positive factors.

    Directory of Open Access Journals (Sweden)

    Linhui Hao

    Full Text Available Systematic, genome-wide RNA interference (RNAi analysis is a powerful approach to identify gene functions that support or modulate selected biological processes. An emerging challenge shared with some other genome-wide approaches is that independent RNAi studies often show limited agreement in their lists of implicated genes. To better understand this, we analyzed four genome-wide RNAi studies that identified host genes involved in influenza virus replication. These studies collectively identified and validated the roles of 614 cell genes, but pair-wise overlap among the four gene lists was only 3% to 15% (average 6.7%. However, a number of functional categories were overrepresented in multiple studies. The pair-wise overlap of these enriched-category lists was high, ∼19%, implying more agreement among studies than apparent at the gene level. Probing this further, we found that the gene lists implicated by independent studies were highly connected in interacting networks by independent functional measures such as protein-protein interactions, at rates significantly higher than predicted by chance. We also developed a general, model-based approach to gauge the effects of false-positive and false-negative factors and to estimate, from a limited number of studies, the total number of genes involved in a process. For influenza virus replication, this novel statistical approach estimates the total number of cell genes involved to be ∼2,800. This and multiple other aspects of our experimental and computational results imply that, when following good quality control practices, the low overlap between studies is primarily due to false negatives rather than false-positive gene identifications. These results and methods have implications for and applications to multiple forms of genome-wide analysis.

  13. Factors that condition the spontaneous reporting of adverse drug reactions among nurses: an integrative review.

    Science.gov (United States)

    De Angelis, Alessia; Colaceci, Sofia; Giusti, Angela; Vellone, Ercole; Alvaro, Rosaria

    2016-03-01

    To describe and synthesise previous research on factors conditioning the spontaneous reporting of adverse drug reactions among nurses. Spontaneous reports of adverse drug reactions by health-care providers, are a main instrument for the continuous evaluation of the risk-benefit ratio of every drug. Under-reporting of adverse drug reactions by all health-care providers, in particular by nurses, is a major limitation to this system. An integrated review of the literature was conducted using MEDLINE, CINAHL, Embase, Scopus databases and Google Scholar. After evaluation for appropriateness related to inclusion/exclusion criteria, 16 studies were included in the final analysis and synthesis. Two factors emerged from the study: (1) intrinsic factors related to nurses' knowledge and attitudes; (2) extrinsic factors related to nurses' interaction with health-care organisations and to the relationship between nurses and physicians. Nurses' attitudes that hinder reporting include ignorance, insecurity, fear and lethargy. Nurses are not fully aware of their role in adverse drug reaction reporting. Nurses must acquire greater knowledge to implement specific skills into their daily clinical practice. To improve nurses' reporting of adverse drug reactions, it is necessary to develop management approaches that modify both intrinsic and extrinsic factors. © 2015 John Wiley & Sons Ltd.

  14. Integration of growth factor signals at the c-fos serum response element.

    Science.gov (United States)

    Price, M A; Hill, C; Treisman, R

    1996-04-29

    A transcription factor ternary complex composed of serum response factor (SRF) and a second factor, ternary complex factor (TCF), mediates the response of the c-fos Serum Response Element to growth factors and mitogens. In NIH3T3 fibroblasts, TCF binding is required for transcriptional activation by the SRE in response to activation of the Ras-Raf-ERK pathway. We compared the properties of three members of the TCF family, Elk-1, SAP-1 and SAP-2 (ERP/NET). Although all the proteins contain sequences required for ternary complex formation with SRF, only Elk-1 and SAP-1 appear to interact with the c-fos SRE efficiently in vivo. Each TCF contains a C-terminal activation domain capable of transcriptional activation in response to activation of the Ras-Raf-ERK pathway, and this is dependent on the integrity of S/T-P motifs conserved between all the TCF family members. In contrast, activation of the SRE by whole serum and the mitogenic phospholipid LPA requires SRF binding alone. Constitutively activated members of the Rho subfamily of Ras-like GTPases are also capable of inducing activation of the SRE in the absence of TCF; unlike activated Ras itself, these proteins do not activate the TCFs in NIH3T3 cells. At the SRE, SRF- and TCF-linked signalling pathways act synergistically to potentiate transcription.

  15. [Integrity].

    Science.gov (United States)

    Gómez Rodríguez, Rafael Ángel

    2014-01-01

    To say that someone possesses integrity is to claim that that person is almost predictable about responses to specific situations, that he or she can prudentially judge and to act correctly. There is a closed interrelationship between integrity and autonomy, and the autonomy rests on the deeper moral claim of all humans to integrity of the person. Integrity has two senses of significance for medical ethic: one sense refers to the integrity of the person in the bodily, psychosocial and intellectual elements; and in the second sense, the integrity is the virtue. Another facet of integrity of the person is la integrity of values we cherish and espouse. The physician must be a person of integrity if the integrity of the patient is to be safeguarded. The autonomy has reduced the violations in the past, but the character and virtues of the physician are the ultimate safeguard of autonomy of patient. A field very important in medicine is the scientific research. It is the character of the investigator that determines the moral quality of research. The problem arises when legitimate self-interests are replaced by selfish, particularly when human subjects are involved. The final safeguard of moral quality of research is the character and conscience of the investigator. Teaching must be relevant in the scientific field, but the most effective way to teach virtue ethics is through the example of the a respected scientist.

  16. An Operator-Integration-Factor Splitting (OIFS) method for Incompressible Flows in Moving Domains

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Saumil S. [Argonne National Lab. (ANL), Argonne, IL (United States); Fischer, Paul F. [Argonne National Lab. (ANL), Argonne, IL (United States); Univ. of Illinois, Urbana-Champaign, IL (United States); Min, Misun [Argonne National Lab. (ANL), Argonne, IL (United States); Tomboulides, Ananias G [Argonne National Lab. (ANL), Argonne, IL (United States); Aristotle Univ., Thessaloniki (Greece)

    2017-10-21

    In this paper, we present a characteristic-based numerical procedure for simulating incompressible flows in domains with moving boundaries. Our approach utilizes an operator-integration-factor splitting technique to help produce an effcient and stable numerical scheme. Using the spectral element method and an arbitrary Lagrangian-Eulerian formulation, we investigate flows where the convective acceleration effects are non-negligible. Several examples, ranging from laminar to turbulent flows, are considered. Comparisons with a standard, semi-implicit time-stepping procedure illustrate the improved performance of the scheme.

  17. The integration of expert-defined importance factors to enrich Bayesian Fault Tree Analysis

    International Nuclear Information System (INIS)

    Darwish, Molham; Almouahed, Shaban; Lamotte, Florent de

    2017-01-01

    This paper proposes an analysis of a hybrid Bayesian-Importance model for system designers to improve the quality of services related to Active Assisted Living Systems. The proposed model is based on two factors: failure probability measure of different service components and, an expert defined degree of importance that each component holds for the success of the corresponding service. The proposed approach advocates the integration of expert-defined importance factors to enrich the Bayesian Fault Tree Analysis (FTA) approach. The evaluation of the proposed approach is conducted using the Fault Tree Analysis formalism where the undesired state of a system is analyzed using Boolean logic mechanisms to combine a series of lower-level events.

  18. Thermal neutron capture cross sections resonance integrals and g-factors

    International Nuclear Information System (INIS)

    Mughabghab, S.F.

    2003-02-01

    The thermal radiative capture cross sections and resonance integrals of elements and isotopes with atomic numbers from 1 to 83 (as well as 232 Th and 238 U) have been re-evaluated by taking into consideration all known pertinent data published since 1979. This work has been undertaken as part of an IAEA co-ordinated research project on 'Prompt capture gamma-ray activation analysis'. Westcott g-factors for radiative capture cross sections at a temperature of 300K were computed by utilizing the INTER code and ENDF-B/VI (Release 8) library files. The temperature dependence of the Westcott g-factor is illustrated for 113 Cd, 124 Xe and 157 Gd at temperatures of 150, 294 and 400K. Comparisons have also been made of the newly evaluated capture cross sections of 6 Li, 7 Li, 12 C and 207 Pb with those determined by the k 0 method. (author)

  19. Factors associated with health risk behaviors among Brazilian adolescents: an integrative review.

    Science.gov (United States)

    Moura, Luciana Ramos de; Torres, Lilian Machado; Cadete, Matilde Meire Miranda; Cunha, Cristiane de Freitas

    2018-01-01

    Identifying knowledge about factors associated with health risk behaviors among Brazilian adolescents. An integrative review of the literature conducted in the Cochrane, IBECS, LILACS, MEDLINE and SciELO databases in relation to risk behaviors recommended by the Centers for Disease Control and Prevention. Thirty-seven (37) studies were analyzed, with a predominance of risky sexual behavior, tobacco use and violent behavior. Advancing age favored unprotected sex, alcohol and tobacco use. Family and friends influence was related to smoking and alcoholism. Males were more involved in situations of violence and the female gender was associated with physical inactivity. Belonging to a lower economic class was related to unprotected sex, physical inactivity, unhealthy dietary behaviors and violence. Studying in private school was related to unhealthy dietary behavior. Risk behaviors were related to social, economic and family factors and they tend to agglomerate.

  20. Sami in the History of the Norwegian-Russian Borderland: Factor of Tension or Regional Integration?

    Directory of Open Access Journals (Sweden)

    Vladislav I. Goldin

    2015-09-01

    Full Text Available This article is based of an extensive array of documents and cartographic materials of the leading archives of the Russian Federation and Norway. The authors focus their attention on the history of Russian-Norwegian border and the Sami aspect of its development. On the Scandinavian continent, the population of frontier areas was often a factor of political tension, but the ethnic picture of the Russian-Norwegian borderland distinguished by the fact that the frontier status of the Skolt was the integration factor for the formation of economic cooperation between the border provinces of Russia and Norway. This thesis the authors explain by the peculiarities of the States policy regarding the border territories, ethnic groups, economic activities and economic interaction of Skolt with other communities, as well as their perception of own inhabited space.

  1. Integrated approach to knowledge acquisition and safety management of complex plants with emphasis on human factors

    International Nuclear Information System (INIS)

    Kosmowski, K.T.

    1998-01-01

    In this paper an integrated approach to the knowledge acquisition and safety management of complex industrial plants is proposed and outlined. The plant is considered within a man-technology-environment (MTE) system. The knowledge acquisition is aimed at the consequent reliability evaluation of human factor and probabilistic modeling of the plant. Properly structured initial knowledge is updated in life-time of the plant. The data and knowledge concerning the topology of safety related systems and their functions are created in a graphical CAD system and are object oriented. Safety oriented monitoring of the plant includes abnormal situations due to external and internal disturbances, failures of hard/software components and failures of human factor. The operation and safety related evidence is accumulated in special data bases. Data/knowledge bases are designed in such a way to support effectively the reliability and safety management of the plant. (author)

  2. Severe hypertriglyceridemia and factors associated with acute pancreatitis in an integrated health care system.

    Science.gov (United States)

    Rashid, Nazia; Sharma, Puza P; Scott, Ronald D; Lin, Kathy J; Toth, Peter P

    2016-01-01

    To evaluate patient characteristics, treatment patterns, comorbidities, and risk factors associated with the development of acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG) in an integrated health care delivery system. We identified a retrospective cohort of severe HTG patients with a fasting triglyceride level ≥ 1000 mg/dL during January 1, 2007 to June 30, 2013 (index date) in an integrated health care delivery system. Patients were aged ≥18 years on index date and had 12 months of continuous membership and drug eligibility before the index date and during postindex including index date. Baseline patient characteristics, comorbidities, and risk factors were evaluated during 12-month preindex. Outcomes such as development of AP, treatment patterns, adherence to index therapy, and change in triglyceride (TG) laboratory levels were evaluated during postindex. Descriptive statistics were used to identify differences between patients developing AP vs no development of AP. A stepwise multivariate logistic regression and backward elimination method were used to assess statistically significant predictive factors associated with development of AP vs no AP. We identified 5550 patients with severe HTG, and 5.4% of these patients developed AP during postindex. Patients were mostly male (≥70%) in both groups; however, younger in the AP group (45 years ± 10.6) vs no AP group (50 years ± 11.4) with P value severe HTG are at a higher risk of developing AP. A number of comorbidities, risk factors, and baseline TG levels are associated with an increased incidence of AP. Patients with severe HTG are underdiagnosed, undertreated and are nonadherent to their index lipid therapy. There is a need to better define optimal approaches to treating severe HTG so as to reduce the incidence of AP. Economic studies are also needed to evaluate the burden of AP on various health care systems. Copyright © 2016 National Lipid Association. Published by

  3. ARE METHODS USED TO INTEGRATE STANDARDIZED MANAGEMENT SYSTEMS A CONDITIONING FACTOR OF THE LEVEL OF INTEGRATION? AN EMPIRICAL STUDY

    Directory of Open Access Journals (Sweden)

    Merce Bernardo

    2011-09-01

    Full Text Available Organizations are increasingly implementing multiple Management System Standards (M SSs and considering managing the related Management Systems (MSs as a single system.The aim of this paper is to analyze if methods us ed to integrate standardized MSs condition the level of integration of those MSs. A descriptive methodology has been applied to 343 Spanish organizations registered to, at least, ISO 9001 and ISO 14001. Seven groups of these organizations using different combinations of methods have been analyzed Results show that these organizations have a high level of integration of their MSs. The most common method used, was the process map. Organizations using a combination of different methods achieve higher levels of integration than those using a single method. However, no evidence has been found to confirm the relationship between the method used and the integration level achieved.

  4. Designing medical technology for resilience: integrating health economics and human factors approaches.

    Science.gov (United States)

    Borsci, Simone; Uchegbu, Ijeoma; Buckle, Peter; Ni, Zhifang; Walne, Simon; Hanna, George B

    2018-01-01

    The slow adoption of innovation into healthcare calls into question the manner of evidence generation for medical technology. This paper identifies potential reasons for this including a lack of attention to human factors, poor evaluation of economic benefits, lack of understanding of the existing healthcare system and a failure to recognise the need to generate resilient products. Areas covered: Recognising a cross-disciplinary need to enhance evidence generation early in a technology's life cycle, the present paper proposes a new approach that integrates human factors and health economic evaluation as part of a wider systems approach to the design of technology. This approach (Human and Economic Resilience Design for Medical Technology or HERD MedTech) supports early stages of product development and is based on the recent experiences of the National Institute for Health Research London Diagnostic Evidence Co-operative in the UK. Expert commentary: HERD MedTech i) proposes a shift from design for usability to design for resilience, ii) aspires to reduce the need for service adaptation to technological constraints iii) ensures value of innovation at the time of product development, and iv) aims to stimulate discussion around the integration of pre- and post-market methods of assessment of medical technology.

  5. Factors associated with the utilization of dental health services by the pediatric population: an integrative review.

    Science.gov (United States)

    Curi, Davi Silva Carvalho; Figueiredo, Andreia Cristina Leal; Jamelli, Silvia Regina

    2018-05-01

    This integrative literature review aimed to analyze studies about factors associated with the utilization of dental health services by the pediatric population between zero and 15 years old, published between 2006 and 2016 and available in Portuguese, English or Spanish. A survey of articles in the Lilacs and Medline databases was carried out, using the search strategy: ("dental care/utilization" OR "dental health services/utilization") AND ("child" OR "child, preschool") AND NOT adult. To analyze the methodological quality, the adapted Critical Appraisal Skill Programme (CASP) and the Agency for Healthcare and Research and Quality (AHRQ) were used. The following predictors of use of dental health services stood out: factors associated with children or adolescents (age, frequency of tooth brushing, chronic conditions), caregivers (schooling, perception of child's dental health, perceived oral health needs), dentists (availability at night and on the weekends) and follow up of oral health by the family health team. These are inherent factors for the planning of oral health policies or programs for the pediatric population. However, these factors vary according to the context, and therefore, a contextual analysis should be conducted.

  6. Factors Related to Healthy Siblings' Psychosocial Adjustment to Children With Cancer: An Integrative Review.

    Science.gov (United States)

    Zegaczewski, Tara; Chang, Karen; Coddington, Jennifer; Berg, Abby

    2016-01-01

    To identify factors related to the psychosocial adjustment of healthy siblings of children with cancer (HSCC). An integrative review was conducted. Controlled vocabularies relevant to siblings, pediatrics, children, neoplasms, and psychosocial adaptation were used to search Cumulative Index to Nursing & Allied Health Literature and PubMed. Articles that met inclusion criteria (eg, quantitative studies related to HSCC's psychosocial adjustment; had sample sizes of at least 30; and HSCC age between 1 and 19 years) were reviewed. Key findings of selected articles were analyzed according to sibling characteristics, social support, and contextual factors. Seven nonexperimental and 5 quasi-experimental studies were reviewed. HSCC's characteristics (eg, age, gender), perceived social support from family and summer camp, and perceived contextual factors (eg, role overload, family adaptability) were significant factors that correlated with HSCC's psychosocial adjustment. When caring for a child diagnosed with cancer, nurses need to include HSCC in the assessment of a family unit's adaptation to cancer distress and provide appropriate interventions to promote HSCC's psychosocial well-being. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

  7. The co-integration analysis of factors affecting electricity consumption : a case study of Thailand

    Energy Technology Data Exchange (ETDEWEB)

    Kongruang, C. [Thaksin Univ., Songkhla (Thailand). Faculty of Economics and Business; Waewsak, J. [Thaksin Univ., Phatthalung (Thailand). Dept. of Physics, Solar and Wind Energy Research Lab

    2008-07-01

    A study was conducted in which the main determinants of electricity demand in Thailand were investigated. Time-series analysis methods were used, notably the unit root test, the Johansen co-integration test and an error correction model (ECM). The objective was to determine the factors affecting short and long-run electricity consumption. This paper presented annual time series data from 1971 to 2006. The unit root test revealed that all series are non-stationary. The Johansen co-integration test revealed the co-integration between variables and the existence of the long-term relationship between them. Electricity consumption accelerated with the increase in gross domestic product (GDP) and population. In contrast, an increase in commodity price would reduce electricity consumption. The coefficient of population indicated that an increase of 1 million in total population would result in an increase in electricity consumption of 0.099 per cent. Last, the results of ECM revealed that nearly 21 per cent of long-term disequilibrium is adjusted to the current period. The factors that affect electricity consumption include GDP growth, inflation rate and population growth. It was concluded that Thailand should prepare for additional power generation from clean energy sources such as solar, biomass and wind energy. Thailand's Energy Policy and Planning Office revealed that electricity consumption in 2008 would be over 130,000 GWh with per capita consumption at nearly 2,000 kWh. The power peak demand will be nearly 24,000 MW in 2008. This result was based on the forecasting model that considered only GDP growth. However, electricity consumption depends not only on the GDP growth, but also upon the other key variables such as population, electricity selling price, consumer price index and temperature. 17 refs., 5 tabs., 4 figs.

  8. Aggregate Exposure and Cumulative Risk Assessment--Integrating Occupational and Non-occupational Risk Factors.

    Science.gov (United States)

    Lentz, T J; Dotson, G S; Williams, P R D; Maier, A; Gadagbui, B; Pandalai, S P; Lamba, A; Hearl, F; Mumtaz, M

    2015-01-01

    Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational.

  9. Risk factors for unstable blood glucose level: integrative review of the risk factors related to the nursing diagnosis.

    Science.gov (United States)

    Teixeira, Andressa Magalhães; Tsukamoto, Rosangela; Lopes, Camila Takáo; Silva, Rita de Cassia Gengo E

    2017-06-05

    to identify evidence in the literature on the possible risk factors for the risk of unstable blood glucose diagnosis in individuals with type 2 diabetes mellitus, and to compare them with the risk factors described by NANDA International. an integrative literature review guided by the question: what are the risk factors for unstable blood glucose level in people with type 2 diabetes mellitus? Primary studies were included whose outcomes were variations in glycemic levels, published in English, Portuguese or Spanish, in PubMed or CINAHL between 2010 and 2015. altered levels of glycated hemoglobin, body mass index>31 kg/m2, previous history of hypoglycemia, cognitive deficit/dementia, autonomic cardiovascular neuropathy, comorbidities and weight loss corresponded to risk factors described in NANDA International. Other risk factors identified were: advanced age, black skin color, longer length of diabetes diagnosis, daytime sleepiness, macroalbuminuria, genetic polymorphisms, insulin therapy, use of oral antidiabetics, and use of metoclopramide, inadequate physical activity and low fasting glycemia. risk factors for the diagnosis, risk for unstable blood glucose level, for persons with type 2 diabetes mellitus were identified, and 42% of them corresponded to those of NANDA International. These findings may contribute to the practice of clinical nurses in preventing the deleterious effects of glycemic variation. identificar evidências na literatura acerca de possíveis fatores de risco do diagnóstico risco de glicemia instável para pessoas com diabetes mellitus tipo 2 e compará-los com os fatores de risco descritos pela NANDA International . revisão integrativa norteada pela pergunta: quais são os fatores de risco de glicemia instável em pessoas com diabetes mellitus tipo 2? Incluíram-se estudos primários cujos desfechos eram variações nos níveis glicêmicos, publicados em inglês, português ou espanhol no PubMed ou CINAHL entre 2010 e 2015. observou

  10. Model-based identification and use of task complexity factors of human integrated systems

    International Nuclear Information System (INIS)

    Ham, Dong-Han; Park, Jinkyun; Jung, Wondea

    2012-01-01

    Task complexity is one of the conceptual constructs that are critical to explain and predict human performance in human integrated systems. A basic approach to evaluating the complexity of tasks is to identify task complexity factors and measure them. Although a great deal of task complexity factors have been studied, there is still a lack of conceptual frameworks for identifying and organizing them analytically, which can be generally used irrespective of the types of domains and tasks. This study proposes a model-based approach to identifying and using task complexity factors, which has two facets—the design aspects of a task and complexity dimensions. Three levels of design abstraction, which are functional, behavioral, and structural aspects of a task, characterize the design aspect of a task. The behavioral aspect is further classified into five cognitive processing activity types. The complexity dimensions explain a task complexity from different perspectives, which are size, variety, and order/organization. Twenty-one task complexity factors are identified by the combination of the attributes of each facet. Identification and evaluation of task complexity factors based on this model is believed to give insights for improving the design quality of tasks. This model for complexity factors can also be used as a referential framework for allocating tasks and designing information aids. The proposed approach is applied to procedure-based tasks of nuclear power plants (NPPs) as a case study to demonstrate its use. Last, we compare the proposed approach with other studies and then suggest some future research directions.

  11. Measuring Integrated Socioemotional Guidance at School: Factor Structure and Reliability of the Socioemotional Guidance Questionnaire (SEG-Q)

    Science.gov (United States)

    Jacobs, Karen; Struyf, Elke

    2013-01-01

    Socioemotional guidance of students has recently become an integral part of education, however no instrument exists to measure integrated socioemotional guidance. This study therefore examines the factor structure and reliability of the Socioemotional Guidance Questionnaire. Psychometric properties of the Socioemotional Guidance Questionnaire and…

  12. Explicit Solutions for the (2 + 1-Dimensional Jaulent–Miodek Equation Using the Integrating Factors Method in an Unbounded Domain

    Directory of Open Access Journals (Sweden)

    Rahma Sadat

    2018-03-01

    Full Text Available In this work, we prove that the integrating factors can be used as a reduction method. Analytical solutions of the Jaulent–Miodek (JM equation are obtained using integrating factors as an extension of a recent work where, through hidden symmetries, the JM was reduced to ordinary differential equations (ODEs. Some of these ODEs had no quadrature. We here derive several new solutions for these non-solvable ODEs.

  13. Interactions between the spatial and temporal stimulus factors that influence multisensory integration in human performance.

    Science.gov (United States)

    Stevenson, Ryan A; Fister, Juliane Krueger; Barnett, Zachary P; Nidiffer, Aaron R; Wallace, Mark T

    2012-05-01

    In natural environments, human sensory systems work in a coordinated and integrated manner to perceive and respond to external events. Previous research has shown that the spatial and temporal relationships of sensory signals are paramount in determining how information is integrated across sensory modalities, but in ecologically plausible settings, these factors are not independent. In the current study, we provide a novel exploration of the impact on behavioral performance for systematic manipulations of the spatial location and temporal synchrony of a visual-auditory stimulus pair. Simple auditory and visual stimuli were presented across a range of spatial locations and stimulus onset asynchronies (SOAs), and participants performed both a spatial localization and simultaneity judgment task. Response times in localizing paired visual-auditory stimuli were slower in the periphery and at larger SOAs, but most importantly, an interaction was found between the two factors, in which the effect of SOA was greater in peripheral as opposed to central locations. Simultaneity judgments also revealed a novel interaction between space and time: individuals were more likely to judge stimuli as synchronous when occurring in the periphery at large SOAs. The results of this study provide novel insights into (a) how the speed of spatial localization of an audiovisual stimulus is affected by location and temporal coincidence and the interaction between these two factors and (b) how the location of a multisensory stimulus impacts judgments concerning the temporal relationship of the paired stimuli. These findings provide strong evidence for a complex interdependency between spatial location and temporal structure in determining the ultimate behavioral and perceptual outcome associated with a paired multisensory (i.e., visual-auditory) stimulus.

  14. Application of variational principles and adjoint integrating factors for constructing numerical GFD models

    Science.gov (United States)

    Penenko, Vladimir; Tsvetova, Elena; Penenko, Alexey

    2015-04-01

    The proposed method is considered on an example of hydrothermodynamics and atmospheric chemistry models [1,2]. In the development of the existing methods for constructing numerical schemes possessing the properties of total approximation for operators of multiscale process models, we have developed a new variational technique, which uses the concept of adjoint integrating factors. The technique is as follows. First, a basic functional of the variational principle (the integral identity that unites the model equations, initial and boundary conditions) is transformed using Lagrange's identity and the second Green's formula. As a result, the action of the operators of main problem in the space of state functions is transferred to the adjoint operators defined in the space of sufficiently smooth adjoint functions. By the choice of adjoint functions the order of the derivatives becomes lower by one than those in the original equations. We obtain a set of new balance relationships that take into account the sources and boundary conditions. Next, we introduce the decomposition of the model domain into a set of finite volumes. For multi-dimensional non-stationary problems, this technique is applied in the framework of the variational principle and schemes of decomposition and splitting on the set of physical processes for each coordinate directions successively at each time step. For each direction within the finite volume, the analytical solutions of one-dimensional homogeneous adjoint equations are constructed. In this case, the solutions of adjoint equations serve as integrating factors. The results are the hybrid discrete-analytical schemes. They have the properties of stability, approximation and unconditional monotony for convection-diffusion operators. These schemes are discrete in time and analytic in the spatial variables. They are exact in case of piecewise-constant coefficients within the finite volume and along the coordinate lines of the grid area in each

  15. In-vehicle human factors for integrated multi-function systems: Making ITS user-friendly

    Energy Technology Data Exchange (ETDEWEB)

    Spelt, P.F.; Scott, S.

    1998-04-01

    As more and more Intelligent Transportation System in-vehicle equipment enters the general consumer market, the authors are about to find out how different design engineers are from ordinary drivers. Driver information systems are being developed and installed in vehicles at an ever-increasing rate. These systems provide information on diverse topics of concern and convenience to the driver, such as routing and navigation, emergency and collision warnings, and a variety of motorists services, or yellow pages functions. Most of these systems are being developed and installed in isolation from each other, with separate means of gathering the information and of displaying it to the driver. The current lack of coordination among on-board systems threatens to create a situation in which different messages on separate displays will be competing with each other for the drivers attention. Urgent messages may go unnoticed, and the number of messages may distract the driver from the most critical task of controlling the vehicle. Thus, without good human factors design and engineering for integrating multiple systems in the vehicle, consumers may find ITS systems confusing and frustrating to use. The current state of the art in human factors research and design for in-vehicle systems has a number of fundamental gaps. Some of these gaps were identified during the Intelligent Vehicle Initiative Human Factors Technology Workshop, sponsored by the US Department of Transportation, in Troy, Michigan, December 10--11, 1997. One task for workshop participants was to identify needed research areas or topics relating to in-vehicle human factors. The top ten unmet research needs from this workshop are presented. Many of these gaps in human factors research knowledge indicate the need for standardization in the functioning of interfaces for safety-related devices such as collision avoidance systems (CAS) and adaptive cruise controls (ACC). Such standards and guidelines will serve to make

  16. Accessible protocol for practice classroom about physical and chemical factors that affect the biomembranes integrity

    Directory of Open Access Journals (Sweden)

    Thiago Barros Galvão

    2012-12-01

    Full Text Available The aim of the current work is to review a protocol used in practical classes to demonstrate some factors that affect biomembrane integrity. Sugar-beet fragments were utilized as the experimental model as membrane damage could be visualized by leakage of betacyanins, hydrophilic pigments accumulated in the cell vacuoles. The tests were carried out as discrete experiments utilizing physical agents and chemical products present in the student daily routine. To test the effect of temperature, sugar-beet fragments were submitted to heat, cold or both at different times of exposition. When chemical products were tested, sugar-beet fragments were exposed to organic solvents (common alcohol and acetone or polar and amphipathic substances (disinfectant, detergent, hydrogen peroxide, and sodium hypochlorite. The obtained results were discussed in terms of the capacity of the physical and chemical factors to cause membrane damage. The review of this protocol using reagents that are present in the student daily routine were able to demonstrate clearly the effect of the different tested factors, allowing the utilization of this practical class under limited conditions.

  17. Safety, reliability, risk management and human factors: an integrated engineering approach applied to nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    Vasconcelos, Vanderley de; Silva, Eliane Magalhaes Pereira da; Costa, Antonio Carlos Lopes da; Reis, Sergio Carneiro dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)], e-mail: vasconv@cdtn.br, e-mail: silvaem@cdtn.br, e-mail: aclc@cdtn.br, e-mail: reissc@cdtn.br

    2009-07-01

    Nuclear energy has an important engineering legacy to share with the conventional industry. Much of the development of the tools related to safety, reliability, risk management, and human factors are associated with nuclear plant processes, mainly because the public concern about nuclear power generation. Despite the close association between these subjects, there are some important different approaches. The reliability engineering approach uses several techniques to minimize the component failures that cause the failure of the complex systems. These techniques include, for instance, redundancy, diversity, standby sparing, safety factors, and reliability centered maintenance. On the other hand system safety is primarily concerned with hazard management, that is, the identification, evaluation and control of hazards. Rather than just look at failure rates or engineering strengths, system safety would examine the interactions among system components. The events that cause accidents may be complex combinations of component failures, faulty maintenance, design errors, human actions, or actuation of instrumentation and control. Then, system safety deals with a broader spectrum of risk management, including: ergonomics, legal requirements, quality control, public acceptance, political considerations, and many other non-technical influences. Taking care of these subjects individually can compromise the completeness of the analysis and the measures associated with both risk reduction, and safety and reliability increasing. Analyzing together the engineering systems and controls of a nuclear facility, their management systems and operational procedures, and the human factors engineering, many benefits can be realized. This paper proposes an integration of these issues based on the application of systems theory. (author)

  18. Safety, reliability, risk management and human factors: an integrated engineering approach applied to nuclear facilities

    International Nuclear Information System (INIS)

    Vasconcelos, Vanderley de; Silva, Eliane Magalhaes Pereira da; Costa, Antonio Carlos Lopes da; Reis, Sergio Carneiro dos

    2009-01-01

    Nuclear energy has an important engineering legacy to share with the conventional industry. Much of the development of the tools related to safety, reliability, risk management, and human factors are associated with nuclear plant processes, mainly because the public concern about nuclear power generation. Despite the close association between these subjects, there are some important different approaches. The reliability engineering approach uses several techniques to minimize the component failures that cause the failure of the complex systems. These techniques include, for instance, redundancy, diversity, standby sparing, safety factors, and reliability centered maintenance. On the other hand system safety is primarily concerned with hazard management, that is, the identification, evaluation and control of hazards. Rather than just look at failure rates or engineering strengths, system safety would examine the interactions among system components. The events that cause accidents may be complex combinations of component failures, faulty maintenance, design errors, human actions, or actuation of instrumentation and control. Then, system safety deals with a broader spectrum of risk management, including: ergonomics, legal requirements, quality control, public acceptance, political considerations, and many other non-technical influences. Taking care of these subjects individually can compromise the completeness of the analysis and the measures associated with both risk reduction, and safety and reliability increasing. Analyzing together the engineering systems and controls of a nuclear facility, their management systems and operational procedures, and the human factors engineering, many benefits can be realized. This paper proposes an integration of these issues based on the application of systems theory. (author)

  19. A plastic stress intensity factor approach to turbine disk structural integrity assessment

    Directory of Open Access Journals (Sweden)

    V. Shlyannikov

    2016-07-01

    Full Text Available This study based on a new fracture mechanics parameter is concerned with assessing the integrity of cracked steam turbine disk which operate under startup-shutdown cyclic loading conditions. Damage accumulation and growth in service have occurred on the inner surface of slot fillet of key. In order to determine elastic-plastic fracture mechanics parameters full-size stress-strain state analysis of turbine disk was performed for a quote-elliptical part-through cracks under considering loading conditions. As a result distributions of elastic and plastic stress intensity factors along crack front in slot fillet of key of turbine disk depending on surface crack form are defined. An engineering approach to the prediction of carrying capacity of cracked turbine disk which is sensitive to the loading history at maintenance is proposed. The predictions of the rate of crack growth and residual lifetime of steam turbine disk are compared for elastic and elastic-plastic solutions. It is shown that the previously proposed elastic crack growth models provide overestimate the lifetime with respect to the present one. An advantage to use the plastic stress intensity factor to characterize the fracture resistance as the self-dependent unified parameter for a variety of turbine disk configurations rather than the magnitude of the elastic stress intensity factors alone is discussed.

  20. Mutations in Encephalomyocarditis Virus 3A Protein Uncouple the Dependency of Genome Replication on Host Factors Phosphatidylinositol 4-Kinase IIIα and Oxysterol-Binding Protein

    NARCIS (Netherlands)

    Dorobantu, Cristina M|info:eu-repo/dai/nl/372622283; Albulescu, Lucian|info:eu-repo/dai/nl/369492382; Lyoo, Heyrhyoung|info:eu-repo/dai/nl/412352931; van Kampen, Mirjam; De Francesco, Raffaele; Lohmann, Volker; Harak, Christian; van der Schaar, Hilde M|info:eu-repo/dai/nl/318007568; Strating, Jeroen R P M|info:eu-repo/dai/nl/298979594; Gorbalenya, Alexander E; van Kuppeveld, Frank J M|info:eu-repo/dai/nl/156614723

    2016-01-01

    Positive-strand RNA [(+)RNA] viruses are true masters of reprogramming host lipid trafficking and synthesis to support virus genome replication. Via their membrane-associated 3A protein, picornaviruses of the genus Enterovirus (e.g., poliovirus, coxsackievirus, and rhinovirus) subvert Golgi

  1. Integrated System Validation of Barakah Nuclear Power Plant in UAE for The Human Factor Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Munsoo [KHNP CRI, Daejeon (Korea, Republic of)

    2016-10-15

    APR1400 simulator has been developed based on the state-of-the-art object-oriented simulation technology of TH(Thermo-Hydraulic) and Reactor Core model, which is applied for the first time in the our country and for the exportation, to well simulate characteristics of APR1400. Barakah unit 1,2 simulator are constructed and supplied with this type simulator model. Integrated system validation was performed using a simulator to verify the HFE(Human Factor Engineering) design of the MCR(Maim Control Room) for instrumentation and control system validation of the UAE nuclear power plant. APR1400 for the Barakah unit 1,2 has many specific features such as digital I and C, and digitalized main control room (MCR) design. From January 2016 to February, during six weeks, the tests carried out three times repeatedly and the various proposals for ergonomical satisfactation were derived. However, the HFE errors that cause significant change of validation target for APR1400 MCR design safety fidelity wasn't found. This has resulted in the conclusion to prove the stability of the basic design of APR1400 MCR. In the future, using the simulator derives the HFE requirements of the MCR systems and continually improve the simulator will be built in close to real high-fidelity power plant. These Integrated system validations are likely to be a great help in operating safety and preventing human errors by operators. Therefore successful completion of the Integrated System Validation for BNPP simulation will be effective to promotion the distinction of our simulator and APR1400 NPP.

  2. Integration of human factors and ergonomics during medical device design and development: it's all about communication.

    Science.gov (United States)

    Vincent, Christopher James; Li, Yunqiu; Blandford, Ann

    2014-05-01

    Manufacturers of interactive medical devices, such as infusion pumps, need to ensure that devices minimise the risk of unintended harm during use. However, development teams face challenges in incorporating Human Factors. The aim of the research reported here was to better understand the constraints under which medical device design and development take place. We report the results of a qualitative study based on 19 semi-structured interviews with professionals involved in the design, development and deployment of interactive medical devices. A thematic analysis was conducted. Multiple barriers to designing for safety and usability were identified. In particular, we identified barriers to communication both between the development organisation and the intended users and between different teams within the development organisation. We propose the use of mediating representations. Artefacts such as personas and scenarios, known to provide integration across multiple perspectives, are an essential component of designing for safety and usability. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  3. Modularity, Integration and IT Personnel Skills Factors in Linking ERP to SCM Systems

    Directory of Open Access Journals (Sweden)

    Sock H Chung

    2010-12-01

    Full Text Available This study investigates some underlying technological factors for linking enterprise resource planning (ERP to supply chain management (SCM systems. ERP systems serve technological requirements across functional areas within a corporate boundary while SCM systems focus on collaborative relationships with partners in the supply chain, emphasizing business process integration and information sharing through IT. In order to facilitate SCM operations for business planning and decision making, an ERP system must be extensible in terms of support for a range of external constituents in the supply chain. The research reported in this paper investigates these linkages and provides a framework for developing and evaluating SCM processes in order to serve enterprise needs in terms of resource management for scalability, implementation costs and operational efficiency for meeting the business objectives.

  4. Success Factors in Integrated Natural Resource Management R&D: Lessons from Practice

    Directory of Open Access Journals (Sweden)

    Jürgen Hagmann

    2002-01-01

    Full Text Available This paper analyzes integrated natural resource management (INRM lessons and success factors based on a practical case study over more than 10 years in Zimbabwe. The work was geared toward enhancing the adaptive management capacity of the stakeholders in their resource-use systems. One main result was the development and institutionalization of an approach for participatory and integrated NRM research and extension. The INRM approach described is grounded in a learning paradigm and a combination of theories: the constructivist perspective to development, systemic intervention, and learning process approaches. Participatory action research and experiential learning, in which researchers engage themselves as actors rather than neutral analysts in an R&D process to explore the livelihood system and develop appropriate solutions together with the resource users, has shown high potential. However, this should be guided by a clear strategy, impact orientation, and high-quality process facilitation at different levels. The case study revealed the importance of a "reflective practitioner" approach by all actors. More effective response to the challenges of increasing complexity in NRM requires a shift in thinking from the linearity of research-extension-farmer to alternative, multiple-actor institutional arrangements and innovation systems. To overcome the weak attribution of research outcomes to actual impact, it also suggests an alternative to conventional impact assessment in INRM R&D interventions.

  5. Human Factors methods concerning integrated validation of nuclear power plant control rooms

    International Nuclear Information System (INIS)

    Oskarsson, Per-Anders; Johansson, Bjoern J.E.; Gonzalez, Natalia

    2010-02-01

    The frame of reference for this work was existing recommendations and instructions from the NPP area, experiences from the review of the Turbic Validation and experiences from system validations performed at the Swedish Armed Forces, e.g. concerning military control rooms and fighter pilots. These enterprises are characterized by complex systems in extreme environments, often with high risks, where human error can lead to serious consequences. A focus group has been performed with representatives responsible for Human Factors issues from all Swedish NPP:s. The questions that were discussed were, among other things, for whom an integrated validation (IV) is performed and its purpose, what should be included in an IV, the comparison with baseline measures, the design process, the role of SSM, which methods of measurement should be used, and how the methods are affected of changes in the control room. The report brings different questions to discussion concerning the validation process. Supplementary methods of measurement for integrated validation are discussed, e.g. dynamic, psychophysiological, and qualitative methods for identification of problems. Supplementary methods for statistical analysis are presented. The study points out a number of deficiencies in the validation process, e.g. the need of common guidelines for validation and design, criteria for different types of measurements, clarification of the role of SSM, and recommendations for the responsibility of external participants in the validation process. The authors propose 12 measures for taking care of the identified problems

  6. Critical factors affecting the integration of biomass gasification and syngas fermentation technology

    Directory of Open Access Journals (Sweden)

    Karthikeyan D. Ramachandriya

    2016-05-01

    Full Text Available Gasification-fermentation is a thermochemical-biological platform for the production of fuels and chemicals. Biomass is gasified at high temperatures to make syngas, a gas composed of CO, CO2, H2, N2 and other minor components. Syngas is then fed to anaerobic microorganisms that convert CO, CO2 and H2 to alcohols by fermentation. This platform offers numerous advantages such as flexibility of feedstock and syngas composition and lower operating temperature and pressure compared to other catalytic syngas conversion processes. In comparison to hydrolysis-fermentation, gasification-fermentation has a major advantage of utilizing all organic components of biomass, including lignin, to yield higher fuel production. Furthermore, syngas fermentation microorganisms do not require strict CO:H2:CO2 ratios, hence gas reforming is not required. However, several issues must be addressed for successful deployment of gasification-fermentation, particularly those that involve the integration of gasification and fermentation. Most previous reviews have focused only on either biomass gasification or syngas fermentation. In this review, the critical factors that affect the integration of biomass gasification with syngas fermentation, such as carbon conversion efficiency, effect of trace gaseous species, H2 to CO ratio requirements, and microbial preference of carbon substrate, are thoroughly discussed.

  7. Cloud Computing Integrated Multi-Factor Authentication Framework Application in Logistics Information Systems

    Directory of Open Access Journals (Sweden)

    Zeynel Erdi Karabulut

    2017-12-01

    Full Text Available As new technology enables firms to perform many daily processes easier the need of authentication and authorization process is becoming an integral part of many businesses. Also mobile applications are very popular nowadays play an important role in our lives. Such demands are not only limited to Logistics Information Systems (LIS but many field of information system as well. In this study multi-dimensional authentication which consist of online biometric face detection integrated as cloud computing software as a Service (SaaS, Near Field Communication (NFC card authentication, location confirmation, and temporal data confirmation are gathered together to fulfill different scenarios of authentication needs of business. Microsoft Face API (Application Program Interface, SAAS (software as a service has been used in face recognition module of developed mobile application. The face recognition module of the mobile application has been tested with Yale Face Database. Location, temporal data and NFC card information are collected and confirmed by the mobile application for authentication and authorization. These images were tested with our facial recognition module and confusion matrices were created. The accuracy of the system after the facial recognition test was found to be 100%. NFC card, location and temporal data authentication not only further increases security level but also fulfils many business authentication scenarios successfully. To the best of our knowledge there is no other authentication model other than implemented one that has a-4-factor confirmation including biometric face identification, NFC card authentication, location confirmation and temporal data confirmation.

  8. Human Factors methods concerning integrated validation of nuclear power plant control rooms; Metodutveckling foer integrerad validering

    Energy Technology Data Exchange (ETDEWEB)

    Oskarsson, Per-Anders; Johansson, Bjoern J.E.; Gonzalez, Natalia (Swedish Defence Research Agency, Information Systems, Linkoeping (Sweden))

    2010-02-15

    The frame of reference for this work was existing recommendations and instructions from the NPP area, experiences from the review of the Turbic Validation and experiences from system validations performed at the Swedish Armed Forces, e.g. concerning military control rooms and fighter pilots. These enterprises are characterized by complex systems in extreme environments, often with high risks, where human error can lead to serious consequences. A focus group has been performed with representatives responsible for Human Factors issues from all Swedish NPP:s. The questions that were discussed were, among other things, for whom an integrated validation (IV) is performed and its purpose, what should be included in an IV, the comparison with baseline measures, the design process, the role of SSM, which methods of measurement should be used, and how the methods are affected of changes in the control room. The report brings different questions to discussion concerning the validation process. Supplementary methods of measurement for integrated validation are discussed, e.g. dynamic, psychophysiological, and qualitative methods for identification of problems. Supplementary methods for statistical analysis are presented. The study points out a number of deficiencies in the validation process, e.g. the need of common guidelines for validation and design, criteria for different types of measurements, clarification of the role of SSM, and recommendations for the responsibility of external participants in the validation process. The authors propose 12 measures for taking care of the identified problems

  9. Sequential induction of three recombination directionality factors directs assembly of tripartite integrative and conjugative elements.

    Directory of Open Access Journals (Sweden)

    Timothy L Haskett

    2018-03-01

    Full Text Available Tripartite integrative and conjugative elements (ICE3 are a novel form of ICE that exist as three separate DNA regions integrated within the genomes of Mesorhizobium spp. Prior to conjugative transfer the three ICE3 regions of M. ciceri WSM1271 ICEMcSym1271 combine and excise to form a single circular element. This assembly requires three coordinated recombination events involving three site-specific recombinases IntS, IntG and IntM. Here, we demonstrate that three excisionases-or recombination directionality factors-RdfS, RdfG and RdfM are required for ICE3 excision. Transcriptome sequencing revealed that expression of ICE3 transfer and conjugation genes was induced by quorum sensing. Quorum sensing activated expression of rdfS, and in turn RdfS stimulated transcription of both rdfG and rdfM. Therefore, RdfS acts as a "master controller" of ICE3 assembly and excision. The dependence of all three excisive reactions on RdfS ensures that ICE3 excision occurs via a stepwise sequence of recombination events that avoids splitting the chromosome into a non-viable configuration. These discoveries expose a surprisingly simple control system guiding molecular assembly of these novel and complex mobile genetic elements and highlight the diverse and critical functions of excisionase proteins in control of horizontal gene transfer.

  10. Sequential induction of three recombination directionality factors directs assembly of tripartite integrative and conjugative elements.

    Science.gov (United States)

    Haskett, Timothy L; Terpolilli, Jason J; Ramachandran, Vinoy K; Verdonk, Callum J; Poole, Phillip S; O'Hara, Graham W; Ramsay, Joshua P

    2018-03-01

    Tripartite integrative and conjugative elements (ICE3) are a novel form of ICE that exist as three separate DNA regions integrated within the genomes of Mesorhizobium spp. Prior to conjugative transfer the three ICE3 regions of M. ciceri WSM1271 ICEMcSym1271 combine and excise to form a single circular element. This assembly requires three coordinated recombination events involving three site-specific recombinases IntS, IntG and IntM. Here, we demonstrate that three excisionases-or recombination directionality factors-RdfS, RdfG and RdfM are required for ICE3 excision. Transcriptome sequencing revealed that expression of ICE3 transfer and conjugation genes was induced by quorum sensing. Quorum sensing activated expression of rdfS, and in turn RdfS stimulated transcription of both rdfG and rdfM. Therefore, RdfS acts as a "master controller" of ICE3 assembly and excision. The dependence of all three excisive reactions on RdfS ensures that ICE3 excision occurs via a stepwise sequence of recombination events that avoids splitting the chromosome into a non-viable configuration. These discoveries expose a surprisingly simple control system guiding molecular assembly of these novel and complex mobile genetic elements and highlight the diverse and critical functions of excisionase proteins in control of horizontal gene transfer.

  11. An Exploratory Study of the Factors Associated with Literacy Teachers' Integration of Technology: A Study of Lebanese Schools

    Science.gov (United States)

    Chaaban, Youmen; Moloney, Robyn

    2016-01-01

    The purpose of this study is to explore Lebanese teachers' perceptions of the factors determining their integration of technology into literacy classrooms. A quantitative survey examining literacy teachers' individual characteristics and their perceptions of contextual factors was conducted at Lebanese schools. The survey collected data on the…

  12. Complexity impact factors on the integration process of ERP and non ERP systems : a basis for an evaluation instrument

    NARCIS (Netherlands)

    Janssens, G.; Hoeijenbos, M.; Kusters, R.J.; Cuaresma, M.J.E.; Shishkov, B.; Cordeiro, J.

    2011-01-01

    This study shows an expert confirmed initial list of factors which influence the complexity of the integration process of ERP systems and non ERP systems. After a thorough search for complexity factors in scientific literature, a survey amongst 8 experts in a leading European long special steel

  13. Contributing factors for therapeutic diet adherence in patients receiving haemodialysis treatment: an integrative review.

    Science.gov (United States)

    Oquendo, Lissete González; Asencio, José Miguel Morales; de Las Nieves, Candela Bonill

    2017-12-01

    The objective of this integrative review is to identify the factors that contribute to diet adherence in people suffering from kidney disease who are receiving haemodialysis treatment. Adherence to the therapeutic regimen determines therapeutic success, quality of life and survival in patients on haemodialysis. Lack of diet adherence ranges from 25%-86% in patients receiving haemodialysis treatment and affects patient morbidity and mortality. An integrative literature review was conducted based on the criteria of Whittemore & Knafl. A literature review was performed by two members of the team using twelve databases including PubMed, CUIDEN, CINAHL, The Cochrane Library and ScienceDirect. The main issues identified after analysing the results were as follows: the intrinsic barriers (age, dialysis time, motivation, perceived benefit, distorted perception of adherence) and facilitators (self-efficacy, perception of disease, perception of control), extrinsic barriers (family dysfunction, lack of social support, cultural patterns of consumption of food) and facilitators (social support, relationship with healthcare providers), and interventions to encourage diet adherence, such as the use of motivational interviewing in educational interventions, and the training and education of relevant professionals in communication skills. Diet nonadherence remains a serious health problem and suffers from a lack of solid criteria to identify this condition. The onset of depression signs and the level of social support available to the patient should be assessed, because these are important factors that determine adherence to treatment. Professionals should be trained in health education and communication techniques to contribute to the patient's self-management and motivation for diet adherence. Controlled and randomised clinical studies involving predialysis stages should be performed to investigate the impact of the assessment and control of barriers to diet adherence. © 2017

  14. Epidermal growth factor treatment decreases mortality and is associated with improved gut integrity in sepsis.

    Science.gov (United States)

    Clark, Jessica A; Clark, Andrew T; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

    2008-07-01

    Epidermal growth factor (EGF) is a cytoprotective peptide that has healing effects on the intestinal mucosa. We sought to determine whether systemic administration of EGF after the onset of sepsis improved intestinal integrity and decreased mortality. FVB/N mice were subjected to either sham laparotomy or 2 x 23 cecal ligation and puncture (CLP). Septic mice were further randomized to receive injection of either 150 microg kg(-1) d(-1) (i.p.) EGF or 0.9% saline (i.p.). Circulating EGF levels were decreased after CLP compared with sham animals but were unaffected by giving exogenous EGF treatment. In contrast, intestinal EGF levels increased after CLP and were further augmented by exogenous EGF treatment. Intestinal EGF receptor was increased after CLP, whether assayed by immunohistochemistry, real-time polymerase chain reaction, or Western blot, and exogenous EGF treatment decreased intestinal EGF receptor. Villus length decreased 2-fold between sham and septic animals, and EGF treatment resulted in near total restitution of villus length. Sepsis decreased intestinal proliferation and increased intestinal apoptosis. This was accompanied by increased expression of the proapoptotic proteins Bid and Fas-associated death domain, as well as the cyclin-dependent kinase inhibitor p21 cip1/waf Epidermal growth factor treatment after the onset of sepsis restored both proliferation and apoptosis to levels seen in sham animals and normalized expression of Bid, Fas-associated death domain, and p21 cip1/waf . To determine whether improvements in gut homeostasis were associated with a decrease in sepsis-induced mortality, septic mice with or without EGF treatment after CLP were followed 7 days for survival. Mortality decreased from 60% to 30% in mice treated with EGF after the onset of sepsis (P < 0.05). Thus, EGF may be a potential therapeutic agent for the treatment of sepsis in part due to its ability to protect intestinal integrity.

  15. A novel Sulfolobus non-conjugative extrachromosomal genetic element capable of integration into the host genome and spreading in the presence of a fusellovirus

    DEFF Research Database (Denmark)

    Wang, Ying; Duan, Zhenhong; Zhu, Haojun

    2007-01-01

    An integrative non-conjugative extrachromosomal genetic element, denoted as pSSVi, has been isolated from a Sulfolobus solfataricus P2 strain and was characterized. This genetic element is a double-stranded DNA of 5740 bp in size and contains eight open reading frames (ORFs). It resembles members....... Interestingly, pSSVi encodes an SSV-type integrase which probably catalyzes the integration of its genome into a specific site (a tRNA(Arg) gene) in the S. solfataricus P2 genome. Like pSSVx, pSSVi can be packaged into a spindle-like viral particle and spread with the help of SSV1 or SSV2. In addition, both SSV......1 and SSV2 appeared to replicate more efficiently in the presence of pSSVi. Given the versatile genetic abilities, pSSVi appears to be well suited for a role in horizontal gene transfer....

  16. Human Factors, Habitability and Environmental Health and the Human Integration Design Handbook. Volume 2

    Science.gov (United States)

    Houbec, Keith; Tillman, Barry; Connolly, Janis

    2010-01-01

    For decades, Space Life Sciences and NASA as an Agency have considered NASA-STD-3000, Man-Systems Integration Standards, a significant contribution to human spaceflight programs and to human-systems integration in general. The document has been referenced in numerous design standards both within NASA and by organizations throughout the world. With research program and project results being realized, advances in technology and new information in a variety of topic areas now available, the time arrived to update this extensive suite of requirements and design information. During the past several years, a multi-NASA center effort has been underway to write the update to NASA-STD-3000 with standards and design guidance that would be applicable to all future human spaceflight programs. NASA-STD-3001 - Volumes 1 and 2 - and the Human Integration Design Handbook (HIDH) were created. Volume 1, Crew Health, establishes NASA s spaceflight crew health standards for the pre-flight, in-flight, and post-flight phases of human spaceflight. Volume 2, Human Factors, Habitability and Environmental Health, focuses on the requirements of human-system integration and how the human crew interacts with other systems, and how the human and the system function together to accomplish the tasks for mission success. The HIDH is a compendium of human spaceflight history and knowledge, and provides useful background information and research findings. And as the HIDH is a stand-alone companion to the Standards, the maintenance of the document has been streamlined. This unique and flexible approach ensures that the content is current and addresses the fundamental advances of human performance and human capabilities and constraints research. Current work focuses on the development of new sections of Volume 2 and collecting updates to the HIDH. The new sections in development expand the scope of the standard and address mission operations and support operations. This effort is again collaboration

  17. Integral emission factors for methane determined using urban flux measurements and local-scale inverse models

    Science.gov (United States)

    Christen, Andreas; Johnson, Mark; Molodovskaya, Marina; Ketler, Rick; Nesic, Zoran; Crawford, Ben; Giometto, Marco; van der Laan, Mike

    2013-04-01

    The most important long-lived greenhouse gas (LLGHG) emitted during combustion of fuels is carbon dioxide (CO2), however also traces of the LLGHGs methane (CH4) and nitrous oxide (N2O) are released, the quantities of which depend largely on the conditions of the combustion process. Emission factors determine the mass of LLGHGs emitted per energy used (or kilometre driven for cars) and are key inputs for bottom-up emission modelling. Emission factors for CH4 are typically determined in the laboratory or on a test stand for a given combustion system using a small number of samples (vehicles, furnaces), yet associated with larger uncertainties when scaled to entire fleets. We propose an alternative, different approach - Can integrated emission factors be independently determined using direct micrometeorological flux measurements over an urban surface? If so, do emission factors determined from flux measurements (top-down) agree with up-scaled emission factors of relevant combustion systems (heating, vehicles) in the source area of the flux measurement? Direct flux measurements of CH4 were carried out between February and May, 2012 over a relatively densely populated, urban surface in Vancouver, Canada by means of eddy covariance (EC). The EC-system consisted of an ultrasonic anemometer (CSAT-3, Campbell Scientific Inc.) and two open-path infrared gas analyzers (Li7500 and Li7700, Licor Inc.) on a tower at 30m above the surface. The source area of the EC system is characterised by a relative homogeneous morphometry (5.3m average building height), but spatially and temporally varying emission sources, including two major intersecting arterial roads (70.000 cars drive through the 50% source area per day) and seasonal heating in predominantly single-family houses (natural gas). An inverse dispersion model (turbulent source area model), validated against large eddy simulations (LES) of the urban roughness sublayer, allows the determination of the spatial area that

  18. Integrating Human Factors Engineering and Information Processing Approaches to Facilitate Evaluations in Criminal Justice Technology Research.

    Science.gov (United States)

    Salvemini, Anthony V; Piza, Eric L; Carter, Jeremy G; Grommon, Eric L; Merritt, Nancy

    2015-06-01

    Evaluations are routinely conducted by government agencies and research organizations to assess the effectiveness of technology in criminal justice. Interdisciplinary research methods are salient to this effort. Technology evaluations are faced with a number of challenges including (1) the need to facilitate effective communication between social science researchers, technology specialists, and practitioners, (2) the need to better understand procedural and contextual aspects of a given technology, and (3) the need to generate findings that can be readily used for decision making and policy recommendations. Process and outcome evaluations of technology can be enhanced by integrating concepts from human factors engineering and information processing. This systemic approach, which focuses on the interaction between humans, technology, and information, enables researchers to better assess how a given technology is used in practice. Examples are drawn from complex technologies currently deployed within the criminal justice system where traditional evaluations have primarily focused on outcome metrics. Although this evidence-based approach has significant value, it is vulnerable to fully account for human and structural complexities that compose technology operations. Guiding principles for technology evaluations are described for identifying and defining key study metrics, facilitating communication within an interdisciplinary research team, and for understanding the interaction between users, technology, and information. The approach posited here can also enable researchers to better assess factors that may facilitate or degrade the operational impact of the technology and answer fundamental questions concerning whether the technology works as intended, at what level, and cost. © The Author(s) 2015.

  19. ImWalkMF: Joint matrix factorization and implicit walk integrative learning for recommendation

    KAUST Repository

    Zhang, Chuxu

    2018-01-15

    Data sparsity and cold-start problems are prevalent in recommender systems. To address such problems, both the observable explicit social information (e.g., user-user trust connections) and the inferable implicit correlations (e.g., implicit neighbors computed by similarity measurement) have been introduced to complement user-item ratings data for improving the performances of traditional model-based recommendation algorithms such as matrix factorization. Although effective, (1) the utilization of the explicit user-user social relationships suffers from the weakness of unavailability in real systems such as Netflix or the issue of sparse observable content like 0.03% trust density in Epinions, thus there is no or little explicit social information that can be employed to improve baseline model in real applications; (2) the current similarity measurement approaches focus on inferring implicit correlations between a user (item) and their direct neighbors or top-k similar neighbors based on user-item ratings bipartite network, so that they fail to comprehensively unfold the indirect potential relationships among users and items. To solve these issues regarding both explicit/implicit social recommendation algorithms, we design a joint model of matrix factorization and implicit walk integrative learning, i.e., ImWalkMF, which only uses explicit ratings information yet models both direct rating feedbacks and multiple direct/indirect implicit correlations among users and items from a random walk perspective. We further propose a combined strategy for training two independent components in the proposed model based on sampling. The experimental results on two real-world sparse datasets demonstrate that ImWalkMF outperforms the traditional regularized/probabilistic matrix factorization models as well as other competitive baselines that utilize explicit/implicit social information.

  20. Factors influencing CO2 emissions in China's power industry: Co-integration analysis

    International Nuclear Information System (INIS)

    Zhao, Xiaoli; Ma, Qian; Yang, Rui

    2013-01-01

    More than 40% of China's total CO 2 emissions originate from the power industry. The realization of energy saving and emission reduction within China's power industry is therefore crucial in order to achieve CO 2 emissions reduction in this country. This paper applies the autoregressive-distributed lag (ARDL) co-integration model to study the major factors which have influenced CO 2 emissions within China's power industry from 1980 to 2010. Results have shown that CO 2 emissions from China's power industry have been increasing rapidly. From 1980 to 2010, the average annual growth rate was 8.5%, and the average growth rate since 2002 has amounted to 10.5%. Secondly, the equipment utilization hour (as an indicator of the power demand) has the greatest influence on CO 2 emissions within China's power industry. In addition, the impact of the industrial added value of the power sector on CO 2 emissions is also positive from a short-term perspective. Thirdly, the Granger causality results imply that one of the important motivators behind China's technological progress, within the power industry, originates from the pressures created by a desire for CO 2 emissions reduction. Finally, this paper provides policy recommendations for energy saving and emission reduction for China's power industry. - Highlights: ► We study the major factors influencing China's power industry CO 2 emissions. ► The average annual growth rate of CO 2 emission from power industry is calculated. ► Installed capacity has the greatest influence on power industry CO 2 emission. ► The Granger causality between CO 2 emission and its effecting factors is analyzed

  1. Factors influencing self-management in chronic obstructive pulmonary disease: an integrative review.

    Science.gov (United States)

    Disler, R T; Gallagher, R D; Davidson, P M

    2012-02-01

    Chronic obstructive pulmonary disease is a common, chronic and burdensome condition requiring the individual to engage in a range of self-management strategies. The capacity to engage in self-management is dependent on a range of internal (e.g., personal) and external (e.g., health service) factors. This paper seeks to define self-management, identify the determinants which influence the individual's ability to cope and adjust to living with chronic obstructive pulmonary disease in the community, and identify implications for clinical practice and research. Integrative review. Medline, Embase, PubMed, CINAHL, Google Scholar. Integrative review using prospective research questions. Papers were included in the review if they were published in peer reviewed journals and written in English between 2000 and 2010. Articles were accepted for inclusion if they discussed the determinants that influenced self-management of chronic obstructive pulmonary disease in the community. Confirmation of results and discussion themes was validated by specialists in chronic obstructive pulmonary disease and complex care. Self-management is less well characterised in chronic obstructive pulmonary disease compared with other chronic conditions. Functional limitation and the need to balance disease management with everyday life are the two key elements that patients face in managing their condition. Provider characteristics, socioeconomic status and health literacy are sparsely discussed yet are known to influence chronic obstructive pulmonary disease self-management. Chronic obstructive pulmonary disease self-management must be a key focus internationally as the disease incidence increases. Collaborative care is required between patients and health providers in order facilitate patients in confident management of their condition. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Analysis of Factors Affect to Organizational Performance In Using Accounting Information Systems Through Users Satisfaction and Integration Information Systems

    Directory of Open Access Journals (Sweden)

    Anton Arisman

    2017-09-01

    Full Text Available The aim of this research is to investigate the factors affecting organizational performance in using accounting information system through users satisfaction and integration information systems. The research respondents were 447 companies that listed in Indonesian Stock Exchange. The data are gathered through consensus method and in total there are 176 responses with complete data. Structural Equation Model (SEM is used in analyzing the data and system theory is utilized in this research. The result shows that knowledge management systems and management control system have significant influence on users satisfaction and integration information systems.  Integration information system and users satisfaction has positive significant on organizational performance.

  3. Road MAPs to engineer host microbiomes.

    Science.gov (United States)

    Oyserman, Ben O; Medema, Marnix H; Raaijmakers, Jos M

    2017-12-02

    Microbiomes contribute directly or indirectly to host health and fitness. Thus far, investigations into these emergent traits, referred to here as microbiome-associated phenotypes (MAPs), have been primarily qualitative and taxonomy-driven rather than quantitative and trait-based. We present the MAPs-first approach, a theoretical and experimental roadmap that involves quantitative profiling of MAPs across genetically variable hosts and subsequent identification of the underlying mechanisms. We outline strategies for developing 'modular microbiomes'-synthetic microbial consortia that are engineered in concert with the host genotype to confer different but mutually compatible MAPs to a single host or host population. By integrating host and microbial traits, these strategies will facilitate targeted engineering of microbiomes to the benefit of agriculture, human/animal health and biotechnology. Copyright © 2017. Published by Elsevier Ltd.

  4. Studies into the Factors that Affects the Service Integrity of Galvanizing Kettle

    Directory of Open Access Journals (Sweden)

    Muhammed Olawale Hakeem AMUDA

    2008-12-01

    Full Text Available The finding of studies into the factors that affects optimal performance of galvanizing kettle is presented in this paper. The production schedule and history of a failed galvanizing kettle for 3-consecutively years in a hot-dip galvanizing industry was collated and analyzed. The analysis of the collated data revealed that average galvanizing temperatures for the 3-year under review were 483.9°C (2003, 482.25°C (2004 and 482°C (2005 respectively. The amount of flux, and dross produced in the corresponding years were 169.15kg and 31.6 tons, 56.31kg and 10.5 tons and 101.14 and 18.91 tonnes for 2003, 2004 and 2005 respectively. During these years, zinc consumed averaged 647, 334 and 446 tonnes respectively.Stochiometry evaluation of flux, and dross in a hot-dip galvanizing process determined flux required as 60 kg/year and dross produced as 90 slabs / month.The study revealed that the lifespan of galvanizing kettle is greatly reduced by temperature fluctuation, dross formation, excess flux additions and combinations of these factors.It is recommended that improved service integrity of galvanizing kettle is assured at galvanizing temperature of 460°C, flux consumption of 0.15 –0.20kg daily and constant removal of dross at 3-5 slabs per day. This reduces the formation of skim lines, which leads to pits on the walls of the kettle.

  5. 'Integration'

    DEFF Research Database (Denmark)

    Olwig, Karen Fog

    2011-01-01

    , while the countries have adopted disparate policies and ideologies, differences in the actual treatment and attitudes towards immigrants and refugees in everyday life are less clear, due to parallel integration programmes based on strong similarities in the welfare systems and in cultural notions...... of equality in the three societies. Finally, it shows that family relations play a central role in immigrants’ and refugees’ establishment of a new life in the receiving societies, even though the welfare society takes on many of the social and economic functions of the family....

  6. Factors associated with integrating self-management support into primary care.

    Science.gov (United States)

    Crespo, Richard; Shrewsberry, Molly

    2007-06-01

    The purpose of this article is to expand the understanding of self-management support by describing factors that contribute to implementing a comprehensive self-management program in primary care. Four rural health centers in medically underserved areas participated in a study to document the implementation of a self-management program. This program consisted of a social marketing plan and decision-making tools to guide patients in making self-management behavior changes. The stages of change constructs of the transtheoretical model were used to design the social marketing plan. Key informant interviews were conducted at 6-month and 9-month intervals to document the implementation process. A standardized set of questions was used in the interviews. The data from the interviews were analyzed using content analysis techniques. One of the principle findings is that self-management support requires putting a system in place, not just adding a new component to primary care. The health centers that fully implemented the self-management program made an organizational commitment to keep self-management on the agenda in management meetings, clinical staff set the example by adopting self-management behaviors, and patient self-management support was implemented in multiple patient care venues. Primary care centers with limited financial resources are able to integrate self-management support into their system of chronic illness care.

  7. Four conceptual issues to consider in integrating social and environmental factors in risk and impact assessments

    Energy Technology Data Exchange (ETDEWEB)

    Domínguez-Gómez, J. Andrés, E-mail: andres@uhu.es

    2016-01-15

    In the last twenty years, both the increase in academic production and the expansion of professional involvement in Environmental Impact Assessment (EIA) and Social Impact Assessment (SIA) have evidenced growing scientific and business interest in risk and impact analysis. However, this growth has not brought with it parallel progress in addressing the main shortcomings of EIA/SIA, i.e. insufficient integration of environmental and social factors into development project analyses and, in cases where the social aspects are considered, technical-methodological failings in their analysis and assessment. It is clear that these weaknesses carry with them substantial threats to the sustainability (social, environmental and economic) of projects which impact on the environment, and consequently to the local contexts where they are carried out and to the delicate balance of the global ecosystem. This paper argues that, in a sociological context of complexity and dynamism, four conceptual elements should underpin approaches to socio-environmental risk and impact assessment in development projects: a theoretical base in actor–network theory; an ethical grounding in values which are internationally recognized (though not always fulfilled in practice); a (new) epistemological-scientific base; and a methodological foundation in social participation. - Highlights: • A theoretical foundation in actor–network theory • An ethical grounding in values which are internationally recognized, but rarely carried through into practice • A (new) epistemological-scientific base • A methodological foundation in social participation.

  8. Causal Factors and Adverse Conditions of Aviation Accidents and Incidents Related to Integrated Resilient Aircraft Control

    Science.gov (United States)

    Reveley, Mary S.; Briggs, Jeffrey L.; Evans, Joni K.; Sandifer, Carl E.; Jones, Sharon Monica

    2010-01-01

    The causal factors of accidents from the National Transportation Safety Board (NTSB) database and incidents from the Federal Aviation Administration (FAA) database associated with loss of control (LOC) were examined for four types of operations (i.e., Federal Aviation Regulation Part 121, Part 135 Scheduled, Part 135 Nonscheduled, and Part 91) for the years 1988 to 2004. In-flight LOC is a serious aviation problem. Well over half of the LOC accidents included at least one fatality (80 percent in Part 121), and roughly half of all aviation fatalities in the studied time period occurred in conjunction with LOC. An adverse events table was updated to provide focus to the technology validation strategy of the Integrated Resilient Aircraft Control (IRAC) Project. The table contains three types of adverse conditions: failure, damage, and upset. Thirteen different adverse condition subtypes were gleaned from the Aviation Safety Reporting System (ASRS), the FAA Accident and Incident database, and the NTSB database. The severity and frequency of the damage conditions, initial test conditions, and milestones references are also provided.

  9. Four conceptual issues to consider in integrating social and environmental factors in risk and impact assessments

    International Nuclear Information System (INIS)

    Domínguez-Gómez, J. Andrés

    2016-01-01

    In the last twenty years, both the increase in academic production and the expansion of professional involvement in Environmental Impact Assessment (EIA) and Social Impact Assessment (SIA) have evidenced growing scientific and business interest in risk and impact analysis. However, this growth has not brought with it parallel progress in addressing the main shortcomings of EIA/SIA, i.e. insufficient integration of environmental and social factors into development project analyses and, in cases where the social aspects are considered, technical-methodological failings in their analysis and assessment. It is clear that these weaknesses carry with them substantial threats to the sustainability (social, environmental and economic) of projects which impact on the environment, and consequently to the local contexts where they are carried out and to the delicate balance of the global ecosystem. This paper argues that, in a sociological context of complexity and dynamism, four conceptual elements should underpin approaches to socio-environmental risk and impact assessment in development projects: a theoretical base in actor–network theory; an ethical grounding in values which are internationally recognized (though not always fulfilled in practice); a (new) epistemological-scientific base; and a methodological foundation in social participation. - Highlights: • A theoretical foundation in actor–network theory • An ethical grounding in values which are internationally recognized, but rarely carried through into practice • A (new) epistemological-scientific base • A methodological foundation in social participation

  10. Causal Factors and Adverse Events of Aviation Accidents and Incidents Related to Integrated Vehicle Health Management

    Science.gov (United States)

    Reveley, Mary S.; Briggs, Jeffrey L.; Evans, Joni K.; Jones, Sharon M.; Kurtoglu, Tolga; Leone, Karen M.; Sandifer, Carl E.

    2011-01-01

    Causal factors in aviation accidents and incidents related to system/component failure/malfunction (SCFM) were examined for Federal Aviation Regulation Parts 121 and 135 operations to establish future requirements for the NASA Aviation Safety Program s Integrated Vehicle Health Management (IVHM) Project. Data analyzed includes National Transportation Safety Board (NSTB) accident data (1988 to 2003), Federal Aviation Administration (FAA) incident data (1988 to 2003), and Aviation Safety Reporting System (ASRS) incident data (1993 to 2008). Failure modes and effects analyses were examined to identify possible modes of SCFM. A table of potential adverse conditions was developed to help evaluate IVHM research technologies. Tables present details of specific SCFM for the incidents and accidents. Of the 370 NTSB accidents affected by SCFM, 48 percent involved the engine or fuel system, and 31 percent involved landing gear or hydraulic failure and malfunctions. A total of 35 percent of all SCFM accidents were caused by improper maintenance. Of the 7732 FAA database incidents affected by SCFM, 33 percent involved landing gear or hydraulics, and 33 percent involved the engine and fuel system. The most frequent SCFM found in ASRS were turbine engine, pressurization system, hydraulic main system, flight management system/flight management computer, and engine. Because the IVHM Project does not address maintenance issues, and landing gear and hydraulic systems accidents are usually not fatal, the focus of research should be those SCFMs that occur in the engine/fuel and flight control/structures systems as well as power systems.

  11. Organizational factors influencing implementation of evidence-based practices for integrated treatment in behavioral health agencies.

    Science.gov (United States)

    Bonham, Caroline A; Sommerfeld, David; Willging, Cathleen; Aarons, Gregory A

    2014-01-01

    Objective. In recent years, New Mexico has prioritized integrated treatment for cooccurring mental health and substance use disorders within its public behavioral health system. This report describes factors likely to be important when implementing evidence-based practices (EBPs) in community agencies. Methods. Our mixed-method research design consisted of observations, semistructured interviews, and surveys undertaken with employees at 14 agencies at baseline and after 18 months. We developed four-agency typologies based on iterative coding and analysis of observations and interviews. We then examined survey data from employees at the four exemplar agencies to validate qualitative findings. Results. Financial resources and strong leadership impacted agency capacity to train providers and implement EBPs. Quantitative analysis of service provider survey responses from these agencies (N = 38) supported qualitative findings and demonstrated significant mean score differences in leadership, organizational climate, and attitudes toward EBPs in anticipated directions. Conclusion. The availability of strong leadership and financial resources were key components to initial implementation success in this study of community agencies in New Mexico. Reliance only on external funding poses risks for sustainment when demoralizing work climates precipitate employee turnover. Strong agency leadership does not always compensate for deficient financial resources in vulnerable communities.

  12. Multivariate co-integration analysis of the Kaya factors in Ghana.

    Science.gov (United States)

    Asumadu-Sarkodie, Samuel; Owusu, Phebe Asantewaa

    2016-05-01

    The fundamental goal of the Government of Ghana's development agenda as enshrined in the Growth and Poverty Reduction Strategy to grow the economy to a middle income status of US$1000 per capita by the end of 2015 could be met by increasing the labour force, increasing energy supplies and expanding the energy infrastructure in order to achieve the sustainable development targets. In this study, a multivariate co-integration analysis of the Kaya factors namely carbon dioxide, total primary energy consumption, population and GDP was investigated in Ghana using vector error correction model with data spanning from 1980 to 2012. Our research results show an existence of long-run causality running from population, GDP and total primary energy consumption to carbon dioxide emissions. However, there is evidence of short-run causality running from population to carbon dioxide emissions. There was a bi-directional causality running from carbon dioxide emissions to energy consumption and vice versa. In other words, decreasing the primary energy consumption in Ghana will directly reduce carbon dioxide emissions. In addition, a bi-directional causality running from GDP to energy consumption and vice versa exists in the multivariate model. It is plausible that access to energy has a relationship with increasing economic growth and productivity in Ghana.

  13. Organizational Factors Influencing Implementation of Evidence-Based Practices for Integrated Treatment in Behavioral Health Agencies

    Directory of Open Access Journals (Sweden)

    Caroline A. Bonham

    2014-01-01

    Full Text Available Objective. In recent years, New Mexico has prioritized integrated treatment for cooccurring mental health and substance use disorders within its public behavioral health system. This report describes factors likely to be important when implementing evidence-based practices (EBPs in community agencies. Methods. Our mixed-method research design consisted of observations, semistructured interviews, and surveys undertaken with employees at 14 agencies at baseline and after 18 months. We developed four-agency typologies based on iterative coding and analysis of observations and interviews. We then examined survey data from employees at the four exemplar agencies to validate qualitative findings. Results. Financial resources and strong leadership impacted agency capacity to train providers and implement EBPs. Quantitative analysis of service provider survey responses from these agencies (N = 38 supported qualitative findings and demonstrated significant mean score differences in leadership, organizational climate, and attitudes toward EBPs in anticipated directions. Conclusion. The availability of strong leadership and financial resources were key components to initial implementation success in this study of community agencies in New Mexico. Reliance only on external funding poses risks for sustainment when demoralizing work climates precipitate employee turnover. Strong agency leadership does not always compensate for deficient financial resources in vulnerable communities.

  14. Organizational factors, planning capacity, and integration challenges constrain provincial planning processes for nutrition in decentralizing Vietnam.

    Science.gov (United States)

    Lapping, Karin; Frongillo, Edward A; Nguyen, Phuong H; Coates, Jennifer; Webb, Patrick; Menon, Purnima

    2014-09-01

    Translating national policies and guidelines into effective action at the subnational level (e.g., province or region) is a prerequisite for ensuring an impact on nutrition. In several countries, including Vietnam, the focus of this paper, this process is affected by the quality of the decentralized process of planning and action. This study examined how provincial planning processes for nutrition occurred in Vietnam during 2009 and 2010. Key goals were to understand variability in processes across provinces, identify factors that influenced the process, and assess the usefulness of the process for individuals involved in planning and action. A qualitative case-study methodology was used. Data were drawn from interviews with 51 government officials in eight provinces. The study found little variability in the planning process among these eight provinces, probably due to a planning process that was predominantly a fiscal exercise within the confines of a largely centralized structure. Respondents were almost unanimous about the main barriers: a top-down approach to planning, limited human capacity for effective planning at subnational levels, and difficulty in integrating actions from multiple sectors. Provincial-level actors were deeply dissatisfied with the nature of their role in the process. Despite the rhetoric to the contrary, too much power is probably still retained at the central level. A strategic multiyear approach is needed to strengthen the provincial planning process and address many of the key barriers identified in this study.

  15. The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X-box binding protein 1 transcription factor.

    Science.gov (United States)

    Dias-Teixeira, Karina Luiza; Calegari-Silva, Teresa Cristina; dos Santos, Guilherme R R M; Vitorino Dos Santos, José; Lima, Carolina; Medina, Jorge Mansur; Aktas, Bertal Huseyin; Lopes, Ulisses G

    2016-04-01

    Endoplasmic reticulum (ER) stress triggers the integrated ER-stress response (IERSR) that ensures cellular survival of ER stress and represents a primordial form of innate immunity. We investigated the role of IERSR duringLeishmania amazonensisinfection. Treatment of RAW 264.7 infected macrophages with the ER stress-inducing agent thapsigargin (TG; 1 μM) increasedL. amazonensisinfectivity in an IFN1-α receptor (IFNAR)-dependent manner. In Western blot assays, we showed thatL. amazonensisactivates the inositol-requiring enzyme (IRE1)/ X-box binding protein (XBP)-1-splicing arms of the IERSR in host cells. In chromatin immunoprecipitation (ChIP) assays, we showed an increased occupancy of enhancer and promoter sequences for theIfnbgene by XBP1 in infected RAW 264.7 cells. Knocking down XBP1 expression by transducing RAW 264.7 cells with the short hairpin XBP1 lentiviral vector significantly reduced the parasite proliferation associated with impaired translocation of phosphorylated IFN regulatory transcription factor (IRF)-3 to the nucleus and a decrease in IFN1-β expression. Knocking down XBP1 expression also increased NO concentration, as determined by Griess reaction and reduced the expression of antioxidant genes, such as heme oxygenase (HO)-1, that protect parasites from oxidative stress. We conclude thatL. amazonensisactivation of XBP1 plays a critical role in infection by protecting the parasites from oxidative stress and increasing IFN1-β expression.-Dias-Teixeira, K. L., Calegari-Silva, T. C., Dos Santos, G. R. R. M., Vitorino dos Santos, J., Lima, C., Medina, J. M., Aktas, B. H., Lopes, U. G. The integrated endoplasmic reticulum stress response inLeishmania amazonensismacrophage infection: the role of X-box binding protein 1 transcription factor. © FASEB.

  16. A retrospective likelihood approach for efficient integration of multiple omics factors in case-control association studies.

    Science.gov (United States)

    Balliu, Brunilda; Tsonaka, Roula; Boehringer, Stefan; Houwing-Duistermaat, Jeanine

    2015-03-01

    Integrative omics, the joint analysis of outcome and multiple types of omics data, such as genomics, epigenomics, and transcriptomics data, constitute a promising approach for powerful and biologically relevant association studies. These studies often employ a case-control design, and often include nonomics covariates, such as age and gender, that may modify the underlying omics risk factors. An open question is how to best integrate multiple omics and nonomics information to maximize statistical power in case-control studies that ascertain individuals based on the phenotype. Recent work on integrative omics have used prospective approaches, modeling case-control status conditional on omics, and nonomics risk factors. Compared to univariate approaches, jointly analyzing multiple risk factors with a prospective approach increases power in nonascertained cohorts. However, these prospective approaches often lose power in case-control studies. In this article, we propose a novel statistical method for integrating multiple omics and nonomics factors in case-control association studies. Our method is based on a retrospective likelihood function that models the joint distribution of omics and nonomics factors conditional on case-control status. The new method provides accurate control of Type I error rate and has increased efficiency over prospective approaches in both simulated and real data. © 2015 Wiley Periodicals, Inc.

  17. A Systematic Investigation on Barriers and Critical Success Factors for Clinical Information Systems in Integrated Care Settings.

    Science.gov (United States)

    Hoerbst, A; Schweitzer, M

    2015-08-13

    Clinical Information Systems (CIS) have ever since the introduction of information technology in healthcare played an important role to support healthcare professionals and the process of treatment. With the rise of the concept of integrated care organizational borders, the sole focus on data aggregation or healthcare professionals as users disappear more and more. The manuscript discusses the concept of CISs and investigates critical success factors for CISs in the context of integrated care and in the course of time. In order to identify critical success factors and barriers for CISs a systematic literature review was conducted based on the results from PubMed and Cochrane, using MaxQDA. Search results were thereby limited to reviews or meta-analysis. We have found 1919 references of which 40 met the inclusion criteria. The analysis of the manuscripts resulted in a comprehensive list of success factors and barriers related to CISs in integrated care settings. Most barriers were user-related whereas for the success factors an even distribution of organizational, technical and user-related factors was observed. The vast majority of publications was focused on healthcare professionals. It is important to incorporate experiences made/ collected over time, as the problems encountered seem to remain almost unvaried. In order to support further systematic investigations on the topic it is necessary to rethink existing concepts and definitions to realign them with the ideas of integrated care.

  18. Integrative review of factors related to the nursing diagnosis nausea during antineoplastic chemotherapy.

    Science.gov (United States)

    Moysés, Aline Maria Bonini; Durant, Lais Corsino; Almeida, Ana Maria de; Gozzo, Thais de Oliveira

    2016-10-10

    to identify factors related to the nursing diagnosis nausea among cancer patients undergoing chemotherapy. integrative review conducted in four electronic databases (PUBMED, EMBASE, CINAHL and LILACS) using the key words: neoplasia, antineoplastic agents and nausea. only 30 out of 1,258 papers identified met the inclusion criteria. The most frequent related factors were: being younger than 50 years old, motion sickness, being a woman, emetogenic potential of the chemotherapy, anxiety, conditioned stimulus, and expecting nausea after treatment. this review's findings, coupled with the incidence of nausea among cancer patients undergoing chemotherapy, reveal an important difference between evidence found and that used by NANDA International, Inc. Even though it provides an appropriate definition of related factors, it does not mention chemotherapy, despite the various studies addressing the topic using different designs and presenting various objectives and outcomes. identificar os fatores relacionados ao diagnóstico de enfermagem náusea entre pacientes oncológicos durante o tratamento quimioterápico. revisão integrativa de quatro bases eletrônicas de dados (PUBMED, EMBASE, CINAHL e LILACS) com as palavras-chaves neoplasia, agentes antineoplásicos e náusea. dos 1258 artigos identificados, somente 30 atenderam aos critérios de inclusão. Os fatores relacionados mais frequentes foram: idade abaixo de 50 anos, doença do movimento, sexo feminino, potencial emético do quimioterápico, ansiedade, estímulo condicionado e expectativa de náuseas depois do tratamento. diante dos resultados encontrados e da incidência de náusea entre os pacientes oncológicos em tratamento quimioterápico, observa-se diferença importante entre as evidências encontradas e as utilizadas pela NANDA International, Inc. Apesar da definição estar adequada entre os fatores relacionados, não há menção à quimioterapia mesmo com inúmeros estudos, com diferentes delineamentos

  19. Establishment and characterization of a novel Hodgkin lymphoma cell line, AM-HLH, carrying the Epstein-Barr virus genome integrated into the host chromosome.

    Science.gov (United States)

    Hayashida, Masahiko; Daibata, Masanori; Tagami, Erika; Taguchi, Takahiro; Maekawa, Fumiyo; Takeoka, Kayo; Fukutsuka, Katsuhiro; Shimomura, Daiki; Hayashi, Takamasa; Iwatani, Yoshinori; Ohno, Hitoshi

    2017-12-01

    We describe the establishment and characterization of a cell line, AM-HLH, obtained from a patient with Epstein-Barr virus-positive (EBV + ) nodular sclerosis-type Hodgkin lymphoma (HL). The cells were positive for CD2 and CD30 and negative for CD15. The immunoglobulin heavy- and κ light-chain genes were rearranged. The karyotype was of the triploid range. Southern blotting using the EBV terminal repeat probe detected 3 hybridizing bands that were identical to those of the parental HL material. The cells expressed EBV-encoded RNAs as well as latent genes (EBNA1, EBNA2, LMP1, and LMP2A) and lytic genes (BZLF1 and BALF2). Fluorescence in situ hybridization (FISH) with the cosmid pJB8 clone containing a fragment of EBV DNA as a probe revealed multiple hybridization signals at a marker chromosome. Additional FISH using whole chromosome painting and centromere probes in combination with multicolor FISH determined that multiple EBV copies were clustered within the chromosome 20 materials of the marker chromosome. Culture supernatants of AM-HLH contained IL-10 as measured by the bead-based immunoassay. It is possible that an integrated EBV genome and cellular genes on chromosome 20 were coamplified, leading to the enhanced expression of genes involved in cell growth control. The AM-HLH cell line will be useful to clarify the role of cytokines in the development of EBV + HL. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Positive semidefinite tensor factorizations of the two-electron integral matrix for low-scaling ab initio electronic structure.

    Science.gov (United States)

    Hoy, Erik P; Mazziotti, David A

    2015-08-14

    Tensor factorization of the 2-electron integral matrix is a well-known technique for reducing the computational scaling of ab initio electronic structure methods toward that of Hartree-Fock and density functional theories. The simplest factorization that maintains the positive semidefinite character of the 2-electron integral matrix is the Cholesky factorization. In this paper, we introduce a family of positive semidefinite factorizations that generalize the Cholesky factorization. Using an implementation of the factorization within the parametric 2-RDM method [D. A. Mazziotti, Phys. Rev. Lett. 101, 253002 (2008)], we study several inorganic molecules, alkane chains, and potential energy curves and find that this generalized factorization retains the accuracy and size extensivity of the Cholesky factorization, even in the presence of multi-reference correlation. The generalized family of positive semidefinite factorizations has potential applications to low-scaling ab initio electronic structure methods that treat electron correlation with a computational cost approaching that of the Hartree-Fock method or density functional theory.

  1. Positive semidefinite tensor factorizations of the two-electron integral matrix for low-scaling ab initio electronic structure

    Energy Technology Data Exchange (ETDEWEB)

    Hoy, Erik P.; Mazziotti, David A., E-mail: damazz@uchicago.edu [Department of Chemistry and The James Franck Institute, The University of Chicago, Chicago, Illinois 60637 (United States)

    2015-08-14

    Tensor factorization of the 2-electron integral matrix is a well-known technique for reducing the computational scaling of ab initio electronic structure methods toward that of Hartree-Fock and density functional theories. The simplest factorization that maintains the positive semidefinite character of the 2-electron integral matrix is the Cholesky factorization. In this paper, we introduce a family of positive semidefinite factorizations that generalize the Cholesky factorization. Using an implementation of the factorization within the parametric 2-RDM method [D. A. Mazziotti, Phys. Rev. Lett. 101, 253002 (2008)], we study several inorganic molecules, alkane chains, and potential energy curves and find that this generalized factorization retains the accuracy and size extensivity of the Cholesky factorization, even in the presence of multi-reference correlation. The generalized family of positive semidefinite factorizations has potential applications to low-scaling ab initio electronic structure methods that treat electron correlation with a computational cost approaching that of the Hartree-Fock method or density functional theory.

  2. Stress concentration factors for integral and pad reinforced nozzles in spherical pressure vessels subjected to radial load and moment

    International Nuclear Information System (INIS)

    Soliman, S.F.; Gill, S.S.

    1979-01-01

    Charts are presented giving the elastic stress concentration factors in spherical pressure vessels with pad and integral reinforcement for radial branches subjected to radial load and moment. The effect of all the geometrical parameters is discussed, including the limitations of thin shell theory on the validity of the results. (author)

  3. Factors from Durkheim's Family Integration Related to Suicidal Ideation among Men with Histories of Child Sexual Abuse

    Science.gov (United States)

    Easton, Scott D.; Renner, Lynette M.

    2013-01-01

    Men who were sexually abused during childhood represent a highly stigmatized, marginalized population at risk for a variety of long-term mental health problems. Using the family integration dimension of Durkheim's theory of suicide, factors associated with suicidal ideation among a purposive sample of 487 men with histories of child sexual…

  4. Factors Influencing Access to Integrated Soil Fertility Management Information and Knowledge and Its Uptake among Smallholder Farmers in Zimbabwe

    Science.gov (United States)

    Gwandu, T.; Mtambanengwe, F.; Mapfumo, P.; Mashavave, T. C.; Chikowo, R.; Nezomba, H.

    2014-01-01

    Purpose: The study evaluated how farmer acquisition, sharing and use patterns of information and knowledge interact with different socioeconomic factors to influence integrated soil fertility management (ISFM) technology uptake. Design/methodology/approach: The study was conducted as part of an evaluation of field-based farmer learning approaches…

  5. Psychological Factors in the Development of Football-Talent from the Perspective of an Integrative Sport-Talent Model

    Science.gov (United States)

    Orosz, Robert; Mezo, Ferenc

    2015-01-01

    This study presents a new, integrative model of sports talent. Following the theoretical part of the study a football-talent research is presented, in which a theoretical framework is provided by this new theory of sports talent. This research examines the role of psychological factors in football talent development. The sample was N = 425…

  6. The strategic decisions and success factors of the global integration-local responsiveness of Japanese MNCs in China

    Institute of Scientific and Technical Information of China (English)

    MAO Yunshi; WANG Jiancheng

    2007-01-01

    This article applies Foreign Direct Investment (FDI) theories to the strategic management analysis of the global integration-local responsiveness of multinational corporations (MNCs) in China, from the perspective of company characteristics (ownership advantages and internalization advantages) and environmental dynamics (locational factors) in order to analyze the success factors influencing the sales activities of Japanese MNCs in China. Based on the analysis of a survey conducted on 230 Japanese parent companies with investments in China, the empirical research findings include: Japanese MNCs in China favor global integration strategies; the more significant the ownership advantages and internalization advantages are, the greater the global integration is; the success factors of their operations in China due to global integration are present in manufacturing know-how, procurement of parts and supplies, financial power, previous investment experience in China as well as sales networks and technologies; locational advantages mainly lie in labor cost among other things; internalization factors do not have any significant correlation with the success and performance of the subsidiary company.

  7. A Test of an Integrative Model Using Social Factors and Personality Traits: Prediction on the Delinquency of South Korean Youth.

    Science.gov (United States)

    Yun, Minwoo; Kim, Eunyoung; Park, Woong-Sub

    2017-08-01

    To more fully comprehend juvenile delinquency, it is necessary to take an integrative approach, with consideration of both personality traits of social risk factors. Many scholars argue the necessity and strength of integrative approach on the ground that juvenile delinquency is an outcome of interplay of individual and social factors. The present study examines the general applicability of an integrative model of personal traits and social risk factors to youth delinquency in the South Korean context. The empirical results show that the delinquency predictors in the current South Korean sample are closely aligned to Loeber and Farrington's theoretical propositions and that found in Western nations. Perhaps this is because South Korea has undergone rapid Westernization for the last decades. Because the correlates in this sample and Western theoretical propositions and studies overlap, an integrative model of personality trait and social risk factors is indeed generally applicable to South Korea. This finding also depicts the extent of Westernization in the South Korean society at least among adolescents. Limitations of the present study and directions for the future study are discussed.

  8. Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor

    Science.gov (United States)

    O'Connell Motherway, Mary; Zomer, Aldert; Leahy, Sinead C.; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J.; O'Brien, Frances; Flynn, Kiera; Casey, Patrick G.; Moreno Munoz, Jose Antonio; Kearney, Breda; Houston, Aileen M.; O'Mahony, Caitlin; Higgins, Des G.; Shanahan, Fergus; Palva, Airi; de Vos, Willem M.; Fitzgerald, Gerald F.; Ventura, Marco; O'Toole, Paul W.; van Sinderen, Douwe

    2011-01-01

    Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated “tad2003.” Mutational analysis demonstrated that the tad2003 gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria. PMID:21690406

  9. Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor.

    Science.gov (United States)

    O'Connell Motherway, Mary; Zomer, Aldert; Leahy, Sinead C; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J; O'Brien, Frances; Flynn, Kiera; Casey, Patrick G; Munoz, Jose Antonio Moreno; Kearney, Breda; Houston, Aileen M; O'Mahony, Caitlin; Higgins, Des G; Shanahan, Fergus; Palva, Airi; de Vos, Willem M; Fitzgerald, Gerald F; Ventura, Marco; O'Toole, Paul W; van Sinderen, Douwe

    2011-07-05

    Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated "tad(2003)." Mutational analysis demonstrated that the tad(2003) gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria.

  10. Factors Influencing the Selection of the Systems Integration Organizational Model Type for Planning and Implementing Government High-Technology Programs

    Science.gov (United States)

    Thomas, Leann; Utley, Dawn

    2006-01-01

    While there has been extensive research in defining project organizational structures for traditional projects, little research exists to support high technology government project s organizational structure definition. High-Technology Government projects differ from traditional projects in that they are non-profit, span across Government-Industry organizations, typically require significant integration effort, and are strongly susceptible to a volatile external environment. Systems Integration implementation has been identified as a major contributor to both project success and failure. The literature research bridges program management organizational planning, systems integration, organizational theory, and independent project reports, in order to assess Systems Integration (SI) organizational structure selection for improving the high-technology government project s probability of success. This paper will describe the methodology used to 1) Identify and assess SI organizational structures and their success rate, and 2) Identify key factors to be used in the selection of these SI organizational structures during the acquisition strategy process.

  11. Risk factors for loss of epithelial flap integrity in laser-assisted subepithelial keratectomy surgery.

    Science.gov (United States)

    Galindo, Joanna; Fadlallah, Ali; Robinson, Steve; Chelala, Elias; Melki, Samir A

    2016-04-01

    To evaluate risk factors leading to loss of epithelial flap integrity in laser-assisted subepithelial keratectomy (LASEK). Boston Eye Group, Brookline, Massachusetts, USA. Retrospective case study. This retrospective chart review was performed for LASEK surgeries that occurred between January 2009 and October 2013. Logistic regression was performed to determine whether epithelium preservation was correlated with age, sex, sphere, cylinder, spherical equivalent (SE), keratometry, and central corneal thickness (CCT). The study reviewed 1009 eyes of 509 patients with a mean age of 29.1 years ± 12.2 (SD). The mean preoperative spherical refraction was -4.7 ± 2.5 diopters (D), and the mean preoperative cylinder was -1.1 ± 0.8 D. The mean preoperative decimal corrected distance visual acuity was 1.01 ± 0.07. Single-sheet mobilization of the loosened epithelium flap was found in 72.3% of cases. Fragmented preservation events occurred in 17.6% of cases; the flap was discarded in 10.0% of cases. Epithelium preservation was significantly correlated with age (P = .048) but not with other parameters (P > .05 for sex, sphere, cylinder, SE, keratometry, CCT, and surgeon experience). Epithelial flap dissection was less likely to lead to a single epithelial sheet in patients older than 50 years than in younger patients (56.3% versus 74.9%). The mean postoperative decimal uncorrected distance visual acuity (UDVA) at 3 months was 0.98 ± 0.08. There was no statistical difference in postoperative UDVA between the undiscarded flap group and discarded flap group (P = .128). Successful dissection of single-sheet epithelial flap diminished with age. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  12. Characterization of a new CAMP factor carried by an integrative and conjugative element in Streptococcus agalactiae and spreading in Streptococci.

    Directory of Open Access Journals (Sweden)

    Sarah Chuzeville

    Full Text Available Genetic exchanges between Streptococci occur frequently and contribute to their genome diversification. Most of sequenced streptococcal genomes carry multiple mobile genetic elements including Integrative and Conjugative Elements (ICEs that play a major role in these horizontal gene transfers. In addition to genes involved in their mobility and regulation, ICEs also carry genes that can confer selective advantages to bacteria. Numerous elements have been described in S. agalactiae especially those integrated at the 3' end of a tRNA(Lys encoding gene. In strain 515 of S. agalactiae, an invasive neonate human pathogen, the ICE (called 515_tRNA(Lys is functional and carries different putative virulence genes including one encoding a putative new CAMP factor in addition to the one previously described. This work demonstrated the functionality of this CAMP factor (CAMP factor II in Lactococcus lactis but also in pathogenic strains of veterinary origin. The search for co-hemolytic factors in a collection of field strains revealed their presence in S. uberis, S. dysgalactiae, but also for the first time in S. equisimilis and S. bovis. Sequencing of these genes revealed the prevalence of a species-specific factor in S. uberis strains (Uberis factor and the presence of a CAMP factor II encoding gene in S. bovis and S. equisimilis. Furthermore, most of the CAMP factor II positive strains also carried an element integrated in the tRNA(Lys gene. This work thus describes a CAMP factor that is carried by a mobile genetic element and has spread to different streptococcal species.

  13. Integrating climate change adaptation into Dutch local policies and the role of contextual factors.

    NARCIS (Netherlands)

    van den Berg, Maya Marieke; Coenen, Franciscus H.J.M.

    2012-01-01

    Moving towards a more sustainable adaptation process requires closer integration of policies related to the environment. An important actor in this is the local government. This paper examines to what extend adaptation is currently being integrated into Dutch local policies, and what the role is of

  14. Influencing Factors and Integration of ICT into Teaching Practices of Pre- Service and Starting Teachers

    Science.gov (United States)

    Aslan, Aydin; Zhu, Chang

    2016-01-01

    Teachers need to be competent in integrating ICT into education to support teaching and learning process. This study aims to investigate both the pre-service and starting teachers' perceptions for ICT-related variables--perceived ICT competence, perceived competence in ICT integration, attitudes towards ICT, anxiety around ICT usage, external…

  15. Modelling the integration-performance relationship : Collaborative practices, enablers and contextual factors

    NARCIS (Netherlands)

    van der Vaart, T.; van Donk, D.P.; Giménez, C.; Sierra, V.

    2012-01-01

    Purpose - The purpose of this paper is to investigate the impact of different dimensions of supply chain integration on performance, while considering both the interconnections between these supply chain integration dimensions and the effect of context. Specifically, the authors investigate the

  16. Design Features of Product-Integrated PV : An Evaluation of Various Factors under Indoor Irradiance Conditions

    NARCIS (Netherlands)

    Apostolou, G.

    2016-01-01

    This thesis explores the field of product-integrated photovoltaics (PIPV), a term which is used for all types of products that contain solar cells in one or more of their surfaces, aiming at providing power during the product’s use. Product-integrated photovoltaics (PIPV) began to be widely

  17. Space Flight Human System Standards (SFHSS). Volume 2; Human Factors, Habitability and Environmental Factors" and Human Integration Design Handbook (HIDH)

    Science.gov (United States)

    Davis, Jeffrey R.; Fitts, David J.

    2009-01-01

    This viewgraph presentation reviews the standards for space flight hardware based on human capabilities and limitations. The contents include: 1) Scope; 2) Applicable documents; 3) General; 4) Human Physical Characteristics and Capabilities; 5) Human Performance and Cognition; 6) Natural and Induced Environments; 7) Habitability Functions; 8) Architecture; 9) Hardware and Equipment; 10) Crew Interfaces; 11) Spacesuits; 12) Operatons: Reserved; 13) Ground Maintenance and Assembly: Reserved; 14) Appendix A-Reference Documents; 15) Appendix N-Acronyms and 16) Appendix C-Definition. Volume 2 is supported by the Human Integration Design Handbook (HIDH)s.

  18. Host and parasite morphology influence congruence between host and parasite phylogenies.

    Science.gov (United States)

    Sweet, Andrew D; Bush, Sarah E; Gustafsson, Daniel R; Allen, Julie M; DiBlasi, Emily; Skeen, Heather R; Weckstein, Jason D; Johnson, Kevin P

    2018-03-23

    Comparisons of host and parasite phylogenies often show varying degrees of phylogenetic congruence. However, few studies have rigorously explored the factors driving this variation. Multiple factors such as host or parasite morphology may govern the degree of phylogenetic congruence. An ideal analysis for understanding the factors correlated with congruence would focus on a diverse host-parasite system for increased variation and statistical power. In this study, we focused on the Brueelia-complex, a diverse and widespread group of feather lice that primarily parasitise songbirds. We generated a molecular phylogeny of the lice and compared this tree with a phylogeny of their avian hosts. We also tested for the contribution of each host-parasite association to the overall congruence. The two trees overall were significantly congruent, but the contribution of individual associations to this congruence varied. To understand this variation, we developed a novel approach to test whether host, parasite or biogeographic factors were statistically associated with patterns of congruence. Both host plumage dimorphism and parasite ecomorphology were associated with patterns of congruence, whereas host body size, other plumage traits and biogeography were not. Our results lay the framework for future studies to further elucidate how these factors influence the process of host-parasite coevolution. Copyright © 2018 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  19. Enhanceosomes as integrators of hypoxia inducible factor (HIF) and other transcription factors in the hypoxic transcriptional response.

    Science.gov (United States)

    Pawlus, Matthew R; Hu, Cheng-Jun

    2013-09-01

    Hypoxia is a prevalent attribute of the solid tumor microenvironment that promotes the expression of genes through posttranslational modifications and stabilization of alpha subunits (HIF1α and HIF2α) of hypoxia-inducible factors (HIFs). Despite significant similarities, HIF1 (HIF1α/ARNT) and HIF2 (HIF2α/ARNT) activate common as well as unique target genes and exhibit different functions in cancer biology. More surprisingly, accumulating data indicates that the HIF1- and/or HIF2-mediated hypoxia responses can be oncogenic as well as tumor suppressive. While the role of HIF in the hypoxia response is well established, recent data support the concept that HIF is necessary, but not sufficient for the hypoxic response. Other transcription factors that are activated by hypoxia are also required for the HIF-mediated hypoxia response. HIFs, other transcription factors, co-factors and RNA poll II recruited by HIF and other transcription factors form multifactorial enhanceosome complexes on the promoters of HIF target genes to activate hypoxia inducible genes. Importantly, HIF1 or HIF2 requires distinct partners in activating HIF1 or HIF2 target genes. Because HIF enhanceosome formation is required for the gene activation and distinct functions of HIF1 and HIF2 in tumor biology, disruption of the HIF1 or HIF2 specific enhanceosome complex may prove to be a beneficial strategy in tumor treatment in which tumor growth is specifically dependent upon HIF1 or HIF2 activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Does vertical integration have an effect on load factor? - A test on coal-fired plants in England and Wales

    International Nuclear Information System (INIS)

    Lopez, Jose A.; Salies, Evens

    2006-02-01

    Today in the British electricity industry, most electricity suppliers hedge a large proportion of their residential customer base requirements by owning their own plant. The non-storability of electricity and the corresponding need for an instantaneous matching of generation and consumption creates a business need for integration. From a sample of half-hour data on load factor for coal-fired power plants in England and Wales, this paper tests the hypothesis that vertical integration with retail businesses affects the extent to which producers utilize their capacity. We also pay attention to this potential effect during periods of peak demand. (authors)

  1. Low cost, small form factor, and integration as the key features for the optical component industry takeoff

    Science.gov (United States)

    Schiattone, Francesco; Bonino, Stefano; Gobbi, Luigi; Groppi, Angelamaria; Marazzi, Marco; Musio, Maurizio

    2003-04-01

    In the past the optical component market has been mainly driven by performances. Today, as the number of competitors has drastically increased, the system integrators have a wide range of possible suppliers and solutions giving them the possibility to be more focused on cost and also on footprint reduction. So, if performances are still essential, low cost and Small Form Factor issues are becoming more and more crucial in selecting components. Another evolution in the market is the current request of the optical system companies to simplify the supply chain in order to reduce the assembling and testing steps at system level. This corresponds to a growing demand in providing subassemblies, modules or hybrid integrated components: that means also Integration will be an issue in which all the optical component companies will compete to gain market shares. As we can see looking several examples offered by electronic market, to combine low cost and SFF is a very challenging task but Integration can help in achieving both features. In this work we present how these issues could be approached giving examples of some advanced solutions applied to LiNbO3 modulators. In particular we describe the progress made on automation, new materials and low cost fabrication methods for the parts. We also introduce an approach in integrating optical and electrical functionality on LiNbO3 modulators including RF driver, bias control loop, attenuator and photodiode integrated in a single device.

  2. Integration of fluvial erosion factors for predicting landslides along meandering rivers

    Science.gov (United States)

    Chen, Yi-chin; Chang, Kang-tsung; Ho, Jui-yi

    2015-04-01

    the bank from erosion. Finally, the results also showed that the integration of fluvial erosion factors can improve the performance in predicting landsliding along meandering rivers.

  3. Models for integrated pest control and their biological implications.

    Science.gov (United States)

    Tang, Sanyi; Cheke, Robert A

    2008-09-01

    Successful integrated pest management (IPM) control programmes depend on many factors which include host-parasitoid ratios, starting densities, timings of parasitoid releases, dosages and timings of insecticide applications and levels of host-feeding and parasitism. Mathematical models can help us to clarify and predict the effects of such factors on the stability of host-parasitoid systems, which we illustrate here by extending the classical continuous and discrete host-parasitoid models to include an IPM control programme. The results indicate that one of three control methods can maintain the host level below the economic threshold (ET) in relation to different ET levels, initial densities of host and parasitoid populations and host-parasitoid ratios. The effects of host intrinsic growth rate and parasitoid searching efficiency on host mean outbreak period can be calculated numerically from the models presented. The instantaneous pest killing rate of an insecticide application is also estimated from the models. The results imply that the modelling methods described can help in the design of appropriate control strategies and assist management decision-making. The results also indicate that a high initial density of parasitoids (such as in inundative releases) and high parasitoid inter-generational survival rates will lead to more frequent host outbreaks and, therefore, greater economic damage. The biological implications of this counter intuitive result are discussed.

  4. Nature protection in Greece: an appraisal of the factors shaping integrative conservation and policy effectiveness

    International Nuclear Information System (INIS)

    Papageorgiou, Kostas; Vogiatzakis, Ioannis N.

    2006-01-01

    The proliferation of designated areas following the implementation of Natura 2000 in Greece has initiated changes in the protected area design and conservation policy making aiming at delivering action for biodiversity and integrative planning on a wider landscape. Following the sustainability concept, an integrative approach cannot realistically take place simply by extending the protected area and designations. The paper addresses public involvement and inter-sectoral coordination as major procedural elements of integrative management and evaluates the nature and strength of their negative or positive influences on the fulfillment of an integrative vision of nature conservation. A review of the history of protected areas and administration developments in Greece provide useful input in the research. The analysis has shown that the selected network of Natura 2000 sites has been superimposed upon the existing system and resulted in duplication of administrative effort and related legislation. As a result the overall picture of protected areas in the country appears complex, confusing and fragmented. Major failures to integrated conservation perspective can be traced to structural causes rooted in politico-economic power structures of mainstream policy and in a rather limited political commitment to conservation. It is concluded that greater realisation of integrated conservation in Greece necessitates policy reforms related mainly to sectoral legal frameworks to promote environmentalism as well as an increased effort by the managing authorities to facilitate a broader framework of public dialogue and give local communities incentives to sustainably benefit from protected areas

  5. Location of Host and Host Habitat by Fruit Fly Parasitoids

    Directory of Open Access Journals (Sweden)

    Pascal Rousse

    2012-11-01

    Full Text Available Augmentative releases of parasitoids may be a useful tool for the area-wide management of tephritid pests. The latter are parasitized by many wasp species, though only a few of them are relevant for augmentative biocontrol purposes. To date, nearly all the actual or potential biocontrol agents for such programs are egg or larval Opiinae parasitoids (Hymenoptera: Braconidae. Here, we review the literature published on their habitat and host location behavior, as well as the factors that modulate this behavior, which is assumed to be sequential; parasitoids forage first for the host habitat and then for the host itself. Parasitoids rely on chemical, visual, and mechanical stimuli, often strongly related to their ecology. Behavioral modulation factors include biotic and abiotic factors including learning, climatic conditions and physiological state of the insect. Finally, conclusions and perspectives for future research are briefly highlighted. A detailed knowledge of this behavior may be very useful for selecting the release sites for both inundative/augmentative releases of mass-reared parasitoids and inoculative releases for classical biocontrol.

  6. Inhibition of the host proteasome facilitates papaya ringspot virus accumulation and proteosomal catalytic activity is modulated by viral factor HcPro.

    Directory of Open Access Journals (Sweden)

    Nandita Sahana

    Full Text Available The ubiquitin/26S proteasome system plays an essential role not only in maintaining protein turnover, but also in regulating many other plant responses, including plant-pathogen interactions. Previous studies highlighted different roles of the 20S proteasome in plant defense during virus infection, either indirectly through viral suppressor-mediated degradation of Argonaute proteins, affecting the RNA interference pathway, or directly through modulation of the proteolytic and RNase activity of the 20S proteasome, a component of the 20S proteasome, by viral proteins, affecting the levels of viral proteins and RNAs. Here we show that MG132, a cell permeable proteasomal inhibitor, caused an increase in papaya ringspot virus (PRSV accumulation in its natural host papaya (Carica papaya. We also show that the PRSV HcPro interacts with the papaya homologue of the Arabidopsis PAA (α1 subunit of the 20S proteasome, but not with the papaya homologue of Arabidopsis PAE (α5 subunit of the 20S proteasome, associated with the RNase activity, although the two 20S proteasome subunits interacted with each other. Mutated forms of PRSV HcPro showed that the conserved KITC54 motif in the N-terminal domain of HcPro was necessary for its binding to PAA. Co-agroinfiltration assays demonstrated that HcPro expression mimicked the action of MG132, and facilitated the accumulation of bothtotal ubiquitinated proteins and viral/non-viral exogenous RNA in Nicotiana benthamiana leaves. These effects were not observed by using an HcPro mutant (KITS54, which impaired the HcPro - PAA interaction. Thus, the PRSV HcPro interacts with a proteasomal subunit, inhibiting the action of the 20S proteasome, suggesting that HcPro might be crucial for modulating its catalytic activities in support of virus accumulation.

  7. Postsurgical recurrence of ileal Crohn's disease: an update on risk factors and intervention points to a central role for impaired host-microflora homeostasis.

    LENUS (Irish Health Repository)

    Cunningham, Michael F

    2010-07-01

    A pressing need exists to identify factors that predispose to recurrence after terminal ileal resection for Crohn\\'s disease (CD) and to determine effective prophylactic strategies. This review presents an up-to-date summary of the literature in the field and points to a role for bacterial overproliferation in recurrence.

  8. Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy

    NARCIS (Netherlands)

    Winston, A.; Stöhr, W.; Antinori, A.; Arenas-Pinto, A.; Llibre, J. M.; Amieva, H.; Cabié, A.; Williams, I.; Di Perri, G.; Tellez, M. J.; Rockstroh, J.; Babiker, A.; Pozniak, A.; Raffi, F.; Richert, L.; Dedes, Nikos; Chene, Genevieve; Allavena, Clotilde; Autran, Brigitte; Bucciardini, Raffaella; Vella, Stefano; Horban, Andrzej; Arribas, Jose; Boffito, Marta; Pillay, Deenan; Franquet, Xavier; Schwarze, Siegfried; Grarup, Jesper; Fischer, Aurelie; Wallet, Cedrick; Diallo, Alpha; Molina, Jean-Michel; Saillard, Juliette; Moecklinghoff, Christiane; Stellbrink, Hans-Jurgen; Leeuwen, Remko; Gatell, Jose; Sandstrom, Eric; Flepp, Markus; Ewings, Fiona; George, Elizabeth C.; Hudson, Fleur; Pearce, Gillian; Quercia, Romina; Rogatto, Felipe; Leavitt, Randi; Nguyen, Bach-Yen; Goebel, Frank; Marcotullio, Simone; Kaur, Navrup; Sasieni, Peter; Spencer-Drake, Christina; Peto, Tim; Miller, Veronica; Chêne, Geneviève; Arnault, Fabien; Boucherie, Céline; Fischer, Aurélie; Jean, Delphine; Paniego, Virginie; Rouch, Elodie; Schwimmer, Christine; Soussi, Malika; Taieb, Audrey; Termote, Monique; Touzeau, Guillaume; Wallet, Cédrick; Cursley, Adam; Dodds, Wendy; Hoppe, Anne; Kummeling, Ischa; Pacciarini, Filippo; Paton, Nick; Russell, Charlotte; Taylor, Kay; Ward, Denise; Aagaard, Bitten; Eid, Marius; Gey, Daniela; Jensen, Birgitte; Jakobsen, Marie-Louise; Jansson, Per O.; Jensen, Karoline; Joensen, Zillah; Larsen, Ellen; Pahl, Christiane; Pearson, Mary; Nielsen, Birgit; Reilev, Søren; Christ, Ilse; Lathouwers, Desiree; Manting, Corry; Mendy, Bienvenu; Metro, Annie; Couffin-Cadiergues, Sandrine; Knellwolf, Anne-Laure; Palmisiano, Lucia; Aznar, Esther; Barea, Cristina; Cotarelo, Manuel; Esteban, Herminia; Girbau, Iciar; Moyano, Beatriz; Ramirez, Miriam; Saiz, Carmen; Sanchez, Isabel; Yllescas, Maria; Binelli, Andrea; Colasanti, Valentina; Massella, Maurizio; Anagnostou, Olga; Gioukari, Vicky; Touloumi, Giota; Schmied, Brigitte; Rieger, Armin; Vetter, Norbert; Wit, Stephane; Florence, Eric; Vandekerckhove, Linos; Gerstoft, Jan; Mathiesen, Lars; Katlama, Christine; Cabie, Andre; Cheret, Antoine; Dupon, Michel; Ghosn, Jade; Girard, Pierre-Marie; Goujard, Cécile; Lévy, Yves; Morlat, Philippe; Neau, Didier; Obadia, Martine; Perre, Philippe; Piroth, Lionel; Reynes, Jacques; Tattevin, Pierre; Ragnaud, Jean; Weiss, Laurence; Yazdan, Yazdanpanah; Yeni, Patrick; Zucman, David; Behrens, Georg; Esser, Stefan; Fätkenheuer, Gerd; Hoffmann, Christian; Jessen, Heiko; Schmidt, Reinhold; Stephan, Christoph; Unger, Stefan; Hatzakis, Angelos; Daikos, George L.; Papadopoulos, Antonios; Skoutelis, Athamasios; Banhegyi, Denes; Mallon, Paddy; Mulcahy, Fiona; Andreoni, Massimo; Bonora, Stefano; Castelli, Francesco; Monforte, Antonella; Galli, Massimo; Lazzarin, Adriano; Mazzotta, Francesco; Carlo, Torti; Vullo, Vincenzo; Prins, Jan; Richter, Clemens; Verhagen, Dominique; Eeden, Arne; Doroana, Manuela; Antunes, Francisco; Maltez, Fernando; Sarmento-Castro, Rui; Garcia, Juan; Aldeguer, José; Clotet, Bonaventura; Domingo, Pere; Gatell, Jose M.; Knobel, Hernando; Marquez, Manuel; Miralles, Martin; Portilla, Joaquin; Soriano, Vicente; Thalme, Anders; Blaxhult, Anders; Gisslen, Magnus; Fox, Julie; Gompels, Mark; Herieka, Elbushra; Johnson, Margaret; Leen, Clifford; Teague, Alastair; Boyd, Mark; Møller, Nina; Frøsig, Ellen; Moing, Vincent; Wit, Ferdinand W. N. M.; Kowalska, Justyna; Berenguer, Juan; Moreno, Santiago; MuHller, Nicolas J.; Török, Estée; Post, Frank; Angus, Brian; Calvez, Vincent; Boucher, Charles; Collins, Simon; Dunn, David; Lambert, Sidonie; Marcelin, Anne-Geneviève; Perno, Carlo; White, Ellen; Ammassari, Adriana; Stoehr, Wolgang; Odermarsky, Michal; Smith, Colette; Thiébaut, Rodolphe; LaSerna, Bernardino; Castagna, Antonella; Furrer, Hans-Jackob; Mocroft, Amanda; Reiss, Peter; Fragola, Vincenzo; Lauriola, Marco; Murri, Rita; Nieuwkerk, Pythia; Spire, Bruno; Volny-Anne, Alain; West, Brian; Maria, Josep; Braggion, Marco; Focà, Emanuele

    2016-01-01

    Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de

  9. Psychological Factors in the Development of Football-Talent from the Perspective of an Integrative Sport-Talent Model

    OpenAIRE

    Robert OROSZ; Ferenc MEZO

    2015-01-01

    This study presents a new, integrative model of sports talent. Following the theoretical part of the study a football-talent research is presented, in which a theoretical framework is provided by this new theory of sports talent. This research examines the role of psychological factors in football talent development. The sample was N=425 football-players of the First Division Men’s Junior and Adolescent Football Championships of the Hungarian Football League, and their coaches (N=21). The app...

  10. Integrating factors and conservation theorems for Hamilton's canonical equations of motion of variable mass nonholonomic nonconservative dynamical systems

    Institute of Scientific and Technical Information of China (English)

    李仁杰; 乔永芬; 刘洋

    2002-01-01

    We present a general approach to the construction of conservation laws for variable mass nonholonomic noncon-servative systems. First, we give the definition of integrating factors, and we study in detail the necessary conditionsfor the existence of the conserved quantities. Then, we establish the conservation theorem and its inverse theorem forHamilton's canonical equations of motion of variable mass nonholonomic nonconservative dynamical systems. Finally,we give an example to illustrate the application of the results.

  11. Integrating factors and conservation theorems for Hamilton‘s canonical equations of motion of variable mass nonholonmic nonconservative dynamical systems

    Institute of Scientific and Technical Information of China (English)

    李仁杰; 刘洋; 等

    2002-01-01

    We present a general approach to the construction of conservation laws for variable mass noholonmic nonconservative systems.First,we give the definition of integrating factors,and we study in detail the necessary conditions for the existence of the conserved quantities,Then,we establish the conservatioin theorem and its inverse theorem for Hamilton's canonical equations of motion of variable mass nonholonomic nonocnservative dynamical systems.Finally,we give an example to illustrate the application of the results.

  12. Factors Affecting the Integration of Information Literacy in the Teaching and Learning Processes of General Education Courses

    Directory of Open Access Journals (Sweden)

    Therdsak Maitaouthong

    2011-11-01

    Full Text Available This article presents the factors affecting the integration of information literacy in the teaching and learning processes of general education courses at an undergraduate level, where information literacy is used as a tool in the student-centered teaching approach. The research was divided into two phases: (1 The study of factors affecting at a policy level – a qualitative research method conducted through an in-depth interview of the vice president for academic affairs and the Director of the General Education Management Center, and (2 The survey of factors affecting in the teaching and learning processes, which is concluded through the questioning of lecturers of general education courses, and librarians. The qualitative data was analyzed on content, and the quantitative data was analyzed through the use of descriptive statistics, weight of score prioritization and percentage. Two major categories were found to have an impact on integrating information literacy in the teaching and learning of general education courses at an undergraduate level. (1 Six factors at a policy level, namely, institutional policy, administrative structure and system, administrators’ roles, resources and infrastructures, learning resources and supporting programs, and teacher evaluation and development. (2 There are eleven instructional factors: roles of lecturers, roles of librarians, roles of learners, knowledge and understanding of information literacy of lecturers and librarians, cooperation between librarians and lecturers, learning outcomes, teaching plans, teaching methods, teaching activities, teaching aids, and student assessment and evaluation.

  13. Host plant adaptation in Drosophila mettleri populations.

    Directory of Open Access Journals (Sweden)

    Sergio Castrezana

    Full Text Available The process of local adaptation creates diversity among allopatric populations, and may eventually lead to speciation. Plant-feeding insect populations that specialize on different host species provide an excellent opportunity to evaluate the causes of ecological specialization and the subsequent consequences for diversity. In this study, we used geographically separated Drosophila mettleri populations that specialize on different host cacti to examine oviposition preference for and larval performance on an array of natural and non-natural hosts (eight total. We found evidence of local adaptation in performance on saguaro cactus (Carnegiea gigantea for populations that are typically associated with this host, and to chemically divergent prickly pear species (Opuntia spp. in a genetically isolated population on Santa Catalina Island. Moreover, each population exhibited reduced performance on the alternative host. This finding is consistent with trade-offs associated with adaptation to these chemically divergent hosts, although we also discuss alternative explanations for this pattern. For oviposition preference, Santa Catalina Island flies were more likely to oviposit on some prickly pear species, but all populations readily laid eggs on saguaro. Experiments with non-natural hosts suggest that factors such as ecological opportunity may play a more important role than host plant chemistry in explaining the lack of natural associations with some hosts.

  14. Fire protection system management in nuclear facilities: strengthening factor of integrated management system - a case study

    International Nuclear Information System (INIS)

    Santos, Joao Regis dos

    2005-01-01

    The present study investigated and analyzed the importance of a system of integrated safety manage, environment and health in a nuclear installation, having as perspective, the fire protection manage. The inquiry was made using a qualitative research involving a case study, where the considered environment was the Reconversion and UO 2 Plant of the Industrias Nucleares do Brasil (INB), located in Resende, Rio de Janeiro and the studied population, the managers and the staff directly involved with the aspects related to the safety of the industrial complex of the related company. The motivation for the research was the search of a bigger interaction of the questions related to the safety, environment and health in the nuclear industry having, as axle of the investigation, the fire protection. As a result, it was observed that in a nuclear installation, although dealing with diversified safety processes, integration is possible and necessary, since there are more reasons for integration than otherwise. (author)

  15. Ontology-based representation and analysis of host-Brucella interactions.

    Science.gov (United States)

    Lin, Yu; Xiang, Zuoshuang; He, Yongqun

    2015-01-01

    Biomedical ontologies are representations of classes of entities in the biomedical domain and how these classes are related in computer- and human-interpretable formats. Ontologies support data standardization and exchange and provide a basis for computer-assisted automated reasoning. IDOBRU is an ontology in the domain of Brucella and brucellosis. Brucella is a Gram-negative intracellular bacterium that causes brucellosis, the most common zoonotic disease in the world. In this study, IDOBRU is used as a platform to model and analyze how the hosts, especially host macrophages, interact with virulent Brucella strains or live attenuated Brucella vaccine strains. Such a study allows us to better integrate and understand intricate Brucella pathogenesis and host immunity mechanisms. Different levels of host-Brucella interactions based on different host cell types and Brucella strains were first defined ontologically. Three important processes of virulent Brucella interacting with host macrophages were represented: Brucella entry into macrophage, intracellular trafficking, and intracellular replication. Two Brucella pathogenesis mechanisms were ontologically represented: Brucella Type IV secretion system that supports intracellular trafficking and replication, and Brucella erythritol metabolism that participates in Brucella intracellular survival and pathogenesis. The host cell death pathway is critical to the outcome of host-Brucella interactions. For better survival and replication, virulent Brucella prevents macrophage cell death. However, live attenuated B. abortus vaccine strain RB51 induces caspase-2-mediated proinflammatory cell death. Brucella-associated cell death processes are represented in IDOBRU. The gene and protein information of 432 manually annotated Brucella virulence factors were represented using the Ontology of Genes and Genomes (OGG) and Protein Ontology (PRO), respectively. Seven inference rules were defined to capture the knowledge of host

  16. Integration of transcriptomic and metabolic data reveals hub transcription factors involved in drought stress response in sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Moschen, Sebastián; Di Rienzo, Julio A; Higgins, Janet; Tohge, Takayuki; Watanabe, Mutsumi; González, Sergio; Rivarola, Máximo; García-García, Francisco; Dopazo, Joaquin; Hopp, H Esteban; Hoefgen, Rainer; Fernie, Alisdair R; Paniego, Norma; Fernández, Paula; Heinz, Ruth A

    2017-07-01

    By integration of transcriptional and metabolic profiles we identified pathways and hubs transcription factors regulated during drought conditions in sunflower, useful for applications in molecular and/or biotechnological breeding. Drought is one of the most important environmental stresses that effects crop productivity in many agricultural regions. Sunflower is tolerant to drought conditions but the mechanisms involved in this tolerance remain unclear at the molecular level. The aim of this study was to characterize and integrate transcriptional and metabolic pathways related to drought stress in sunflower plants, by using a system biology approach. Our results showed a delay in plant senescence with an increase in the expression level of photosynthesis related genes as well as higher levels of sugars, osmoprotectant amino acids and ionic nutrients under drought conditions. In addition, we identified transcription factors that were upregulated during drought conditions and that may act as hubs in the transcriptional network. Many of these transcription factors belong to families implicated in the drought response in model species. The integration of transcriptomic and metabolomic data in this study, together with physiological measurements, has improved our understanding of the biological responses during droughts and contributes to elucidate the molecular mechanisms involved under this environmental condition. These findings will provide useful biotechnological tools to improve stress tolerance while maintaining crop yield under restricted water availability.

  17. Design Features of Product-Integrated PV: An Evaluation of Various Factors under Indoor Irradiance Conditions

    OpenAIRE

    Apostolou, G.

    2016-01-01

    This thesis explores the field of product-integrated photovoltaics (PIPV), a term which is used for all types of products that contain solar cells in one or more of their surfaces, aiming at providing power during the product’s use. Product-integrated photovoltaics (PIPV) began to be widely introduced around 2000, although the use of PV systems in products dates back to the 70s. PIPV includes products such as PV-powered boats, aircrafts, cars, bicycles, camping tents, street lights, recycling...

  18. Expression of the human blood coagulation protein factor XIIIa in Saccharomyces cerevisiae: dependence of the expression levels from host-vector systems and medium conditions.

    Science.gov (United States)

    Bröker, M; Bäuml, O; Göttig, A; Ochs, J; Bodenbenner, M; Amann, E

    1991-03-01

    The human blood coagulation protein Factor XIIIa (FXIIIa) was expressed in Saccharomyces cerevisiae employing Escherichia coli-yeast shuttle vectors based on a 2-mu plasmid. Several factors affecting high production yield of recombinant FXIIIa were analysed. The use of the regulatable GAL-CYC1 hybrid promoter resulted in higher FXIIIa expression when compared with the constitutive ADCI promoter. Screening for suitable yeast strains for expression of FXIIIa under the transcriptional control of the GAL-CYC1 hybrid promoter revealed a broad spectrum of productivity. No obvious correlation between the expression rate and the genetic markers of the strains could be identified. The medium composition markedly influenced the FXIIIa expression rates. The expression of FXIIIa was strictly regulated by the carbon source. Glucose as the only sugar and energy source repressed the synthesis of FXIIIa, whereas addition of galactose induced FXIIIa expression. Special feeding schemes resulted in a productivity of up to 100 mg FXIIIa/l in shake flasks.

  19. Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy

    DEFF Research Database (Denmark)

    Winston, A; Stöhr, W; Antinori, A

    2016-01-01

    OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence...... Nationale de Recherche sur le SIDA (ANRS) 143 study. METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean...... and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models. RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile...

  20. Derivation of a JC virus-resistant human glial cell line: implications for the identification of host cell factors that determine viral tropism

    International Nuclear Information System (INIS)

    Gee, Gretchen V.; Manley, Kate; Atwood, Walter J.

    2003-01-01

    JC virus (JCV) is a common human polyomavirus that infects 70-80% of the population worldwide. In immunosuppressed individuals, JCV infects oligodendrocytes and causes a fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). The tropism of JCV is restricted to oligodendrocytes, astrocytes, and B lymphocytes. Several mechanisms may contribute to the restricted tropism of JCV, including the presence or absence of cell-type-specific transcription and replication factors and the presence or absence of cell-type-specific receptors. We have established a system to investigate cellular factors that influence viral tropism by selecting JCV-resistant cells from a susceptible glial cell line (SVG-A). SVG-A cells were subjected to several rounds of viral infection using JC virus (M1/SVEΔ). A population of resistant cells emerged (SVGR2) that were refractory to infection with the Mad-4 strain of JCV, the hybrid virus M1/SVEΔ, as well as to the related polyomavirus SV40. SVGR2 cells were as susceptible as the SVG-A cells to infection with an unrelated amphotropic retrovirus. The stage at which these cells are resistant to infection was investigated and the block appears to be at early viral gene transcription. This system should ultimately allow us to identify glial specific factors that influence the tropism of JCV

  1. On the minima of the time integrated perturbation factor in the Scherer-Blume theory

    International Nuclear Information System (INIS)

    Silveira, E.F. da; Freire Junior, F.L.; Massolo, C.P.; Schaposnik, F.A.

    1981-09-01

    The minima in the correlation time dependence of the Scherer-Blume time integrated attenuation coefficients for the hyperfine perturbation of ions recoiling in gas are studied. Its position and depth are determined for different physical situations and comparison with experimental data is shown. (Author) [pt

  2. Factors affecting farmers' adoption of integrated rice-fish farming systems in the Mekong delta, Vietnam

    NARCIS (Netherlands)

    Bosma, R.H.; Nhan, D.K.; Udo, H.M.J.; Kaymak, U.

    2012-01-01

    This study investigated the determinants of the adoption of improved rice–fish farming systems in the Mekong delta to support policy making, agricultural land-use planning and extension of integrated rice–fish farming. Recently these systems have been referred to as adaptations to climate change,

  3. Factors influencing economic profitability of dampling-based integrated management of wheat in country elevators

    Science.gov (United States)

    Integrated pest management provides the potential for better insect management in stored wheat, as well as increased worker safety and reduced environmental concerns. Many country elevators, however, continue to use chemical-based approaches. To determine if this choice is economically justified, to...

  4. Teacher Identity in Language Teaching: Integrating Personal, Contextual, and Professional Factors

    Science.gov (United States)

    Pennington, Martha C.; Richards, Jack C.

    2016-01-01

    This article reviews notions of identity and teacher identity, how these relate to the specific characteristics of language teaching, and how teacher identity can evolve or be developed through experience and teacher education. The notion of teacher identity highlights the individual characteristics of the teacher and how these are integrated with…

  5. Understanding Risk and Protective Factors for Child Maltreatment: The Value of Integrated, Population-Based Data

    Science.gov (United States)

    Putnam-Hornstein, Emily; Needell, Barbara; Rhodes, Anne E.

    2013-01-01

    In this article, we argue for expanded efforts to integrate administrative data systems as a "practical strategy" for developing a richer understanding of child abuse and neglect. Although the study of child maltreatment is often critiqued for being atheoretical, we believe that a more pressing concern is the absence of population-based and…

  6. Factors Influencing College Women's Contraceptive Behavior: An Application of the Integrative Model of Behavioral Prediction

    Science.gov (United States)

    Sutton, Jazmyne A.; Walsh-Buhi, Eric R.

    2017-01-01

    Objective: This study investigated variables within the Integrative Model of Behavioral Prediction (IMBP) as well as differences across socioeconomic status (SES) levels within the context of inconsistent contraceptive use among college women. Participants: A nonprobability sample of 515 female college students completed an Internet-based survey…

  7. Preparing Teachers for Technology Integration: Programs, Competencies, and Factors from the Literature

    Science.gov (United States)

    Oliver, Kevin; Townsend, Latricia

    2013-01-01

    This article presents a review of recent literature about preparing teachers for technology integration. The review found six types of training programs are commonly implemented: pre-service training, long-term courses, short-term workshops and institutes, coaching/mentoring, learning communities, and product/assessment approaches. The review…

  8. Factors That Influence Teachers' Adoption and Integration of ICT in Teaching/Learning Process

    Science.gov (United States)

    Lawrence, Japhet E.; Tar, Usman A.

    2018-01-01

    Information communication technology (ICT) is becoming increasingly important in our daily lives and in our educational system. There is a growing demand on educational institutions to use ICT to teach the skills and knowledge students need for the digital age. The adoption and integration of ICT into teaching and learning environment provides…