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Sample records for lentiviruses including human

  1. Functional Crosstalk between Human Papillomaviruses and Lentiviruses

    OpenAIRE

    Pryszlak, Anna Marta

    2016-01-01

    Human papillomaviruses (HPVs) and human immunodeficiency virus‐1 (HIV‐1) are human pathogens of high biomedical significance worldwide. Interestingly, increasing epidemiological evidence indicates that individuals with active HPV infections possess an enhanced risk of being infected by HIV‐1. These findings raise the possibility that HPVs may directly or indirectly increase the pathogenicity of lentiviruses, such as HIV‐1. Using a Vesicular Stomatitis Virus‐G‐(VSV‐G)‐pseudotype...

  2. Therapeutic effects of lentivirus-mediated shRNA targeting of cyclin D1 in human gastric cancer

    International Nuclear Information System (INIS)

    Seo, Jin-Hee; Jeong, Eui-Suk; Choi, Yang-Kyu

    2014-01-01

    Gastric cancer is the second most common cause of cancer-related death in males and the fourth in females. Traditional treatment has poor prognosis because of recurrence and systemic side effects. Therefore, the development of new therapeutic strategies is an important issue. Lentivirus-mediated shRNA stably inhibits target genes and can efficiently transduce most cells. Since overexpressed cyclin D1 is closely related to human gastric cancer progression, inhibition of cyclin D1 using specific targeting could be an effective treatment method of human gastric cancer. The therapeutic effect of lentivirus-mediated shRNA targeting of cyclin D1 (ShCCND1) was analyzed both in vitro and in vivo experiments. In vitro, NCI-N87 cells with downregulation of cyclin D1 by ShCCND1 showed significant inhibition of cell proliferation, cell motility, and clonogenicity. Downregulation of cyclin D1 in NCI-N87 cells also resulted in significantly increased G1 arrest and apoptosis. In vivo, stable NCI-N87 cells expressing ShCCND1 were engrafted into nude mice. Then, the cancer-growth inhibition effect of lentivirus was confirmed. To assess lentivirus including ShCCND1 as a therapeutic agent, intratumoral injection was conducted. Tumor growth of the lentivirus-treated group was significantly inhibited compared to growth of the control group. These results are in accordance with the in vitro data and lend support to the mitotic figure count and apoptosis analysis of the tumor mass. The lentivirus-mediated ShCCND1 was constructed, which effectively inhibited growth of NCI-N87-derived cancer both in vitro and in vivo. The efficiency of shRNA knockdown and variation in the degree of inhibition is mediated by different shRNA sequences and cancer cell lines. These experimental results suggest the possibility of developing new gastric cancer therapies using lentivirus-mediated shRNA

  3. Lentivirus display: stable expression of human antibodies on the surface of human cells and virus particles.

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    Ran Taube

    Full Text Available BACKGROUND: Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv antibody fragments on human cells and lentivirus particles. METHODOLOGY/PRINCIPAL FINDINGS: Bivalent scFvFc human antibodies were fused in frame with different transmembrane (TM anchoring moieties to allow efficient high-level expression on human cells and the optimal TM was identified. The addition of an eight amino acid HIV-1 gp41 envelope incorporation motif further increased scFvFc expression on human cells and incorporation into lentiviral particles. Both antibody-displaying human cells and virus particles bound antigen specifically. Sulfation of CDR tyrosine residues, a property recently shown to broaden antibody binding affinity and antigen recognition was also demonstrated. High level scFvFc expression and stable integration was achieved in human cells following transduction with IRES containing bicistronic SIN lentivectors encoding ZsGreen when scFvFc fusion proteins were expressed from the first cassette. Up to 10(6-fold enrichment of antibody expressing cells was achieved with one round of antigen coupled magnetic bead pre-selection followed by FACS sorting. Finally, the scFvFc displaying human cells could be used directly in functional biological screens with remarkable sensitivity. CONCLUSIONS/SIGNIFICANCE: This antibody display platform will complement existing technologies by virtue of providing properties unique to lentiviruses and antibody expression in human cells, which, in turn, may aid the discovery of novel therapeutic human mAbs.

  4. The experimental study of genetic engineering human neural stem cells mediated by lentivirus to express multigene.

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    Cai, Pei-qiang; Tang, Xun; Lin, Yue-qiu; Martin, Oudega; Sun, Guang-yun; Xu, Lin; Yang, Yun-kang; Zhou, Tian-hua

    2006-02-01

    To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs) mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI). Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3 (NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot. Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot. Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.

  5. Hybrid Lentivirus-transposon Vectors With a Random Integration Profile in Human Cells

    DEFF Research Database (Denmark)

    Staunstrup, Nicklas H; Moldt, Brian; Mátés, Lajos

    2009-01-01

    Gene delivery by human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors (LVs) is efficient, but genomic integration of the viral DNA is strongly biased toward transcriptionally active loci resulting in an increased risk of insertional mutagenesis in gene therapy protocols. Nonviral...... Sleeping Beauty (SB) transposon vectors have a significantly safer insertion profile, but efficient delivery into relevant cell/tissue types is a limitation. In an attempt to combine the favorable features of the two vector systems we established a novel hybrid vector technology based on SB transposase......-mediated insertion of lentiviral DNA circles generated during transduction of target cells with integrase (IN)-defective LVs (IDLVs). By construction of a lentivirus-transposon hybrid vector allowing transposition exclusively from circular viral DNA substrates, we demonstrate that SB transposase added in trans...

  6. A Single Nucleotide Polymorphism in Human APOBEC3C Enhances Restriction of Lentiviruses.

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    Cristina J Wittkopp

    2016-10-01

    Full Text Available Humans express seven human APOBEC3 proteins, which can inhibit viruses and endogenous retroelements through cytidine deaminase activity. The seven paralogs differ in the potency of their antiviral effects, as well as in their antiviral targets. One APOBEC3, APOBEC3C, is exceptional as it has been found to only weakly block viruses and endogenous retroelements compared to other APOBEC3s. However, our positive selection analyses suggest that APOBEC3C has played a role in pathogen defense during primate evolution. Here, we describe a single nucleotide polymorphism in human APOBEC3C, a change from serine to isoleucine at position 188 (I188 that confers potent antiviral activity against HIV-1. The gain-of-function APOBEC3C SNP results in increased enzymatic activity and hypermutation of target sequences when tested in vitro, and correlates with increased dimerization of the protein. The I188 is widely distributed in human African populations, and is the ancestral primate allele, but is not found in chimpanzees or gorillas. Thus, while other hominids have lost activity of this antiviral gene, it has been maintained, or re-acquired, as a more active antiviral gene in a subset of humans. Taken together, our results suggest that APOBEC3C is in fact involved in protecting hosts from lentiviruses.

  7. CXCR4 Is Required by a Nonprimate Lentivirus: Heterologous Expression of Feline Immunodeficiency Virus in Human, Rodent, and Feline Cells

    Science.gov (United States)

    Poeschla, Eric M.; Looney, David J.

    1998-01-01

    A heterologous feline immunodeficiency virus (FIV) expression system permitted high-level expression of FIV proteins and efficient production of infectious FIV in human cells. These results identify the FIV U3 element as the sole restriction to the productive phase of replication in nonfeline cells. Heterologous FIV expression in a variety of human cell lines resulted in profuse syncytial lysis that was FIV env specific, CD4 independent, and restricted to cells that express CXCR4, the coreceptor for T-cell-line-adapted strains of human immunodeficiency virus. Stable expression of human CXCR4 in CXCR4-negative human and rodent cell lines resulted in extensive FIV Env-mediated, CXCR4-dependent cell fusion and infection. In feline cells, stable overexpression of human CXCR4 resulted in increased FIV infectivity and marked syncytium formation during FIV replication or after infection with FIV Env-expressing vectors. The use of CXCR4 is a fundamental feature of lentivirus biology independent of CD4 and a shared cellular link to infection and cytopathicity for distantly related lentiviruses that cause AIDS. Their conserved use implicates chemokine receptors as primordial lentivirus receptors. PMID:9658135

  8. A lentivirus-free inducible CRISPR-Cas9 system for efficient targeting of human genes.

    Science.gov (United States)

    Bisht, Kamlesh; Grill, Sherilyn; Graniel, Jacqueline; Nandakumar, Jayakrishnan

    2017-08-01

    CRISPR-Cas9 is a cutting-edge tool for modifying genomes. The efficacy with which Cas9 recognizes its target has revolutionized the engineering of knockouts. However this efficacy complicates the knocking out of important genes in cultured cells. Unedited cells holding a survival advantage within an edited population can confound the knockout phenotype. Here we develop a HeLa-based system that overcomes this limitation, incorporating several attractive features. First, we use Flp-recombinase to generate clones stably integrated for Cas9 and guide RNAs, eliminating the possibility of unedited cells. Second, Cas9 can be induced uniformly in the clonal cultures using doxycycline to measure the knockout phenotype. Third, two genes can be simultaneously knocked out using this approach. Finally, by not involving lentiviruses, our method is appealing to a broad research audience. Using this methodology we generated an inducible AGO2-knockout cell line showing normal RNA interference in the absence of doxycycline. Upon induction of Cas9, the AGO2 locus was cleaved, the AGO2 protein was depleted, and RNA interference was compromised. In addition to generating inducible knockouts, our technology can be adapted to improve other applications of Cas9, including transcriptional/epigenetic modulation and visualization of cellular DNA loci. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Regression of established renal cell carcinoma in nude mice using lentivirus-transduced human T cells expressing a human anti-CAIX chimeric antigen receptor

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    Agnes Shuk-Yee Lo

    2014-01-01

    Full Text Available Carbonic anhydrase IX (CAIX is a tumor-associated antigen and marker of hypoxia that is overexpressed on > 90% of clear-cell type renal cell carcinoma (RCC but not on neighboring normal kidney tissue. Here, we report on the construction of two chimeric antigen receptors (CARs that utilize a carbonic anhydrase (CA domain mapped, human single chain antibody (scFv G36 as a targeting moiety but differ in their capacity to provide costimulatory signaling for optimal T cell proliferation and tumor cell killing. The resulting anti-CAIX CARs were expressed on human primary T cells via lentivirus transduction. CAR-transduced T cells (CART cells expressing second-generation G36-CD28-TCRζ exhibited more potent in vitro antitumor effects on CAIX+ RCC cells than first-generation G36-CD8-TCRζ including cytotoxicity, cytokine secretion, proliferation, and clonal expansion. Adoptive G36-CD28-TCRζ CART cell therapy combined with high-dose interleukin (IL-2 injection also lead to superior regression of established RCC in nude mice with evidence of tumor cell apoptosis and tissue necrosis. These results suggest that the fully human G36-CD28-TCRζ CARs should provide substantial improvements over first-generation mouse anti-CAIX CARs in clinical use through reduced human anti-mouse antibody responses against the targeting scFv and administration of lower doses of T cells during CART cell therapy of CAIX+ RCC.

  10. Formation of RNA Granule-Derived Capsid Assembly Intermediates Appears To Be Conserved between Human Immunodeficiency Virus Type 1 and the Nonprimate Lentivirus Feline Immunodeficiency Virus.

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    Reed, Jonathan C; Westergreen, Nick; Barajas, Brook C; Ressler, Dylan T B; Phuong, Daryl J; Swain, John V; Lingappa, Vishwanath R; Lingappa, Jaisri R

    2018-05-01

    During immature capsid assembly in cells, human immunodeficiency virus type 1 (HIV-1) Gag co-opts a host RNA granule, forming a pathway of intracellular assembly intermediates containing host components, including two cellular facilitators of assembly, ABCE1 and DDX6. A similar assembly pathway has been observed for other primate lentiviruses. Here we asked whether feline immunodeficiency virus (FIV), a nonprimate lentivirus, also forms RNA granule-derived capsid assembly intermediates. First, we showed that the released FIV immature capsid and a large FIV Gag-containing intracellular complex are unstable during analysis, unlike for HIV-1. We identified harvest conditions, including in situ cross-linking, that overcame this problem, revealing a series of FIV Gag-containing complexes corresponding in size to HIV-1 assembly intermediates. Previously, we showed that assembly-defective HIV-1 Gag mutants are arrested at specific assembly intermediates; here we identified four assembly-defective FIV Gag mutants, including three not previously studied, and demonstrated that they appear to be arrested at the same intermediate as the cognate HIV-1 mutants. Further evidence that these FIV Gag-containing complexes correspond to assembly intermediates came from coimmunoprecipitations demonstrating that endogenous ABCE1 and the RNA granule protein DDX6 are associated with FIV Gag, as shown previously for HIV-1 Gag, but are not associated with a ribosomal protein, at steady state. Additionally, we showed that FIV Gag associates with another RNA granule protein, DCP2. Finally, we validated the FIV Gag-ABCE1 and FIV Gag-DCP2 interactions with proximity ligation assays demonstrating colocalization in situ Together, these data support a model in which primate and nonprimate lentiviruses form intracellular capsid assembly intermediates derived from nontranslating host RNA granules. IMPORTANCE Like HIV-1 Gag, FIV Gag assembles into immature capsids; however, it is not known whether

  11. Lentivirus-Mediated Knockdown of Astrocyte Elevated Gene-1 Inhibits Growth and Induces Apoptosis through MAPK Pathways in Human Retinoblastoma Cells.

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    Ying Chang

    Full Text Available To explore expression and function of astrocyte elevated gene-1 (AEG-1 in human retinoblastoma (RB.The expression of AEG-1 in histological sections of human RBs and in RB cell lines was examined using immunohistochemical staining and RT-PCR and Western blotting respectively. We knocked down AEG-1 gene levels by AEG-1-siRNA lentivirus transfection of human RB cell lines SO-RB50 and Y79, and using an MTT assay, we assessed the role of AEG-1 on RB cell proliferation. The biological significance of lentivirus transfection induced AEG-1 down-regulation was examined by assessing the apoptosis rate in the transfected RB cells by Annexin V-APC staining and flow cytometry. We additionally measured the expression of Bcl-2, Bax, cleaved-caspase-3 and caspase-3, and the phosphorylation and non-phosphorylation alternation of MAPKs.AEG-1 expression was detected to be strongly positive in the histological slides of 35 out of 54 (65% patients with RB. AEG-1 expression increased significantly (P<0.05 with tumor stage. In the RB cell lines SO-RB50, Y79 and WERI-RB1 as compared with retinal pigment epithelium cells, expression of AEG-1 mRNA and AEG-1 protein was significantly higher. In AEG-1-siRNA lentivirus transfected cell cultures as compared with negative control lentivirus transfected cell cultures, levels of AEG-1 mRNA and of AEG-1 protein (P<0.05 and cell growth rates (P<0.01 were significantly lower, and apoptosis rate (P<0.001, Bax/Bcl-2 ratio and cleaved-caspase-3 protein level were significantly increased. The P-ERK/ERK ratio was significantly decreased in the AEG-1-siRNA lentivirus transfected cell lines.Expression of AEG-1 was associated with RB, in histological slides of patients and in cell culture experiments. Lentivirus transfection induced knockdown of AEG-1 had a tumor suppressive effect, potentially by tumor cell apoptosis induction through inhibition of ERK.

  12. Parallel germline infiltration of a lentivirus in two Malagasy lemurs.

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    Clément Gilbert

    2009-03-01

    Full Text Available Retroviruses normally infect the somatic cells of their host and are transmitted horizontally, i.e., in an exogenous way. Occasionally, however, some retroviruses can also infect and integrate into the genome of germ cells, which may allow for their vertical inheritance and fixation in a given species; a process known as endogenization. Lentiviruses, a group of mammalian retroviruses that includes HIV, are known to infect primates, ruminants, horses, and cats. Unlike many other retroviruses, these viruses have not been demonstrably successful at germline infiltration. Here, we report on the discovery of endogenous lentiviral insertions in seven species of Malagasy lemurs from two different genera -- Cheirogaleus and Microcebus. Combining molecular clock analyses and cross-species screening of orthologous insertions, we show that the presence of this endogenous lentivirus in six species of Microcebus is the result of one endogenization event that occurred about 4.2 million years ago. In addition, we demonstrate that this lentivirus independently infiltrated the germline of Cheirogaleus and that the two endogenization events occurred quasi-simultaneously. Using multiple proviral copies, we derive and characterize an apparently full length and intact consensus for this lentivirus. These results provide evidence that lentiviruses have repeatedly infiltrated the germline of prosimian species and that primates have been exposed to lentiviruses for a much longer time than what can be inferred based on sequence comparison of circulating lentiviruses. The study sets the stage for an unprecedented opportunity to reconstruct an ancestral primate lentivirus and thereby advance our knowledge of host-virus interactions.

  13. Endogenous lentivirus in Malayan colugo (Galeopterus variegatus), a close relative of primates.

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    Hron, Tomáš; Fábryová, Helena; Pačes, Jan; Elleder, Daniel

    2014-10-04

    A significant fraction of mammalian genomes is composed of endogenous retroviral (ERV) sequences that are formed by germline infiltration of various retroviruses. In contrast to other retroviral genera, lentiviruses only rarely form ERV copies. We performed a computational search aimed at identification of novel endogenous lentiviruses in vertebrate genomes. Using the in silico strategy, we have screened 104 publicly available vertebrate genomes for the presence of endogenous lentivirus sequences. In addition to the previously described cases, the search revealed the presence of endogenous lentivirus in the genome of Malayan colugo (Galeopterus variegatus). At least three complete copies of this virus, denoted ELVgv, were detected in the colugo genome, and approximately one hundred solo LTR sequences. The assembled consensus sequence of ELVgv had typical lentivirus genome organization including three predicted accessory genes. Phylogenetic analysis placed this virus as a distinct subgroup within the lentivirus genus. The time of insertion into the dermopteran lineage was estimated to be more than thirteen million years ago. We report the discovery of the first endogenous lentivirus in the mammalian order Dermoptera, which is a taxon close to the Primates. Lentiviruses have infiltrated the mammalian germline several times across millions of years. The colugo virus described here represents possibly the oldest documented endogenization event and its discovery can lead to new insights into lentivirus evolution. This is also the first report of an endogenous lentivirus in an Asian mammal, indicating a long-term presence of this retrovirus family in Asian continent.

  14. A novel self-replicating chimeric lentivirus-like particle.

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    Jurgens, Christy K; Young, Kelly R; Madden, Victoria J; Johnson, Philip R; Johnston, Robert E

    2012-01-01

    Successful live attenuated vaccines mimic natural exposure to pathogens without causing disease and have been successful against several viruses. However, safety concerns prevent the development of attenuated human immunodeficiency virus (HIV) as a vaccine candidate. If a safe, replicating virus vaccine could be developed, it might have the potential to offer significant protection against HIV infection and disease. Described here is the development of a novel self-replicating chimeric virus vaccine candidate that is designed to provide natural exposure to a lentivirus-like particle and to incorporate the properties of a live attenuated virus vaccine without the inherent safety issues associated with attenuated lentiviruses. The genome from the alphavirus Venezuelan equine encephalitis virus (VEE) was modified to express SHIV89.6P genes encoding the structural proteins Gag and Env. Expression of Gag and Env from VEE RNA in primate cells led to the assembly of particles that morphologically and functionally resembled lentivirus virions and that incorporated alphavirus RNA. Infection of CD4⁺ cells with chimeric lentivirus-like particles was specific and productive, resulting in RNA replication, expression of Gag and Env, and generation of progeny chimeric particles. Further genome modifications designed to enhance encapsidation of the chimeric virus genome and to express an attenuated simian immunodeficiency virus (SIV) protease for particle maturation improved the ability of chimeric lentivirus-like particles to propagate in cell culture. This study provides proof of concept for the feasibility of creating chimeric virus genomes that express lentivirus structural proteins and assemble into infectious particles for presentation of lentivirus immunogens in their native and functional conformation.

  15. The Role of the Antiviral APOBEC3 Gene Family in Protecting Chimpanzees against Lentiviruses from Monkeys.

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    Lucie Etienne

    2015-09-01

    Full Text Available Cross-species transmissions of viruses from animals to humans are at the origin of major human pathogenic viruses. While the role of ecological and epidemiological factors in the emergence of new pathogens is well documented, the importance of host factors is often unknown. Chimpanzees are the closest relatives of humans and the animal reservoir at the origin of the human AIDS pandemic. However, despite being regularly exposed to monkey lentiviruses through hunting, chimpanzees are naturally infected by only a single simian immunodeficiency virus, SIVcpz. Here, we asked why chimpanzees appear to be protected against the successful emergence of other SIVs. In particular, we investigated the role of the chimpanzee APOBEC3 genes in providing a barrier to infection by most monkey lentiviruses. We found that most SIV Vifs, including Vif from SIVwrc infecting western-red colobus, the chimpanzee's main monkey prey in West Africa, could not antagonize chimpanzee APOBEC3G. Moreover, chimpanzee APOBEC3D, as well as APOBEC3F and APOBEC3H, provided additional protection against SIV Vif antagonism. Consequently, lentiviral replication in primary chimpanzee CD4(+ T cells was dependent on the presence of a lentiviral vif gene that could antagonize chimpanzee APOBEC3s. Finally, by identifying and functionally characterizing several APOBEC3 gene polymorphisms in both common chimpanzees and bonobos, we found that these ape populations encode APOBEC3 proteins that are uniformly resistant to antagonism by monkey lentiviruses.

  16. Immunization against Small Ruminant Lentiviruses

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    Beatriz Amorena

    2013-08-01

    Full Text Available Multisystemic disease caused by Small Ruminant Lentiviruses (SRLV in sheep and goats leads to production losses, to the detriment of animal health and welfare. This, together with the lack of treatments, has triggered interest in exploring different strategies of immunization to control the widely spread SRLV infection and, also, to provide a useful model for HIV vaccines. These strategies involve inactivated whole virus, subunit vaccines, DNA encoding viral proteins in the presence or absence of plasmids encoding immunological adjuvants and naturally or artificially attenuated viruses. In this review, we revisit, comprehensively, the immunization strategies against SRLV and analyze this double edged tool individually, as it may contribute to either controlling or enhancing virus replication and/or disease.

  17. A primitive endogenous lentivirus in a colugo: insights into the early evolution of lentiviruses.

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    Han, Guan-Zhu; Worobey, Michael

    2015-01-01

    Lentiviruses infect a wide range of mammal species. Much remains unknown about their deep history and host distribution. Here, we report the discovery of an endogenous lentivirus within the genome of the Sunda flying lemur (Galeopterus variegatus) (which we designate "Galeopterus variegatus endogenous lentivirus" [GvaELV]). We estimate the GvaELV genome invasion to have occurred more than 14 Ma, supporting an ancient origin of the lentivirus clade and an ancient lentiviral infection in colugo. Phylogenetic analyses show that GvaELV is a sister group of all previously known lentiviruses. The GvaELV genome appears to possess some primitive genomic features of a lentivirus, encoding not only a trans-activator of transcription (tat) gene but also two additional putative accessory genes that share no discernible similarity with other lentiviral accessory genes. The discovery of GvaELV provides novel insights into the prehistory and host distribution of lentivirus. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Efficient in vivo gene transfer to xenotransplanted human skin by lentivirus-mediated, but not by AAV-directed, gene delivery

    DEFF Research Database (Denmark)

    Jakobsen, Maria Vad; Askou, Anne Louise; Dokkedahl, Karin Stenderup

    skin graft, and firefly luciferase expression was observed primarily in neighboring tissue beneath or surrounding the graft. In contrast, gene delivery by intradermally injected lentiviral vectors was efficient and led to extensive and persistent firefly luciferase expression within the human skin...... graft only. The study demonstrates limited capacity of single-stranded AAV vectors of six commonly used serotypes for gene delivery to human skin in vivo....

  19. Generation of a human embryonic stem cell line, NERCe003-A-1, with lentivirus vector-mediated inducible CTNNB1 overexpression

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    Yang Wang

    2018-04-01

    Full Text Available The human embryonic stem cell (hESC line NERCe003-A-1 was generated by introducing lentiviral-vector–mediated tetracycline-inducible β-catenin expression into a normal hESC line, NERCe003-A. The resulting cell line can overexpress the β-catenin protein, encoded by the CTNNB1 gene, after exposure to doxycycline (Dox. CTNNB1 gene expression was confirmed by quantitative PCR (qPCR and immunofluorescence assays. Further characterization confirmed that the NERCe003-A-1 cell line expresses typical pluripotency markers and has the ability to form the three germ layers both in vitro and in vivo.

  20. Hybrid lentivirus-phiC31-int-NLS vector allows site-specific recombination in murine and human cells but induces DNA damage.

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    Nicolas Grandchamp

    Full Text Available Gene transfer allows transient or permanent genetic modifications of cells for experimental or therapeutic purposes. Gene delivery by HIV-derived lentiviral vector (LV is highly effective but the risk of insertional mutagenesis is important and the random/uncontrollable integration of the DNA vector can deregulate the cell transcriptional activity. Non Integrative Lentiviral Vectors (NILVs solve this issue in non-dividing cells, but they do not allow long term expression in dividing cells. In this context, obtaining stable expression while avoiding the problems inherent to unpredictable DNA vector integration requires the ability to control the integration site. One possibility is to use the integrase of phage phiC31 (phiC31-int which catalyzes efficient site-specific recombination between the attP site in the phage genome and the chromosomal attB site of its Streptomyces host. Previous studies showed that phiC31-int is active in many eukaryotic cells, such as murine or human cells, and directs the integration of a DNA substrate into pseudo attP sites (pattP which are homologous to the native attP site. In this study, we combined the efficiency of NILV for gene delivery and the specificity of phiC31-int for DNA substrate integration to engineer a hybrid tool for gene transfer with the aim of allowing long term expression in dividing and non-dividing cells preventing genotoxicity. We demonstrated the feasibility to target NILV integration in human and murine pattP sites with a dual NILV vectors system: one which delivers phiC31-int, the other which constitute the substrate containing an attB site in its DNA sequence. These promising results are however alleviated by the occurrence of significant DNA damages. Further improvements are thus required to prevent chromosomal rearrangements for a therapeutic use of the system. However, its use as a tool for experimental applications such as transgenesis is already applicable.

  1. A lion lentivirus related to feline immunodeficiency virus: epidemiologic and phylogenetic aspects.

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    Brown, E W; Yuhki, N; Packer, C; O'Brien, S J

    1994-09-01

    Feline immunodeficiency virus (FIV) is a novel lentivirus that is genetically homologous and functionally analogous to the human AIDS viruses, human immunodeficiency virus types 1 and 2. FIV causes immunosuppression in domestic cats by destroying the CD4 T-lymphocyte subsets in infected hosts. A serological survey of over 400 free-ranging African and Asian lions (Panthera leo) for antibodies to FIV revealed endemic lentivirus prevalence with an incidence of seropositivity as high as 90%. A lion lentivirus (FIV-Ple) was isolated by infection of lion lymphocytes in vitro. Seroconversion was documented in two Serengeti lions, and discordance of mother-cub serological status argues against maternal transmission (in favor of horizontal spread) as a major route of infection among lions. A phylogenetic analysis of cloned FIV-Ple pol gene sequences from 27 lions from four African populations (from the Serengeti reserve, Ngorongoro Crater, Lake Manyara, and Kruger Park) revealed remarkably high intra- and interindividual genetic diversity at the sequence level. Three FIV-Ple phylogenetic clusters or clades were resolved with phenetic, parsimony, and likelihood analytical procedures. The three clades, which occurred not only together in the same population but throughout Africa, were as divergent from each other as were homologous pol sequences of lentivirus isolated from distinct feline species, i.e., puma and domestic cat. The FIV-Ple clades, however, were more closely related to each other than to other feline lentiviruses (monophyletic for lion species), suggesting that the ancestors of FIV-Ple evolved in allopatric (geographically isolated) lion populations that converged recently. To date, there is no clear evidence of FIV-Ple-associated pathology, raising the possibility of a historic genetic accommodation of the lion lentivirus and its host leading to a coevolved host-parasite symbiosis (or commensalism) in the population similar to that hypothesized for endemic

  2. Reduced lentivirus susceptibility in sheep with TMEM154 mutations.

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    Heaton, Michael P; Clawson, Michael L; Chitko-Mckown, Carol G; Leymaster, Kreg A; Smith, Timothy P L; Harhay, Gregory P; White, Stephen N; Herrmann-Hoesing, Lynn M; Mousel, Michelle R; Lewis, Gregory S; Kalbfleisch, Theodore S; Keen, James E; Laegreid, William W

    2012-01-01

    Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154) that exceeded genome-wide significance (unadjusted p-value 3×10(-9)). Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E) at position 35 were associated with infection while a third haplotype with lysine (K) at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-valuesheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-valuesheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection.

  3. Reduced lentivirus susceptibility in sheep with TMEM154 mutations.

    Directory of Open Access Journals (Sweden)

    Michael P Heaton

    2012-01-01

    Full Text Available Visna/Maedi, or ovine progressive pneumonia (OPP as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154 that exceeded genome-wide significance (unadjusted p-value 3×10(-9. Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E at position 35 were associated with infection while a third haplotype with lysine (K at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-value<0.0001, 95% CI 5-1,100. In a combined analysis of nine cohorts with 2,705 sheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-value<0.0001, 95% CI 2.36-3.43. Although rare, some sheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection.

  4. Pathological and Molecular Based Study of Naturally Occurring Lentivirus Infection

    Directory of Open Access Journals (Sweden)

    Fazal Mahmood*, Ahrar Khan, Muhammad Zargham Khan, Riaz Hussain1, Shafia Tehseen Gul and Abu Baker Siddique2

    2012-10-01

    Full Text Available The present study describes the multicentric lymphosarcoma associated with lymphoid interstitial pneumonia in indigenous breeds of sheep and goats in Pakistan. Serum samples from sheep (n=93 and goats (n=129 were screened for ovine lentivirus using agar gel immunodiffusion test. Overall, 7.52 and 3.87% seroprevalence was recorded in sheep and goat, respectively. During necropsy of sheep (n=3 and goats (n=4, gross lesions including dark color liver with multifocal whitish areas, unilaterally lungs consolidation with granular appearance of cut surface were observed. Mediastinal lymph nodes were swollen and arranged in chain like fashion. Histopathologically, liver parenchyma exhibited extensive proliferation of neoplastic cells of lymphocytic series. Metastatic cells in the form of follicular pattern in the lungs, spleen and mediastinal lymph nodes were also observed. Brain tissue exhibited degenerative changes in the neuron and perivascular cuffing. The PCR product size approximately 300 bp from lung tissue confirmed viral infection.

  5. Renal Alterations in Feline Immunodeficiency Virus (FIV-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

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    Mauro Pistello

    2012-08-01

    Full Text Available Human immunodeficiency virus (HIV is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

  6. Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural model of lentivirus-induced renal disease changes.

    Science.gov (United States)

    Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

    2012-09-01

    Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

  7. The epidemiology of lion lentivirus infection among a population of free-ranging lions (Panthera leo) in the Kruger National Park, South Africa.

    Science.gov (United States)

    Adams, H; van Vuuren, M; Bosman, A-M; Keet, D; New, J; Kennedy, M

    2009-09-01

    Feline immunodeficiency virus is a lentivirus of domestic cats that causes significant lifelong infection. Infection with this or similar lentiviruses has been detected in several nondomestic feline species, including African lions (Panthera leo). Although lion lentivirus (FIVple) infection is endemic in certain lion populations in eastern and southern Africa, little is known about its pathogenic effects or its epidemiological impact in free-ranging lions. This report describes the epidemiological investigation of lentivirus positivity of free-ranging lions in the Kruger National Park, South Africa. A nested polymerase chain reaction assay for virus detection was performed on all whole blood samples collected. In addition, serum samples were tested for cross-reactive antibodies to domestic feline lentivirus antigens and to puma lentivirus synthetic envelope peptide antigen. The results were analysed in conjunction with epidemiological data to provide a descriptive epidemiological study on lion lentivirus infection in a free-ranging population of lions. The overall prevalence of lentivirus infection was 69%, with a prevalence of 41% in the north of the park, and 80% in the south. Adult males had the highest prevalence when combining the factors of sex and age: 94%. The lowest prevalences were found among juveniles, with male juveniles at 29%. Adults were 5.58 times more likely to test positive for FIVple than juveniles, with adult males being 35 times more likely to be test positive for FIVple compared with juvenile males. This research represents the 1st epidemiological study of the lion lentivirus among free-ranging lions in the Kruger National Park.

  8. The epidemiology of lion lentivirus infection among a population of free-ranging lions (Panthera leo in the Kruger National Park, South Africa

    Directory of Open Access Journals (Sweden)

    H. Adams

    2009-05-01

    Full Text Available Feline immunodeficiency virus is a lentivirus of domestic cats that causes significant lifelong infection. Infection with this or similar lentiviruses has been detected in several non-domestic feline species, including African lions (Panthera leo. Although lion lentivirus (FIVple infection is endemic in certain lion populations in eastern and southern Africa, little is known about its pathogenic effects or its epidemiological impact in free-ranging lions. This report describes the epidemiological investigation of lentivirus positivity of free-ranging lions in the Kruger National Park, South Africa. A nested polymerase chain reaction assay for virus detection was performed on all whole blood samples collected. In addition, serum samples were tested for cross-reactive antibodies to domestic feline lentivirus antigens and to puma lentivirus synthetic envelope peptide antigen. The results were analysed in conjunction with epidemiological data to provide a descriptive epidemiological study on lion lentivirus infection in a free-ranging population of lions. The overall prevalence of lentivirus infection was 69 %, with a prevalence of 41 % in the north of the park, and 80 %in the south. Adult males had the highest prevalence when combining the factors of sex and age: 94 %. The lowest prevalences were found among juveniles, with male juveniles at 29 %. Adults were 5.58 times more likely to test positive for FIVple than juveniles, with adult males being 35 times more likely to be test positive for FIVple compared with juvenile males. This research represents the 1st epidemiological study of the lion lentivirus among free-ranging lions in the Kruger National Park.

  9. Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding

    Science.gov (United States)

    White, Stephen N.; Knowles, Donald P.

    2013-01-01

    Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus) and goats (caprine arthritis encephalitis virus [CAEV]). Breed differences in seroprevalence and proviral concentration of OvLV had suggested a strong genetic component in susceptibility to infection by OvLV in sheep. A genetic marker test for susceptibility to OvLV has been developed recently based on the TMEM154 gene with validation data from over 2,800 sheep representing nine cohorts. While no single genotype has been shown to have complete resistance to OvLV, consistent association in thousands of sheep from multiple breeds and management conditions highlight a new strategy for intervention by selective breeding. This genetic marker-assisted selection (MAS) has the potential to be a useful addition to existing viral control measures. Further, the discovery of multiple additional genomic regions associated with susceptibility to or control of OvLV suggests that additional genetic marker tests may be developed to extend the reach of MAS in the future. This review will cover the strengths and limitations of existing data from host genetics as an intervention and outline additional questions for future genetic research in sheep, goats, small ruminant lentiviruses, and their host-pathogen interactions. PMID:23771240

  10. Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding

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    Donald P. Knowles

    2013-06-01

    Full Text Available Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus and goats (caprine arthritis encephalitis virus [CAEV]. Breed differences in seroprevalence and proviral concentration of OvLV had suggested a strong genetic component in susceptibility to infection by OvLV in sheep. A genetic marker test for susceptibility to OvLV has been developed recently based on the TMEM154 gene with validation data from over 2,800 sheep representing nine cohorts. While no single genotype has been shown to have complete resistance to OvLV, consistent association in thousands of sheep from multiple breeds and management conditions highlight a new strategy for intervention by selective breeding. This genetic marker-assisted selection (MAS has the potential to be a useful addition to existing viral control measures. Further, the discovery of multiple additional genomic regions associated with susceptibility to or control of OvLV suggests that additional genetic marker tests may be developed to extend the reach of MAS in the future. This review will cover the strengths and limitations of existing data from host genetics as an intervention and outline additional questions for future genetic research in sheep, goats, small ruminant lentiviruses, and their host-pathogen interactions.

  11. Mutations in Ovis aries TMEM154 are associated with lower small ruminant lentivirus proviral concentration in one sheep flock.

    Science.gov (United States)

    Alshanbari, F A; Mousel, M R; Reynolds, J O; Herrmann-Hoesing, L M; Highland, M A; Lewis, G S; White, S N

    2014-08-01

    Small ruminant lentivirus (SRLV), also called ovine progressive pneumonia virus or maedi-visna, is present in 24% of US sheep. Like human immunodeficiency virus, SRLV is a macrophage-tropic lentivirus that causes lifelong infection. The production impacts from SRLV are due to a range of disease symptoms, including pneumonia, arthritis, mastitis, body condition wasting and encephalitis. There is no cure and no effective vaccine for preventing SRLV infection. However, breed differences in prevalence and proviral concentration indicate a genetic basis for susceptibility to SRLV. Animals with high blood proviral concentration show increased tissue lesion severity, so proviral concentration represents a live animal test for control post-infection in terms of proviral replication and disease severity. Recently, it was found that sheep with two copies of TMEM154 haplotype 1 (encoding lysine at position 35) had lower odds of SRLV infection. In this study, we examined the relationship between SRLV control post-infection and variants in two genes, TMEM154 and CCR5, in four flocks containing 1403 SRLV-positive sheep. We found two copies of TMEM154 haplotype 1 were associated with lower SRLV proviral concentration in one flock (P < 0.02). This identified the same favorable diplotype for SRLV control post-infection as for odds of infection. However, frequencies of haplotypes 2 and 3 were too low in the other three flocks to test. The CCR5 promoter deletion did not have consistent association with SRLV proviral concentration. Future work in flocks with more balanced allele frequencies is needed to confirm or refute TMEM154 association with control of SRLV post-infection. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

  12. Oligopeptide-based enzyme immunoassay for ovine lentivirus antibody detection.

    OpenAIRE

    Kwang, J; Torres, J V

    1994-01-01

    Ovine progressive pneumonia virus (OPPV) is a lentivirus which causes a progressive disease in sheep. Immunodominant epitopes have been identified in the envelope gp40 glycoprotein. Synthetic peptides representing these regions are able to detect the presence of OPPV antibodies in 96% of infected sheep.

  13. Rational site-directed mutations of the LLP-1 and LLP-2 lentivirus lytic peptide domains in the intracytoplasmic tail of human immunodeficiency virus type 1 gp41 indicate common functions in cell-cell fusion but distinct roles in virion envelope incorporation.

    Science.gov (United States)

    Kalia, Vandana; Sarkar, Surojit; Gupta, Phalguni; Montelaro, Ronald C

    2003-03-01

    Two highly conserved cationic amphipathic alpha-helical motifs, designated lentivirus lytic peptides 1 and 2 (LLP-1 and LLP-2), have been characterized in the carboxyl terminus of the transmembrane (TM) envelope glycoprotein (Env) of lentiviruses. Although various properties have been attributed to these domains, their structural and functional significance is not clearly understood. To determine the specific contributions of the Env LLP domains to Env expression, processing, and incorporation and to viral replication and syncytium induction, site-directed LLP mutants of a primary dualtropic infectious human immunodeficiency virus type 1 (HIV-1) isolate (ME46) were examined. Substitutions were made for highly conserved arginine residues in either the LLP-1 or LLP-2 domain (MX1 or MX2, respectively) or in both domains (MX4). The HIV-1 mutants with altered LLP domains demonstrated distinct phenotypes. The LLP-1 mutants (MX1 and MX4) were replication defective and showed an average of 85% decrease in infectivity, which was associated with an evident decrease in gp41 incorporation into virions without a significant decrease in Env expression or processing in transfected 293T cells. In contrast, MX2 virus was replication competent and incorporated a full complement of Env into its virions, indicating a differential role for the LLP-1 domain in Env incorporation. Interestingly, the replication-competent MX2 virus was impaired in its ability to induce syncytia in T-cell lines. This defect in cell-cell fusion did not correlate with apparent defects in the levels of cell surface Env expression, oligomerization, or conformation. The lack of syncytium formation, however, correlated with a decrease of about 90% in MX2 Env fusogenicity compared to that of wild-type Env in quantitative luciferase-based cell-cell fusion assays. The LLP-1 mutant MX1 and MX4 Envs also exhibited an average of 80% decrease in fusogenicity. Altogether, these results demonstrate for the first time that

  14. A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System

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    Broder Christopher C

    2010-11-01

    Full Text Available Abstract Background Hendra virus (HeV and Nipah virus (NiV are newly emerged zoonotic paramyxoviruses discovered during outbreaks in Queensland, Australia in 1994 and peninsular Malaysia in 1998/9 respectively and classified within the new Henipavirus genus. Both viruses can infect a broad range of mammalian species causing severe and often-lethal disease in humans and animals, and repeated outbreaks continue to occur. Extensive laboratory studies on the host cell infection stage of HeV and NiV and the roles of their envelope glycoproteins have been hampered by their highly pathogenic nature and restriction to biosafety level-4 (BSL-4 containment. To circumvent this problem, we have developed a henipavirus envelope glycoprotein pseudotyped lentivirus assay system using either a luciferase gene or green fluorescent protein (GFP gene encoding human immunodeficiency virus type-1 (HIV-1 genome in conjunction with the HeV and NiV fusion (F and attachment (G glycoproteins. Results Functional retrovirus particles pseudotyped with henipavirus F and G glycoproteins displayed proper target cell tropism and entry and infection was dependent on the presence of the HeV and NiV receptors ephrinB2 or B3 on target cells. The functional specificity of the assay was confirmed by the lack of reporter-gene signals when particles bearing either only the F or only G glycoprotein were prepared and assayed. Virus entry could be specifically blocked when infection was carried out in the presence of a fusion inhibiting C-terminal heptad (HR-2 peptide, a well-characterized, cross-reactive, neutralizing human mAb specific for the henipavirus G glycoprotein, and soluble ephrinB2 and B3 receptors. In addition, the utility of the assay was also demonstrated by an examination of the influence of the cytoplasmic tail of F in its fusion activity and incorporation into pseudotyped virus particles by generating and testing a panel of truncation mutants of NiV and HeV F

  15. A Polytropic Caprine Arthritis Encephalitis Virus Promoter Isolated from Multiple Tissues from a Sheep with Multisystemic Lentivirus-Associated Inflammatory Disease

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    Brian Murphy

    2013-08-01

    Full Text Available Caprine arthritis encephalitis virus (CAEV is a lentivirus that infects both goats and sheep and is closely related to maedi-visna virus that infects sheep; collectively, these viruses are known as small ruminant lentiviruses (SRLV. Infection of goats and sheep with SRLV typically results in discrete inflammatory diseases which include arthritis, mastitis, pneumonia or encephalomyelitis. SRLV-infected animals concurrently demonstrating lentivirus-associated lesions in tissues of lung, mammary gland, joint synovium and the central nervous system are either very rare or have not been reported. Here we describe a novel CAEV promoter isolated from a sheep with multisystemic lentivirus-associated inflammatory disease including interstitial pneumonia, mastitis, polyarthritis and leukomyelitis. A single, novel SRLV promoter was cloned and sequenced from five different anatomical locations (brain stem, spinal cord, lung, mammary gland and carpal joint synovium, all of which demonstrated lesions characteristic of lentivirus associated inflammation. This SRLV promoter isolate was found to be closely related to CAEV promoters isolated from goats in northern California and other parts of the world. The promoter was denoted CAEV-ovine-MS (multisystemic disease; the stability of the transcription factor binding sites within the U3 promoter sequence are discussed.

  16. Vaccination delays maedi-visna lentivirus infection in a naturally-infected sheep flock

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    Gudnadóttir Margrét

    2013-01-01

    Full Text Available Abstract Background The Maedi-Visna (MV lentivirus causes two slowly progressive eventually fatal diseases of sheep, Maedi, a progressive interstitial pneumonia, and Visna, a progressive demyelinating disease of the central nervous system. Other lentiviruses also cause fatal slow infections in their natural hosts, e.g. the HIV virus in humans. Results of experimental vaccination against any lentivirus where vaccinees are challenged by natural routes, may therefore be of general interest. From 1991–1998 experiments with formalin-inactivated whole Maedi-Visna virus vaccine were carried out in the Department of Microbiology at the University of Iceland. Western Blot tests showed good immune response to all major proteins of the virus. When aluminium hydroxide was added to the vaccine all vaccinees developed neutralizing antibodies to the vaccine strain at titers 1/8 – 1/256. After housing 5 twin pairs, one twin in each pair vaccinated, the other unvaccinated, with infected sheep for 4 years, all the unvaccinated twins became infected, but only 2 of their vaccinated siblings as confirmed by virus cultivation experiments on tissues from their lungs spleens lymph nodes and choroid plexuses. Results One twin in each of 40 female twin pairs, born into a Maedi-Visna-infected sheep flock and kept under natural farming conditions in Cyprus, was vaccinated at birth, 3 weeks and 3 months, with formalin-inactivated whole Maedi-Visna lentivirus vaccine adjuvanted with aluminium hydroxide. 17 mothers of the twins were seronegative, 13 seroconverting and 10 had old infection. Of 17 vaccinees born to seronegative mothers 9 were uninfected at 28 months, but only 2 of their unvaccinated siblings. Of 13 unvaccinated twins born to seroconverting mothers, 12 caught infection during their first 10 weeks, but only 4 of their vaccinated siblings. Vaccination had no effects on 10 vaccinees born to mothers with long-standing Maedi-Visna infections and broad andibody

  17. BIOLOGY OF HUMAN MALARIA PLASMODIA INCLUDING PLASMODIUM KNOWLESI

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    Spinello Antinori

    2012-03-01

    Full Text Available Malaria is a vector-borne infection caused by unicellular parasite of the genus Plasmodium. Plasmodia are obligate intracellular parasites that in humans after a clinically silent replication phase in the liver are able to infect and replicate within the erythrocytes. Four species (P.falciparum, P.malariae, P.ovale and P.vivax are traditionally recognized as responsible of natural infection in human beings but the recent upsurge of P.knowlesi malaria in South-East Asia has led clinicians to consider it as the fifth human malaria parasite. Recent studies in wild-living apes in Africa have revealed that P.falciparum, the most deadly form of human malaria, is not only human-host restricted as previously believed and its phylogenetic lineage is much more complex with new species identified in gorilla, bonobo and chimpanzee. Although less impressive, new data on biology of P.malariae, P.ovale and P.vivax are also emerging and will be briefly discussed in this review.

  18. Evolutionary Analyses Suggest a Function of MxB Immunity Proteins Beyond Lentivirus Restriction.

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    Patrick S Mitchell

    2015-12-01

    Full Text Available Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host

  19. Oat have multifunctional uses including animal feed, human food ...

    African Journals Online (AJOL)

    Akademia Rolnicza

    2014-07-11

    Jul 11, 2014 ... 10 Judyma Street, 71-460 Szczecin, Poland. (Received 1 ... Increasing interest in oat utilization for human consumption has been stimulated by the need for ... Helium was used as a carrier gas at a flow rate of 1.4 cm3/min.

  20. Deletion variant near ZNF389 is associated with control of ovine lentivirus in multiple sheep flocks

    Science.gov (United States)

    White, S N; Mousel, M R; Reynolds, J O; Herrmann-Hoesing, L M; Knowles, D P

    2014-01-01

    Ovine lentivirus (OvLV) is a macrophage-tropic lentivirus found in many countries that causes interstitial pneumonia, mastitis, arthritis and cachexia in sheep. There is no preventive vaccine and no cure, but breed differences suggest marker-assisted selective breeding might improve odds of infection and control of OvLV post-infection. Although variants in TMEM154 have consistent association with odds of infection, no variant in any gene has been associated with host control of OvLV post-infection in multiple animal sets. Proviral concentration is a live-animal diagnostic measure of OvLV control post-infection related to severity of OvLV-induced lesions. A recent genome-wide association study identified a region including four zinc finger genes associated with proviral concentration in one Rambouillet flock. To refine this region, we tested additional variants and identified a small insertion/deletion variant near ZNF389 that showed consistent association with proviral concentration in three animal sets (P sheep from multiple locations and management conditions. Strikingly, one flock had exceptionally high prevalence (>87%, including yearlings) and mean proviral concentration (>950 copies/μg), possibly due to needle sharing. The best estimate of proviral concentration by genotype, obtained from all 1310 OvLV-positive animals tested, showed insertion homozygotes had less than half the proviral concentration of other genotypes (P sheep flocks. PMID:24303974

  1. Non-Human Primates Harbor Diverse Mammalian and Avian Astroviruses Including Those Associated with Human Infections.

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    Erik A Karlsson

    Full Text Available Astroviruses (AstVs are positive sense, single-stranded RNA viruses transmitted to a wide range of hosts via the fecal-oral route. The number of AstV-infected animal hosts has rapidly expanded in recent years with many more likely to be discovered because of the advances in viral surveillance and next generation sequencing. Yet no study to date has identified human AstV genotypes in animals, although diverse AstV genotypes similar to animal-origin viruses have been found in children with diarrhea and in one instance of encephalitis. Here we provide important new evidence that non-human primates (NHP can harbor a wide variety of mammalian and avian AstV genotypes, including those only associated with human infection. Serological analyses confirmed that >25% of the NHP tested had antibodies to human AstVs. Further, we identified a recombinant AstV with parental relationships to known human AstVs. Phylogenetic analysis suggests AstVs in NHP are on average evolutionarily much closer to AstVs from other animals than are AstVs from bats, a frequently proposed reservoir. Our studies not only demonstrate that human astroviruses can be detected in NHP but also suggest that NHP are unique in their ability to support diverse AstV genotypes, further challenging the paradigm that astrovirus infection is species-specific.

  2. Mannose receptor may be involved in small ruminant lentivirus pathogenesis

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    Crespo Helena

    2012-05-01

    Full Text Available Abstract Thirty-one sheep naturally infected with small ruminant lentiviruses (SRLV of known genotype (A or B, and clinically affected with neurological disease, pneumonia or arthritis were used to analyse mannose receptor (MR expression (transcript levels and proviral load in virus target tissues (lung, mammary gland, CNS and carpal joints. Control sheep were SRLV-seropositive asymptomatic (n = 3, seronegative (n = 3 or with chronic listeriosis, pseudotuberculosis or parasitic cysts (n = 1 in each case. MR expression and proviral load increased with the severity of lesions in most analyzed organs of the SRLV infected sheep and was detected in the affected tissue involved in the corresponding clinical disease (CNS, lung and carpal joint in neurological disease, pneumonia and arthritis animal groups, respectively. The increased MR expression appeared to be SRLV specific and may have a role in lentiviral pathogenesis.

  3. Evolutionary and Functional Analysis of Old World Primate TRIM5 Reveals the Ancient Emergence of Primate Lentiviruses and Convergent Evolution Targeting a Conserved Capsid Interface.

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    Kevin R McCarthy

    2015-08-01

    Full Text Available The widespread distribution of lentiviruses among African primates, and the lack of severe pathogenesis in many of these natural reservoirs, are taken as evidence for long-term co-evolution between the simian immunodeficiency viruses (SIVs and their primate hosts. Evidence for positive selection acting on antiviral restriction factors is consistent with virus-host interactions spanning millions of years of primate evolution. However, many restriction mechanisms are not virus-specific, and selection cannot be unambiguously attributed to any one type of virus. We hypothesized that the restriction factor TRIM5, because of its unique specificity for retrovirus capsids, should accumulate adaptive changes in a virus-specific fashion, and therefore, that phylogenetic reconstruction of TRIM5 evolution in African primates should reveal selection by lentiviruses closely related to modern SIVs. We analyzed complete TRIM5 coding sequences of 22 Old World primates and identified a tightly-spaced cluster of branch-specific adaptions appearing in the Cercopithecinae lineage after divergence from the Colobinae around 16 million years ago. Functional assays of both extant TRIM5 orthologs and reconstructed ancestral TRIM5 proteins revealed that this cluster of adaptations in TRIM5 specifically resulted in the ability to restrict Cercopithecine lentiviruses, but had no effect (positive or negative on restriction of other retroviruses, including lentiviruses of non-Cercopithecine primates. The correlation between lineage-specific adaptations and ability to restrict viruses endemic to the same hosts supports the hypothesis that lentiviruses closely related to modern SIVs were present in Africa and infecting the ancestors of Cercopithecine primates as far back as 16 million years ago, and provides insight into the evolution of TRIM5 specificity.

  4. Isolation and identification of a South African lentivirus from jaagsiekte lungs

    International Nuclear Information System (INIS)

    Payne, A.; York, D.F.; De Villiers, E-M.; Verwoerd, D.W.; Querat, G.; Barban, V.; Sauze, N.; Vigne, R.

    1986-01-01

    In the course of attempts to grow the jaagsiekte retrovirus in cell culture, a typical lentivirus was isolated for the first time in South Africa from adenomatous lungs. Morphologically the virus could not be distinguished from other lentiviruses, but serologically it was shown to be more closely related to visna virus than to caprine arthritis-encephalitis virus. However, a preliminary restriction enzyme analysis of the linear proviral DNA of this new lentivirus (SA-DMVV) revealed that it is significantly district from visna virus and CAEV and therefore may represent a third type of lentivirus. Antibodies to the virus were demonstrated in a number of sheep in various parts of the country, but a direct link to a disease condition was not found. Attempts to produce lung lesions by intratracheal injection of the virus have been unsuccessful to date but a transient arthritis was produced by intra-articular inoculation. Viral replication seems to be enhanced in jaagsiekte lungs

  5. Detection of Replication Competent Lentivirus Using a qPCR Assay for VSV-G

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    Lindsey M. Skrdlant

    2018-03-01

    Full Text Available Lentiviral vectors are a common tool used to introduce new and corrected genes into cell therapy products for treatment of human diseases. Although lentiviral vectors are ideal for delivery and stable integration of genes of interest into the host cell genome, they potentially pose risks to human health, such as integration-mediated transformation and generation of a replication competent lentivirus (RCL capable of infecting non-target cells. In consideration of the latter risk, all cell-based products modified by lentiviral vectors and intended for patient use must be tested for RCL prior to treatment of the patient. Current Food and Drug Administration (FDA guidelines recommend use of cell-based assays to this end, which can take up to 6 weeks for results. However, qPCR-based assays are a quick alternative for rapid assessment of RCL in products intended for fresh infusion. We describe here the development and qualification of a qPCR assay based on detection of envelope gene sequences (vesicular stomatitis virus G glycoprotein [VSV-G] for RCL in accordance with Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE guidelines. Our results demonstrate the sensitivity, linearity, specificity, and reproducibility of detection of VSV-G sequences, with a low false-positive rate. These procedures are currently being used in our phase 1 clinical investigations.

  6. Genome-wide association identifies multiple genomic regions associated with susceptibility to and control of ovine lentivirus.

    Directory of Open Access Journals (Sweden)

    Stephen N White

    Full Text Available BACKGROUND: Like human immunodeficiency virus (HIV, ovine lentivirus (OvLV is macrophage-tropic and causes lifelong infection. OvLV infects one quarter of U.S. sheep and induces pneumonia and body condition wasting. There is no vaccine to prevent OvLV infection and no cost-effective treatment for infected animals. However, breed differences in prevalence and proviral concentration have indicated a genetic basis for susceptibility to OvLV. A recent study identified TMEM154 variants in OvLV susceptibility. The objective here was to identify additional loci associated with odds and/or control of OvLV infection. METHODOLOGY/PRINCIPAL FINDINGS: This genome-wide association study (GWAS included 964 sheep from Rambouillet, Polypay, and Columbia breeds with serological status and proviral concentration phenotypes. Analytic models accounted for breed and age, as well as genotype. This approach identified TMEM154 (nominal P=9.2×10(-7; empirical P=0.13, provided 12 additional genomic regions associated with odds of infection, and provided 13 regions associated with control of infection (all nominal P<1 × 10(-5. Rapid decline of linkage disequilibrium with distance suggested many regions included few genes each. Genes in regions associated with odds of infection included DPPA2/DPPA4 (empirical P=0.006, and SYTL3 (P=0.051. Genes in regions associated with control of infection included a zinc finger cluster (ZNF192, ZSCAN16, ZNF389, and ZNF165; P=0.001, C19orf42/TMEM38A (P=0.047, and DLGAP1 (P=0.092. CONCLUSIONS/SIGNIFICANCE: These associations provide targets for mutation discovery in sheep susceptibility to OvLV. Aside from TMEM154, these genes have not been associated previously with lentiviral infection in any species, to our knowledge. Further, data from other species suggest functional hypotheses for future testing of these genes in OvLV and other lentiviral infections. Specifically, SYTL3 binds and may regulate RAB27A, which is required for enveloped

  7. S5-4: Formal Modeling of Affordance in Human-Included Systems

    Directory of Open Access Journals (Sweden)

    Namhun Kim

    2012-10-01

    Full Text Available In spite of it being necessary for humans to consider modeling, analysis, and control of human-included systems, it has been considered a challenging problem because of the critical role of humans in complex systems and of humans' capability of executing unanticipated actions–both beneficial and detrimental ones. Thus, to provide systematic approaches to modeling human actions as a part of system behaviors, a formal modeling framework for human-involved systems in which humans play a controlling role based on their perceptual information is presented. The theory of affordance provides definitions of human actions and their associated properties; Finite State Automata (FSA based modeling is capable of mapping nondeterministic humans into computable components in the system representation. In this talk, we investigate the role of perception in human actions in the system operation and examine the representation of perceptual elements in affordance-based modeling formalism. The proposed framework is expected to capture the natural ways in which humans participate in the system as part of its operation. A human-machine cooperative manufacturing system control example and a human agent simulation example will be introduced for the illustrative purposes at the end of the presentation.

  8. Adventitial transduction of lentivirus-shRNA-VEGF-A in arteriovenous fistula reduces venous stenosis formation.

    Science.gov (United States)

    Yang, Binxia; Janardhanan, Rajiv; Vohra, Pawan; Greene, Eddie L; Bhattacharya, Santanu; Withers, Sarah; Roy, Bhaskar; Nieves Torres, Evelyn C; Mandrekar, Jaywant; Leof, Edward B; Mukhopadhyay, Debabrata; Misra, Sanjay

    2014-02-01

    Venous neointimal hyperplasia (VNH) causes hemodialysis vascular access failure. Here we tested whether VNH formation occurs in part due to local vessel hypoxia caused by surgical trauma to the vasa vasorum of the outflow vein at the time of arteriovenous fistula placement. Selective targeting of the adventitia of the outflow vein at the time of fistula creation was performed using a lentivirus-delivered small-hairpin RNA that inhibits VEGF-A expression. This resulted in significant increase in mean lumen vessel area, decreased media/adventitia area, and decreased constrictive remodeling with a significant increase in apoptosis (increase in caspase 3 activity and TUNEL staining) accompanied with decreased cellular proliferation and hypoxia-inducible factor-1α at the outflow vein. There was significant decrease in cells staining positive for α-smooth muscle actin (a myofibroblast marker) and VEGFR-1 expression with a decrease in MMP-2 and MMP-9. These results were confirmed in animals that were treated with humanized monoclonal antibody to VEGF-A with similar results. Since hypoxia can cause fibroblast to differentiate into myofibroblasts, we silenced VEGF-A gene expression in fibroblasts and subjected them to hypoxia. This decreased myofibroblast production, cellular proliferation, cell invasion, MMP-2 activity, and increased caspase 3. Thus, VEGF-A reduction at the time of arteriovenous fistula placement results in increased positive vascular remodeling.

  9. [Construction of BAD Lentivirus Vector and Its Effect on Proliferation in A549 Cell Lines].

    Science.gov (United States)

    Huang, Na; He, Yan-qi; Zhu, Jing; Li, Wei-min

    2015-05-01

    To construct the recombinant lentivirus expressing vector BAD (Bcl-2-associated death protein) gene and to study its effect on A549 cell proliferation. The BAD gene was amplified from plasmid pAV-MCMV-BAD-GFP by PCR. The purified BAD gene fragment was inserted into a lentivirus vector (pLVX-IRES-ZsGreen 1), and the insertion was identified by PCR, restriction endonuclease analysis and DNA sequencing. A549 cells were then transfected with the packaged recombinant lentivirus, and resistant cell clones were selected with flow cytometry. The expression of BAD in A549 cell lines stably transduction with a lentivirus was examined using Western blot. The effect of BAD overexpression on proliferation of A549 cells was evaluated by using CCK-8 kit. Restriction enzyme digestion and DNA sequencing showed that the full-length BAD gene (507 bp) had been successfully subcloned into the lentiviral vector to result in the recombinant vector pLVX-IRES-ZsGreen 1. Monoclonal cell lines BAD-A549 was produced after transfection with the recombinant lentivirus and selected with flow cytometry. Stable expression of BAD protein was verified by Western blot. In vitro, the OD value in BAD group was significantly lower than that of control groups from 120-144 h (PBAD gene had been successfully generated. In vitro, BAD overexpression significantly inhibited A549 cells proliferation.

  10. The base excision repair pathway is required for efficient lentivirus integration.

    Directory of Open Access Journals (Sweden)

    Kristine E Yoder

    Full Text Available An siRNA screen has identified several proteins throughout the base excision repair (BER pathway of oxidative DNA damage as important for efficient HIV infection. The proteins identified included early repair factors such as the base damage recognition glycosylases OGG1 and MYH and the late repair factor POLß, implicating the entire BER pathway. Murine cells with deletions of the genes Ogg1, Myh, Neil1 and Polß recapitulate the defect of HIV infection in the absence of BER. Defective infection in the absence of BER proteins was also seen with the lentivirus FIV, but not the gammaretrovirus MMLV. BER proteins do not affect HIV infection through its accessory genes nor the central polypurine tract. HIV reverse transcription and nuclear entry appear unaffected by the absence of BER proteins. However, HIV integration to the host chromosome is reduced in the absence of BER proteins. Pre-integration complexes from BER deficient cell lines show reduced integration activity in vitro. Integration activity is restored by addition of recombinant BER protein POLß. Lentiviral infection and integration efficiency appears to depend on the presence of BER proteins.

  11. Permanent, lowered HLA class I expression using lentivirus vectors with shRNA constructs: Averting cytotoxicity by alloreactive T lymphocytes.

    Science.gov (United States)

    Haga, K; Lemp, N A; Logg, C R; Nagashima, J; Faure-Kumar, E; Gomez, G G; Kruse, C A; Mendez, R; Stripecke, R; Kasahara, N; Kasahara, N A; Cicciarelli, J C

    2006-12-01

    Transplantation of many tissues requires histocompatibility matching of human leukocyte antigens (HLA) to prevent graft rejection, to reduce the level of immunosuppression needed to maintain graft survival, and to minimize the risk of graft-versus-host disease, particularly in the case of bone marrow transplantation. However, recent advances in fields of gene delivery and genetic regulation technologies have opened the possibility of engineering grafts that display reduced levels of HLA expression. Suppression of HLA expression could help to overcome the limitations imposed by extensive HLA polymorphisms that restrict the availability of suitable donors, necessitate the maintenance of large donor registries, and complicate the logistics of procuring and delivering matched tissues and organs to the recipient. Accordingly, we investigated whether knockdown of HLA by RNA interference (RNAi), a ubiquitous regulatory system that can efficiently and selectively inhibit the expression of specific gene products, would enable allogeneic cells to evade immune recognition. For efficient and stable delivery of short hairpin-type RNAi constructs (shRNA), we employed lentivirus-based gene transfer vectors, which provide a delivery system that can achieve integration into genomic DNA, thereby permanently modifying transduced graft cells. Our results show that lentivirus-mediated delivery of shRNA targeting pan-Class I and allele-specific HLA can achieve efficient and dose-dependent reduction in surface expression of HLA in human cells, associated with enhanced resistance to alloreactive T lymphocyte-mediated cytotoxicity, while avoiding MHC-non-restricted killing. We hypothesize that RNAi-induced silencing of HLA expression has the potential to create histocompatibility-enhanced, and, eventually, perhaps "universally" compatible cellular grafts.

  12. Endogenous lentivirus in Malayan colugo (Galeopterus variegatus), a close relative of primates

    Czech Academy of Sciences Publication Activity Database

    Hron, Tomáš; Fábryová, Helena; Pačes, Jan; Elleder, Daniel

    2014-01-01

    Roč. 11, č. 84 (2014) ISSN 1742-4690 R&D Projects: GA MŠk(CZ) LK11215 Grant - others:GA MŠk(CZ) LM2010005 Institutional support: RVO:68378050 Keywords : Endogenous lentiviruses * Dermoptera * Paleovirology Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.185, year: 2014

  13. Lentivirus administration to rat muscle provides efficient sustained expression of erythropoietin

    NARCIS (Netherlands)

    Seppen, J.; Barry, S. C.; Harder, B.; Osborne, W. R.

    2001-01-01

    A lentivirus pseudotyped with vesicular stomatitis virus G protein (VSV-G) encoding rat erythropoietin (EPO) complementary DNA was administered to rat skeletal muscle and red blood cell production was serially monitored. After a single intramuscular injection hematocrit values increased and reached

  14. Effects of deoxycycline induced lentivirus encoding FasL gene on ...

    African Journals Online (AJOL)

    Abstract. Fas/Fas ligand (FasL)-mediated apoptosis plays a critical role in deletion of activated T cells. This study aimed to construct the lentivirus encoding FasL gene induced by deoxycycline and evaluate its effects on apoptosis of Th1 cells. A plasmid expression system encoding FasL was constructed through utilizing the ...

  15. Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and metastasis

    Directory of Open Access Journals (Sweden)

    Lv MT

    2016-11-01

    Full Text Available Mutian Lv,1 Yaming Li,1 Xin Tian,2 Shundong Dai,3,4 Jing Sun,5 Guojiang Jin,6 Shenyi Jiang7 1Department of Nuclear Medicine, 2Molecular Oncology Laboratory of Cancer Research Institute, The First Affiliated Hospital of China Medical University, 3Department of Pathology, The First Affiliated Hospital, College of Basic Medical Sciences of China Medical University, 4Department of Pathology, Institute of Pathology and Pathophysiology, 5Department of Immunology and Biotherapy, Liaoning Cancer Hospital and Institute, 6Department of Laboratory Medicine, 7Department of Rheumatology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China Abstract: Nemo-like kinase (NLK, an evolutionarily conserved serine/threonine kinase, has been recognized as a critical regulator of various cancers. In this study, we investigated the role of NLK in human small-cell lung cancer (SCLC, which is the most aggressive form of lung cancer. NLK expression was evaluated by quantitative real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi efficiently suppressed NLK expression in NCI-H446 cells, resulting in a significant reduction in cell viability and proliferation in vitro. Moreover, knockdown of NLK led to cell cycle arrest at the S-phase via suppression of Cyclin A, CDK2, and CDC25A, which could contribute to cell growth inhibition. Furthermore, knockdown of NLK decreased the migration of NCI-H446 cells and downregulated matrix metalloproteinase 9. Treatment with NLK short hairpin RNA significantly reduced SCLC tumor growth in vivo. In conclusion, this study suggests that NLK plays an important role in the growth and metastasis of SCLC and may serve as a potential therapeutic target for the treatment of SCLC. Keywords: NLK, SCLC, RNAi, proliferation, migration

  16. Targeting SPARC by lentivirus-mediated RNA interference inhibits cervical cancer cell growth and metastasis

    International Nuclear Information System (INIS)

    Chen, Jie; Shi, Dehuan; Liu, Xiaoyan; Fang, Shuang; Zhang, Jie; Zhao, Yueran

    2012-01-01

    Secreted protein acidic and rich in cysteine (SPARC), a calcium-binding matricellular glycoprotein, is implicated in the progressions of some cancers. However, no information has been available to date regarding the function of SPARC in cervical cancer cell growth and metastasis. In this study, we isolated and established high invasive subclones and low invasive subclones from human cervical cancer cell lines HeLa and SiHa by the limited dilution method. Real-time q-RT-PCR, Western Blot and ICC were performed to investigate SPARC mRNA and protein expressions in high invasive subclones and low invasive subclones. Then lentivirus vector with SPARC shRNA was constructed and infected the highly invasive subclones. Real-time q-RT-PCR, Western Blot and ICC were also performed to investigate the changes of SPARC expression after viral infection. In functional assays, effects of SPARC knockdown on the biological behaviors of cervical cancer cells were investigated. The mechanisms of SPARC in cervical cancer proliferation, apoptosis and invasion were also researched. SPARC was over-expressed in the highly invasive subclones compared with the low invasive subclones. Knockdown of SPARC significantly suppressed cervical cancer cell proliferation, and induced cell cycle arrest at the G1/G0 phase through the p53/p21 pathway, also caused cell apoptosis accompanied by the decreased ratio of Bcl-2/Bax, and inhibited cell invasion and metastasis accompanied by down-regulated MMP2 and MMP9 expressions and up-regulated E-cadherin expression. SPARC is related to the invasive phenotype of cervical cancer cells. Knockdown of SPARC significantly suppresses cervical cancer cell proliferation, induces cell apoptosis and inhibits cell invasion and metastasis. SPARC as a promoter improves cervical cancer cell growth and metastasis

  17. Targeting SPARC by lentivirus-mediated RNA interference inhibits cervical cancer cell growth and metastasis

    Directory of Open Access Journals (Sweden)

    Chen Jie

    2012-10-01

    Full Text Available Abstract Background Secreted protein acidic and rich in cysteine (SPARC, a calcium-binding matricellular glycoprotein, is implicated in the progressions of some cancers. However, no information has been available to date regarding the function of SPARC in cervical cancer cell growth and metastasis. Methods In this study, we isolated and established high invasive subclones and low invasive subclones from human cervical cancer cell lines HeLa and SiHa by the limited dilution method. Real-time q-RT-PCR, Western Blot and ICC were performed to investigate SPARC mRNA and protein expressions in high invasive subclones and low invasive subclones. Then lentivirus vector with SPARC shRNA was constructed and infected the highly invasive subclones. Real-time q-RT-PCR, Western Blot and ICC were also performed to investigate the changes of SPARC expression after viral infection. In functional assays, effects of SPARC knockdown on the biological behaviors of cervical cancer cells were investigated. The mechanisms of SPARC in cervical cancer proliferation, apoptosis and invasion were also researched. Results SPARC was over-expressed in the highly invasive subclones compared with the low invasive subclones. Knockdown of SPARC significantly suppressed cervical cancer cell proliferation, and induced cell cycle arrest at the G1/G0 phase through the p53/p21 pathway, also caused cell apoptosis accompanied by the decreased ratio of Bcl-2/Bax, and inhibited cell invasion and metastasis accompanied by down-regulated MMP2 and MMP9 expressions and up-regulated E-cadherin expression. Conclusion SPARC is related to the invasive phenotype of cervical cancer cells. Knockdown of SPARC significantly suppresses cervical cancer cell proliferation, induces cell apoptosis and inhibits cell invasion and metastasis. SPARC as a promoter improves cervical cancer cell growth and metastasis.

  18. Manufacture of Third-Generation Lentivirus for Preclinical Use, with Process Development Considerations for Translation to Good Manufacturing Practice.

    Science.gov (United States)

    Gándara, Carolina; Affleck, Valerie; Stoll, Elizabeth Ann

    2018-02-01

    Lentiviral vectors are used in laboratories around the world for in vivo and ex vivo delivery of gene therapies, and increasingly clinical investigation as well as preclinical applications. The third-generation lentiviral vector system has many advantages, including high packaging capacity, stable gene expression in both dividing and post-mitotic cells, and low immunogenicity in the recipient organism. Yet, the manufacture of these vectors is challenging, especially at high titers required for direct use in vivo, and further challenges are presented by the process of translating preclinical gene therapies toward manufacture of products for clinical investigation. The goals of this paper are to report the protocol for manufacturing high-titer third-generation lentivirus for preclinical testing and to provide detailed information on considerations for translating preclinical viral vector manufacture toward scaled-up platforms and processes in order to make gene therapies under Good Manufacturing Practice that are suitable for clinical trials.

  19. Sensitivity and specificity of a nested polymerase chain reaction for detection of lentivirus infection in lions (Panthera leo).

    Science.gov (United States)

    Adams, Hayley; van Vuuren, Moritz; Kania, Stephen; Bosman, Anna-Mari; Keet, Dewald; New, John; Kennedy, Melissa

    2010-12-01

    Feline immunodeficiency virus (FIV) is a lentivirus in the Retroviridae family that causes lifelong infection in domestic cats. The lentivirus of African lions (Panthera leo), referred to as FIVple, is endemic in certain lion populations in eastern and southern Africa. Lentivirus infection leads to immunologic dysfunction and immunosuppressive disease in domestic cats; however, little is known about the pathogenic effects of infection in lions, nor about the epidemiologic impact on free-ranging and captive populations. Whole blood and serum samples were collected opportunistically from free-ranging lions in Kruger National Park, Republic of South Africa (RSA). Whole blood and serum samples were also collected from captive wild lions in the RSA. A nested polymerase chain reaction (PCR) assay for detection of FIV was performed on all whole blood samples. In addition, serum samples were tested for cross-reactive antibodies to domestic feline lentivirus antigens and puma lentivirus synthetic envelope peptide antigen. The PCR assay successfully amplified the lion lentivirus from African lions. The relative sensitivity and relative specificity were 79% and 100%, respectively, and the positive and negative predictive values were 100% and 67%, respectively. This research represents the first study to compare genetic material with antibody-based methods of lentivirus detection on lions in RSA. Using PCR as an additional diagnostic test for FIV in lions will increase screening sensitivity and will allow viral characterization among circulating isolates and monitoring of changes in the viral epidemiology within geographic regions and populations over time.

  20. A decision support system prototype including human factors based on the TOGA meta-theory approach

    International Nuclear Information System (INIS)

    Cappelli, M.; Memmi, F.; Gadomski, A. M.; Sepielli, M.

    2012-01-01

    The human contribution to the risk of operation of complex technological systems is often not negligible and sometimes tends to become significant, as shown by many reports on incidents and accidents occurred in the past inside Nuclear Power Plants (NPPs). An error of a human operator of a NPP can derive by both omission and commission. For instance, complex commission errors can also lead to significant catastrophic technological accidents, as for the case of the Three Mile Island accident. Typically, the problem is analyzed by focusing on the single event chain that has provoked the incident or accident. What is needed is a general framework able to include as many parameters as possible, i.e. both technological and human factors. Such a general model could allow to envisage an omission or commission error before it can happen or, alternatively, suggest preferred actions to do in order to take countermeasures to neutralize the effect of the error before it becomes critical. In this paper, a preliminary Decision Support System (DSS) based on the so-called (-) TOGA meta-theory approach is presented. The application of such a theory to the management of nuclear power plants has been presented in the previous ICAPP 2011. Here, a human factor simulator prototype is proposed in order to include the effect of human errors in the decision path. The DSS has been developed using a TRIGA research reactor as reference plant, and implemented using the LabVIEW programming environment and the Finite State Machine (FSM) model The proposed DSS shows how to apply the Universal Reasoning Paradigm (URP) and the Universal Management Paradigm (UMP) to a real plant context. The DSS receives inputs from instrumentation data and gives as output a suggested decision. It is obtained as the result of an internal elaborating process based on a performance function. The latter, describes the degree of satisfaction and efficiency, which are dependent on the level of responsibility related to

  1. A model for Huanglongbing spread between citrus plants including delay times and human intervention

    Science.gov (United States)

    Vilamiu, Raphael G. d'A.; Ternes, Sonia; Braga, Guilherme A.; Laranjeira, Francisco F.

    2012-09-01

    The objective of this work was to present a compartmental deterministic mathematical model for representing the dynamics of HLB disease in a citrus orchard, including delay in the disease's incubation phase in the plants, and a delay period on the nymphal stage of Diaphorina citri, the most important HLB insect vector in Brazil. Numerical simulations were performed to assess the possible impacts of human detection efficiency of symptomatic plants, as well as the influence of a long incubation period of HLB in the plant.

  2. Feline glycoprotein A repetitions predominant anchors transforming growth factor beta on the surface of activated CD4(+)CD25(+) regulatory T cells and mediates AIDS lentivirus-induced T cell immunodeficiency.

    Science.gov (United States)

    Miller, Michelle M; Fogle, Jonathan E; Ross, Peter; Tompkins, Mary B

    2013-04-01

    Using the feline immunodeficiency virus (FIV) model for AIDS-lentivirus infection, our laboratory has previously demonstrated that T regulatory (Treg) cell-mediated immune T and B cell dysfunction contributes to lentivirus persistence and chronic disease through membrane bound transforming growth factor beta (mTGFb). Studying Treg cells in the context of infection has been problematic as no inducible marker for activated Treg cells had been identified. However, recent reports in human Treg studies have described a novel protein, glycoprotein A repetitions predominant (GARP), as a unique marker of activated human Treg cells that anchors mTGFb. Herein we extend these studies to the feline Treg system, identifying feline GARP and demonstrating that human and feline GARP proteins are homologous in structure, expression pattern, and ability to form a complex with TGFb. We further demonstrate that GARP and TGFb form a complex on the surface of activated Treg cells and that these GARP(+)TGFb(+) Treg cells are highly efficient suppressor cells. Analysis of expression of this Treg activation marker in the FIV-AIDS model reveals an up-regulation of GARP expressing Treg cells during chronic FIV infection. We demonstrate that the GARP(+) Treg cells from FIV-infected cats suppress T helper cells in vivo and that blocking GARP or TGFb eliminates this suppression. These data suggest that GARP is expressed in complex with TGFb on the surface of activated Treg cells and plays an important role in TGFb(+) Treg-mediated T cell immune suppression during lentivirus infection.

  3. Lentivirus-mediated Knockdown of HDAC1 Uncovers Its Role in Esophageal Cancer Metastasis and Chemosensitivity

    OpenAIRE

    Song, Min; He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

    2016-01-01

    Histone deacetylationase 1 (HDAC1) is ubiquitously expressed in various cell lines and tissues and play an important role of regulation gene expression. Overexpression of HDAC1 has been observed in various types of cancers, which indicated that it might be a target for cancer therapy. To test HDAC1 inhibition for cancer treatment, the gene expression of HDAC1 was knockdown mediated by a lentivirus system. Our data showed the gene expression of HDAC1 could be efficiently knockdown by RNAi medi...

  4. [Lentivirus-mediated shRNA silencing of LAMP2A inhibits the proliferation of multiple myeloma cells].

    Science.gov (United States)

    Li, Lixuan; Li, Jia

    2015-05-01

    To study the effects of lentivirus-mediated short hairpin RNA (shRNA) silencing of lysosome-associated membrane protein type 2A (LAMP2A) expression on the proliferation of multiple myeloma cells. The constructed shRNA lentiviral vector was applied to infect human multiple myeloma cell line MM.1S, and stable expression cell line was obtained by puromycin screening. Western blotting was used to verify the inhibitory effect on LAMP2A protein expression. MTT assay was conducted to detect the effect of knocked-down LAMP2A on MM.1S cell proliferation, and the anti-tumor potency of suberoylanilide hydroxamic acid (SAHA) against the obtained MM.1S LAMP2A(shRNA) stable cell line. Lactate assay was performed to observe the impact of low LAMP2A expression on cell glycolysis. The stable cell line with low LAMP2A expression were obtained with the constructed human LAMP2A-shRNA lentiviral vector. Down-regulation of LAMP2A expression significantly inhibited MM.1S cell proliferation and enhanced the anti-tumor activity of SAHA. Interestingly, decreased LAMP2A expression also inhibited MM.1S cell lactic acid secretion. Down-regulation of LAMP2A expression could inhibit cell proliferation in multiple myeloma cells.

  5. The interferon-induced antiviral protein PML (TRIM19) promotes the restriction and transcriptional silencing of lentiviruses in a context-specific, isoform-specific fashion.

    Science.gov (United States)

    Masroori, Nasser; Merindol, Natacha; Berthoux, Lionel

    2016-03-22

    The promyelocytic leukemia (PML) protein, a type I interferon (IFN-I)-induced gene product and a member of the tripartite motif (TRIM) family, modulates the transcriptional activity of viruses belonging to various families. Whether PML has an impact on the replication of HIV-1 has not been fully addressed, but recent studies point to its possible involvement in the restriction of HIV-1 in human cells and in the maintenance of transcriptional latency in human cell lines in which HIV-1 is constitutively repressed. We investigated further the restriction of HIV-1 and a related lentivirus, SIVmac, by PML in murine cells and in a lymphocytic human cell line. In particular, we studied the relevance of PML to IFN-I-mediated inhibition and the role of individual human isoforms. We demonstrate that both human PML (hPML) and murine PML (mPML) inhibit the early post-entry stages of the replication of HIV-1 and a related lentivirus, SIVmac. In addition, HIV-1 was transcriptionally silenced by mPML and by hPML isoforms I, II, IV and VI in MEFs. This PML-mediated transcriptional repression was attenuated in presence of the histone deacetylase inhibitor SAHA. In contrast, depletion of PML had no effect on HIV-1 gene expression in a human T cell line. PML was found to contribute to the inhibition of HIV-1 by IFN-I. Specifically, IFN-α and IFN-β treatments of MEFs enhanced the PML-dependent inhibition of HIV-1 early replication stages. We show that PML can inhibit HIV-1 and other lentiviruses as part of the IFN-I-mediated response. The restriction takes place at two distinct steps, i.e. reverse transcription and transcription, and in an isoform-specific, cellular context-specific fashion. Our results support a model in which PML activates innate immune antilentiviral effectors. These data are relevant to the development of latency reversal-inducing pharmacological agents, since PML was previously proposed as a pharmacological target for such inhibitors. This study also has

  6. What Is Humane Education and Why It Should Be Included in Modern Education

    Science.gov (United States)

    Jacobs, G. M.

    2016-01-01

    Humane education has existed since at least the 18th century (Unti & DeRosa, 2003). This brief chapter begins with a brief definition of humane education and examples of how it can be incorporated in linguistics, cross cultural studies and foreign language education. Next, the chapter discusses why humane education constitutes an important…

  7. The Social Studies Should Include More Discussion of International Human Rights.

    Science.gov (United States)

    Torney, Judith V.

    1980-01-01

    Students need more exposure to the concept of human rights. They need to know The Universal Declaration of Human Rights and the subsequent covenants. Also, they need to know that substantial agreement exists in the international community about what constitutes human rights. (Author/KC)

  8. Broader prevalence of Wolbachia in insects including potential human disease vectors.

    Science.gov (United States)

    de Oliveira, C D; Gonçalves, D S; Baton, L A; Shimabukuro, P H F; Carvalho, F D; Moreira, L A

    2015-06-01

    Wolbachia are intracellular, maternally transmitted bacteria considered the most abundant endosymbionts found in arthropods. They reproductively manipulate their host in order to increase their chances of being transmitted to the offspring, and currently are being used as a tool to control vector-borne diseases. Studies on distribution of Wolbachia among its arthropod hosts are important both for better understanding why this bacterium is so common, as well as for its potential use as a biological control agent. Here, we studied the incidence of Wolbachia in a broad range of insect species, collected from different regions of Brazil, using three genetic markers (16S rRNA, wsp and ftsZ), which varied in terms of their sensitivity to detect this bacterium. The overall incidence of Wolbachia among species belonging to 58 families and 14 orders was 61.9%. The most common positive insect orders were Coleoptera, Diptera, Hemiptera and Hymenoptera, with Diptera and Hemiptera having the highest numbers of Wolbachia-positive families. They included potential human disease vectors whose infection status has never been reported before. Our study further shows the importance of using quantitative polymerase chain reaction for high-throughput and sensitive Wolbachia screening.

  9. Perfluorooctanesulfonate and related fluorochemicals in several organisms including humans from Italy

    Energy Technology Data Exchange (ETDEWEB)

    Corsolini, S. [Siena Univ. (Italy); Kannan, K. [New York State Univ., Albany, NY (United States)

    2004-09-15

    Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant, extremely resistant to environmental degradation and is ubiquitous in the environment. Traditional monitoring studies for persistent chemicals failed to identify this contaminant for a long time because of its unique physicochemical properties and its tendency to bind to proteins instead of accumulating in fatty tissues. PFOS is known to be toxic in laboratory animals (rats, mice, monkeys) at levels close to the range already found in organisms and people. PFOS has been commercially produced by an electrochemical fluorination process for over 40 years. Perfluorooctane sulfonylfluoride (POSF; C{sub 8}F{sub 17}SO{sub 2}F) is used as a building block for further reactions that produce several other sulfonated fluorinated compounds, including perfluorooctane sulfonate (C{sub 8}F{sub 17}SO{sub 3}{sup -}) and other precursor molecules such as n-ethyl or n-methyl perfluorooctanesulfonamidoethanol. POSF-based fluorochemicals have been used in a wide variety of industrial and consumer products, including protective coatings for carpets and apparel, paper coatings, insecticide formulations, and surfactants. These compounds repel water and oil, reduce surface tension, catalyze oligomerization and polymerization, and maintain their properties under extreme conditions. Depending upon the specific functional derivatization or the degree of polymerization, POSF-based chemicals may degrade or metabolize to PFOS, which is known to be the final metabolite of POSF-based fluorochemicals. PFOS is stable, chemically inert, and non-reactive and has the potential to bioaccumulate. It has been found in polar bears from the Arctic, albatross and other fish-eating water birds in the mid-Pacific, and aquatic organisms11 and people world-wide. PFOS and other perfluorinated chemicals such as perfluorooctanesulfonamide (PFOSA), perfluorohexanesulfonate (PFHxS), and perfluorooctanoate (PFOA) have been detected in human blood. In

  10. [VEGF165 transfected endothelial progenitor cells mediated by lentivirus alleviated ALI in rats].

    Science.gov (United States)

    He, Zhaohui; He, Huiwei; Lu, Yuanhua; Chen, Zhi; Xu, Fanghua; Wang, Rongsheng; Yang, Chunli

    2017-11-01

    To investigate the protective effects of vascular endothelial growth factor-165 (VEGF165) transfected the endothelial progenitor cells (EPCs) mediated by lentivirus on acute lung injury (ALI) in rats. The mononuclear cells from the male Sprague-Dawley (SD) rats were isolated and cultured to get the EPCs for study. The lentivirus vector carrying the human VEGF165 gene was constructed. According to the random number table method, 90 male SD rats were divided into ALI model group, phosphate buffer solution (PBS) group, EPCs treatment group, none transfected EPCs treatment group and VEGF165 transfected EPCs treatment group, and the rats in each group were subdivided into 4, 12 and 48 hours subgroups, with 6 rats in each subgroup. The rat model of ALI was reproduced by intravenous injection of oleic acid (0.15 μL/g). Then each treatment group was given PBS, EPCs, none transfected EPCs and VEGF165 transfected EPCs respectively with the same volume of 0.2 mL. For the groups with cells, about 1×10 6 cells were contained. Abdominal aortic blood and lung tissue were harvested at 4, 12 and 48 hours. Arterial blood gas analysis was performed. The lung wet/dry weight ratio (W/D) was calculated. The expressions of induced nitric oxide synthase (iNOS), endothelin-1 (ET-1) and VEGF165 were determined by enzyme-linked immunosorbent assay (ELISA). After dyed with hematoxylin-eosin (HE), the lung tissue pathology was observed and the lung injury score was performed. Compared with the ALI model group, the arterial partial pressure of oxygen (PaO 2 ) in EPCs, none transfected EPCs and VEGF165 transfected EPCs treatment groups was significantly increased from 4 hours, and lung W/D, expressions of iNOS and ET-1 were significantly decreased, and VEGF165 expression was significantly increased. Compared with the EPCs treatment group, the increase in PaO 2 , the decrease in lung W/D and expressions of iNOS and ET-1, and the increase in VEGF165 expression in VEGF165 transfected EPCs

  11. The Human Bathtub: Safety and Risk Predictions Including the Dynamic Probability of Operator Errors

    International Nuclear Information System (INIS)

    Duffey, Romney B.; Saull, John W.

    2006-01-01

    Reactor safety and risk are dominated by the potential and major contribution for human error in the design, operation, control, management, regulation and maintenance of the plant, and hence to all accidents. Given the possibility of accidents and errors, now we need to determine the outcome (error) probability, or the chance of failure. Conventionally, reliability engineering is associated with the failure rate of components, or systems, or mechanisms, not of human beings in and interacting with a technological system. The probability of failure requires a prior knowledge of the total number of outcomes, which for any predictive purposes we do not know or have. Analysis of failure rates due to human error and the rate of learning allow a new determination of the dynamic human error rate in technological systems, consistent with and derived from the available world data. The basis for the analysis is the 'learning hypothesis' that humans learn from experience, and consequently the accumulated experience defines the failure rate. A new 'best' equation has been derived for the human error, outcome or failure rate, which allows for calculation and prediction of the probability of human error. We also provide comparisons to the empirical Weibull parameter fitting used in and by conventional reliability engineering and probabilistic safety analysis methods. These new analyses show that arbitrary Weibull fitting parameters and typical empirical hazard function techniques cannot be used to predict the dynamics of human errors and outcomes in the presence of learning. Comparisons of these new insights show agreement with human error data from the world's commercial airlines, the two shuttle failures, and from nuclear plant operator actions and transient control behavior observed in transients in both plants and simulators. The results demonstrate that the human error probability (HEP) is dynamic, and that it may be predicted using the learning hypothesis and the minimum

  12. Microsatellite polymorphisms associated with human behavioural and psychological phenotypes including a gene-environment interaction.

    Science.gov (United States)

    Bagshaw, Andrew T M; Horwood, L John; Fergusson, David M; Gemmell, Neil J; Kennedy, Martin A

    2017-02-03

    The genetic and environmental influences on human personality and behaviour are a complex matter of ongoing debate. Accumulating evidence indicates that short tandem repeats (STRs) in regulatory regions are good candidates to explain heritability not accessed by genome-wide association studies. We tested for associations between the genotypes of four selected repeats and 18 traits relating to personality, behaviour, cognitive ability and mental health in a well-studied longitudinal birth cohort (n = 458-589) using one way analysis of variance. The repeats were a highly conserved poly-AC microsatellite in the upstream promoter region of the T-box brain 1 (TBR1) gene and three previously studied STRs in the activating enhancer-binding protein 2-beta (AP2-β) and androgen receptor (AR) genes. Where significance was found we used multiple regression to assess the influence of confounding factors. Carriers of the shorter, most common, allele of the AR gene's GGN microsatellite polymorphism had fewer anxiety-related symptoms, which was consistent with previous studies, but in our study this was not significant following Bonferroni correction. No associations with two repeats in the AP2-β gene withstood this correction. A novel finding was that carriers of the minor allele of the TBR1 AC microsatellite were at higher risk of conduct problems in childhood at age 7-9 (p = 0.0007, which did pass Bonferroni correction). Including maternal smoking during pregnancy (MSDP) in models controlling for potentially confounding influences showed that an interaction between TBR1 genotype and MSDP was a significant predictor of conduct problems in childhood and adolescence (p behaviour up to age 25 years (p ≤ 0.02). This interaction remained significant after controlling for possible confounders including maternal age at birth, socio-economic status and education, and offspring birth weight. The potential functional importance of the TBR1 gene's promoter microsatellite

  13. Effect of changes in human ecology and behavior on patterns of sexually transmitted diseases, including human immunodeficiency virus infection.

    Science.gov (United States)

    Wasserheit, J N

    1994-01-01

    The last 20 years have witnessed six striking changes in patterns of sexually transmitted diseases (STDs): emergence of new STD organisms and etiologies, reemergence of old STDs, shifts in the populations in which STDs are concentrated, shifts in the etiological spectra of STD syndromes, alterations in the incidence of STD complications, and increases in antimicrobial resistance. For example, human immunodeficiency virus (HIV) emerged to devastate the United States with a fatal pandemic involving at least 1 million people. The incidence of syphilis rose progressively after 1956 to reach a 40-year peak by 1990. In both cases, disease patterns shifted from homosexual men to include minority heterosexuals. Over the last decade, gonorrhea became increasingly concentrated among adolescents, and several new types of antimicrobial resistance appeared. Three interrelated types of environments affect STD patterns. The microbiologic, hormonal, and immunologic microenvironments most directly influence susceptibility, infectiousness, and development of sequelae. These microenvironments are shaped, in part, by the personal environments created by an individual's sexual, substance-use, and health-related behaviors. The personal environments are also important determinants of acquisition of infection and development of sequelae but, in addition, they mediate risk of exposure to infection. These are, therefore, the environments that most directly affect changing disease patterns. Finally, individuals' personal environments are, in turn, molded by powerful macroenvironmental forces, including socioeconomic, demographic, geographic, political, epidemiologic, and technological factors. Over the past 20 years, the profound changes that have occurred in many aspects of the personal environment and the macroenvironment have been reflected in new STD patterns. PMID:8146135

  14. Self-association of the Lentivirus protein, Nef

    Directory of Open Access Journals (Sweden)

    Garcia J Victor

    2010-09-01

    Full Text Available Abstract Background The HIV-1 pathogenic factor, Nef, is a multifunctional protein present in the cytosol and on membranes of infected cells. It has been proposed that a spatial and temporal regulation of the conformation of Nef sequentially matches Nef's multiple functions to the process of virion production. Further, it has been suggested that dimerization is required for multiple Nef activities. A dimerization interface has been proposed based on intermolecular contacts between Nefs within hexagonal Nef/FynSH3 crystals. The proposed dimerization interface consists of the hydrophobic B-helix and flanking salt bridges between R105 and D123. Here, we test whether Nef self-association is mediated by this interface and address the overall significance of oligomerization. Results By co-immunoprecipitation assays, we demonstrated that HIV-1Nef exists as monomers and oligomers with about half of the Nef protomers oligomerized. Nef oligomers were found to be present in the cytosol and on membranes. Removal of the myristate did not enhance the oligomerization of soluble Nef. Also, SIVNef oligomerizes despite lacking a dimerization interface functionally homologous to that proposed for HIV-1Nef. Moreover, HIV-1Nef and SIVNef form hetero-oligomers demonstrating the existence of homologous oligomerization interfaces that are distinct from that previously proposed (R105-D123. Intracellular cross-linking by formaldehyde confirmed that SF2Nef dimers are present in intact cells, but surprisingly self-association was dependent on R105, but not D123. SIVMAC239Nef can be cross-linked at its only cysteine, C55, and SF2Nef is also cross-linked, but at C206 instead of C55, suggesting that Nefs exhibit multiple dimeric structures. ClusPro dimerization analysis of HIV-1Nef homodimers and HIV-1Nef/SIVNef heterodimers identified a new potential dimerization interface, including a dibasic motif at R105-R106 and a six amino acid hydrophobic surface. Conclusions We have

  15. Development of a quantitative safety assessment method for nuclear I and C systems including human operators

    International Nuclear Information System (INIS)

    Kim, Man Cheol

    2004-02-01

    Conventional PSA (probabilistic safety analysis) is performed in the framework of event tree analysis and fault tree analysis. In conventional PSA, I and C systems and human operators are assumed to be independent for simplicity. But, the dependency of human operators on I and C systems and the dependency of I and C systems on human operators are gradually recognized to be significant. I believe that it is time to consider the interdependency between I and C systems and human operators in the framework of PSA. But, unfortunately it seems that we do not have appropriate methods for incorporating the interdependency between I and C systems and human operators in the framework of Pasa. Conventional human reliability analysis (HRA) methods are not developed to consider the interdependecy, and the modeling of the interdependency using conventional event tree analysis and fault tree analysis seem to be, event though is does not seem to be impossible, quite complex. To incorporate the interdependency between I and C systems and human operators, we need a new method for HRA and a new method for modeling the I and C systems, man-machine interface (MMI), and human operators for quantitative safety assessment. As a new method for modeling the I and C systems, MMI and human operators, I develop a new system reliability analysis method, reliability graph with general gates (RGGG), which can substitute conventional fault tree analysis. RGGG is an intuitive and easy-to-use method for system reliability analysis, while as powerful as conventional fault tree analysis. To demonstrate the usefulness of the RGGG method, it is applied to the reliability analysis of Digital Plant Protection System (DPPS), which is the actual plant protection system of Ulchin 5 and 6 nuclear power plants located in Republic of Korea. The latest version of the fault tree for DPPS, which is developed by the Integrated Safety Assessment team in Korea Atomic Energy Research Institute (KAERI), consists of 64

  16. Prior Puma Lentivirus Infection Modifies Early Immune Responses and Attenuates Feline Immunodeficiency Virus Infection in Cats

    Directory of Open Access Journals (Sweden)

    Wendy S. Sprague

    2018-04-01

    Full Text Available We previously showed that cats that were infected with non-pathogenic Puma lentivirus (PLV and then infected with pathogenic feline immunodeficiency virus (FIV (co-infection with the host adapted/pathogenic virus had delayed FIV proviral and RNA viral loads in blood, with viral set-points that were lower than cats infected solely with FIV. This difference was associated with global CD4+ T cell preservation, greater interferon gamma (IFN-γ mRNA expression, and no cytotoxic T lymphocyte responses in co-infected cats relative to cats with a single FIV infection. In this study, we reinforced previous observations that prior exposure to an apathogenic lentivirus infection can diminish the effects of acute infection with a second, more virulent, viral exposure. In addition, we investigated whether the viral load differences that were observed between PLV/FIV and FIV infected cats were associated with different immunocyte phenotypes and cytokines. We found that the immune landscape at the time of FIV infection influences the infection outcome. The novel findings in this study advance our knowledge about early immune correlates and documents an immune state that is associated with PLV/FIV co-infection that has positive outcomes for lentiviral diseases.

  17. Molecular characterization and phylogenetic analysis of small ruminant lentiviruses isolated from Canadian sheep and goats

    Directory of Open Access Journals (Sweden)

    Bertoni Giuseppe

    2011-06-01

    Full Text Available Abstract Background Small Ruminant Lentiviruses (SRLV are widespread in Canadian sheep and goats and represent an important health issue in these animals. There is however no data about the genetic diversity of Caprine Arthritis Encephalitis Virus (CAEV or Maedi Visna Virus (MVV in this country. Findings We performed a molecular and phylogenetic analysis of sheep and goat lentiviruses from a small geographic area in Canada using long sequences from the gag region of 30 infected sheep and 36 infected goats originating from 14 different flocks. Pairwise DNA distance and phylogenetic analyses revealed that all SRLV sequences obtained from sheep clustered tightly with prototypical Maedi visna sequences from America. Similarly, all SRLV strains obtained from goats clustered tightly with prototypical US CAEV-Cork strain. Conclusions The data reported in this study suggests that Canadian and US SRLV strains share common origins. In addition, the molecular data failed to bring to light any evidence of past cross species transmission between sheep and goats, which is consistent with the type of farming practiced in this part of the country where single species flocks predominate and where opportunities of cross species transmissions are proportionately low.

  18. Estudios estructurales de la proteína mayoritaria de la cápsida de lentivirus

    OpenAIRE

    Yélamos López, María Belén

    1998-01-01

    Los Lentivirus son un grupo de virus, subfamilia de los Retrovirus. Incluyen virus de gran importancia tanto veterinaria, como el virus de la anemia infecciosa equina (EIAV) o el virus de la inmunodeficiencia felina (FIV), como clínica como el virus de la inmunodeficiencia humana (HIV). Nuestro sistema de estudio es la proteína mayoritaria de la cápsida de lentivirus. Las proteínas de las cápsidas lentivirales tienen una gran homología de secuencia. Este alto grado de similitud, junto con la ...

  19. Development of the nervus terminalis in mammals including toothed whales and humans.

    Science.gov (United States)

    Oelschläger, H A; Buhl, E H; Dann, J F

    1987-01-01

    The early ontogenesis and topography of the mammalian terminalis system was investigated in 43 microslide series of toothed whale and human embryos and fetuses. In early embryonal stages the development of the nasal pit, the olfacto-terminalis placode, and the olfactory bulb anlage is rather similar in toothed whales and humans. However, toothed whales do not show any trace of the vomeronasalis complex. In early fetal stages the olfactory bulb anlage in toothed whales is reduced and leaves the isolated future terminalis ganglion (ganglia) which contains the greatest number of cells within Mammalia. The ganglion is connected with the nasal mucosa via peripheral fiber bundles and with the telencephalon via central terminalis rootlets. The functional implications of the terminalis system in mammals and its evolution in toothed whales are discussed. Obviously, the autonomic component has been enlarged in the course of perfect adaptation to an aquatic environment.

  20. Noninvasive Electrical Neuroimaging of the Human Brain during Mobile Tasks including Walking and Running

    Science.gov (United States)

    2012-01-01

    experiment. All procedures were approved by the University of Michigan Internal Review Board and complied with the standards defined in the...subjects performed two experimental blocks. In the first block, subjects were asked to press a button on a wireless Wii controller (Nintendo, Kyoto...evidence of cortical involvement in human locomotion. Dual-task experiments have demonstrated that balance during walking can be negatively affected by

  1. Lentivirus-Induced Dendritic Cells (iDC for Immune-Regenerative Therapies in Cancer and Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Renata Stripecke

    2014-08-01

    Full Text Available Conventional dendritic cells (cDC are ex vivo differentiated professional antigen presenting cells capable of potently stimulating naïve T cells and with vast potential for immunotherapeutic applications. The manufacture of clinical-grade cDC is relatively complex and requires several days for completion. Clinical trials showed poor trafficking of cDC from subcutaneous injection sites to lymph nodes (LN, where DC can optimally stimulate naïve lymphocytes for long-lasting memory responses. We demonstrated in mouse and human systems that a single overnight ex vivo lentiviral (LV gene transfer into DC precursors for production of combination of cytokines and antigens was capable to induce autonomous self-differentiation of antigen-loaded DC in vitro and in vivo. These highly viable induced DC (iDC effectively migrated from the injected skin to LN, where they effectively activated de novo antigen-specific effector memory T cells. Two iDC modalities were validated in relevant animal models and are now in clinical development: Self-differentiated Myeloid-derived Antigen-presenting-cells Reactive against Tumors co-expressing GM-CSF/IL-4/TRP2 for melanoma immunotherapy in the autologous setting (SmartDCtrp2, and Self-differentiated Myeloid-derived Lentivirus-induced against human cytomegalovirus as an allogeneic matched adoptive cell after stem cell transplantation (SmyleDCpp65. The lentiviral vector design and packaging methodology has “evolved” continuously in order to simplify and optimize function and biosafety of in vitro and in vivo genetic reprogramming of iDC. Here, we address the challenges seeking for new creations of genetically programmed iDC and integrase-defective LV vaccines for immune regeneration.

  2. The human genome and sport, including epigenetics, gene doping, and athleticogenomics.

    Science.gov (United States)

    Sharp, N C Craig

    2010-03-01

    Hugh Montgomery's discovery of the first of more than 239 fitness genes together with rapid advances in human gene therapy have created a prospect of using genes, genetic elements, and cells that have the capacity to enhance athletic performance (to paraphrase the World Anti-Doping Agency's definition of gene doping). This brief overview covers the main areas of interface between genetics and sport, attempts to provide a context against which gene doping may be viewed, and predicts a futuristic legitimate use of genomic (and possibly epigenetic) information in sport. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Modelling of safety barriers including human and organisational factors to improve process safety

    DEFF Research Database (Denmark)

    Markert, Frank; Duijm, Nijs Jan; Thommesen, Jacob

    2013-01-01

    It is believed that traditional safety management needs to be improved on the aspect of preparedness for coping with expected and unexpected deviations, avoiding an overly optimistic reliance on safety systems. Remembering recent major accidents, such as the Deep Water Horizon, the Texas City....... A valuable approach is the inclusion of human and organisational factors into the simulation of the reliability of the technical system using event trees and fault trees and the concept of safety barriers. This has been demonstrated e.g. in the former European research project ARAMIS (Accidental Risk...

  4. Occurance of Staphylococcus nepalensis strains in different sources including human clinical material.

    Science.gov (United States)

    Nováková, Dana; Pantůcek, Roman; Petrás, Petr; Koukalová, Dagmar; Sedlácek, Ivo

    2006-10-01

    Five isolates of coagulase-negative staphylococci were obtained from human urine, the gastrointestinal tract of squirrel monkeys, pig skin and from the environment. All key biochemical characteristics of the tested strains corresponded with the description of Staphylococcus xylosus species. However, partial 16S rRNA gene sequences obtained from analysed strains corresponded with those of Staphylococcus nepalensis reference strains, except for two strains which differed in one residue. Ribotyping with EcoRI and HindIII restriction enzymes, whole cell protein profile analysis performed by SDS-PAGE and SmaI macrorestriction analysis were used for more precise characterization and identification of the analysed strains. Obtained results showed that EcoRI and HindIII ribotyping and whole cell protein fingerprinting are suitable and reliable methods for the differentiation of S. nepalensis strains from the other novobiocin resistant staphylococci, whereas macrorestriction analysis was found to be a good tool for strain typing. The isolation of S. nepalensis is sporadic, and according to our best knowledge this study is the first report of the occurrence of this species in human clinical material as well as in other sources.

  5. The Incidence and Topographic Distribution of Sutures Including Wormian Bones in Human Skulls.

    Science.gov (United States)

    Cirpan, Sibel; Aksu, Funda; Mas, Nuket

    2015-07-01

    The Wormian Bones are accessory bones located within the cranial sutures and fontanelles. The present article examines the incidence of Wormian Bones and compares the number and topographic distribution between the sutures including Wormian Bones in skulls of West Anatolian Population. One hundred fifty crania were examined. The parameters evaluated in the present study were as follows: the rate of skulls including Wormian Bones; the topographic distribution and frequencies of the sutures including Wormian Bones; the number of these sutures for each skull; the name and number of sutures that were bilaterally and symmetrically located on the right and left side of skull (paired sutures) and which coincidentally had Wormian Bones for each skull; the differences of frequencies between the paired sutures including Wormian Bones. The rate of skulls including Wormian Bones was determined as 59.3%. The maximum and minimum numbers of sutures, including Wormian Bones, were 6 in 1 skull and 1 in each of 30 skulls, respectively. The maximum and minimum rates of sutures that had Wormian Bones were found in left lambdoid 40.7% and right occipitomastoid 1.3% sutures, respectively. There was only a significant difference between the rate of right and left squamous sutures (P = 0.04). Forty-five skulls were including 55 pairs of bilaterally and symmetrically located sutures that coincidentally had Wormian Bones in each pair. Each of 35 skulls had 1 pair of sutures including Wormian Bones and each of 10 skulls had 2 pairs. In the present study, the rate of Wormian Bones was determined as 59.3% in West Anatolian Population. This incidence rate is considerably lower than the other reports, and it may be as a result of racial variations. These divergent bones were more frequently found in left lambdoid sutures (40.7%) and less frequently in right occipitomastoid sutures (1.3%). This study may guide the investigators dealing with the neurosurgery, orthopedy, radiology, anatomy, and

  6. Human Gait Feature Extraction Including a Kinematic Analysis toward Robotic Power Assistance

    Directory of Open Access Journals (Sweden)

    Mario I. Chacon-Murguia

    2012-09-01

    Full Text Available The present work proposes a method for human gait and kinematic analysis. Gait analysis consists of the determination of hip, knee and ankle positions through video analysis. Gait kinematic for the thigh and knee is then generated from this data. Evaluations of the gait analysis method indicate an acceptable performance of 86.66% for hip and knee position estimation, and comparable findings with other reported works for gait kinematic. A coordinate systems assignment is performed according to the DH algorithm and a direct kinematic model of the legs is obtained. The legs' angles obtained from the video analysis are applied to the kinematic model in order to revise the application of this model to robotic legs in a power assisted system.

  7. Microscopic age determination of human skeletons including an unknown but calculable variable

    DEFF Research Database (Denmark)

    Wallin, Johan Albert; Tkocz, Izabella; Kristensen, Gustav

    1994-01-01

    estimation, which includes the covariance matrix of four single equation residuals, improves the accuracy of age determination. The standard deviation, however, of age prediction remains 12.58 years. An experimental split of the data was made in order to demonstrate that the use of subgroups gives a false...

  8. Over-expression of brain-derived neurotrophic factor in mesenchymal stem cells transfected with recombinant lentivirus BDNF gene.

    Science.gov (United States)

    Zhang, X; Zhu, J; Zhang, K; Liu, T; Zhang, Z

    2016-12-30

    This study was aimed at investigating the expression of brain-derived neurotrophic factor (BDNF) in mesenchymal stem cells (MSCs) modified with recombinant lentivirus bearing BDNF gene. Lentivirus vectors bearing BDNF gene were constructed. MSCs were isolated from rats and cultured. The lentiviral vectors containing BDNF gene were transfected into the MSCs, and BDNF gene and protein expressions were monitored with enhanced green fluorescent protein (EGFP). RT-PCR and Western blot were used to measure gene and protein expressions, respectibvely in MSCs, MSCs-EGFP and MSCs-EGFP-BDNF groups. Green fluorescence assay confirmed successful transfection of BDNF gene recombinant lentivirus into MSCs. RT-PCR and Western blot revealed that BDNF gene and protein expressions in the MSCs-EGFP-BDNF group were significantly higher than that in MSCs group and MSCs-EGFP group. There were no statistically significant differences in gene expression between MSCs and MSCs-EGFP groups. MSCs can over-express BDNF when transfected with recombinant lentivirus bearing BDNF gene.

  9. Human factors design of nuclear power plant control rooms including computer-based operator aids

    International Nuclear Information System (INIS)

    Bastl, W.; Felkel, L.; Becker, G.; Bohr, E.

    1983-01-01

    The scientific handling of human factors problems in control rooms began around 1970 on the basis of safety considerations. Some recent research work deals with the development of computerized systems like plant balance calculation, safety parameter display, alarm reduction and disturbance analysis. For disturbance analysis purposes it is necessary to homogenize the information presented to the operator according to the actual plant situation in order to supply the operator with the information he most urgently needs at the time. Different approaches for solving this problem are discussed, and an overview is given on what is being done. Other research projects concentrate on the detailed analysis of operators' diagnosis strategies in unexpected situations, in order to obtain a better understanding of their mental processes and the influences upon them when such situations occur. This project involves the use of a simulator and sophisticated recording and analysis methods. Control rooms are currently designed with the aid of mock-ups. They enable operators to contribute their experience to the optimization of the arrangement of displays and controls. Modern control rooms are characterized by increasing use of process computers and CRT (Cathode Ray Tube) displays. A general concept for the integration of the new computerized system and the conventional control panels is needed. The technical changes modify operators' tasks, and future ergonomic work in nuclear plants will need to consider the re-allocation of function between man and machine, the incorporation of task changes in training programmes, and the optimal design of information presentation using CRTs. Aspects of developments in control room design are detailed, typical research results are dealt with, and a brief forecast of the ergonomic contribution to be made in the Federal Republic of Germany is given

  10. Lentivirus-mediated RNA interference of vascular endothelial growth factor in monkey eyes with iris neovascularization.

    Science.gov (United States)

    Yuan, Meng-Ke; Tao, Yong; Yu, Wen-Zhen; Kai, Wang; Jiang, Yan-Rong

    2010-08-25

    To explore the in vivo anti-angiogenesis effects resulting from lentivirus-mediated RNAi of vascular endothelial growth factor (VEGF) in monkeys with iris neovascularization (INV). Five specific recombinant lentiviral vectors for RNA interference, targeting Macaca mulatta VEGFA, were designed and the one with best knock down efficacy (LV-GFP-VEGFi1) in H1299 cells and RF/6A cells was selected by real-time PCR for in vivo use. A laser-induced retinal vein occlusion model was established in one eye of seven cynomolgus monkeys. In monkeys number 1, 3, and 5 (Group 1), the virus (1x10(8) particles) was intravitreally injected into the preretinal space of the animal's eye immediately after laser coagulation; and in monkeys number 2, 4, and 6 (Group 2), the virus (1x10(8) particles) was injected at 10 days after laser coagulation. In monkey number 7, a blank control injection was performed. In monkeys number 1 and 2, virus without RNAi sequence was used; in monkeys number 3 and 4, virus with nonspecific RNAi sequence was used; and in monkeys 5 and 6, LV-GFP-VEGFi1 was used. In monkey number 5, at 23 days after laser treatment, no obvious INV was observed, while fluorescein angiography of the iris revealed high fluorescence at the margin of pupil and point posterior synechiae. At 50 days after laser treatment, only a slight ectropion uvea was found. However, in the other eyes, obvious INV or hyphema was observed. The densities of new iridic vessels all significantly varied: between monkey number 5 and number 3 (36.01+/-4.49/mm(2) versus 48.68+/-9.30/mm(2), p=0.025), between monkey number 3 and monkey number 7 (48.68+/-9.30/mm(2) versus 74.38+/-9.23/mm(2), p=0.002), and between monkey number 5 and number 7 (36.01+/-4.49/mm(2) versus 74.38+/-9.23/mm(2), p<0.001). Lentivirus-mediated RNAi of VEGF may be a new strategy to treat iris neovascularization, while further studies are needed to investigate the long-term effect.

  11. Effect of lentiviruses carrying enhanced green fluorescent protein injected into the scala media through a cochleostomy in rats.

    Science.gov (United States)

    Wei, Yan; Fu, Yong; Liu, Shaosheng; Xia, Guihua; Pan, Song

    2013-01-01

    The purposes of the current study were to assess the feasibility of post-auricular microinjection of lentiviruses carrying enhanced green fluorescent protein (EGFP) into the scala media through cochleostomies in rats, determine the expression of viral gene in the cochlea, and record the post-operative changes in the number and auditory function of cochlear hair cells (HCs). Healthy rats were randomly divided into two groups. The left ears of the animals in group I were injected with lentivirus carrying EGFP (n=10) via scala media lateral wall cochleostomies, and the left ears of the animals in group II were similarly injected with artificial endolymph (n=10). Prior to and 30 days post-injection, auditory function was assessed with click-auditory brainstem response (ABR) testing, EGFP expression was determined with cochlear frozen sections under fluorescence microscopy, and survival of HCs was estimated based on whole mount preparations. Thirty days after surgery, click-ABR testing revealed that there were significant differences in the auditory function, EGFP expression, and survival of HCs in the left ears before and after surgery in the same rats from each group. In group I, EGFP was noted in the strial marginal cells of the scala media, the organ of Corti, spiral nerves, and spiral ganglion cells. Lentiviruses were successfully introduced into the scala media through cochleostomies in rats, and the EGFP reporter gene was efficiently expressed in the organ of Corti, spiral nerves, and spiral ganglion cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. [Construction and selection of effective mouse Smad6 recombinant lenti-virus interference vectors].

    Science.gov (United States)

    Yu, Jing; Qi, Mengchun; Deng, Jiupeng; Liu, Gang; Chen, Huaiqing

    2010-10-01

    This experiment was designed to construct mouse Smad6 recombinant RNA interference vectors and determine their interference effects on bone marrow mesenchymal stem cells (BMSCs). Three recombinant Smad6 RNA interference vectors were constructed by molecular clone techniques with a lenti-virus vector expressing green fluorescent protein (GFP), and the correctness of recombinant vectors was verified by DNA sequencing. Mouse BMSCs were used for transfection experiments and BMP-2 was in use for osteogenic induction of MSCs. The transfection efficiency of recombinant vectors was examined by Laser confocal scanning microscope and the interference effect of recombinant vectors on Smad6 gene expression was determined by real-time RT-PCR and Western blot, respectively. Three Smad6 recombinant RNA interference vectors were successfully constructed and their correctness was proved by DNA sequencing. After transfection, GFPs were effectively expressed in MSCs and all of three recombinant vectors gained high transfection efficiency (> 95%). Both real-time PCR and Western blot examination indicated that among three recombinant vectors, No. 2 Svector had the best interference effect and the interference effect was nearly 91% at protein level. In conclusion, Mouse recombinant Smad6 RNA interference (RNAi) vector was successfully constructed and it provided an effective tool for further studies on BMP signal pathways.

  13. Development of a replication-competent lentivirus assay for dendritic cell-targeting lentiviral vectors

    Directory of Open Access Journals (Sweden)

    Daniel C Farley

    Full Text Available It is a current regulatory requirement to demonstrate absence of detectable replication-competent lentivirus (RCL in lentiviral vector products prior to use in clinical trials. Immune Design previously described an HIV-1-based integration-deficient lentiviral vector for use in cancer immunotherapy (VP02. VP02 is enveloped with E1001, a modified Sindbis virus glycoprotein which targets dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN expressed on dendritic cells in vivo. Vector enveloped with E1001 does not transduce T-cell lines used in standard HIV-1-based RCL assays, making current RCL testing formats unsuitable for testing VP02. We therefore developed a novel assay to test for RCL in clinical lots of VP02. This assay, which utilizes a murine leukemia positive control virus and a 293F cell line expressing the E1001 receptor DC-SIGN, meets a series of evaluation criteria defined in collaboration with US regulatory authorities and demonstrates the ability of the assay format to amplify and detect a hypothetical RCL derived from VP02 vector components. This assay was qualified and used to test six independent GMP production lots of VP02, in which no RCL was detected. We propose that the evaluation criteria used to rationally design this novel method should be considered when developing an RCL assay for any lentiviral vector.

  14. Apoptotic block in colon cancer cells may be rectified by lentivirus mediated overexpression of caspase-9.

    Science.gov (United States)

    Xu, D; Wang, C; Shen, X; Yu, Y; Rui, Y; Zhang, D; Zhou, Z

    2013-12-01

    At present, the inhibition of apoptosis during pathogenesis of colorectal cancer is widely recognized while the role of caspase-9 in this process remains controversial. We aimed to investigate the differential expression of caspase-9 and evaluate the therapeutic potential of expression intervention in this study. We first examined the different expression of caspase-9 in normal colon mucosa, adenoma and cancer, investigating the relationship between its expression and clinico-pathological characteristics. Secondly, overexpression of caspase-9 was established in colon cancer cell lines by lentivirus infection to study the changes in growth, proliferation and apoptosis. Compared with normal colon mucosa, the expression of caspase-9 was higher in adenoma while lower in cancer both at mRNA and protein level (P expression is more common in poorly differentiated cancers (P expression of caspase-9, poorer colony formation and slower cell proliferation. In terms of apoptosis related indicators, caspase-9 overexpression leads to higher apoptosis rate and GO/G1 arrest, while up-regulating the expression of caspase-3 (P expression from colon mucosa, adenoma to cancer suggested it may be involved in the carcinogenesis of colon cancer. The overexpression of caspase-9 exhibits an inhibitory role in cancer growth and proliferation while promoting apoptosis. However, a non-apoptotic role of caspase-9 facilitating differentiation was also implied.

  15. Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites

    Science.gov (United States)

    2010-01-01

    Background Bile salts are the major end-metabolites of cholesterol and are also important in lipid and protein digestion and in influencing the intestinal microflora. We greatly extend prior surveys of bile salt diversity in both reptiles and mammals, including analysis of 8,000 year old human coprolites and coprolites from the extinct Shasta ground sloth (Nothrotherium shastense). Results While there is significant variation of bile salts across species, bile salt profiles are generally stable within families and often within orders of reptiles and mammals, and do not directly correlate with differences in diet. The variation of bile salts generally accords with current molecular phylogenies of reptiles and mammals, including more recent groupings of squamate reptiles. For mammals, the most unusual finding was that the Paenungulates (elephants, manatees, and the rock hyrax) have a very different bile salt profile from the Rufous sengi and South American aardvark, two other mammals classified with Paenungulates in the cohort Afrotheria in molecular phylogenies. Analyses of the approximately 8,000 year old human coprolites yielded a bile salt profile very similar to that found in modern human feces. Analysis of the Shasta ground sloth coprolites (approximately 12,000 years old) showed the predominant presence of glycine-conjugated bile acids, similar to analyses of bile and feces of living sloths, in addition to a complex mixture of plant sterols and stanols expected from an herbivorous diet. Conclusions The bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution, with some bile salt modifications only found within single groups such as marsupials. Analysis of the evolution of bile salt structures in different species provides a potentially rich model system for the evolution of a complex biochemical pathway in vertebrates. Our results also demonstrate the stability of bile salts in coprolites preserved in arid climates

  16. Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites

    Directory of Open Access Journals (Sweden)

    Hofmann Alan F

    2010-05-01

    Full Text Available Abstract Background Bile salts are the major end-metabolites of cholesterol and are also important in lipid and protein digestion and in influencing the intestinal microflora. We greatly extend prior surveys of bile salt diversity in both reptiles and mammals, including analysis of 8,000 year old human coprolites and coprolites from the extinct Shasta ground sloth (Nothrotherium shastense. Results While there is significant variation of bile salts across species, bile salt profiles are generally stable within families and often within orders of reptiles and mammals, and do not directly correlate with differences in diet. The variation of bile salts generally accords with current molecular phylogenies of reptiles and mammals, including more recent groupings of squamate reptiles. For mammals, the most unusual finding was that the Paenungulates (elephants, manatees, and the rock hyrax have a very different bile salt profile from the Rufous sengi and South American aardvark, two other mammals classified with Paenungulates in the cohort Afrotheria in molecular phylogenies. Analyses of the approximately 8,000 year old human coprolites yielded a bile salt profile very similar to that found in modern human feces. Analysis of the Shasta ground sloth coprolites (approximately 12,000 years old showed the predominant presence of glycine-conjugated bile acids, similar to analyses of bile and feces of living sloths, in addition to a complex mixture of plant sterols and stanols expected from an herbivorous diet. Conclusions The bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution, with some bile salt modifications only found within single groups such as marsupials. Analysis of the evolution of bile salt structures in different species provides a potentially rich model system for the evolution of a complex biochemical pathway in vertebrates. Our results also demonstrate the stability of bile salts in coprolites

  17. Genetic Testing for TMEM154 Mutations Associated with Lentivirus Susceptibility in Sheep

    Science.gov (United States)

    Petrik, Dustin T.; Simpson, Barry; Kijas, James W.; Clawson, Michael L.; Chitko-McKown, Carol G.; Harhay, Gregory P.; Leymaster, Kreg A.

    2013-01-01

    In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal’s health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E) at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V) and the extracellular domains (E31Q, I74F, and I102T) of TMEM154. A matrix-assisted laser desorption/ionization–time-of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes). The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks. PMID:23408992

  18. Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.

    Directory of Open Access Journals (Sweden)

    Michael P Heaton

    Full Text Available In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV in the U.S., and Visna/Maedi virus (VMV elsewhere, these viruses reduce an animal's health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154 has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V and the extracellular domains (E31Q, I74F, and I102T of TMEM154. A matrix-assisted laser desorption/ionization-time-of flight mass spectrometry (MALDI-TOF MS assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes. The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks.

  19. Study of compartmentalization in the visna clinical form of small ruminant lentivirus infection in sheep

    Directory of Open Access Journals (Sweden)

    Ramírez Hugo

    2012-01-01

    Full Text Available Abstract Background A central nervous system (CNS disease outbreak caused by small ruminant lentiviruses (SRLV has triggered interest in Spain due to the rapid onset of clinical signs and relevant production losses. In a previous study on this outbreak, the role of LTR in tropism was unclear and env encoded sequences, likely involved in tropism, were not investigated. This study aimed to analyze heterogeneity of SRLV Env regions - TM amino terminal and SU V4, C4 and V5 segments - in order to assess virus compartmentalization in CNS. Results Eight Visna (neurologically affected sheep of the outbreak were used. Of the 350 clones obtained after PCR amplification, 142 corresponded to CNS samples (spinal cord and choroid plexus and the remaining to mammary gland, blood cells, bronchoalveolar lavage cells and/or lung. The diversity of the env sequences from CNS was 11.1-16.1% between animals and 0.35-11.6% within each animal, except in one animal presenting two sequence types (30% diversity in the CNS (one grouping with those of the outbreak, indicative of CNS virus sequence heterogeneity. Outbreak sequences were of genotype A, clustering per animal and compartmentalizing in the animal tissues. No CNS specific signature patterns were found. Conclusions Bayesian approach inferences suggested that proviruses from broncoalveolar lavage cells and peripheral blood mononuclear cells represented the common ancestors (infecting viruses in the animal and that neuroinvasion in the outbreak involved microevolution after initial infection with an A-type strain. This study demonstrates virus compartmentalization in the CNS and other body tissues in sheep presenting the neurological form of SRLV infection.

  20. Factors that contribute to biomarker responses in humans including a study in individuals taking Vitamin C supplementation.

    Science.gov (United States)

    Anderson, D

    2001-09-01

    It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and in the environment. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure-related problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. However, for interpretation of responses, the issue of confounding factors must be addressed. There are endogenous confounding factors, such as age, gender, and genetic make-up and exogenous ones, including lifestyle habits (smoking, drinking, etc.) There are biomarkers of exposure, effect/response and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects on cytogenetic damage and ras oncoproteins will be considered in relation to workers exposed to vinyl chloride and petroleum emissions and to volunteers taking Vitamin C supplementation. Smoking history, exposure and duration of employment affected the worker studies. For petroleum emissions, so did gender and season of exposure. For the non-smoking volunteer Vitamin C supplementation study, cholesterol levels, plasma Vitamin C levels, lipid peroxidation products and DNA damage in the Comet assay were also measured. Gender affected differences in Vitamin C levels, antioxidant capacity and the number of chromosome aberrations induced by bleomycin challenge in vitro. The results were the same for both high and low cholesterol subjects. The relationship between biomarkers and the various factors which

  1. Radiological protection of the environment, including non-human species-views from the global nuclear industry

    International Nuclear Information System (INIS)

    Saint-Pierre, S.; RPWG

    2008-01-01

    This paper updates the WNA key messages on the RP of the environment. This paper shows that the chronology of views (2000-2008) leads to a recognition that the current RP system has provided adequate protection of people and of the environment. In early 2000s, doubts were raised on the adequacy of the RP system. Next (2002-2005), the international community forged the view that the current RP system has in practice provided appropriate standards of environmental protection, but also acknowledged that the system needs further development to fill a 'conceptual gap'. In 2005, the IAEA plan of activities on the RP of the environment formalized international developments and conditioned the future revision (if any) of current standards. During 2006-2008, ICRP issued new guidance on RP of non-human species which offers little on an assessment framework of practical use and on a compelling case for such assessments. This guidance, based on the new ICRP concept of Reference Animals and Plants, falls short in terms of environmental protection approach. A milestone study on the RP of non-human species is the SENES independent overview (2007) which 'confirmed that both people and nature have been adequately protected from radioactive releases from all kinds of nuclear sites, old and new'. This overview covers case studies for nuclear sites including some that had experienced major accidents. It derives that the earlier acknowledgement on the 'conceptual gap' appears no longer valid or at the very least, that the gap (if any) is extremely small. The RP of the environment is part of the on-going revision of the current IAEA Basic Safety Standards (BSS). We emphasize that the recently published BSS draft 1.0 in July 2008 covers (with adequacy) RP of the environment through general provisions (free of provisions to non-human species) on the assessment of environmental impact. (author)

  2. In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Che-Ming Liu

    Full Text Available Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene expression by lentivirus-delivered small hairpin RNA (shRNA significantly inhibited proliferation of human prostate cancer cell lines and blocked tumor growth in a murine model of prostate cancer bone metastasis. Cell cycle studies confirmed an increase in the G1-phase and decrease in the S-phase population of cancer cells under starvation stress conditions, which correlated with elevated intracellular superoxide levels. Microarray data showed significantly decreased levels of regenerating islet-derived family member 4 (REG4 expression in prostate cancer cells with knockdown of ADAM9 gene expression. This REG4 downregulation also resulted in induction of expression of p21(Cip1/WAF1, which negatively regulates cyclin D1 and blocks the G1/S transition. Our data reveal a novel molecular mechanism of ADAM9 in the regulation of prostate cancer cell proliferation, and suggests a combined modality of ADAM9 shRNA gene therapy and cytotoxic agents for hormone refractory and bone metastatic prostate cancer.

  3. Diallylthiosulfinate (Allicin), a Volatile Antimicrobial from Garlic (Allium sativum), Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a Vapor.

    Science.gov (United States)

    Reiter, Jana; Levina, Natalja; van der Linden, Mark; Gruhlke, Martin; Martin, Christian; Slusarenko, Alan J

    2017-10-12

    Garlic ( Allium sativum ) has potent antimicrobial activity due to allicin (diallylthiosulfinate) synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98% pure) by oxidation of diallyl disulfide by H₂O₂ using formic acid as a catalyst and the growth inhibitory effect of allicin vapor and allicin in solution to clinical isolates of lung pathogenic bacteria from the genera Pseudomonas , Streptococcus , and Staphylococcus , including multi-drug resistant (MDR) strains, was demonstrated. Minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) were determined and compared to clinical antibiotics using standard European Committee on Antimicrobial Susceptibility Testing (EUCAST) procedures. The cytotoxicity of allicin to human lung and colon epithelial and murine fibroblast cells was tested in vitro and shown to be ameliorated by glutathione (GSH). Similarly, the sensitivity of rat precision-cut lung slices (PCLS) to allicin was decreased by raising the [GSH] to the approximate blood plasma level of 1 mM. Because allicin inhibited bacterial growth as a vapor, it could be used to combat bacterial lung infections via direct inhalation. Since there are no volatile antibiotics available to treat pulmonary infections, allicin, particularly at sublethal doses in combination with oral antibiotics, could make a valuable addition to currently available treatments.

  4. “An Environment Built to Include Rather than Exclude Me”: Creating Inclusive Environments for Human Well-Being

    Directory of Open Access Journals (Sweden)

    Natasha A. Layton

    2015-09-01

    Full Text Available Contemporary discourses which challenge the notion of health as the “absence of disease” are prompting changes in health policy and practice. People with disability have been influential in progressing our understanding of the impact of contextual factors in individual and population health, highlighting the impact of environmental factors on functioning and inclusion. The World Health Organization’s (WHO more holistic definition of health as “wellbeing” is now applied in frameworks and legislation, and has long been understood in occupational therapy theory. In practice, however, occupational therapists and other professionals often address only local and individual environmental factors to promote wellbeing, within systems and societies that limit equity in population health and restrict inclusion in communities. This paper presents an in-depth analysis of the supports and accommodations identified by a cohort of individuals (n-100 living with disability. A range of environmental facilitators and barriers were identified in peoples’ experience of “inclusive community environs” and found to influence inclusion and wellbeing. The roles and responsibilities of individuals, professionals, and society to enact change in environments are discussed in light of these findings. Recommendations include a focus on the subjective experience of environments, and application of theory from human rights and inclusive economics to address the multiple dimensions and levels of environments in working towards inclusion and wellbeing.

  5. Diallylthiosulfinate (Allicin, a Volatile Antimicrobial from Garlic (Allium sativum, Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a Vapor

    Directory of Open Access Journals (Sweden)

    Jana Reiter

    2017-10-01

    Full Text Available Garlic (Allium sativum has potent antimicrobial activity due to allicin (diallylthiosulfinate synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98% pure by oxidation of diallyl disulfide by H2O2 using formic acid as a catalyst and the growth inhibitory effect of allicin vapor and allicin in solution to clinical isolates of lung pathogenic bacteria from the genera Pseudomonas, Streptococcus, and Staphylococcus, including multi-drug resistant (MDR strains, was demonstrated. Minimal inhibitory (MIC and minimal bactericidal concentrations (MBC were determined and compared to clinical antibiotics using standard European Committee on Antimicrobial Susceptibility Testing (EUCAST procedures. The cytotoxicity of allicin to human lung and colon epithelial and murine fibroblast cells was tested in vitro and shown to be ameliorated by glutathione (GSH. Similarly, the sensitivity of rat precision-cut lung slices (PCLS to allicin was decreased by raising the [GSH] to the approximate blood plasma level of 1 mM. Because allicin inhibited bacterial growth as a vapor, it could be used to combat bacterial lung infections via direct inhalation. Since there are no volatile antibiotics available to treat pulmonary infections, allicin, particularly at sublethal doses in combination with oral antibiotics, could make a valuable addition to currently available treatments.

  6. Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection.

    Science.gov (United States)

    Axelsson, Lars; Nyman, Jan; Haugen-Cange, Hedda; Bove, Mogens; Johansson, Leif; De Lara, Shahin; Kovács, Anikó; Hammerlid, Eva

    2017-06-10

    Head and neck cancer of unknown primary (HNCUP) is rare and prospective studies are lacking. The impact of different prognostic factors such as age and N stage is not completely known, the optimal treatment is not yet established, and the reported survival rates vary. In the last decade, human papilloma virus (HPV) has been identified as a common cause of and important prognostic factor in oropharyngeal cancer, and there is now growing interest in the importance of HPV for HNCUP. The aim of the present study on curatively treated HNCUP was to investigate the prognostic importance of different factors, including HPV status, treatment, and overall survival. A search for HNCUP was performed in the Swedish Cancer Registry, Western health district, between the years 1992-2009. The medical records were reviewed, and only patients with squamous cell carcinoma or undifferentiated carcinoma treated with curative intent were included. The tumor specimens were retrospectively analyzed for HPV with p16 immunostaining. Sixty-eight patients were included. The mean age was 59 years. The majority were males, and had N2 tumors. Sixty-nine percent of the tumors were HPV positive using p16 staining. Patients who were older than 70 years, patients with N3-stage tumors, and patients with tumors that were p16 negative had a significantly worse prognosis. The overall 5-year survival rate for patients with p16-positive tumors was 88% vs 61% for p16-negative tumors. Treatment with neck dissection and postoperative radiation or (chemo) radiation had 81 and 88% 5-year survival rates, respectively. The overall and disease-free 5-year survival rates for all patients in the study were 82 and 74%. Curatively treated HNCUP had good survival. HPV infection was common. Independent prognostic factors for survival were age over 70 years, HPV status and N3 stage. We recommend that HPV analysis should be performed routinely for HNCUP. Treatment with neck dissection and postoperative radiation or

  7. A call to include medical humanities in the curriculum of colleges of osteopathic medicine and in applicant selection.

    Science.gov (United States)

    Hoff, Gary; Hirsch, Norma J; Means, J Jeffrey; Streyffeler, Lisa

    2014-10-01

    Medicine stands at a crossroad. Disruptive physician behavior has increased, and patient satisfaction has decreased. A growing body of knowledge demonstrates that the medical humanities assist in the creation of compassionate, resilient physicians. Incorporating medical humanities into the medical school curriculum promotes the development of compassionate, culturally sensitive physicians, and also encourages the development of resilience in health care professionals at a time when internal and external pressures on physicians are increasing. © 2014 The American Osteopathic Association.

  8. Preliminary Data on the Safety of Phytoene- and Phytofluene-Rich Products for Human Use including Topical Application

    Directory of Open Access Journals (Sweden)

    Fabien Havas

    2018-01-01

    Full Text Available The colorless carotenoids phytoene and phytofluene are comparatively understudied compounds found in common foods (e.g., tomatoes and in human plasma, internal tissues, and skin. Being naturally present in common foods, their intake at dietary levels is not expected to present a safety concern. However, since the interest in these compounds in the context of many applications is expanding, it is important to conduct studies aimed at assessing their safety. We present here results of in vitro cytotoxicity and genotoxicity studies, revealing no significant cytotoxic or genotoxic potential and of short- and long-term human in vivo skin compatibility studies with phytoene- and phytofluene-rich tomato and Dunaliella salina alga extracts, showing a lack of irritancy or sensitization reactions. These results support the safe use of phytoene- and phytofluene-rich products in human topical applications.

  9. Slit-scanning technique using standard cell sorter instruments for analyzing and sorting nonacrocentric human chromosomes, including small ones

    NARCIS (Netherlands)

    Rens, W.; van Oven, C. H.; Stap, J.; Jakobs, M. E.; Aten, J. A.

    1994-01-01

    We have investigated the performance of two types of standard flow cell sorter instruments, a System 50 Cytofluorograph and a FACSTar PLUS cell sorter, for the on-line centromeric index (CI) analysis of human chromosomes. To optimize the results, we improved the detection efficiency for centromeres

  10. Including the Other: Regulation of the Human Rights of Mobile Students in a Nation-Bound World

    Science.gov (United States)

    Marginson, Simon

    2012-01-01

    The world's three million cross-border international students are located in a "gray zone" of regulation with incomplete human rights, security and capabilities. Like other mobile persons such as short-term business and labour entrants, and refugees, students located on foreign soil do not enjoy the same protections and entitlements as…

  11. Identification of a novel gene family that includes the interferon-inducible human genes 6–16 and ISG12

    Directory of Open Access Journals (Sweden)

    Parker Nadeene

    2004-01-01

    Full Text Available Abstract Background The human 6–16 and ISG12 genes are transcriptionally upregulated in a variety of cell types in response to type I interferon (IFN. The predicted products of these genes are small (12.9 and 11.5 kDa respectively, hydrophobic proteins that share 36% overall amino acid identity. Gene disruption and over-expression studies have so far failed to reveal any biochemical or cellular roles for these proteins. Results We have used in silico analyses to identify a novel family of genes (the ISG12 gene family related to both the human 6–16 and ISG12 genes. Each ISG12 family member codes for a small hydrophobic protein containing a conserved ~80 amino-acid motif (the ISG12 motif. So far we have detected 46 family members in 25 organisms, ranging from unicellular eukaryotes to humans. Humans have four ISG12 genes: the 6–16 gene at chromosome 1p35 and three genes (ISG12(a, ISG12(b and ISG12(c clustered at chromosome 14q32. Mice have three family members (ISG12(a, ISG12(b1 and ISG12(b2 clustered at chromosome 12F1 (syntenic with human chromosome 14q32. There does not appear to be a murine 6–16 gene. On the basis of phylogenetic analyses, genomic organisation and intron-alignments we suggest that this family has arisen through divergent inter- and intra-chromosomal gene duplication events. The transcripts from human and mouse genes are detectable, all but two (human ISG12(b and ISG12(c being upregulated in response to type I IFN in the cell lines tested. Conclusions Members of the eukaryotic ISG12 gene family encode a small hydrophobic protein with at least one copy of a newly defined motif of ~80 amino-acids (the ISG12 motif. In higher eukaryotes, many of the genes have acquired a responsiveness to type I IFN during evolution suggesting that a role in resisting cellular or environmental stress may be a unifying property of all family members. Analysis of gene-function in higher eukaryotes is complicated by the possibility of

  12. Bicistronic lentiviruses containing a viral 2A cleavage sequence reliably co-express two proteins and restore vision to an animal model of LCA1.

    Directory of Open Access Journals (Sweden)

    Jonathan D Verrier

    Full Text Available The disease processes underlying inherited retinal disease are complex and are not completely understood. Many of the corrective gene therapies designed to treat diseases linked to mutations in genes specifically expressed in photoreceptor cells restore function to these cells but fail to stop progression of the disease. There is growing consensus that effective treatments for these diseases will require delivery of multiple therapeutic proteins that will be selected to treat specific aspects of the disease process. The purpose of this study was to design a lentiviral transgene that reliably expresses all of the proteins it encodes and does so in a consistent manner among infected cells. We show, using both in vitro and in vivo analyses, that bicistronic lentiviral transgenes encoding two fluorescent proteins fused to a viral 2A-like cleavage peptide meet these expression criteria. To determine if this transgene design is suitable for therapeutic applications, we replaced one of the fluorescent protein genes with the gene encoding guanylate cyclase-1 (GC1 and delivered lentivirus carrying this transgene to the retinas of the GUCY1*B avian model of Leber congenital amaurosis-1 (LCA1. GUCY1*B chickens carry a null mutation in the GC1 gene that disrupts photoreceptor function and causes blindness at hatching, a phenotype that closely matches that observed in humans with LCA1. We found that treatment of these animals with the 2A lentivector encoding GC1 restored vision to these animals as evidenced by the presence of optokinetic reflexes. We conclude that 2A-like peptides, with proper optimization, can be successfully incorporated into therapeutic vectors designed to deliver multiple proteins to neural retinal. These results highlight the potential of this vector design to serve as a platform for the development of combination therapies designed to enhance or prolong the benefits of corrective gene therapies.

  13. Biomechanical analysis of a salt-modified polyvinyl alcohol hydrogel for knee meniscus applications, including comparison with human donor samples.

    Science.gov (United States)

    Hayes, Jennifer C; Curley, Colin; Tierney, Paul; Kennedy, James E

    2016-03-01

    The primary objective of this research was the biomechanical analysis of a salt-modified polyvinyl alcohol hydrogel, in order to assess its potential for use as an artificial meniscal implant. Aqueous polyvinyl alcohol (PVA) was treated with a sodium sulphate (Na2SO4) solution to precipitate out the polyvinyl alcohol resulting in a pliable hydrogel. The freeze-thaw process, a strictly physical method of crosslinking, was employed to crosslink the hydrogel. Development of a meniscal shaped mould and sample housing unit allowed the production of meniscal shaped hydrogels for direct comparison to human meniscal tissue. Results obtained show that compressive responses were slightly higher in PVA/Na2SO4 menisci, displaying maximum compressive loads of 2472N, 2482N and 2476N for samples having undergone 1, 3 and 5 freeze-thaw cycles respectively. When compared to the human meniscal tissue tested under the same conditions, an average maximum load of 2467.5N was observed. This suggests that the PVA/Na2SO4 menisci are mechanically comparable to the human meniscus. Biocompatibility analysis of PVA/Na2SO4 hydrogels revealed no acute cytotoxicity. The work described herein has innovative potential in load bearing applications, specifically as an alternative to meniscectomy as replacement of critically damaged meniscal tissue in the knee joint where repair is not viable. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Neuroprotective effects of lentivirus-mediated cystathionine-beta-synthase overexpression against 6-OHDA-induced parkinson's disease rats.

    Science.gov (United States)

    Yin, Wei-Lan; Yin, Wei-Guo; Huang, Bai-Sheng; Wu, Li-Xiang

    2017-09-14

    Parkinson's disease (PD) is age-related neurodegenerative disorder by a progressive loss of dopaminergic(DA) neurons in the substantia nigra (SN) and striatum, which is at least partly associated with α-synuclein protein accumulation in these neurons. Hydrogen sulfide (H 2 S) plays an important role in the nervous system. Studies have shown that H 2 S has a protective effect on PD. However, as a kind of gas molecules, H 2 S is lively, volatile, and not conducive to scientific research and clinical application. Cystathionine-beta-synthase(CBS) is the main enzymes of synthesis of H 2 S in the brain. In order to examine the neuroprotective effects of CBS on PD, we detected the effects of CBS overexpression on 6-Hydroxydopamine (6-OHDA)-lesioned PD rats using lentivirus-mediated gene transfection techniques. In the injured SN of 6-OHDA-induced PD rats, the CBS expression and the endogenous H 2 S level markedly decreased, while administration of lentivirus-mediated CBS overexpression increased the CBS expression and the endogenous H 2 S production.CBS overexpression dramatically reversed apomorphine-induced rotation of the 6-OHDA model rats, decreased the number of TUNEL-positive neurons and the loss of the nigral DA neurons,specifically inhibited 6-OHDA-induced oxidase stress injury, and down-regulated the expression of α-synuclein(α-SYN) in the injured SN. NaHS (an H 2 S donor) had similar effects to CBS overexpression, while Amino-oxyacetate(AOAA, a CBS inhibitor) had opposite effects on PD rats. In summary, we demonstrated that CBS overexpression was able to provide neuroprotective on PD rats and improving the expression of CBS may be a potential therapeutic method for PD. Copyright © 2017. Published by Elsevier B.V.

  15. The human genome and sport, including epigenetics and athleticogenomics: a brief look at a rapidly changing field.

    Science.gov (United States)

    Sharp, N C Craig

    2008-09-01

    Since Hugh Montgomery discovered the first of what are now nearly 200 "fitness genes", together with rapid advances in human gene therapy, there is now a real prospect of the use of genes, genetic elements, and/or cells that have the capacity to enhance athletic performance (to paraphrase the World Anti-Doping Agency's definition of gene doping). This overview covers the main areas of interface between genetics and sport, attempts to provide a context against which gene doping may be viewed, and suggests a futuristic legitimate use of genomic (and possibly epigenetic) information in sport.

  16. PREVALENCE OF SOME HELMINTHS IN RODENTS CAPTURED FROM DIFFERENT CITY STRUCTURES INCLUDING POULTRY FARMS AND HUMAN POPULATION OF FAISALABAD, PAKISTAN

    Directory of Open Access Journals (Sweden)

    A. RAFIQUE, S. A. RANA, H. A. KHAN AND A. SOHAIL1

    2009-07-01

    Full Text Available The aim of the present study was to investigate prevalence of zoonotic helminths from human, Rattus rattus (R. rattus, Rattus norvegicus (R. norvegicus and Mus musculus of eight different structures, namely grain shops in grain market, departmental stores, railway godowns, food processing plants (bakeries, poultry farms, houses in kachi-abadies, houses in departmental colonies and posh residences and banglows in Faisalabad city. All the structures were sampled for 2 months each and completed in 16 months. Highest prevalence (70% of Vsmpirolepis spp. was observed in R. rattus sampled from poultry farms, which was significantly higher (P<0.05 than the prevalence of all the helminths recovered from other structures. Hymenolepis nana (H. nana was observed in 60% of the sampled Mus musculus collected from kachi-abadies, which was significantly higher (P<0.05 than all other structures studies for H. nana, except R. rattus from kachi-abadies (55% and R. norvegicus from grain shops in grain market (55%. The rodent’s endo-parasites viz., Hymenolepis nana, Teania taenaeformis, Entrobius spps and Trichuiris spps observed in R. rattus, R. norvegicus and M. musculus at different percentages were also recorded in human stool samples with an incidence of 48, 21, 76 and 10%, respectively.

  17. Mercury stable isotope fractionation in a tropical ecosystem including human hair: New insights for an isotope balance

    Science.gov (United States)

    Laffont, Laure; Sonke, Jeroen; Maurice, Laurence; Behra, Philippe

    2010-05-01

    Mercury contamination is an environmental problem in the Amazon basin still relevant today as impacts on human health are poorly studied. In Bolivia, indigenous people have elevated methylmercury concentrations (between 2719 and 23701 ng.g-1) in their hair. This highly toxic molecule is formed after methylation of inorganic Hg released by chemical and physical weathering and from human activities. The aim of our study is to propose a first isotope balance in a Bolivian Amazon ecosystem, through variations in Hg isotopic compositions. The discovery of mass-independent fracionation (MIF) of odd-isotopes in our organic samples (fish and human hair) opened a new way of research in tracing the sources and the processes involved in the cycle of Hg. Four types of samples are studied: liquid Hg0 from gold mining, sediment samples, fish coming from the Beni River basin (from the main channel and an associated floodplain lake) and hair from gold miners and fish-eating native populations. Hg isotopic compositions were analyzed on a Thermo-Finnigan Neptune MC-ICP-MS at the LMTG after sample digestion by HCl/HNO3 or by H2O2/HNO3 for fish samples, at 120°C. The δ202Hg values (relative to NIST 3133) are signicantly different with respect to the external precision on UM-Almaden#2 of 0.18 ‰ (2σ, n = 42): -0.34 ± 0.02 ‰ for liquid mercury, between -1.33 and -0.81 ‰ for bottom and floodplain sediments (n=18), between -0.87 and 2.22 ‰ for miners hair (n=26), +1.29 ± 0.41 ‰ for native hair (n=13) and between -0.91 and -0.21 ‰ for fish samples (n=53). A large mass-independent isotope fractionation (MIF) was observed for odd isotope ratios in all hair samples and fish samples whereas weak anomalies were measured for sediment samples: - ∆199Hg anomaly: -0.12 to -0.04 ‰ for sediment, -0.22 to +0.63 ‰ for fish samples and +0.13 to +1.63 ‰ for hair - ∆201Hg anomaly: -0.12 to -0.02 ‰ for sediment, -0.21 to +0.43 ‰ for fish samples and +0.06 to +1.25 ‰ for hair

  18. A collection of annotated and harmonized human breast cancer transcriptome datasets, including immunologic classification [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jessica Roelands

    2018-02-01

    Full Text Available The increased application of high-throughput approaches in translational research has expanded the number of publicly available data repositories. Gathering additional valuable information contained in the datasets represents a crucial opportunity in the biomedical field. To facilitate and stimulate utilization of these datasets, we have recently developed an interactive data browsing and visualization web application, the Gene Expression Browser (GXB. In this note, we describe a curated compendium of 13 public datasets on human breast cancer, representing a total of 2142 transcriptome profiles. We classified the samples according to different immune based classification systems and integrated this information into the datasets. Annotated and harmonized datasets were uploaded to GXB. Study samples were categorized in different groups based on their immunologic tumor response profiles, intrinsic molecular subtypes and multiple clinical parameters. Ranked gene lists were generated based on relevant group comparisons. In this data note, we demonstrate the utility of GXB to evaluate the expression of a gene of interest, find differential gene expression between groups and investigate potential associations between variables with a specific focus on immunologic classification in breast cancer. This interactive resource is publicly available online at: http://breastcancer.gxbsidra.org/dm3/geneBrowser/list.

  19. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex

    Directory of Open Access Journals (Sweden)

    Gregory D. Scott

    2014-03-01

    Full Text Available Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl’s gyrus. In addition to reorganized auditory cortex (cross-modal plasticity, a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case, as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral versus perifoveal visual stimulation (11-15° vs. 2°-7° in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl’s gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl’s gyrus indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral versus perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory and multisensory and/or supramodal regions, such as posterior parietal cortex, frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal and multisensory regions, to altered visual processing in

  20. Assessment of a respiratory face mask for capturing air pollutants and pathogens including human influenza and rhinoviruses.

    Science.gov (United States)

    Zhou, S Steve; Lukula, Salimatu; Chiossone, Cory; Nims, Raymond W; Suchmann, Donna B; Ijaz, M Khalid

    2018-03-01

    Prevention of infection with airborne pathogens and exposure to airborne particulates and aerosols (environmental pollutants and allergens) can be facilitated through use of disposable face masks. The effectiveness of such masks for excluding pathogens and pollutants is dependent on the intrinsic ability of the masks to resist penetration by airborne contaminants. This study evaluated the relative contributions of a mask, valve, and Micro Ventilator on aerosol filtration efficiency of a new N95 respiratory face mask. The test mask was challenged, using standardized methods, with influenza A and rhinovirus type 14, bacteriophage ΦΧ174, Staphylococcus aureus ( S . aureus ), and model pollutants. The statistical significance of results obtained for different challenge microbial agents and for different mask configurations (masks with operational or nonoperational ventilation fans and masks with sealed Smart Valves) was assessed. The results demonstrate >99.7% efficiency of each test mask configuration for exclusion of influenza A virus, rhinovirus 14, and S . aureus and >99.3% efficiency for paraffin oil and sodium chloride (surrogates for PM 2.5 ). Statistically significant differences in effectiveness of the different mask configurations were not identified. The efficiencies of the masks for excluding smaller-size (i.e., rhinovirus and bacteriophage ΦΧ174) vs. larger-size microbial agents (influenza virus, S . aureus ) were not significantly different. The masks, with or without features intended for enhancing comfort, provide protection against both small- and large-size pathogens. Importantly, the mask appears to be highly efficient for filtration of pathogens, including influenza and rhinoviruses, as well as the fine particulates (PM 2.5 ) present in aerosols that represent a greater challenge for many types of dental and surgical masks. This renders this individual-use N95 respiratory mask an improvement over the former types of masks for protection against

  1. Serum levels of IGF-1 are related to human skin characteristics including the conspicuousness of facial pores.

    Science.gov (United States)

    Sugiyama-Nakagiri, Y; Naoe, A; Ohuchi, A; Kitahara, T

    2011-04-01

    Conspicuous facial pores are one type of serious aesthetic defects for many women. However, the mechanism(s) that underlie the conspicuousness of facial pores remains unclear. We previously characterized the epidermal architecture around facial pores that correlates with the appearance of those pores in various ethnic groups including Japanese. The goal of this study was to evaluate the possible relationships between facial pore size, the severity of impairment of epidermal architecture around facial pores and sebum output levels to investigate the possible role of IGF-1 in the pathogenesis of conspicuous facial pores. The subjects consisted of 38 healthy Japanese women (aged 22-41 years). IGF-1 was measured using immunoradiometric assay. Surface replicas were collected to compare pore sizes of cheek skin and horizontal cross-section images of cheek skin were obtained non-invasively from the same subjects using in vivo confocal laser scanning microscopy and the severity of impairment of epidermal architecture around facial pores was determined. The skin surface lipids of each subject were collected from their cheeks and lipid classes were determined using gas chromatography/flame ionization detection. The serum level of IGF-1 correlated significantly with total pore area (R = 0.36, P facial pores (R = 0.43, P pore area (R = 0.32, P facial skin characteristics including facial pore size and with the severity of impairment of epidermal architecture around facial pores. © 2010 The Authors. Journal compilation © 2010 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  2. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    Energy Technology Data Exchange (ETDEWEB)

    Malur, Anagha; Huizar, Isham [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Wells, Greg [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Barna, Barbara P. [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Malur, Achut G. [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Thomassen, Mary Jane, E-mail: thomassenm@ecu.edu [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by

  3. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    International Nuclear Information System (INIS)

    Malur, Anagha; Huizar, Isham; Wells, Greg; Barna, Barbara P.; Malur, Achut G.; Thomassen, Mary Jane

    2011-01-01

    Highlights: ► Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. ► Up-regulation of ABCG1 improves lung function. ► Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ) and the PPARγ-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte–macrophage colony stimulating factor (GM-CSF), an upregulator of PPARγ. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPARγ plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPARγ or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice

  4. Slowing the rate of loss of mineral wetlands on human dominated landscapes - Diversification of farmers markets to include carbon (Invited)

    Science.gov (United States)

    Creed, I. F.; Badiou, P.; Lobb, D.

    2013-12-01

    Canada is the fourth-largest exporter of agriculture and agri-food products in the world (exports valued at 28B), but instability of agriculture markets can make it difficult for farmers to cope with variability, and new mechanisms are needed for farmers to achieve economic stability. Capitalizing on carbon markets will help farmers achieve environmentally sustainable economic performance. In order to have a viable carbon market, governments and industries need to know what the carbon capital is and what potential there is for growth, and farmers need financial incentives that will not only allow them to conserve existing wetlands but that will also enable them to restore wetlands while making a living. In southern Ontario, farmers' needs to maximize the return on investment on marginal lands have resulted in loss of 70-90% of wetlands, making this region one of the most threatened region in terms of wetland degradation and loss in Canada. Our project establishes the role that mineral wetlands have in the net carbon balance by contributing insight into the potential benefits to carbon management provided by wetland restoration efforts in these highly degraded landscapes. The goal was to establish the magnitude of carbon offsets that could be achieved through wetland conservation (securing existing carbon stocks) and restoration (creating new carbon stocks). The experimental design was to focus on (1) small (0.2-2.0 ha) and (2) isolated (no inflow or outflow) mineral wetlands with the greatest restoration potential that included (3) a range of restoration ages (drained (0 yr), 3 yr, 6 yr, 12 yr, 20 yr, 35 yr, intact marshes) to capture potential changes in rates of carbon sequestration with restoration age of wetland. From each wetland, wetland soil carbon pools samples were collected at four positions: centre of wetland (open-water); emergent vegetation zone; wet meadow zone where flooding often occurs (i.e., high water mark); and upland where flooding rarely

  5. High water-stressed population estimated by world water resources assessment including human activities under SRES scenarios

    Science.gov (United States)

    Kiguchi, M.; Shen, Y.; Kanae, S.; Oki, T.

    2009-04-01

    In an argument of the reduction and the adaptation for the climate change, the evaluation of the influence by the climate change is important. When we argue in adaptation plan from a damage scale and balance with the cost, it is particularly important. Parry et al (2001) evaluated the risks in shortage of water, malaria, food, the risk of the coast flood by temperature function and clarified the level of critical climate change. According to their evaluation, the population to be affected by the shortage of water suddenly increases in the range where temperature increases from 1.5 to 2.0 degree in 2080s. They showed how much we need to reduce emissions in order to draw-down significantly the number at risk. This evaluation of critical climate change threats and targets of water shortage did not include the water withdrawal divided by water availability. Shen et al (2008a) estimated the water withdrawal of projection of future world water resources according to socio-economic driving factors predicted for scenarios A1b, A2, B1, and B2 of the Special Report on Emission Scenarios (SRES). However, these results were in function of not temperature but time. The assessment of the highly water-stressed population considered the socioeconomic development is necessary for a function of the temperature. Because of it is easy to understand to need to reduce emission. We present a multi-GCM analysis of the global and regional populations lived in highly water-stressed basin for a function of the temperature using the socioeconomic data and the outputs of GCMs. In scenario A2, the population increases gradually with warming. On the other hand, the future projection population in scenario A1b and B1 increase gradually until the temperature anomaly exceeds around from +1 to +1.5 degree. After that the population is almost constant. From Shen et al (2008b), we evaluated the HWSP and its ratio in the world with temperature function for scenarios A1B, A2, and B1 by the index of W

  6. Integron, Plasmid and Host Strain Characteristics of Escherichia coli from Humans and Food Included in the Norwegian Antimicrobial Resistance Monitoring Programs.

    Science.gov (United States)

    Sunde, Marianne; Simonsen, Gunnar Skov; Slettemeås, Jannice Schau; Böckerman, Inger; Norström, Madelaine

    2015-01-01

    Antimicrobial resistant Escherichia coli (n=331) isolates from humans with bloodstream infections were investigated for the presence of class 1 and class 2 integrons. The integron cassettes arrays were characterized and the findings were compared with data from similar investigations on resistant E. coli from meat and meat products (n=241) produced during the same time period. All isolates were obtained from the Norwegian monitoring programs for antimicrobial resistance in human pathogens and in the veterinary sector. Methods used included PCR, sequencing, conjugation experiments, plasmid replicon typing and subtyping, pulsed-field-gel-electrophoresis and serotyping. Integrons of class 1 and 2 occurred significantly more frequently among human isolates; 45.4% (95% CI: 39.9-50.9) than among isolates from meat; 18% (95% CI: 13.2 -23.3), (pfood source and from a human clinical sample highlights the possible role of meat as a source of resistance elements for pathogenic bacteria.

  7. Demonstrating an Approach for Including Pesticide Use in Life Cycle Assessment: Estimating Human and Ecosystem Toxicity of Pesticide Use in Midwest Corn Farming

    Science.gov (United States)

    Purpose This study demonstrates an approach to assess human health and ecotoxicity impacts of pesticide use by including multiple environmental pathways and various exposure routes using the case of corn grown for bio-based fuel or chemical production in US Midwestern states.Meth...

  8. Demonstrating an approach for including pesticide use in life-cycle assessment: Estimating human and ecosystem toxicity of pesticide use in Midwest corn farming

    Science.gov (United States)

    PurposeThis study demonstrates an approach to assess human health and ecotoxicity impacts of pesticide use by including multiple environmental pathways and various exposure routes using the case of corn grown for bio-based fuel or chemical production in US Midwestern states.Metho...

  9. Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.

    Science.gov (United States)

    Zhang, Yi; Dong, Weiren; Guo, Suiqun; Zhao, Shu; He, Suifen; Zhang, Lihua; Tang, Yinjuan; Wang, Haihong

    2014-12-01

    Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.

  10. Targeting S100P Inhibits Colon Cancer Growth and Metastasis by Lentivirus-Mediated RNA Interference and Proteomic Analysis

    Science.gov (United States)

    Jiang, Lei; Lai, Yiu-Kay; Zhang, Jinfang; Wang, Hua; Lin, Marie CM; He, Ming-liang; Kung, Hsiang-fu

    2011-01-01

    S100P was recently found to be overexpressed in a variety of cancers and is considered a potential target for cancer therapy, but the functional role or mechanism of action of S100P in colon cancer is not fully understood. In the present study, we knocked down the gene expression of S100P in colon cancer cells using lentivirus-mediated RNA interference. This step resulted in significant inhibition of cancer cell growth, migration and invasion in vitro and tumor growth and liver metastasis in vivo. Moreover, S100P downstream target proteins were identified by proteomic analysis in colon cancer DLD-1 cells with deletion of S100P. Knockdown of S100P led to downregulation of thioredoxin 1 and β-tubulin and upregulation of Rho guanosine diphosphate (GDP) dissociation inhibitor α (RhoGDIA), all potential therapeutic targets in cancer. Taken together, these findings suggest that S100P plays an important role in colon tumorigenesis and metastasis, and the comprehensive and comparative analyses of proteins associated with S100P could contribute to understanding the downstream signal cascade of S100P, leading to tumorigenesis and metastasis. PMID:21327297

  11. Impaired Expression of Cytokines as a Result of Viral Infections with an Emphasis on Small Ruminant Lentivirus Infection in Goats

    Directory of Open Access Journals (Sweden)

    Justyna Jarczak

    2016-07-01

    Full Text Available Knowing about the genes involved in immunity, and being able to identify the factors influencing their expressions, helps in gaining awareness of the immune processes. The qPCR method is a useful gene expression analysis tool, but studies on immune system genes are still limited, especially on the caprine immune system. Caprine arthritis encephalitis, a disease caused by small ruminant lentivirus (SRLV, causes economic losses in goat breeding, and there is no therapy against SRLV. The results of studies on vaccines against other viruses are promising. Moreover, the Marker-Assisted Selection strategy against SRLV is possible, as has been shown in sheep breeding. However, there are still many gaps in our knowledge on the caprine immune response to infection. All types of cytokines play pivotal roles in immunity, and SRLV infection influences the expression of many cytokines in different types of cells. This information encouraged the authors to examine the results of studies conducted on SRLV and other viral infections, with an emphasis on the expression of cytokine genes. This review attempts to summarize the results of studies on the expression of cytokines in the context of the SRLV infection.

  12. Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein

    International Nuclear Information System (INIS)

    Hoetzel, Isidro; Cheevers, William P.

    2005-01-01

    The caprine arthritis-encephalitis (CAEV) and ovine maedi-visna (MVV) viruses are resistant to antibody neutralization, a feature shared with all other lentiviruses. Whether the CAEV gp135 receptor binding site(s) (RBS) in the functional surface envelope glycoprotein (Env) is protected from antibody binding, allowing the virus to resist neutralization, is not known. Two CAEV gp135 regions were identified by extrapolating a gp135 structural model that could affect binding of antibodies to the RBS: the V1 region and a short sequence analogous in position to the human immunodeficiency virus type 1 gp120 loop B postulated to be located between two major domains of CAEV gp135. Mutation of isoleucine-166 to alanine in the putative loop B of gp135 increased the affinity of soluble gp135 for the CAEV receptor(s) and goat monoclonal antibody (Mab) F7-299 which recognizes an epitope overlapping the gp135 RBS. The I166A mutation also stabilized or exposed the F7-299 epitope in anionic detergent buffers, indicating that the I166A mutation induces conformational changes and stabilizes the RBS of soluble gp135 and enhances Mab F7-299 binding. In contrast, the affinity of a V1 deletion mutant of gp135 for the receptor and Mab F7-299 and its structural stability did not differ from that of the wild-type gp135. However, both the I166A mutation and the V1 deletion of gp135 increased cell-to-cell fusion activity and binding of Mab F7-299 to the oligomeric Env. Therefore, the CAEV gp135 RBS is protected from antibody binding by mechanisms both dependent and independent of Env oligomerization which are disrupted by the V1 deletion and the I166A mutation, respectively. In addition, we found a correlation between side-chain β-branching at amino acid position 166 and binding of Mab F7-299 to oligomeric Env and cell-to-cell fusion, suggesting local secondary structure constraints in the region around isoleucine-166 as one determinant of gp135 RBS exposure and antibody binding

  13. Including pathogen risk in life cycle assessment of wastewater management. 2. Quantitative comparison of pathogen risk to other impacts on human health.

    Science.gov (United States)

    Heimersson, Sara; Harder, Robin; Peters, Gregory M; Svanström, Magdalena

    2014-08-19

    Resource recovery from sewage sludge has the potential to save natural resources, but the potential risks connected to human exposure to heavy metals, organic micropollutants, and pathogenic microorganisms attract stakeholder concern. The purpose of the presented study was to include pathogen risks to human health in life cycle assessment (LCA) of wastewater and sludge management systems, as this is commonly omitted from LCAs due to methodological limitations. Part 1 of this article series estimated the overall pathogen risk for such a system with agricultural use of the sludge, in a way that enables the results to be integrated in LCA. This article (part 2) presents a full LCA for two model systems (with agricultural utilization or incineration of sludge) to reveal the relative importance of pathogen risk in relation to other potential impacts on human health. The study showed that, for both model systems, pathogen risk can constitute an important part (in this study up to 20%) of the total life cycle impacts on human health (expressed in disability adjusted life years) which include other important impacts such as human toxicity potential, global warming potential, and photochemical oxidant formation potential.

  14. Targeted knockout of TNF-α by injection of lentivirus-mediated siRNA into the subacromial bursa for the treatment of subacromial bursitis in rats.

    Science.gov (United States)

    Wang, Yi; Li, Quan; Wei, Xianzhao; Xu, Jie; Chen, Qi; Song, Shuang; Lu, Zhe; Wang, Zimin

    2015-09-01

    Subacromial bursitis (SAB) is the major source of pain in rotator cuff disease. Although multiple investigations have provided support for the role of inflammatory cytokines in SAB, few have focussed on the use these cytokines in the treatment of SAB. The aim of the present study was to observe the therapeutic efficacy of lentivirus‑mediated RNA interference (RNAi) on carrageenan‑induced SAB by injecting lentivirus‑tumor necrosis factor (TNF)‑α‑RNAi expressing TNF‑α small interfering (si)RNA. Using screened siRNA segments, an siRNA was designed. A lentivirus vector expressing siRNA was established and packed as lentivirus particles. A lentivirus that expressed the negative sequence was used as a lentivirus‑negative control (NC). The carrageenan‑induced SAB model was established in 32 male Sprague‑Dawley rats. The modeled rats were randomly assigned to four groups: Lentivirus‑RNAi treatment group, lentivirus‑NC group, SAB group and phosphate‑buffered saline (PBS) blank control group. The lentivirus was injected (1x10(7) transducing units) into the subacromial bursa of the rats in the lentivirus‑RNAi group and lentivirus‑NC group, whereas 100 µl PBS was injected at the same site in the SAB group and the PBS blank control group. At 5 weeks following injection, the animals were sacrificed and venous blood was obtained. The effect of TNF‑α interference and the expression of inflammatory cytokines were determined by reverse transcription‑quantitative polymerase chain reaction, western blotting, hematoxylin and eosin staining, Van Gieson's staining and immunofluorescence. The expression of TNF‑α was decreased in the lentivirus‑TNF‑α‑RNAi group compared with that in the SAB group. Morphological observations revealed that the number of inflammatory cells were reduced and damage to tendon fibers was attenuated in this group, suggesting that the downregulation of the protein expression levels of TNF‑α‑associated nuclear

  15. How Are Gender Equality and Human Rights Interventions Included in Sexual and Reproductive Health Programmes and Policies: A Systematic Review of Existing Research Foci and Gaps

    Science.gov (United States)

    Khosla, Rajat; Krishnan, Suneeta; George, Asha; Gruskin, Sofia; Amin, Avni

    2016-01-01

    The importance of promoting gender equality and human rights in sexual and reproductive health (SRH) programmes and policies has been affirmed in numerous international and regional agreements, most recently the 2030 Agenda for Sustainable Development. Given the critical role of research to determine what works, we aimed to identify research gaps as part of a broader priority setting exercise on integrating gender equality and human rights approaches in SRH programmes and policies. A systematic literature review of reviews was conducted to examine the question: what do we know about how research in the context of SRH programmes and policies has addressed gender equality and human rights and what are the current gaps in research. We searched three databases for reviews that addressed the research question, were published between 1994–2014, and met methodological standards for systematic reviews, qualitative meta-syntheses and other reviews of relevance to the research question. Additional grey literature was identified based on expert input. Articles were appraised by the primary author and examined by an expert panel. An abstraction and thematic analysis process was used to synthesize findings. Of the 3,073 abstracts identified, 56 articles were reviewed in full and 23 were included along with 10 from the grey literature. The majority focused on interventions addressing gender inequalities; very few reviews explicitly included human rights based interventions. Across both topics, weak study designs and use of intermediate outcome measures limited evidence quality. Further, there was limited evidence on interventions that addressed marginalized groups. Better quality studies, longer-term indicators, and measurement of unintended consequences are needed to better understand the impact of these types of interventions on SRH outcomes. Further efforts are needed to cover research on gender equality and human rights issues as they pertain to a broader set of SRH topics

  16. How Are Gender Equality and Human Rights Interventions Included in Sexual and Reproductive Health Programmes and Policies: A Systematic Review of Existing Research Foci and Gaps.

    Directory of Open Access Journals (Sweden)

    Miriam Hartmann

    Full Text Available The importance of promoting gender equality and human rights in sexual and reproductive health (SRH programmes and policies has been affirmed in numerous international and regional agreements, most recently the 2030 Agenda for Sustainable Development. Given the critical role of research to determine what works, we aimed to identify research gaps as part of a broader priority setting exercise on integrating gender equality and human rights approaches in SRH programmes and policies. A systematic literature review of reviews was conducted to examine the question: what do we know about how research in the context of SRH programmes and policies has addressed gender equality and human rights and what are the current gaps in research. We searched three databases for reviews that addressed the research question, were published between 1994-2014, and met methodological standards for systematic reviews, qualitative meta-syntheses and other reviews of relevance to the research question. Additional grey literature was identified based on expert input. Articles were appraised by the primary author and examined by an expert panel. An abstraction and thematic analysis process was used to synthesize findings. Of the 3,073 abstracts identified, 56 articles were reviewed in full and 23 were included along with 10 from the grey literature. The majority focused on interventions addressing gender inequalities; very few reviews explicitly included human rights based interventions. Across both topics, weak study designs and use of intermediate outcome measures limited evidence quality. Further, there was limited evidence on interventions that addressed marginalized groups. Better quality studies, longer-term indicators, and measurement of unintended consequences are needed to better understand the impact of these types of interventions on SRH outcomes. Further efforts are needed to cover research on gender equality and human rights issues as they pertain to a broader

  17. How Are Gender Equality and Human Rights Interventions Included in Sexual and Reproductive Health Programmes and Policies: A Systematic Review of Existing Research Foci and Gaps.

    Science.gov (United States)

    Hartmann, Miriam; Khosla, Rajat; Krishnan, Suneeta; George, Asha; Gruskin, Sofia; Amin, Avni

    2016-01-01

    The importance of promoting gender equality and human rights in sexual and reproductive health (SRH) programmes and policies has been affirmed in numerous international and regional agreements, most recently the 2030 Agenda for Sustainable Development. Given the critical role of research to determine what works, we aimed to identify research gaps as part of a broader priority setting exercise on integrating gender equality and human rights approaches in SRH programmes and policies. A systematic literature review of reviews was conducted to examine the question: what do we know about how research in the context of SRH programmes and policies has addressed gender equality and human rights and what are the current gaps in research. We searched three databases for reviews that addressed the research question, were published between 1994-2014, and met methodological standards for systematic reviews, qualitative meta-syntheses and other reviews of relevance to the research question. Additional grey literature was identified based on expert input. Articles were appraised by the primary author and examined by an expert panel. An abstraction and thematic analysis process was used to synthesize findings. Of the 3,073 abstracts identified, 56 articles were reviewed in full and 23 were included along with 10 from the grey literature. The majority focused on interventions addressing gender inequalities; very few reviews explicitly included human rights based interventions. Across both topics, weak study designs and use of intermediate outcome measures limited evidence quality. Further, there was limited evidence on interventions that addressed marginalized groups. Better quality studies, longer-term indicators, and measurement of unintended consequences are needed to better understand the impact of these types of interventions on SRH outcomes. Further efforts are needed to cover research on gender equality and human rights issues as they pertain to a broader set of SRH topics

  18. Genome-Wide Association Identifies Multiple Genomic Regions Associated with Susceptibility to and Control of Ovine Lentivirus

    Science.gov (United States)

    2012-10-17

    to varying degrees of dyspnea (respiratory distress), cachexia (body condition wasting), mastitis , arthritis, and/or encephalitis [5,6]. One of the...General Transcription Factor IIH, polypeptide 5), the gene order does not agree with other mammal genomes including cow , human, dog, and mouse, and it may

  19. Sequence-specific 1H-NMR assignments for the aromatic region of several biologically active, monomeric insulins including native human insulin.

    Science.gov (United States)

    Roy, M; Lee, R W; Kaarsholm, N C; Thøgersen, H; Brange, J; Dunn, M F

    1990-06-12

    The aromatic region of the 1H-FT-NMR spectrum of the biologically fully-potent, monomeric human insulin mutant, B9 Ser----Asp, B27 Thr----Glu has been investigated in D2O. At 1 to 5 mM concentrations, this mutant insulin is monomeric above pH 7.5. Coupling and amino acid classification of all aromatic signals is established via a combination of homonuclear one- and two-dimensional methods, including COSY, multiple quantum filters, selective spin decoupling and pH titrations. By comparisons with other insulin mutants and with chemically modified native insulins, all resonances in the aromatic region are given sequence-specific assignments without any reliance on the various crystal structures reported for insulin. These comparisons also give the sequence-specific assignments of most of the aromatic resonances of the mutant insulins B16 Tyr----Glu, B27 Thr----Glu and B25 Phe----Asp and the chemically modified species des-(B23-B30) insulin and monoiodo-Tyr A14 insulin. Chemical dispersion of the assigned resonances, ring current perturbations and comparisons at high pH have made possible the assignment of the aromatic resonances of human insulin, and these studies indicate that the major structural features of the human insulin monomer (including those critical to biological function) are also present in the monomeric mutant.

  20. PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators

    International Nuclear Information System (INIS)

    Lamba, Vishal; Yasuda, Kazuto; Lamba, Jatinder K.; Assem, Mahfoud; Davila, Julio; Strom, Stephen; Schuetz, Erin G.

    2004-01-01

    To gain insight on the expression of pregnane X receptor (PXR), we analyzed PXR.1 and PXR alternatively spliced transcripts in a panel of 36 human tissues. PXR.1 was expressed in many more tissues than previously determined, including human bone marrow and select regions of the human brain. In each of these tissues, we observed alternative splicing of various exons of PXR that generated multiple distinct PXR isoforms. The most abundant PXR alternative mRNA transcripts lacked 111 nucleotides, deleting 37 amino acids from the PXR LBD (PXR.2), or lacked 123 nt, deleting 41 amino acids from the PXR LBD (PXR.3). CYP3A4, a gene transcriptionally regulated by PXR, showed incomplete overlap with PXR in its tissue distribution. Quantitation of PXR mRNAs in human liver demonstrated that PXR.2 and PXR.3 represented 6.7% and 0.32% of total PXR mRNA transcripts. Brain expression of PXR prompted analysis of whether some brain acting chemicals were PXR ligands. The neurosteroids allopregnanolone and pregnanolone activated PXR and induced transcription of a CYP3A4-luciferase reporter. Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues

  1. PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators.

    Science.gov (United States)

    Lamba, Vishal; Yasuda, Kazuto; Lamba, Jatinder K; Assem, Mahfoud; Davila, Julio; Strom, Stephen; Schuetz, Erin G

    2004-09-15

    To gain insight on the expression of pregnane X receptor (PXR), we analyzed PXR.1 and PXR alternatively spliced transcripts in a panel of 36 human tissues. PXR.1 was expressed in many more tissues than previously determined, including human bone marrow and select regions of the human brain. In each of these tissues, we observed alternative splicing of various exons of PXR that generated multiple distinct PXR isoforms. The most abundant PXR alternative mRNA transcripts lacked 111 nucleotides, deleting 37 amino acids from the PXR LBD (PXR.2), or lacked 123 nt, deleting 41 amino acids from the PXR LBD (PXR.3). CYP3A4, a gene transcriptionally regulated by PXR, showed incomplete overlap with PXR in its tissue distribution. Quantitation of PXR mRNAs in human liver demonstrated that PXR.2 and PXR.3 represented 6.7% and 0.32% of total PXR mRNA transcripts. Brain expression of PXR prompted analysis of whether some brain acting chemicals were PXR ligands. The neurosteroids allopregnanolone and pregnanolone activated PXR and induced transcription of a CYP3A4-luciferase reporter. Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues.

  2. Comparison of three techniques for production goat lentivirus antigen used in the agar gel immunodifusion test

    Directory of Open Access Journals (Sweden)

    Raymundo Rizaldo Pinheiro

    2005-12-01

    Full Text Available The Caprine Arthritis Encephalitis (CAE is a disease who cause considerable economic losses, including loss in the milk production and reduction of the useful life of the animal. In the diagnosis of this disease the agar gel immunodifusion test (AGID is used worldwide as the selection test. The objective of thid work was to test three different concentrations of bovine fetal serum (BFS in the production of the antigen (Ag for the diagnosis of the CAE virus (CAEV, to verify amongst the three methods the most efficient concentration and which the antigen concentration of the antigen produced is appropriate for the test. The method of the AMICON and the concentration of the Ag for dialysis was indicated, however the system AMICON, despite the implantation costs, promoted minor loss of antigen, little time expense in the processing and greater simplicity. With relation to the amount of BFS placed after the viral inoculation it was verified that 5% of BFS the amount that presented better resulted. The antigen concentration 100 times was more indicated, therefore it allowed the diagnosis of the CAEV for two proteins (gp 135 and p28. The concentration of the Ag for precipitation/ultracentrifugation, used for imunoenzimatic tests, did not present resulted satisfactory used in the AGID.

  3. Emended description of Campylobacter sputorum and revision of its infrasubspecific (biovar) divisions, including C-sputorum biovar paraureolyticus, a urease-producing variant from cattle and humans

    DEFF Research Database (Denmark)

    On, S.L.W.; Atabay, H.I.; Corry, J.E.L.

    1998-01-01

    A polyphasic taxonomic study of 15 bovine and human strains assigned to the catalase-negative, urease-positive campylobacter (CNUPC) group identified these bacteria as a novel, ureolytic biovar of Campylobacter sputorum for which we propose the name C. sputorum bv. paraureolyticus: suitable...... should be revised to include by. sputorum for catalase-negative strains; by. fecalis for catalase-positive strains; and by. paraureolyticus for urease-positive strains. Strains classified previously as by. bubulus should be reclassified as by. sputorum. The species description of C. sputorum is revised...

  4. ALOX12 in Human Toxoplasmosis

    Science.gov (United States)

    Witola, William H.; Liu, Susan Ruosu; Montpetit, Alexandre; Welti, Ruth; Hypolite, Magali; Roth, Mary; Zhou, Ying; Mui, Ernest; Cesbron-Delauw, Marie-France; Fournie, Gilbert J.; Cavailles, Pierre; Bisanz, Cordelia; Boyer, Kenneth; Withers, Shawn; Noble, A. Gwendolyn; Swisher, Charles N.; Heydemann, Peter T.; Rabiah, Peter; Muench, Stephen P.

    2014-01-01

    ALOX12 is a gene encoding arachidonate 12-lipoxygenase (12-LOX), a member of a nonheme lipoxygenase family of dioxygenases. ALOX12 catalyzes the addition of oxygen to arachidonic acid, producing 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can be reduced to the eicosanoid 12-HETE (12-hydroxyeicosatetraenoic acid). 12-HETE acts in diverse cellular processes, including catecholamine synthesis, vasoconstriction, neuronal function, and inflammation. Consistent with effects on these fundamental mechanisms, allelic variants of ALOX12 are associated with diseases including schizophrenia, atherosclerosis, and cancers, but the mechanisms have not been defined. Toxoplasma gondii is an apicomplexan parasite that causes morbidity and mortality and stimulates an innate and adaptive immune inflammatory reaction. Recently, it has been shown that a gene region known as Toxo1 is critical for susceptibility or resistance to T. gondii infection in rats. An orthologous gene region with ALOX12 centromeric is also present in humans. Here we report that the human ALOX12 gene has susceptibility alleles for human congenital toxoplasmosis (rs6502997 [P, <0.000309], rs312462 [P, <0.028499], rs6502998 [P, <0.029794], and rs434473 [P, <0.038516]). A human monocytic cell line was genetically engineered using lentivirus RNA interference to knock down ALOX12. In ALOX12 knockdown cells, ALOX12 RNA expression decreased and levels of the ALOX12 substrate, arachidonic acid, increased. ALOX12 knockdown attenuated the progression of T. gondii infection and resulted in greater parasite burdens but decreased consequent late cell death of the human monocytic cell line. These findings suggest that ALOX12 influences host responses to T. gondii infection in human cells. ALOX12 has been shown in other studies to be important in numerous diseases. Here we demonstrate the critical role ALOX12 plays in T. gondii infection in humans. PMID:24686056

  5. Lentivirus mediated RNA interference of EMMPRIN (CD147) gene inhibits the proliferation, matrigel invasion and tumor formation of breast cancer cells.

    Science.gov (United States)

    Yang, Jing; Wang, Rong; Li, Hongjiang; Lv, Qing; Meng, Wentong; Yang, Xiaoqin

    2016-07-08

    Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147), a glycoprotein enriched on the plasma membrane of tumor cells, promotes proliferation, invasion, metastasis, and survival of malignant tumor cells. In this study, we sought to examine the expression of EMMPRIN in breast tumors, and to identify the potential roles of EMMPRIN on breast cancer cells. EMMPRIN expression in breast cancer tissues was assessed by immunohistochemistry. We used a lentivirus vector-based RNA interference (RNAi) approach expressing short hairpin RNA (shRNA) to knockdown EMMPRIN gene in breast cancer cell lines MDA-MB-231 and MCF-7. In vitro, Cell proliferative, invasive potential were determined by Cell Counting Kit (CCK-8), cell cycle analysis and matrigel invasion assay, respectively. In vivo, tumorigenicity was monitored by inoculating tumor cells into breast fat pad of female nude mice. EMMPRIN was over-expressed in breast tumors and breast cancer cell lines. Down-regulation of EMMPRIN by lentivirus vector-based RNAi led to decreased cell proliferative, decreased matrigel invasion in vitro, and attenuated tumor formation in vivo. High expression of EMMPRIN plays a crucial role in breast cancer cell proliferation, matrigel invasion and tumor formation.

  6. Poly(I:C) induces expressions of MMP-1, -2, and -3 through various signaling pathways including IRF3 in human skin fibroblasts.

    Science.gov (United States)

    Yao, Cheng; Lee, Dong Hun; Oh, Jang-Hee; Kim, Min-Kyoung; Kim, Kyu Han; Park, Chi-Hyun; Chung, Jin Ho

    2015-10-01

    Ultraviolet (UV) irradiation can result in premature skin aging (photoaging) which is characterized by decreased expression of collagen and increased expression of matrix metalloproteinases (MMPs). Double-stranded RNAs (dsRNAs) can be generated at various conditions including virally infected cells or UV-damaged skin cells. Recent studies have shown that a synthetic dsRNA, polyinosinic-polycytidylic acid (poly(I:C)), can reduce procollagen expression in human skin fibroblasts. However, little is known about the effect of poly(I:C) on the expression of MMPs in skin fibroblasts and its underlying mechanisms. We examined the effect of poly(I:C) on MMP-1, -2, and -3 expressions in human skin fibroblasts. Then, we further explored the underlying signaling pathways involved in the processes. Human skin fibroblasts were treated with poly(I:C) for the indicated times in the presence or the absence of various chemical inhibitors or small interfering RNAs (siRNAs) at the indicated concentrations. Protein and mRNA levels of various target molecules were examined by Western blotting and quantitative real-time PCR, respectively. Poly(I:C) induced MMP-1, -2, and -3 expressions, which were dependent on TLR3. Poly(I:C) also induced activations of the mitogen-activated protein kinases (MAPKs), the nuclear factor-kappaB (NF-κB) and the interferon regulatory factor 3 (IRF3) pathways. By using specific inhibitors, we found that poly(I:C)-induced expressions of MMP-1, -2, and -3 were differentially regulated by these signaling pathways. In particular, we found that the inhibition of IRF3 signaling pathways attenuated poly(I:C)-induced expressions of all the three MMPs. Our data show that the expressions of MMP-1, -2, and -3 are induced by poly(I:C) through various signaling pathways in human skin fibroblasts and suggest that TLR3 and/or IRF3 may be good targets for regulating the expressions of MMP-1, -2, and -3 induced by dsRNAs. Copyright © 2015 Elsevier Ireland Ltd. All rights

  7. Synthesis and evaluation of the potential deleterious effects of ZnO nanomaterials (nanoneedles and nanoflowers) on blood components, including albumin, erythrocytes and human isolated primary neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Pastrello, Bruna [São Paulo State University (UNESP), Department of Chemistry, Faculty of Sciences (Brazil); Paracatu, Luana Chiquetto [São Paulo State University (UNESP), Department of Clinical Analysis, School of Pharmaceutical Sciences (Brazil); Carvalho Bertozo, Luiza de [São Paulo State University (UNESP), Department of Chemistry, Faculty of Sciences (Brazil); Paino, Iêda Maria Martinez [University of São Paulo (USP), Nanomedicine and Nanotoxicology Group, Physics Institute of São Carlos (IFSC) (Brazil); Lisboa-Filho, Paulo Noronha [São Paulo State University (UNESP), Department of Physics, Faculty of Sciences (Brazil); Ximenes, Valdecir Farias, E-mail: vfximenes@fc.unesp.br [São Paulo State University (UNESP), Department of Chemistry, Faculty of Sciences (Brazil)

    2016-07-15

    The application of zinc oxide (ZnO) nanoparticles in biomaterials has increased significantly in the recent years. Here, we aimed to study the potential deleterious effects of ZnO on blood components, including human serum albumin (HSA), erythrocytes and human isolated primary neutrophils. To test the influence of the morphology of the nanomaterials, ZnO nanoneedles (ZnO-nn) and nanoflowers (ZnO-nf) were synthesized. The zeta potential and mean size of ZnO-nf and ZnO-nn suspensions in phosphate-buffered saline were −10.73 mV and 3.81 nm and −5.27 mV and 18.26 nm, respectively. The incubation of ZnO with HSA did not cause its denaturation as verified by the absence of significant alterations in the intrinsic and extrinsic fluorescence and in the circular dichroism spectrum of the protein. The capacity of HSA as a drug carrier was not affected as verified by employing site I and II fluorescent markers. Neither type of ZnO was able to provoke the activation of neutrophils, as verified by lucigenin- and luminol-dependent chemiluminescence and by the extracellular release of hydrogen peroxide. ZnO-nf, but not ZnO-nn, induced the haemolysis of erythrocytes. In conclusion, our results reinforce the concept that ZnO nanomaterials are relatively safe for usage in biomaterials. A potential exception is the capacity of ZnO-nf to promote the lysis of erythrocytes, a discovery that shows the importance of the morphology in the toxicity of nanoparticles.

  8. 慢病毒法生产转基因鸡的初步研究%Production of Transgenic Chickens with Lentivirus Method

    Institute of Scientific and Technical Information of China (English)

    崔奎青; 刘庆友; 赵一广; 王晓丽; 钟俊洁; 熊建明; 李爱友; 黄钦华

    2012-01-01

    [Objective] The aim was to explore optimal method for transgenic chickens production with lentivirus. [Method] Lentiviral vector was constructed with enhanced green fluorescent protein (EGFP) and fertilized ova at early stages were inoculated after virus packaging. In addition, effects of injection and virus liter on survival rate of embryos were detected and GFP expressions of inoculated embryos were observed. [Result] The hatching rates of embryo were 87% , 72% and 66.7% with tilers of lentivirus at 105, 106 and 102 IU/ml, respectively. Transgenic positive rate was 45.5% through PCR with genome of chick blood as template. Expression of GFP genes in different tissues differed significantly through frozen section technology, for example, expression in immune system was the highest and expression was not proved in genital syatem and muscular tissue. [Conclusion] The research primarily selected optimal lentivirus tiler, laying basis for development of bio-reactor (egg&chicken) and the new transgenic disease-resistant chicken.%[目的]探索利用慢病毒生产转基因鸡的适宜方法.[方法]以增强型绿色荧光蛋白为报告基因构建慢病毒载体,包装病毒后感染鸡早期受精卵,并检测不同注射操作和不同接种滴度对鸡胚存活率的影响,同时对接种病毒鸡胚的GFP表达情况进行检测.[结果]采用105、106和107IU/ml的慢病毒滴度,鸡胚孵化率分别为87%、72%和66.7%.以雏鸡血液基因组为模板PCR鉴定转基因阳性率为45.5%;冰冻切片技术发现GFP基因在鸡体内不同组织的表达强度差异显著,免疫系统内表达最强,生殖系统和肌肉组织中GFP基因无表达.[结论]试验初步筛选出较适宜的慢病毒感染滴度,该结果为研制蛋鸡生物反应器和转基因鸡抗病新品系奠定了基础.

  9. Tumor cell anaplasia and multinucleation are predictors of disease recurrence in oropharyngeal squamous cell carcinoma, including among just the human papillomavirus-related cancers.

    Science.gov (United States)

    Lewis, James S; Scantlebury, Juliette B; Luo, Jingqin; Thorstad, Wade L

    2012-07-01

    Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any × 40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any × 40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (Panaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (Panaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P=0.04; and hazard ratio 11.9, P=0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival.

  10. First comparative study of primate morphological and molecular evolutionary rates including muscle data: implications for the tempo and mode of primate and human evolution

    Science.gov (United States)

    Diogo, Rui; Peng, Zuogang; Wood, Bernard

    2013-01-01

    Here we provide the first report about the rates of muscle evolution derived from Bayesian and parsimony cladistic analyses of primate higher-level phylogeny, and compare these rates with published rates of molecular evolution. It is commonly accepted that there is a ‘general molecular slow-down of hominoids’, but interestingly the rates of muscle evolution in the nodes leading and within the hominoid clade are higher than those in the vast majority of other primate clades. The rate of muscle evolution at the node leading to Homo (1.77) is higher than that at the nodes leading to Pan (0.89) and particularly to Gorilla (0.28). Notably, the rates of muscle evolution at the major euarchontan and primate nodes are different, but within each major primate clade (Strepsirrhini, Platyrrhini, Cercopithecidae and Hominoidea) the rates at the various nodes, and particularly at the nodes leading to the higher groups (i.e. including more than one genera), are strikingly similar. We explore the implications of these new data for the tempo and mode of primate and human evolution. PMID:23320764

  11. Incident AIDS or Death After Initiation of Human Immunodeficiency Virus Treatment Regimens Including Raltegravir or Efavirenz Among Adults in the United States.

    Science.gov (United States)

    Cole, Stephen R; Edwards, Jessie K; Hall, H Irene; Brookhart, M Alan; Mathews, W Christopher; Moore, Richard D; Crane, Heidi M; Kitahata, Mari M; Mugavero, Michael J; Saag, Michael S; Eron, Joseph J

    2017-06-01

    The long-term effectiveness of human immunodeficiency virus (HIV) treatments containing integrase inhibitors is unknown. We use observational data from the Centers for AIDS Research Network of Integrated Clinical Systems and the Centers for Disease Control and Prevention to estimate 4-year risk of AIDS and all-cause mortality among 415 patients starting a raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens include emtricitabine and tenofovir disoproxil fumarate). We account for confounding and selection bias as well as generalizability by standardization for measured variables, and present both observational intent-to-treat and per-protocol estimates. At treatment initiation, 12% of patients were female, 36% black, 13% Hispanic; median age was 37 years, CD4 count 321 cells/µL, and viral load 4.5 log10 copies/mL. Two hundred thirty-five patients incurred an AIDS-defining illness or died, and 741 patients left follow-up. After accounting for measured differences, the 4-year risk was similar among those starting both regimens (ie, intent-to treat hazard ratio [HR], 0.96 [95% confidence interval {CI}, .63-1.45]; risk difference, -0.9 [95% CI, -4.5 to 2.7]), as well as among those remaining on regimens (ie, per-protocol HR, 0.95 [95% CI, .59-1.54]; risk difference, -0.5 [95% CI, -3.8 to 2.9]). Raltegravir and efavirenz-based initial antiretroviral therapy have similar 4-year clinical effects. Vigilance regarding longer-term comparative effectiveness of HIV regimens using observational data is needed because large-scale experimental data are not forthcoming. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  12. Data in support of transcriptional regulation and function of Fas-antisense long noncoding RNA during human erythropoiesis

    Directory of Open Access Journals (Sweden)

    Olga Villamizar

    2016-06-01

    Full Text Available This paper describes data related to a research article titled, “Fas-antisense long noncoding RNA is differentially expressed during maturation of human erythrocytes and confers resistance to Fas-mediated cell death” [1]. Long noncoding RNAs (lncRNAs are increasingly appreciated for their capacity to regulate many steps of gene expression. While recent studies suggest that many lncRNAs are functional, the scope of their actions throughout human biology is largely undefined including human red blood cell development (erythropoiesis. Here we include expression data for 82 lncRNAs during early, intermediate and late stages of human erythropoiesis using a commercial qPCR Array. From these data, we identified lncRNA Fas-antisense 1 (Fas-AS1 or Saf described in the research article. Also included are 5′ untranslated sequences (UTR for lncRNA Saf with transcription factor target sequences identified. Quantitative RT-PCR data demonstrate relative levels of critical erythroid transcription factors, GATA-1 and KLF1, in K562 human erythroleukemia cells and maturing erythroblasts derived from human CD34+ cells. End point and quantitative RT-PCR data for cDNA prepared using random hexamers versus oligo(dT18 revealed that lncRNA Saf is not effectively polyadenylated. Finally, we include flow cytometry histograms demonstrating Fas levels on maturing erythroblasts derived from human CD34+ cells transduced using mock conditions or with lentivirus particles encoding for Saf.

  13. Optimization of methods for the genetic modification of human T cells.

    Science.gov (United States)

    Bilal, Mahmood Y; Vacaflores, Aldo; Houtman, Jon Cd

    2015-11-01

    CD4(+) T cells are not only critical in the fight against parasitic, bacterial and viral infections, but are also involved in many autoimmune and pathological disorders. Studies of protein function in human T cells are confined to techniques such as RNA interference (RNAi) owing to ethical reasons and relative simplicity of these methods. However, introduction of RNAi or genes into primary human T cells is often hampered by toxic effects from transfection or transduction methods that yield cell numbers inadequate for downstream assays. Additionally, the efficiency of recombinant DNA expression is frequently low because of multiple factors including efficacy of the method and strength of the targeting RNAs. Here, we describe detailed protocols that will aid in the study of primary human CD4(+) T cells. First, we describe a method for development of effective microRNA/shRNAs using available online algorithms. Second, we illustrate an optimized protocol for high efficacy retroviral or lentiviral transduction of human T-cell lines. Importantly, we demonstrate that activated primary human CD4(+) T cells can be transduced efficiently with lentiviruses, with a highly activated population of T cells receiving the largest number of copies of integrated DNA. We also illustrate a method for efficient lentiviral transduction of hard-to-transduce un-activated primary human CD4(+) T cells. These protocols will significantly assist in understanding the activation and function of human T cells and will ultimately aid in the development or improvement of current drugs that target human CD4(+) T cells.

  14. Why industry propaganda and political interference cannot disguise the inevitable role played by human exposure to aluminum in neurodegenerative diseases, including Alzheimer's disease.

    Science.gov (United States)

    Exley, Christopher

    2014-01-01

    In the aluminum age, it is clearly unpalatable for aluminum, the globe's most successful metal, to be implicated in human disease. It is unpalatable because for approximately 100 years human beings have reaped the rewards of the most abundant metal of the Earth's crust without seriously considering the potential consequences for human health. The aluminum industry is a pillar of the developed and developing world and irrespective of the tyranny of human exposure to aluminum it cannot be challenged without significant consequences for businesses, economies, and governments. However, no matter how deep the dependency or unthinkable the withdrawal, science continues to document, if not too slowly, a burgeoning body burden of aluminum in human beings. Herein, I will make the case that it is inevitable both today and in the future that an individual's exposure to aluminum is impacting upon their health and is already contributing to, if not causing, chronic diseases such as Alzheimer's disease. This is the logical, if uncomfortable, consequence of living in the aluminum age.

  15. Human factors issues and approaches in the spatial layout of a space station control room, including the use of virtual reality as a design analysis tool

    Science.gov (United States)

    Hale, Joseph P., II

    1994-01-01

    Human Factors Engineering support was provided for the 30% design review of the late Space Station Freedom Payload Control Area (PCA). The PCA was to be the payload operations control room, analogous to the Spacelab Payload Operations Control Center (POCC). This effort began with a systematic collection and refinement of the relevant requirements driving the spatial layout of the consoles and PCA. This information was used as input for specialized human factors analytical tools and techniques in the design and design analysis activities. Design concepts and configuration options were developed and reviewed using sketches, 2-D Computer-Aided Design (CAD) drawings, and immersive Virtual Reality (VR) mockups.

  16. Analysis of 6-mercaptopurine in human plasma with a high-performance liquid chromatographic method including post-column derivatization and fluorimetric detection

    NARCIS (Netherlands)

    Jonkers, R. E.; Oosterhuis, B.; ten Berge, R. J.; van Boxtel, C. J.

    1982-01-01

    A relatively simple assay with improved reliability and sensitivity for measuring levels of 6-mercaptopurine in human plasma is presented. After extraction of the compound and the added internal standard with phenyl mercury acetate, samples were separated by ion-pair reversed-phase high-performance

  17. The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44.

    Science.gov (United States)

    Allcock, Richard J N; Barrow, Alexander D; Forbes, Simon; Beck, Stephan; Trowsdale, John

    2003-02-01

    We have characterized a cluster of single immunoglobulin variable (IgV) domain receptors centromeric of the major histocompatibility complex (MHC) on human chromosome 6. In addition to triggering receptor expressed on myeloid cells (TREM)-1 and TREM2, the cluster contains NKp44, a triggering receptor whose expression is limited to NK cells. We identified three new related genes and two gene fragments within a cluster of approximately 200 kb. Two of the three new genes lack charged residues in their transmembrane domain tails. Further, one of the genes contains two potential immunotyrosine Inhibitory motifs in its cytoplasmic tail, suggesting that it delivers inhibitory signals. The human and mouse TREM clusters appear to have diverged such that there are unique sequences in each species. Finally, each gene in the TREM cluster was expressed in a different range of cell types.

  18. Characteristics of mineral nutrition of plants in the bio-technical life support system with human wastes included in mass exchange

    Science.gov (United States)

    Tikhomirova, Natalia; Ushakova, Sofya; Kalacheva, Galina; Tikhomirov, Alexander

    2016-09-01

    The study addresses the effectiveness of using ion exchange substrates (IES) to optimize mineral nutrition of plants grown in the nutrient solutions containing oxidized human wastes for application in bio-technical life support systems. The study shows that the addition of IES to the root-inhabited substrate is favorable for the growth of wheat vegetative organs but causes a decrease in the grain yield. By contrast, the addition of IES to the nutrient solution does not influence the growth of vegetative organs but favors normal development of wheat reproductive organs. Thus, to choose the proper method of adjusting the solution with IES, one should take into account specific parameters of plant growth and development and the possibility of multiple recycling of IES based on the liquid products of mineralization of human wastes.

  19. Tumor Cell Anaplasia and Multinucleation Are Predictors of Disease Recurrence in Oropharyngeal Squamous Cell Carcinoma, Including Among Just the Human Papillomavirus-Related Cancers

    OpenAIRE

    Lewis, James S.; Scantlebury, Juliette B.; Luo, Jingqin; Thorstad, Wade L.

    2012-01-01

    Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all su...

  20. A pacemaker powered by an implantable biofuel cell operating under conditions mimicking the human blood circulatory system--battery not included.

    Science.gov (United States)

    Southcott, Mark; MacVittie, Kevin; Halámek, Jan; Halámková, Lenka; Jemison, William D; Lobel, Robert; Katz, Evgeny

    2013-05-07

    Biocatalytic electrodes made of buckypaper were modified with PQQ-dependent glucose dehydrogenase on the anode and with laccase on the cathode and were assembled in a flow biofuel cell filled with serum solution mimicking the human blood circulatory system. The biofuel cell generated an open circuitry voltage, Voc, of ca. 470 mV and a short circuitry current, Isc, of ca. 5 mA (a current density of 0.83 mA cm(-2)). The power generated by the implantable biofuel cell was used to activate a pacemaker connected to the cell via a charge pump and a DC-DC converter interface circuit to adjust the voltage produced by the biofuel cell to the value required by the pacemaker. The voltage-current dependencies were analyzed for the biofuel cell connected to an Ohmic load and to the electronic loads composed of the interface circuit, or the power converter, and the pacemaker to study their operation. The correct pacemaker operation was confirmed using a medical device - an implantable loop recorder. Sustainable operation of the pacemaker was achieved with the system closely mimicking human physiological conditions using a single biofuel cell. This first demonstration of the pacemaker activated by the physiologically produced electrical energy shows promise for future electronic implantable medical devices powered by electricity harvested from the human body.

  1. Production of Transgenic Chickens Using Lentivirus Method%沼液养分和重金属农用安全风险分析

    Institute of Scientific and Technical Information of China (English)

    刘研萍; 张继方; 邹德勋; 袁海荣; 李秀金

    2012-01-01

    [Objective] The aim was to explore optimal method for transgenic chickens production with lentivirus, [Method] Lentiviral vector was constructed with enhanced green fluorescent protein (EGFP) and fertilized ova at early stages were inoculated after virus packaging. In addition, effects of injection and virus titer on survival rate of embryos were detected and GFP expressions of inoculated embryos were ob- served. [Result] The hatching rates of embryo were 87%, 72% and 66.7% with titers of lentivirus at 105, 106 and 107 IU/ml, respectively. Transgenic positive rate was 45.5% through PCR with genome of chick blood as template. Expression of GFP genes in different tissues differed significantly through frozen section technology, for example, expression in immune system was the highest and expression was not proved in genital system and muscular tissue. [Conclusion] The research primarily selected optimal lentivirus titer, laying basis for development of bioreactor (egg&chicken) and the new transgenic disease-resistant chicken.%[目的]对沼液养分和重金属农用安全风险进行分析,以期为沼液的安全农用提供科学依据。[方法]对秸秆及粪便中温厌氧消化的沼液进行重金属养分分析,并利用不同类型和浓度的沼液进行种子发芽试验。[结果]物料的类型及配比、碱液预处理均对沼液的成分和性质产生影响。碱液预处理可降低沼液中的重金属含量,可提高氮、磷、有机质以及速效成分的含量。沼液中重金属的最高含量分别为镉8.76μg/kg,铬52μg/kg,铅210μg/kg,汞0.512μg/kg,砷140μg/kg,铜、锌的含量较高,分别可达279和680μg/kg,但均低于城镇垃圾农用限定标准值。种子在沼液中的发芽试验验证了5%以下低浓度沼液的催芽作用,但盐胁迫作用使幼苗在沼液中的长期生长受到抑制。[结论]以粪便作为沼液发酵原料时麻适当的控制其在进料中

  2. [Experimental study on human periodontal ligament cells transfected with human amelogenin gene].

    Science.gov (United States)

    Yu, Guang; Shu, Rong; Sun, Ying; Cheng, Lan; Song, Zhong-Chen; Zhang, Xiu-Li

    2008-02-01

    To construct the recombinant lentiviral vector of human amelogenin gene, infect human periodontal ligament cells with the recombinant lentivirus, and evaluate the feasibility of applying modified PDLCs as seeds for a further periodontal reconstruction. The mature peptide of hAm cDNA was cloned and linked into the vector plasmid, the recombinant plasmid FUAmW was confirmed by double enzyme digestion and sequence analysis. Recombinant lentivirus was prepared from 293T cells by polytheylenimine (PEI)-mediated transient cotransfection. The hPDLCs and 293T cells were infected with the generated lentivirus. The infection efficiency was analysed by detection of green fluorescence protein (GFP) with fluorescent microscope and flow cytometer 72 hours later. The expression of hAm gene was detected by reverse transcription polymerase chain reaction (RT-PCR). The sequence of inserted fragment in recombinant plasmid was identical to the hAm sequence reported in Genebank. Green fluorescence was visible under fluorescent microscope, FCM assay showed that positive percentage was 69.46% and 33.99% in 293T and hPDLCs, respectively. The targeted gene was obtained in the experimental groups by RT-PCR. The recombinan lentiviral vector of hAm gene is constructed successfully and it could be transfected into cultured hPDLCs. hAm gene and seed cells may be used for further study in the fields periodontal tissue engineering. Supported by National Natural Science Foundation of China (Grant No. 30672315).

  3. Immunofluorescence Microscopy and mRNA Analysis of Human Embryonic Stem Cells (hESCs) Including Primary Cilia Associated Signaling Pathways

    DEFF Research Database (Denmark)

    Vestergaard, Maj Linea; Awan, Aashir; Warzecha, Caroline Becker

    2016-01-01

    onto 16-well glass chambers, and continuing with the general IFM and qPCR anlysis. The techniques are illustrated with results on cellular localization of transcriptional factors and components of the Hedgehog, Wnt, PDGF, and TGFβ signaling pathways to primary cilia in stem cell maintenance......This chapter describes the procedures for immunofluorescence microscopy (IFM) and quantitative PCR (qPCR) analyses of human embryonic stem cells (hESCs) grown specifically under feeder-free conditions. A detailed protocol is provided outlining the steps from initially growing the cells, passaging...

  4. Prediction of temperature and damage in an irradiated human eye-Utilization of a detailed computer model which includes a vectorial blood stream in the choroid.

    Science.gov (United States)

    Heussner, Nico; Holl, Lukas; Nowak, Timo; Beuth, Thorsten; Spitzer, Martin S; Stork, Wilhelm

    2014-08-01

    The work presented here describes the development and use of a three-dimensional thermo-dynamic model of the human eye for the prediction of temperatures and damage thresholds under irradiation. This model takes into account the blood flow by the implementation of a vectorial blood stream in the choroid and also uses the actual physiological extensions and tissue parameters of the eye. Furthermore it considers evaporation, radiation and convection at the cornea as well as the eye lid. The predicted temperatures were successfully validated against existing eye models in terms of corneal and global thermal behaviour. The model׳s predictions were additionally checked for consistency with in-vivo temperature measurements of the cornea, the irradiated retina and its damage thresholds. These thresholds were calculated from the retinal temperatures using the Arrhenius integral. Hence the model can be used to predict the temperature increase and irradiation hazard within the human eye as long as the absorption values and the Arrhenius coefficients are known and the damage mechanism is in the thermal regime. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Analysis of 6-mercaptopurine in human plasma with a high-performance liquid chromatographic method including post-column derivatization and fluorimetric detection.

    Science.gov (United States)

    Jonkers, R E; Oosterhuis, B; ten Berge, R J; van Boxtel, C J

    1982-12-10

    A relatively simple assay with improved reliability and sensitivity for measuring levels of 6-mercaptopurine in human plasma is presented. After extraction of the compound and the added internal standard with phenyl mercury acetate, samples were separated by ion-pair reversed-phase high-performance liquid chromatography. On-line the analytes were oxidized to fluorescent products and detected in a flow-fluorimeter. The within-day coefficient of variation was 3.8% at a concentration of 25 ng/ml. The lower detection limit was 2 ng/ml when 1.0 ml of plasma was used. Mercaptopurine concentration versus time curves of two subjects after a single oral dose of azathioprine are shown.

  6. Response to Therapy and Outcomes in Oropharyngeal Cancer Are Associated With Biomarkers Including Human Papillomavirus, Epidermal Growth Factor Receptor, Gender, and Smoking

    International Nuclear Information System (INIS)

    Kumar, Bhavna; Cordell, Kitrina G.; Lee, Julia S.; Prince, Mark E.; Tran, Huong H.; Wolf, Gregory T.; Urba, Susan G.; Worden, Francis P.; Chepeha, Douglas B.; Teknos, Theodoros N.; Eisbruch, Avraham; Tsien, Christina I.; Taylor, Jeremy; D'Silva, Nisha J.; Yang, Kun; Kurnit, David M.; Bradford, Carol R.

    2007-01-01

    Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specific survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile

  7. Dose-intensive chemotherapy including rituximab is highly effective but toxic in human immunodeficiency virus-infected patients with Burkitt lymphoma/leukemia: parallel study of 81 patients.

    Science.gov (United States)

    Xicoy, Blanca; Ribera, Josep-Maria; Müller, Markus; García, Olga; Hoffmann, Christian; Oriol, Albert; Hentrich, Marcus; Grande, Carlos; Wasmuth, Jan-Christian; Esteve, Jordi; van Lunzen, Jan; Del Potro, Eloy; Knechten, Heribert; Brunet, Salut; Mayr, Christoph; Escoda, Lourdes; Schommers, Philipp; Alonso, Natalia; Vall-Llovera, Ferran; Pérez, Montserrat; Morgades, Mireia; González, José; Fernández, Angeles; Thoden, Jan; Gökbuget, Nicola; Hoelzer, Dieter; Fätkenheuer, Gerd; Wyen, Christoph

    2014-10-01

    The results of intensive immunochemotherapy were analyzed in human immunodeficiency virus (HIV)-related Burkitt lymphoma/leukemia (BLL) in two cohorts (Spain and Germany). Alternating cycles of chemotherapy were administered, with dose reductions for patients over 55 years. Eighty percent of patients achieved remission, 11% died during induction, 9% failed and 7% died in remission. Four-year overall survival (OS) and progression-free survival (PFS) probabilities were 72% (95% confidence interval [CI]: 62-82%) and 71% (95% CI: 61-81%). CD4 T-cell count 2 (odds ratio [OR] 11.9 [1.4-99.9]) with induction death. In HIV-related BLL, intensive immunochemotherapy was feasible and effective, but toxic. Prognostic factors were performance status, CD4 T-cell count and bone marrow involvement.

  8. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells

    International Nuclear Information System (INIS)

    Gao Jiayu; Morgan, Winston A.; Sanchez-Medina, Alberto; Corcoran, Olivia

    2011-01-01

    Despite a lack of scientific authentication, Scutellaria baicalensis is clinically used in Chinese medicine as a traditional adjuvant to chemotherapy of lung cancer. In this study, cytotoxicity assays demonstrated that crude ethanolic extracts of S. baicalensis were selectively toxic to human lung cancer cell lines A549, SK-LU-1 and SK-MES-1 compared with normal human lung fibroblasts. The active compounds baicalin, baicalein and wogonin did not exhibit such selectivity. Following exposure to the crude extracts, cellular protein expression in the cancer cell lines was assessed using 2D gel electrophoresis coupled with MALDI-TOF-MS/Protein Fingerprinting. The altered protein expression indicated that cell growth arrest and apoptosis were potential mechanisms of cytotoxicity. These observations were supported by PI staining cell cycle analysis using flow cytometry and Annexin-V apoptotic analysis by fluorescence microscopy of cancer cells treated with the crude extract and pure active compounds. Moreover, specific immunoblotting identification showed the decreased expression of cyclin A results in the S phase arrest of A549 whereas the G 0 /G 1 phase arrest in SK-MES-1 cells results from the decreased expression of cyclin D1. Following treatment, increased expression in the cancer cells of key proteins related to the enhancement of apoptosis was observed for p53 and Bax. These results provide further insight into the molecular mechanisms underlying the clinical use of this herb as an adjuvant to lung cancer therapy. - Research highlights: → Scutellaria baicalensis is a clinical adjuvant to lung cancer chemotherapy in China. → Scutellaria ethanol extracts selectively toxic to A549, SK-LU-1 and SK-MES-1. → Baicalin, baicalein and wogonin were toxic to all lung cancer cell lines. → Proteomics identified increased p53 and BAX in response to Scutellaria extracts.

  9. Radiochemical and biological studies, including in non-human primates, towards indigenous development of 153Sm-EDTMP for metastatic bone pain palliation

    International Nuclear Information System (INIS)

    Saraswathy, P.; Mehra, K.S.; Ranganatha, D.K.; Das, M.K.; Balasubramanian, P.S.; Ananthakrishnan, M.; Ramamoorthy, N.; Gunasekaran, S.; Shanthly, N.; Retna Ponmalar, J.; Narasimhan, S.

    2001-01-01

    The combination of ease of formulation and superior biological features of 153 Sm-EDTMP in terms of safety and efficacy for metastatic bone pain palliation, together with the prospect of better logistics of production, has prompted extensive efforts by many groups world over for its preparation and evaluation. Our efforts have been directed towards exploring the feasibility for formulation of 153 Sm-EDTMP suitable for human use by neutron activation in medium flux reactors of the freely available and inexpensive natural samarium oxide target. The emphasis in biological studies was placed on tests in larger animals (monkeys) as a prelude to clinical evaluation. Feasibility to achieve reasonably high specific activity of 300-700 mCi/mg Sm at EOB with natural samarium has been adequately demonstrated. The radioeuropium contamination, estimated by γ-spectrometry to be 153 Sm-EDTMP from natural samarium at high radioactive concentrations of 40-50 mCi 153 Sm/mL, acceptable biolocalization, as revealed by both biodistribution studies in rats (femur uptake of 2-3% injected dose at 1h p.i. and retention up to 120 h p.i.) and gamma camera images in monkeys and adequate stability have been feasible. Excellent quality bone images of monkeys were recorded showing rapid clearance from blood, visualization of skeleton, clearance from kidneys within 2 hours and retention in skeleton up to 116 hours p.i. No significant activity in other soft tissues was noted. Comparative evaluation of the product prepared from enriched samarium as well as using in-house synthesized EDTMP has, likewise, revealed identical biolocalization features. EDTMP dose tolerance test in mice showed a safety factor of about 100 for a product made from natural samarium at an adult human dose of 50 mCi 153 Sm. Feasibility for production, reasonable safety and satisfactory biolocalisation of the indigenous product has been adequately established so as to warrant clinical trials in patients. (author)

  10. Cryopreservation does not alter main characteristics of Good Manufacturing Process-grade human multipotent mesenchymal stromal cells including immunomodulating potential and lack of malignant transformation.

    Science.gov (United States)

    Luetzkendorf, Jana; Nerger, Katrin; Hering, Julian; Moegel, Angelika; Hoffmann, Katrin; Hoefers, Christiane; Mueller-Tidow, Carsten; Mueller, Lutz P

    2015-02-01

    The immunomodulating capacity of multipotent mesenchymal stromal cells (MSCs) qualifies them as a therapeutic tool in several diseases. However, repeated transplantation with products of reproducible characteristics may be required. This could be achieved with cryopreserved aliquots of Good Manufacturing Practice (GMP)-grade MSCs. However, the impact of cryopreservation on the characteristics of GMP-MSCs is ill defined. We produced fresh and cryopreserved MSCs from human donors with a xenogen-free GMP protocol. Immunogenicity and immunomodulating capacity were tested in co-culture with putative recipient-specific peripheral blood mononuclear cells (PBMCs). Risk of malignant transformation was assessed in vitro and in vivo. Cryopreservation had no impact on viability and consensus criteria of MSCs. In co-culture with PBMCs, MSCs showed low immunogenicity and suppressed mitogen-stimulated proliferation of PBMC irrespective of cryopreservation. Cytogenetic aberrations were not observed consistently in fresh and cryopreserved products, and no signs of malignant transformation occurred in functional assays. MSC products from an elderly pretreated donor showed reduced functional quality, but imminent failure of functional criteria could be detected by an increased population doubling time in early passages. This study is the first systematic analysis on cryopreservation of xenogen-free human bone marrow-derived GMP-MSCs. The data support that cryopreservation does not alter the characteristics of the cells and thus may allow the generation of products for serial transplantation. In addition, the protocol allowed early detection of MSC products with low functional capacity. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  11. Evolutionary trends of European bat lyssavirus type 2 including genetic characterization of Finnish strains of human and bat origin 24 years apart.

    Science.gov (United States)

    Jakava-Viljanen, Miia; Miia, Jakava-Viljanen; Nokireki, Tiina; Tiina, Nokireki; Sironen, Tarja; Tarja, Sironen; Vapalahti, Olli; Olli, Vapalahti; Sihvonen, Liisa; Liisa, Sihvonen; Huovilainen, Anita; Anita, Huovilainen

    2015-06-01

    Among other Lyssaviruses, Daubenton's and pond-bat-related European bat lyssavirus type 2 (EBLV-2) can cause human rabies. To investigate the diversity and evolutionary trends of EBLV-2, complete genome sequences of two Finnish isolates were analysed. One originated from a human case in 1985, and the other originated from a bat in 2009. The overall nucleotide and deduced amino acid sequence identity of the two Finnish isolates were high, as well as the similarity to fully sequenced EBLV-2 strains originating from the UK and the Netherlands. In phylogenetic analysis, the EBLV-2 strains formed a monophyletic group that was separate from other bat-type lyssaviruses, with significant support. EBLV-2 shared the most recent common ancestry with Bokeloh bat lyssavirus (BBLV) and Khujan virus (KHUV). EBLV-2 showed limited diversity compared to RABV and appears to be well adapted to its host bat species. The slow tempo of viral evolution was evident in the estimations of divergence times for EBLV-2: the current diversity was estimated to have built up during the last 2000 years, and EBLV-2 diverged from KHUV about 8000 years ago. In a phylogenetic tree of partial N gene sequences, the Finnish EBLV-2 strains clustered with strains from Central Europe, supporting the hypothesis that EBLV-2 circulating in Finland might have a Central European origin. The Finnish EBLV-2 strains and a Swiss strain were estimated to have diverged from other EBLV-2 strains during the last 1000 years, and the two Finnish strains appear to have evolved from a common ancestor during the last 200 years.

  12. Expanding Free School-based Human Papilloma Virus (HPV Vaccination Programs to Include School-aged Males in Nova Scotia, Canada

    Directory of Open Access Journals (Sweden)

    Hannah Krater-Melamed

    2017-06-01

    Full Text Available Bill 70 (HPV Vaccine Act was presented to the Nova Scotia House of Assembly with the aim of expanding the current Nova Scotia school-based HPV vaccination program to include males. In recent years, increased awareness of HPV and HPV-caused cancers has led to the implementation of school-based female HPV vaccination programs across Canada. Changing guidelines, based on recent evidence, suggest that males should also be included in these programs. Program expansion to include males aims to reduce the prevalence of HPV-causing cancers and their ensuing costs, to promote equal access to healthcare services, and to make Nova Scotia a leader in HPV prevention. Support from the Canadian public and high profile political actors along with pressure from other provinces and interest groups, including the Society of Obstetricians and Gynaecologists of Canada, influenced the passing of the HPV Vaccine Act. In order to implement this reform, the provincial financial commitment to the previous HPV program was expanded to cover the cost of male vaccination.

  13. Immobilized Lentivirus Vector on Chondroitin Sulfate-Hyaluronate Acid-Silk Fibroin Hybrid Scaffold for Tissue-Engineered Ligament-Bone Junction

    Directory of Open Access Journals (Sweden)

    Liguo Sun

    2014-01-01

    Full Text Available The lack of a fibrocartilage layer between graft and bone remains the leading cause of graft failure after anterior cruciate ligament (ACL reconstruction. The objective of this study was to develop a gene-modified silk cable-reinforced chondroitin sulfate-hyaluronate acid-silk fibroin (CHS hybrid scaffold for reconstructing the fibrocartilage layer. The scaffold was fabricated by lyophilizing the CHS mixture with braided silk cables. The scanning electronic microscopy (SEM showed that microporous CHS sponges were formed around silk cables. Each end of scaffold was modified with lentiviral-mediated transforming growth factor-β3 (TGF-β3 gene. The cells on scaffold were transfected by bonded lentivirus. In vitro culture demonstrated that mesenchymal stem cells (MSCs on scaffolds proliferated vigorously and produced abundant collagen. The transcription levels of cartilage-specific genes also increased with culture time. After 2 weeks, the MSCs were distributed uniformly throughout scaffold. Deposited collagen was also found to increase. The chondral differentiation of MSCs was verified by expressions of collagen II and TGF-β3 genes in mRNA and protein level. Histology also confirmed the production of cartilage extracellular matrix (ECM components. The results demonstrated that gene-modified silk cable-reinforced CHS scaffold was capable of supporting cell proliferation and differentiation to reconstruct the cartilage layer of interface.

  14. Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy.

    Science.gov (United States)

    Tschernutter, M; Schlichtenbrede, F C; Howe, S; Balaggan, K S; Munro, P M; Bainbridge, J W B; Thrasher, A J; Smith, A J; Ali, R R

    2005-04-01

    The Royal College of Surgeons (RCS) rat is a well-characterized model of autosomal recessive retinitis pigmentosa (RP) due to a defect in the retinal pigment epithelium (RPE). It is homozygous for a null mutation in the gene encoding , a receptor tyrosine kinase found in RPE cells, that is required for phagocytosis of shed photoreceptor outer segments. The absence of Mertk results in accumulation of outer segment debris. This subsequently leads to progressive loss of photoreceptor cells. In order to evaluate the efficacy of lentiviral-mediated gene replacement therapy in the RCS rat, we produced recombinant VSV-G pseudotyped HIV-1-based lentiviruses containing a murine Mertk cDNA driven by a spleen focus forming virus (SFFV) promoter. The vector was subretinally injected into the right eye of 10-day-old RCS rats; the left eye was left untreated as an internal control. Here, we present a detailed assessment of the duration and extent of the morphological rescue and the resulting functional benefits. We examined animals at various time points over a period of 7 months by light and electron microscopy, and electroretinography. We observed correction of the phagocytic defect, slowing of photoreceptor cell loss and preservation of retinal function for up to 7 months. This study demonstrates the potential of gene therapy approaches for the treatment of retinal degenerations caused by defects specific to the RPE and supports the use of lentiviral vectors for the treatment of such disorders.

  15. [Intramuscular injection of lentivirus-mediated EPAS1 gene improves hind limb ischemia and its mechanism in a rat model of peripheral artery vascular disease].

    Science.gov (United States)

    Wang, Zhihong; Gu, Hongbin; Yang, Fan; Xie, Huajie; Sheng, Lei; Li, Mingfei

    2017-11-01

    Objective To investigate the effect of over-expressed endothelial Per-Arnt-Sim domain protein 1 (EPAS1) on peripheral arterial disease (PAD) in a rat model. Methods PAD rat model was established by external iliac artery ligation followed by lentivirus-mediated EPAS1 gene injection into rat right adductor magnus. The models were evaluated by quantitative analysis of gait disturbance. The changes of blood flow in the posterior extremity of the rats were detected using laser Doppler. The expressions of EPAS1, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) mRNAs were tested by real-time quantitative PCR. The expression of α-smooth muscle actin (αSMA) was detected by immunohistochemical staining. Results Compared with lenti-EGFP group, rat hind limb function and circulation got recovered obviously 7 days after lenti-EPAS1 injection. The mRNA expressions of EPAS1, HGF, bFGF, and VEGF were up-regulated in the lenti-EPAS1-treated sites.The expression of αSMA showed an obvious increase in the lenti-EPAS1-treated muscles. Conclusion Over-expressed lenti-EPAS1 can promote angiogenesis via the up-regulation of EPAS1-related angiogenic factors in the muscles of the affected hind limb and reduce gait disturbance.

  16. A comparative assessment of human exposure to tetrabromobisphenol A and eight bisphenols including bisphenol A via indoor dust ingestion in twelve countries.

    Science.gov (United States)

    Wang, Wei; Abualnaja, Khalid O; Asimakopoulos, Alexandros G; Covaci, Adrian; Gevao, Bondi; Johnson-Restrepo, Boris; Kumosani, Taha A; Malarvannan, Govindan; Minh, Tu Binh; Moon, Hyo-Bang; Nakata, Haruhiko; Sinha, Ravindra K; Kannan, Kurunthachalam

    2015-10-01

    Tetrabromobisphenol A (TBBPA) and eight bisphenol analogues (BPs) including bisphenol A (BPA) were determined in 388 indoor (including homes and microenvironments) dust samples collected from 12 countries (China, Colombia, Greece, India, Japan, Kuwait, Pakistan, Romania, Saudi Arabia, South Korea, U.S., and Vietnam). The concentrations of TBBPA and sum of eight bisphenols (ƩBPs) in dust samples ranged from exposure doses through diet, dust ingestion accounted for less than 10% of the total exposure doses in China and the U.S. For TBBPA, the EDI for infants and toddlers ranged from 0.01 to 3.4 ng/kg bw/day, and dust ingestion is an important pathway for exposure accounting for 3.8-35% (median) of exposure doses in China. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Insulin-induced inhibition of gluconeogenesis genes, including glutamic pyruvic transaminase 2, is associated with reduced histone acetylation in a human liver cell line.

    Science.gov (United States)

    Honma, Kazue; Kamikubo, Michiko; Mochizuki, Kazuki; Goda, Toshinao

    2017-06-01

    Hepatic glutamic pyruvic transaminase (GPT; also known as alanine aminotransferase) is a gluconeogenesis enzyme that catalyzes conversions between alanine and pyruvic acid. It is also used as a blood biomarker for hepatic damage. In this study, we investigated whether insulin regulates GPT expression, as it does for other gluconeogenesis genes, and if this involves the epigenetic modification of histone acetylation. Human liver-derived HepG2 cells were cultured with 0.5-100nM insulin for 8h, and the mRNA expression of GPT, glutamic-oxaloacetic transaminase (GOT), γ-glutamyltransferase (GGT), PCK1, G6PC and FBP1 was measured. We also investigated the extent of histone acetylation around these genes. Insulin suppressed the mRNA expression of gluconeogenesis genes (GPT2, GOT1, GOT2, GGT1, GGT2, G6PC, and PCK1) in HepG2 cells in a dose-dependent manner. mRNA levels of GPT2, but not GPT1, were decreased by insulin. Histone acetylation was also reduced around GPT2, G6PC, and PCK1 in response to insulin. The expression of GPT2 and other gluconeogenesis genes such as G6PC and PCK1 was suppressed by insulin, in association with decreases in histone H3 and H4 acetylation surrounding these genes. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Human 45,X fibroblast transcriptome reveals distinct differentially expressed genes including long noncoding RNAs potentially associated with the pathophysiology of Turner syndrome.

    Directory of Open Access Journals (Sweden)

    Shriram N Rajpathak

    Full Text Available Turner syndrome is a chromosomal abnormality characterized by the absence of whole or part of the X chromosome in females. This X aneuploidy condition is associated with a diverse set of clinical phenotypes such as gonadal dysfunction, short stature, osteoporosis and Type II diabetes mellitus, among others. These phenotypes differ in their severity and penetrance among the affected individuals. Haploinsufficiency for a few X linked genes has been associated with some of these disease phenotypes. RNA sequencing can provide valuable insights to understand molecular mechanism of disease process. In the current study, we have analysed the transcriptome profiles of human untransformed 45,X and 46,XX fibroblast cells and identified differential expression of genes in these two karyotypes. Functional analysis revealed that these differentially expressing genes are associated with bone differentiation, glucose metabolism and gonadal development pathways. We also report differential expression of lincRNAs in X monosomic cells. Our observations provide a basis for evaluation of cellular and molecular mechanism(s in the establishment of Turner syndrome phenotypes.

  19. An Atypical Human Induced Pluripotent Stem Cell Line With a Complex, Stable, and Balanced Genomic Rearrangement Including a Large De Novo 1q Uniparental Disomy

    Science.gov (United States)

    Steichen, Clara; Maluenda, Jérôme; Tosca, Lucie; Luce, Eléanor; Pineau, Dominique; Dianat, Noushin; Hannoun, Zara; Tachdjian, Gérard; Melki, Judith

    2015-01-01

    Human induced pluripotent stem cells (hiPSCs) hold great promise for cell therapy through their use as vital tools for regenerative and personalized medicine. However, the genomic integrity of hiPSCs still raises some concern and is one of the barriers limiting their use in clinical applications. Numerous articles have reported the occurrence of aneuploidies, copy number variations, or single point mutations in hiPSCs, and nonintegrative reprogramming strategies have been developed to minimize the impact of the reprogramming process on the hiPSC genome. Here, we report the characterization of an hiPSC line generated by daily transfections of modified messenger RNAs, displaying several genomic abnormalities. Karyotype analysis showed a complex genomic rearrangement, which remained stable during long-term culture. Fluorescent in situ hybridization analyses were performed on the hiPSC line showing that this karyotype is balanced. Interestingly, single-nucleotide polymorphism analysis revealed the presence of a large 1q region of uniparental disomy (UPD), demonstrating for the first time that UPD can occur in a noncompensatory context during nonintegrative reprogramming of normal fibroblasts. PMID:25650439

  20. Phage T4 endonuclease V stimulates DNA repair replication in isolated nuclei from ultraviolet-irradiated human cells, including xeroderma pigmentosum fibroblasts

    International Nuclear Information System (INIS)

    Smith, C.A.; Hanawalt, P.C.

    1978-01-01

    The repair mode of DNA replication has been demonstrated in isolated nuclei from uv-irradiated human cells. Nuclei are incubated in a mixture containing [ 3 H]thymidine triphosphate and bromodeoxyuridine triphosphate in a 1:5 ratio. The 3 H at the density of parental DNA in alkaline CsCl density gradients is then a measure of repair. In nuclei prepared from WI38 cells 30 min after irradiation, repair replication is uv-dependent and proceeds at approximately the in vivo rate for 5 min. Repair replication is reduced in irradiated nuclei or in nuclei prepared immediately after irradiation. It is Mg 2+ -dependent and stimulated by added ATP and deoxyribonucleoside triphosphates. No repair replication is observed in nuclei from xeroderma pigmentosum (complementation group A) cells. However, upon addition of coliphage T4 endonuclease V, which specifically nicks DNA containing pyrimidine dimers, repair replication is observed in nuclei from irradiated xeroderma pigmentosum cells and is stimulated in WI38 nuclei. The reaction then persists for an hour and is dependent upon added ATP and deoxyribonucleoside triphosphates. The repair label is in stretches of roughly 35 nucleotides, as it is in intact cells. Added pancreatic DNase does not promote uv-dependent repair synthesis. Our results support the view that xeroderma pigmentosum (group A) cells are defective in the incision step of the DNA excision repair pathway, and demonstrate the utility of this system for probing DNA repair mechanisms

  1. Peptide binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes, and include HLA-B27-like alleles

    OpenAIRE

    Mothé, Bianca R.; Southwood, Scott; Sidney, John; English, A. Michelle; Wriston, Amanda; Hoof, Ilka; Shabanowitz, Jeffrey; Hunt, Donald F.; Sette, Alessandro

    2013-01-01

    Chinese rhesus macaques are of particular interest in SIV/HIV research as these animals have prolonged kinetics of disease progression to AIDS, compared to their Indian counterparts, suggesting that they may be a better model for HIV. Nevertheless, the specific mechanism(s) accounting for these kinetics remains unclear. The study of Major Histocompatibility Complex (MHC) molecules, including their MHC:peptide binding motifs, provides valuable information for measuring cellular immune response...

  2. Digital Genome-Wide ncRNA Expression, Including SnoRNAs, across 11 Human Tissues Using PolyA-Neutral Amplification

    Science.gov (United States)

    Castle, John C.; Armour, Christopher D.; Löwer, Martin; Haynor, David; Biery, Matthew; Bouzek, Heather; Chen, Ronghua; Jackson, Stuart; Johnson, Jason M.; Rohl, Carol A.; Raymond, Christopher K.

    2010-01-01

    Non-coding RNAs (ncRNAs) are an essential class of molecular species that have been difficult to monitor on high throughput platforms due to frequent lack of polyadenylation. Using a polyadenylation-neutral amplification protocol and next-generation sequencing, we explore ncRNA expression in eleven human tissues. ncRNAs 7SL, U2, 7SK, and HBII-52 are expressed at levels far exceeding mRNAs. C/D and H/ACA box snoRNAs are associated with rRNA methylation and pseudouridylation, respectively: spleen expresses both, hypothalamus expresses mainly C/D box snoRNAs, and testes show enriched expression of both H/ACA box snoRNAs and RNA telomerase TERC. Within the snoRNA 14q cluster, 14q(I-6) is expressed at much higher levels than other cluster members. More reads align to mitochondrial than nuclear tRNAs. Many lincRNAs are actively transcribed, particularly those overlapping known ncRNAs. Within the Prader-Willi syndrome loci, the snoRNA HBII-85 (group I) cluster is highly expressed in hypothalamus, greater than in other tissues and greater than group II or III. Additionally, within the disease locus we find novel transcription across a 400,000 nt span in ovaries. This genome-wide polyA-neutral expression compendium demonstrates the richness of ncRNA expression, their high expression patterns, their function-specific expression patterns, and is publicly available. PMID:20668672

  3. Digital genome-wide ncRNA expression, including SnoRNAs, across 11 human tissues using polyA-neutral amplification.

    Directory of Open Access Journals (Sweden)

    John C Castle

    Full Text Available Non-coding RNAs (ncRNAs are an essential class of molecular species that have been difficult to monitor on high throughput platforms due to frequent lack of polyadenylation. Using a polyadenylation-neutral amplification protocol and next-generation sequencing, we explore ncRNA expression in eleven human tissues. ncRNAs 7SL, U2, 7SK, and HBII-52 are expressed at levels far exceeding mRNAs. C/D and H/ACA box snoRNAs are associated with rRNA methylation and pseudouridylation, respectively: spleen expresses both, hypothalamus expresses mainly C/D box snoRNAs, and testes show enriched expression of both H/ACA box snoRNAs and RNA telomerase TERC. Within the snoRNA 14q cluster, 14q(I-6 is expressed at much higher levels than other cluster members. More reads align to mitochondrial than nuclear tRNAs. Many lincRNAs are actively transcribed, particularly those overlapping known ncRNAs. Within the Prader-Willi syndrome loci, the snoRNA HBII-85 (group I cluster is highly expressed in hypothalamus, greater than in other tissues and greater than group II or III. Additionally, within the disease locus we find novel transcription across a 400,000 nt span in ovaries. This genome-wide polyA-neutral expression compendium demonstrates the richness of ncRNA expression, their high expression patterns, their function-specific expression patterns, and is publicly available.

  4. Human rotavirus vaccine is highly efficacious when coadministered with routine expanded program of immunization vaccines including oral poliovirus vaccine in Latin America.

    Science.gov (United States)

    Tregnaghi, Miguel W; Abate, Héctor J; Valencia, Alejandra; Lopez, Pio; Da Silveira, Themis Reverbel; Rivera, Luis; Rivera Medina, Doris Maribel; Saez-Llorens, Xavier; Gonzalez Ayala, Silvia Elena; De León, Tirza; Van Doorn, Leen-Jan; Pilar Rubio, Maria Del; Suryakiran, Pemmaraju Venkata; Casellas, Javier M; Ortega-Barria, Eduardo; Smolenov, Igor V; Han, Htay-Htay

    2011-06-01

    The efficacy of a rotavirus vaccine against severe rotavirus gastroenteritis when coadministered with routine Expanded Program on Immunization (EPI) vaccines including oral polio vaccine (OPV) was evaluated in this study. Double-blind, randomized (2:1), placebo-controlled study conducted across 6 Latin American countries. Healthy infants (N = 6568) 6 to 12 weeks of age received 2 doses of RIX4414 vaccine or placebo following a 0, 1- to 2-month schedule. Routine vaccines including OPV were coadministered according to local EPI schedule. Vaccine efficacy (VE) against severe rotavirus gastroenteritis caused by circulating wild-type rotavirus from 2 weeks post-Dose 2 until 1 year of age was calculated with 95% confidence interval [CI]. Safety was assessed during the entire study period. Immunogenicity of RIX4414 and OPV was also assessed. During the efficacy follow-up period (mean duration = 7.4 months), 7 and 19 cases of severe rotavirus gastroenteritis were reported in the vaccine and placebo groups, respectively, with a VE of 81.6% (95% CI: 54.4-93.5). VE against severe rotavirus gastroenteritis caused by G1 type was 100% (95% CI: rotavirus types, respectively. There was no difference (P = 0.514) in the incidence of serious adverse events reported in the 2 groups. Antirotavirus IgA seropositivity rate at 1 to 2 months post-Dose 2 was 61.4% (95% CI: 53.7-68.6) in the RIX4414 group; similar seroprotection rates (≥96.0%) against the 3 antipoliovirus types was observed 1 month post-Dose 3 of OPV in both groups. RIX4414 was highly efficacious against severe rotavirus gastroenteritis caused by the circulating wild-type rotavirus (G1 and non-G1) when coadministered with routine EPI vaccines including OPV.

  5. An optimized method for fatty acid analysis, including quantification of trans fatty acids, in human adipose tissue by gas-liquid chromatography

    DEFF Research Database (Denmark)

    Bysted, Anette; Cold, S; Hølmer, Gunhild Kofoed

    1999-01-01

    Considering the need for a quick direct method for measurement of the fatty acid composition including trans isomers ofhuman adipose tissue we have developed a procedure using gas-liquid chromatography (GLC) alone, which is thussuitable for validation of fatty acid status in epidemiological studies...... for 25 min, and finally raised at 25 degrees C/min to 225 degrees C. The trans and cis isomers of18:1 were well separated from each other, as shown by silver-ion thin-layer chromatography. Verification by standardsshowed that the trans 18:1 isomers with a double bond in position 12 or lower were...

  6. Rare events in earth history include the LB1 human skeleton from Flores, Indonesia, as a developmental singularity, not a unique taxon

    Science.gov (United States)

    Eckhardt, Robert B.; Henneberg, Maciej; Weller, Alex S.; Hsü, Kenneth J.

    2014-08-01

    The original centrally defining features of "Homo floresiensis" are based on bones represented only in the single specimen LB1. Initial published values of 380-mL endocranial volume and 1.06-m stature are markedly lower than later attempts to confirm them, and facial asymmetry originally unreported, then denied, has been established by our group and later confirmed independently. Of nearly 200 syndromes in which microcephaly is one sign, more than half include asymmetry as another sign and more than one-fourth also explicitly include short stature. The original diagnosis of the putative new species noted and dismissed just three developmental abnormalities. Subsequent independent attempts at diagnosis (Laron Syndrome, Majewski osteodysplastic primordial dwarfism type II, cretinism) have been hampered a priori by selectively restricted access to specimens, and disparaged a posteriori using data previously unpublished, without acknowledging that all of the independent diagnoses corroborate the patent abnormal singularity of LB1. In this report we establish in detail that even in the absence of a particular syndromic diagnosis, the originally defining features of LB1 do not establish either the uniqueness or normality necessary to meet the formal criteria for a type specimen of a new species. In a companion paper we present a new syndromic diagnosis for LB1.

  7. The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation.

    Science.gov (United States)

    Janardhanan, Rajiv; Yang, Binxia; Kilari, Sreenivasulu; Leof, Edward B; Mukhopadhyay, Debabrata; Misra, Sanjay

    2016-04-01

    To determine if a second dose of a lentivirus mediated small hairpin RNA that inhibits Vegf-A gene expression (LV-shRNA-Vegf-A) can improve lumen vessel area (LVA) of the outflow vein of an arteriovenous fistula (AVF) and decrease venous neointimal hyperplasia. Chronic kidney disease was created in C57BL/6 mice; 28 days later, an AVF was created by connecting the right carotid artery to the ipsilateral jugular vein. Immediately after AVF creation, 5 × 10(6) plaque-forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein, and a second dose of the same treatment was administered 14 days later. Animals were sacrificed at 21 days, 28 days, and 42 days after AVF creation for reverse transcription polymerase chain reaction and histomorphometric analyses. By day 21, there was a 125% increase in the average LVA (day 21, P = .11), with a decrease in cell proliferation (day 21, P = .0079; day 28, P = .28; day 42, P = .5), decrease in α-smooth muscle cell actin staining (day 21, P < .0001; day 28, P < .05; day 42, P = .59), and decrease in hypoxic stress (day 21, P < .001; day 28, P = .28; day 42, P = .46) in LV versus control shRNA vessels. A second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  8. Partial Correction of Psoriasis upon Genetic Knock-Down of Human TNF-α by Lentivirus-Encoded shRNAs in a Xenograft Mouse Model

    DEFF Research Database (Denmark)

    Jakobsen, Maria; Stenderup, Karin; Rosada, Cecilia

    samples treated with irrelevant shRNAs, were selected and cloned into lentiviral vectors. The lentiviral vectors expressing TNF- shRNAs were used to transduce HEK-293 cells and verify vector-derived knock-down of stable TNF- expression in vitro. The most efficient TNF- -directed shRNA, which in cell lines...

  9. Radiochemotherapy of hepatocarcinoma via lentivirus-mediated transfer of human sodium iodide symporter gene and herpes simplex virus thymidine kinase gene

    Energy Technology Data Exchange (ETDEWEB)

    Chen Libo, E-mail: libochen888@hotmail.com [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China); Guo Guoying [Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018 (China); Liu Tianjing; Guo Lihe [Division of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Zhu Ruisen [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China)

    2011-07-15

    Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system has been widely used as a traditional gene therapy modality, and the sodium/iodide symporter gene (NIS) has been found to be a novel therapeutic gene. Since the therapeutic effects of radioiodine therapy or prodrug chemotherapy on cancers following NIS or HSV-TK gene transfer need to be enhanced, this study was designed to investigate the feasibility of radiochemotherapy for hepatocarcinoma via coexpression of NIS gene and HSV-TK gene. Methods: HepG2 cells were stably transfected with NIS, TK and GFP gene via recombinant lentiviral vector and named HepG2/NTG. Gene expression was examined by reverse transcriptase polymerase chain reaction, fluorescence imaging and iodide uptake. The therapeutic effects were assessed by MTT assay and clonogenic assay. Results: HepG2/NTG cells concentrated {sup 125}I{sup -} up to 76-fold higher than the wild-type cells within 20 min, and the efflux happened with a T{sub 1/2eff} of less than 10 min. The iodide uptake in HepG2/NTG cells was specifically inhibited by sodium perchlorate. Dose-dependent toxicity to HepG2/NTG cells by either GCV or {sup 131}I was revealed by clonogenic assay and MTT assay, respectively. The survival rate of HepG2/NTG cells decreased to 49.7%{+-}2.5%, 43.4%{+-}2.8% and 8.6%{+-}1.2% after exposure to {sup 131}I, GCV and combined therapy, respectively. Conclusion: We demonstrate that radiochemotherapy of hepatocarcinoma via lentiviral-mediated coexpression of NIS gene and HSV-TK gene leads to stronger killing effect than single treatment, and in vivo studies are needed to verify these findings.

  10. Radiochemotherapy of hepatocarcinoma via lentivirus-mediated transfer of human sodium iodide symporter gene and herpes simplex virus thymidine kinase gene

    International Nuclear Information System (INIS)

    Chen Libo; Guo Guoying; Liu Tianjing; Guo Lihe; Zhu Ruisen

    2011-01-01

    Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system has been widely used as a traditional gene therapy modality, and the sodium/iodide symporter gene (NIS) has been found to be a novel therapeutic gene. Since the therapeutic effects of radioiodine therapy or prodrug chemotherapy on cancers following NIS or HSV-TK gene transfer need to be enhanced, this study was designed to investigate the feasibility of radiochemotherapy for hepatocarcinoma via coexpression of NIS gene and HSV-TK gene. Methods: HepG2 cells were stably transfected with NIS, TK and GFP gene via recombinant lentiviral vector and named HepG2/NTG. Gene expression was examined by reverse transcriptase polymerase chain reaction, fluorescence imaging and iodide uptake. The therapeutic effects were assessed by MTT assay and clonogenic assay. Results: HepG2/NTG cells concentrated 125 I - up to 76-fold higher than the wild-type cells within 20 min, and the efflux happened with a T 1/2eff of less than 10 min. The iodide uptake in HepG2/NTG cells was specifically inhibited by sodium perchlorate. Dose-dependent toxicity to HepG2/NTG cells by either GCV or 131 I was revealed by clonogenic assay and MTT assay, respectively. The survival rate of HepG2/NTG cells decreased to 49.7%±2.5%, 43.4%±2.8% and 8.6%±1.2% after exposure to 131 I, GCV and combined therapy, respectively. Conclusion: We demonstrate that radiochemotherapy of hepatocarcinoma via lentiviral-mediated coexpression of NIS gene and HSV-TK gene leads to stronger killing effect than single treatment, and in vivo studies are needed to verify these findings.

  11. Optimization of in vitro cell labeling methods for human umbilical cord-derived mesenchymal stem cells.

    Science.gov (United States)

    Tao, R; Sun, T-J; Han, Y-Q; Xu, G; Liu, J; Han, Y-F

    2014-01-01

    Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are a novel source of seed cells for cell therapy and tissue engineering. However, in vitro labeling methods for hUCMSCs need to be optimized for better detection of transplanted cells. To identify the most stable and efficient method for labeling hUCMSCs in vitro. hUCMSCs were isolated using a modified enzymatic digestion procedure and cultured. hUCMSCs of passage three (P3) were then labeled with BrdU, PKH26, or lentivirus-GFP and passaged further. Cells from the first labeled passage (LP1), the fourth labeled passage (LP4) and later passages were observed using a fluorescence microscope. The differentiation potential of LP4 cells was assessed by induction with adipogenic and osteogenic medium. Flow cytometry was used to measure the percentage of labeled cells and the percentage of apoptotic or dead cells. The labeling efficiencies of the three hUCMSC-labeling methods were compared in vitro. BrdU, PKH26, and lentivirus-GFP all labeled LP1 cells with high intensity and clarity. However, the BrdU labeling of the LP4 cells was vague and not localized to the cell nuclei; LP9 cells were not detected under a fluorescence microscope. There was also a significant decrease in the fluorescence intensity of PKH26-labeled LP4 cells, and LP11 cells were not detected under a fluorescence microscope. However, the fluorescence of LP4 cells labeled with lentivirus-GFP remained strong, and cells labeled with lentivirus-GFP were detected up to LP14 under a fluorescence microscope. Statistical analyses indicated that percentages of LP1 cells labeled with PKH26 and lentivirus-GFP were significantly higher than that of cells labeled with BrdU (p 0.05) was observed between the death rates of labeled and unlabeled cells. Lentivirus-GFP is a valid method for long-term in vitro labeling, and it may be used as a long-term hUCMSC tracker following transplantation in vivo.

  12. New seismograph includes filters

    Energy Technology Data Exchange (ETDEWEB)

    1979-11-02

    The new Nimbus ES-1210 multichannel signal enhancement seismograph from EG and G geometrics has recently been redesigned to include multimode signal fillers on each amplifier. The ES-1210F is a shallow exploration seismograph for near subsurface exploration such as in depth-to-bedrock, geological hazard location, mineral exploration, and landslide investigations.

  13. Analytic device including nanostructures

    KAUST Repository

    Di Fabrizio, Enzo M.; Fratalocchi, Andrea; Totero Gongora, Juan Sebastian; Coluccio, Maria Laura; Candeloro, Patrizio; Cuda, Gianni

    2015-01-01

    A device for detecting an analyte in a sample comprising: an array including a plurality of pixels, each pixel including a nanochain comprising: a first nanostructure, a second nanostructure, and a third nanostructure, wherein size of the first nanostructure is larger than that of the second nanostructure, and size of the second nanostructure is larger than that of the third nanostructure, and wherein the first nanostructure, the second nanostructure, and the third nanostructure are positioned on a substrate such that when the nanochain is excited by an energy, an optical field between the second nanostructure and the third nanostructure is stronger than an optical field between the first nanostructure and the second nanostructure, wherein the array is configured to receive a sample; and a detector arranged to collect spectral data from a plurality of pixels of the array.

  14. Saskatchewan resources. [including uranium

    Energy Technology Data Exchange (ETDEWEB)

    1979-09-01

    The production of chemicals and minerals for the chemical industry in Saskatchewan are featured, with some discussion of resource taxation. The commodities mentioned include potash, fatty amines, uranium, heavy oil, sodium sulfate, chlorine, sodium hydroxide, sodium chlorate and bentonite. Following the successful outcome of the Cluff Lake inquiry, the uranium industry is booming. Some developments and production figures for Gulf Minerals, Amok, Cenex and Eldorado are mentioned.

  15. Being Included and Excluded

    DEFF Research Database (Denmark)

    Korzenevica, Marina

    2016-01-01

    Following the civil war of 1996–2006, there was a dramatic increase in the labor mobility of young men and the inclusion of young women in formal education, which led to the transformation of the political landscape of rural Nepal. Mobility and schooling represent a level of prestige that rural...... politics. It analyzes how formal education and mobility either challenge or reinforce traditional gendered norms which dictate a lowly position for young married women in the household and their absence from community politics. The article concludes that women are simultaneously excluded and included from...... community politics. On the one hand, their mobility and decision-making powers decrease with the increase in the labor mobility of men and their newly gained education is politically devalued when compared to the informal education that men gain through mobility, but on the other hand, schooling strengthens...

  16. Identification of a developmental gene expression signature, including HOX genes, for the normal human colonic crypt stem cell niche: overexpression of the signature parallels stem cell overpopulation during colon tumorigenesis.

    Science.gov (United States)

    Bhatlekar, Seema; Addya, Sankar; Salunek, Moreh; Orr, Christopher R; Surrey, Saul; McKenzie, Steven; Fields, Jeremy Z; Boman, Bruce M

    2014-01-15

    Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, 68 in the middle, and 131 in the top. Among genes upregulated in the bottom, ∼30% were classified as growth and/or developmental genes including several in the PI3 kinase pathway, a six-transmembrane protein STAMP1, and two homeobox (HOXA4, HOXD10) genes. qPCR and immunostaining validated that HOXA4 and HOXD10 are selectively expressed in the normal crypt bottom and are overexpressed in colon carcinomas (CRCs). Immunostaining showed that HOXA4 and HOXD10 are co-expressed with the SC markers CD166 and ALDH1 in cells at the normal crypt bottom, and the number of these co-expressing cells is increased in CRCs. Thus, our findings show that these two HOX genes are selectively expressed in colonic SCs and that HOX overexpression in CRCs parallels the SC overpopulation that occurs during CRC development. Our study suggests that developmental genes play key roles in the maintenance of normal SCs and crypt renewal, and contribute to the SC overpopulation that drives colon tumorigenesis.

  17. The Protection of the Right to Education by International Law: Including a Systematic Analysis of Article 13 of the International Covenant on Economic, Social and Cultural Rights. International Studies in Human Rights, 82

    Science.gov (United States)

    Beiter, Klaus Dieter

    2006-01-01

    A trend has emerged of not defining education as a "human right" anymore, but of rather calling it a "human need". This has paved the way for an ever increasing commercialisation of education, excluding the poor from access to education. A problem at a different level is that states often do not know what is expected of them…

  18. Anatomy of the pectoral and forelimb muscles of wildtype and green fluorescent protein-transgenic axolotls and comparison with other tetrapods including humans: a basis for regenerative, evolutionary and developmental studies

    Science.gov (United States)

    Diogo, R; Tanaka, E M

    2012-01-01

    The axolotl Ambystoma mexicanum is one of the most used model organisms in evolutionary, developmental and regenerative studies, particularly because it can reconstitute a fully functional and complete forelimb/hindlimb. Surprisingly, there is no publication that describes all the pectoral and forelimb muscles of this species or provides a comparative framework between these muscles and those of other model organisms and of modern humans. In the present paper we describe and illustrate all these muscles in A. mexicanum and provide the first report about the myology of adults of a model organism that is based on analyses and dissections of both wildtype animals and transgenic animals that express green fluorescent protein (GFP) in muscle fibers. On the one hand, the inclusion of GFP-transgenic animals allows us to show the muscles as more commonly seen, and thus easier to understand, by current developmental and regenerative biologists. On the other hand, by including wildtype and GFP-transgenic animals and by visualizing these latter animals with and without a simultaneous transmission laser light, we were able to obtain a more complete and clearer understanding of the exact limit of the fleshy and tendinous parts of the muscles and their specific connections with the skeletal elements. This in turn allowed us to settle some controversies in previous anatomical and comparative studies. As most developmental, regenerative and evolutionary biologists are interested in comparing their observations of A. mexicanum with observations in other model organisms, and ultimately in using this information to increase the understanding of human evolution and medicine, we also provide tables showing the homologies between the pectoral and forelimb muscles of axolotls, of model organisms such as mice, frogs and chicken, and of Homo sapiens. An example illustrating the outcomes of using our methodology and of our observations is that they revealed that, contrary to what is often

  19. Anatomy of the pectoral and forelimb muscles of wildtype and green fluorescent protein-transgenic axolotls and comparison with other tetrapods including humans: a basis for regenerative, evolutionary and developmental studies.

    Science.gov (United States)

    Diogo, R; Tanaka, E M

    2012-12-01

    The axolotl Ambystoma mexicanum is one of the most used model organisms in evolutionary, developmental and regenerative studies, particularly because it can reconstitute a fully functional and complete forelimb/hindlimb. Surprisingly, there is no publication that describes all the pectoral and forelimb muscles of this species or provides a comparative framework between these muscles and those of other model organisms and of modern humans. In the present paper we describe and illustrate all these muscles in A. mexicanum and provide the first report about the myology of adults of a model organism that is based on analyses and dissections of both wildtype animals and transgenic animals that express green fluorescent protein (GFP) in muscle fibers. On the one hand, the inclusion of GFP-transgenic animals allows us to show the muscles as more commonly seen, and thus easier to understand, by current developmental and regenerative biologists. On the other hand, by including wildtype and GFP-transgenic animals and by visualizing these latter animals with and without a simultaneous transmission laser light, we were able to obtain a more complete and clearer understanding of the exact limit of the fleshy and tendinous parts of the muscles and their specific connections with the skeletal elements. This in turn allowed us to settle some controversies in previous anatomical and comparative studies. As most developmental, regenerative and evolutionary biologists are interested in comparing their observations of A. mexicanum with observations in other model organisms, and ultimately in using this information to increase the understanding of human evolution and medicine, we also provide tables showing the homologies between the pectoral and forelimb muscles of axolotls, of model organisms such as mice, frogs and chicken, and of Homo sapiens. An example illustrating the outcomes of using our methodology and of our observations is that they revealed that, contrary to what is often

  20. Erratum : De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies (American Journal of Human Genetics 95(4) (360–370)(S0002929714003838)(10.1016/j.ajhg.2014.08.013))

    NARCIS (Netherlands)

    Appenzeller, Silke; Balling, Rudi; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Craiu, Dana; De Jonghe, Peter; Depienne, Christel; Dimova, Petia; Djémié, Tania; Gormley, Padhraig; Guerrini, Renzo; Helbig, Ingo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jähn, Johanna A.; Klein, Karl Martin; Koeleman, Bobby; Komarek, Vladimir; Krause, Roland; Kuhlenbäumer, Gregor; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes R.; Lerche, Holger; Linnankivi, Tarja; Marini, Carla; May, Patrick; Møller, Rikke S.; Muhle, Hiltrud; Pal, Deb; Palotie, Aarno; Pendziwiat, Manuela; Robbiano, Angela; Roelens, Filip; Rosenow, Felix; Selmer, Kaja; Serratosa, Jose M.; Sisodiya, Sanjay M.; Stephani, Ulrich; Sterbova, Katalin; Striano, Pasquale; Suls, Arvid; Talvik, Tiina; von Spiczak, Sarah; Weber, Yvonne G.; Weckhuysen, Sarah; Zara, Federico; Abou-Khalil, Bassel; Alldredge, Brian K.; Andermann, Eva; Andermann, Frederick; Amrom, Dina; Bautista, Jocelyn F.; Berkovic, Samuel F.; Bluvstein, Judith; Boro, Alex; Cascino, Gregory; Consalvo, Damian; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael P.; Fiol, Miguel; Fountain, Nathan B.; French, Jacqueline; Friedman, Daniel; Geller, Eric B.; Glauser, Tracy; Glynn, Simon; Haas, Kevin; Haut, Sheryl R.; Hayward, Jean; Helmers, Sandra L.; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi E.; Knowlton, Robert C.; Kossoff, Eric H.; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel H.; McGuire, Shannon M.; Motika, Paul V.; Novotny, Edward J.; Ottman, Ruth; Paolicchi, Juliann M.; Parent, Jack; Park, Kristen; Poduri, Annapurna; Sadleir, Lynette G.; Scheffer, Ingrid E.; Shellhaas, Renée A; Sherr, Elliott; Shih, Jerry J.; Singh, Rani; Sirven, Joseph; Smith, Michael C.; Sullivan, Joe; Thio, Liu Lin; Venkat, Anu; Vining, Eileen P. G.; Von Allmen, Gretchen K.; Weisenberg, Judith L.; Widdess-Walsh, Peter; Winawer, Melodie R.; Allen, Andrew S.; Berkovic, Samuel F.; Cossette, Patrick; Delanty, Norman; Dlugos, Dennis; Eichler, Evan E.; Epstein, Michael P.; Glauser, Tracy; Goldstein, David B.; Han, Yujun; Heinzen, Erin L.; Johnson, Michael R.; Kuzniecky, Ruben; Lowenstein, Daniel H.; Marson, Anthony G.; Mefford, Heather C.; Nieh, Sahar Esmaeeli; O'Brien, Terence J.; Ottman, Ruth; Petrou, Stephen; Petrovski, Slavé; Poduri, Annapurna; Ruzzo, Elizabeth K.; Scheffer, Ingrid E.; Sherr, Elliott

    2017-01-01

    (The American Journal of Human Genetics 95, 360–370; October 2, 2014) In the list of consortium members for the Epilepsy Phenome/Genome Project, member Dina Amrom's name was misspelled as Amron. The authors regret the error.

  1. Births and deaths including fetal deaths

    Data.gov (United States)

    U.S. Department of Health & Human Services — Access to a variety of United States birth and death files including fetal deaths: Birth Files, 1968-2009; 1995-2005; Fetal death file, 1982-2005; Mortality files,...

  2. MiR-9 is overexpressed in spontaneous canine osteosarcoma and promotes a metastatic phenotype including invasion and migration in osteoblasts and osteosarcoma cell lines.

    Science.gov (United States)

    Fenger, Joelle M; Roberts, Ryan D; Iwenofu, O Hans; Bear, Misty D; Zhang, Xiaoli; Couto, Jason I; Modiano, Jaime F; Kisseberth, William C; London, Cheryl A

    2016-10-10

    MicroRNAs (miRNAs) regulate the expression of networks of genes and their dysregulation is well documented in human malignancies; however, limited information exists regarding the impact of miRNAs on the development and progression of osteosarcoma (OS). Canine OS exhibits clinical and molecular features that closely resemble the corresponding human disease and it is considered a well-established spontaneous animal model to study OS biology. The purpose of this study was to investigate miRNA dysregulation in canine OS. We evaluated miRNA expression in primary canine OS tumors and normal canine osteoblast cells using the nanoString nCounter system. Quantitative PCR was used to validate the nanoString findings and to assess miR-9 expression in canine OS tumors, OS cell lines, and normal osteoblasts. Canine osteoblasts and OS cell lines were stably transduced with pre-miR-9 or anti-miR-9 lentiviral constructs to determine the consequences of miR-9 on cell proliferation, apoptosis, invasion and migration. Proteomic and gene expression profiling of normal canine osteoblasts with enforced miR-9 expression was performed using 2D-DIGE/tandem mass spectrometry and RNA sequencing and changes in protein and mRNA expression were validated with Western blotting and quantitative PCR. OS cell lines were transduced with gelsolin (GSN) shRNAs to investigate the impact of GSN knockdown on OS cell invasion. We identified a unique miRNA signature associated with primary canine OS and identified miR-9 as being significantly overexpressed in canine OS tumors and cell lines compared to normal osteoblasts. Additionally, high miR-9 expression was demonstrated in tumor-specific tissue obtained from primary OS tumors. In normal osteoblasts and OS cell lines transduced with miR-9 lentivirus, enhanced invasion and migration were observed, but miR-9 did not affect cell proliferation or apoptosis. Proteomic and transcriptional profiling of normal canine osteoblasts overexpressing miR-9 identified

  3. Non-Primate Lentiviral Vectors and Their Applications in Gene Therapy for Ocular Disorders

    Directory of Open Access Journals (Sweden)

    Vincenzo Cavalieri

    2018-06-01

    Full Text Available Lentiviruses have a number of molecular features in common, starting with the ability to integrate their genetic material into the genome of non-dividing infected cells. A peculiar property of non-primate lentiviruses consists in their incapability to infect and induce diseases in humans, thus providing the main rationale for deriving biologically safe lentiviral vectors for gene therapy applications. In this review, we first give an overview of non-primate lentiviruses, highlighting their common and distinctive molecular characteristics together with key concepts in the molecular biology of lentiviruses. We next examine the bioengineering strategies leading to the conversion of lentiviruses into recombinant lentiviral vectors, discussing their potential clinical applications in ophthalmological research. Finally, we highlight the invaluable role of animal organisms, including the emerging zebrafish model, in ocular gene therapy based on non-primate lentiviral vectors and in ophthalmology research and vision science in general.

  4. 4-IBP, a σ1 Receptor Agonist, Decreases the Migration of Human Cancer Cells, Including Glioblastoma Cells, In Vitro and Sensitizes Them In Vitro and In Vivo to Cytotoxic Insults of Proapoptotic and Proautophagic Drugs

    Directory of Open Access Journals (Sweden)

    Veronique Mégalizzi

    2007-05-01

    Full Text Available Although the molecular function of cr receptors has not been fully defined and the natural ligand(s is still not known, there is increasing evidence that these receptors and their ligands might play a significant role in cancer biology. 4-(N-tibenzylpiperidin-4-yl-4iodobenzamide (4-IBP, a selective σ1, agonist, has been used to investigate whether this compound is able to modify: 1 in vitro the migration and proliferation of human cancer cells; 2 in vitro the sensitivity of human glioblastoma cells to cytotoxic drugs; and 3 in vivo in orthotopic glioblastoma and non-small cell lung carcinoma (NSCLC models the survival of mice coadministered cytotoxic agents. 4-IBP has revealed weak anti proliferative effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked concentration-dependent decreases in the growth of human A549 NSCLC and PC3 prostate cancer cells. The compound was also significantly antimigratory in all four cancer cell lines. This may result, at least in U373-MG cells, from modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373-MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and markedly decreased the expression of two proteins involved in drug resistance: glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.

  5. Stable shRNA Silencing of Lactate Dehydrogenase A (LDHA) in Human MDA-MB-231 Breast Cancer Cells Fails to Alter Lactic Acid Production, Glycolytic Activity, ATP or Survival.

    Science.gov (United States)

    Mack, Nzinga; Mazzio, Elizabeth A; Bauer, David; Flores-Rozas, Hernan; Soliman, Karam F A

    2017-03-01

    In the US, African Americans have a high death rate from triple-negative breast cancer (TNBC), characterized by lack of hormone receptors (ER, PR, HER2/ERRB2) which are otherwise valuable targets of chemotherapy. There is a need to identify novel targets that negatively impact TNBC tumorigenesis. TNBCs release an abundance of lactic acid, under normoxic, hypoxic and hyperoxic conditions; this referred to as the Warburg effect. Accumulated lactic acid sustains peri-cellular acidity which propels metastatic invasion and malignant aggressive transformation. The source of lactic acid is believed to be via conversion of pyruvate by lactate dehydrogenase (LDH) in the last step of glycolysis, with most studies focusing on the LDHA isoform. In this study, LDHA was silenced using long-term MISSION® shRNA lentivirus in human breast cancer MDA-MB-231 cells. Down-regulation of LDHA transcription and protein expression was confirmed by western blot, immunocytochemistry and qPCR. A number of parameters were measured in fully viable vector controls versus knock-down (KD) clones, including levels of lactic acid produced, glucose consumed, ATP and basic metabolic rates. The data show that lentivirus V-165 generated a knock-down clone most effective in reducing both gene and protein levels to less than 1% of vector controls. Stable KD showed absolutely no changes in cell viability, lactic acid production, ATP, glucose consumption or basic metabolic rate. Given the complete absence of impact on any observed parameter by LDH-A KD and this being somewhat contrary to findings in the literature, further analysis was required to determine why. Whole-transcriptome analytic profile on MDA-MB-231 for LDH subtypes using Agilent Human Genome 4×44k microarrays, where the data show the following component breakdown. Transcripts: 30.47 % LDHA, 69.36% LDHB, 0.12% LDHC and 0.05% LDHD. These findings underscore the importance of alternative isoforms of LDH in cancer cells to produce lactic acid

  6. An Assessment of Hazards Caused by Electromagnetic Interaction on Humans Present near Short-Wave Physiotherapeutic Devices of Various Types Including Hazards for Users of Electronic Active Implantable Medical Devices (AIMD

    Directory of Open Access Journals (Sweden)

    Jolanta Karpowicz

    2013-01-01

    Full Text Available Leakage of electromagnetic fields (EMF from short-wave radiofrequency physiotherapeutic diathermies (SWDs may cause health and safety hazards affecting unintentionally exposed workers (W or general public (GP members (assisting patient exposed during treatment or presenting there for other reasons. Increasing use of electronic active implantable medical devices (AIMDs, by patients, attendants, and workers, needs attention because dysfunctions of these devices may be caused by electromagnetic interactions. EMF emitted by 12 SWDs (with capacitive or inductive applicators were assessed following international guidelines on protection against EMF exposure (International Commission on Nonionizing Radiation Protection for GP and W, new European directive 2013/35/EU for W, European Recommendation for GP, and European Standard EN 50527-1 for AIMD users. Direct EMF hazards for humans near inductive applicators were identified at a distance not exceeding 45 cm for W or 62 cm for GP, but for AIMD users up to 90 cm (twice longer than that for W and 50% longer than that for GP because EMF is pulsed modulated. Near capacitive applicators emitting continuous wave, the corresponding distances were: 120 cm for W or 150 cm for both—GP or AIMD users. This assessment does not cover patients who undergo SWD treatment (but it is usually recommended for AIMD users to be careful with EMF treatment.

  7. The use of nuclear and related techniques for the studies of airborne particulate matter in workplace including tissue analysis and possible impacts on human health in a metal industry

    International Nuclear Information System (INIS)

    Widjajakusuma, B.; Djojosubroto, H.; Kumolowati, E.

    1998-01-01

    Various processes in a metal industry may produce gases and fine airborne particulate matter that hazardous to human health. The present study deals with assessment of levels and health effects of airborne particulate matter in a metal industry. The objective is achieved by determination of elemental levels in blood, nail and hair of workers and airborne particulate matter that are collected from their workplace. The elemental levels in blood, nail and hair of the workers will be compared to those of control. Their health condition are examined by medical examination and biochemical analysis of their blood. The blood was drawn following an overnight fast before breakfast, by means of I.V. catheter into three polyethylene tubes. The blood samples in the first tubes were sent to clinical laboratory for biochemical examination. Those in the second and third tubes, which are considered free from metal contamination by the needle of the catheter, are used for trace element study. Sera in the polyethylene tubes were separated from erythrocyte by centrifugation, then cooled by liquid nitrogen and freeze dried. Approximately 1 g of toe nail and hair samples were taken respectively from every worker. To eliminate grease and surface contamination the hair samples were rinse with acetone. Airborne particulate samples were collected from the workplace using Gent sampler. These samples are ready for elemental analysis. Results of biochemical analysis and medical examinations of the workers are presented in this report. The correlation among various parameters will be determined by statistical analysis. (author)

  8. NetMHCIIpan-3.0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ

    DEFF Research Database (Denmark)

    Karosiene, Edita; Rasmussen, Michael; Blicher, Thomas

    2013-01-01

    Major histocompatibility complex class II (MHCII) molecules play an important role in cell-mediated immunity. They present specific peptides derived from endosomal proteins for recognition by T helper cells. The identification of peptides that bind to MHCII molecules is therefore of great importa......MHCIIpan-3.0 method is the first pan-specific predictor covering all HLA class II molecules with known sequences including HLA-DR, HLA-DP, and HLA-DQ. The NetMHCpan-3.0 method is available at http://www.cbs.dtu.dk/services/NetMHCIIpan-3.0....

  9. Activation of nucleotide oligomerization domain 2 (NOD2 by human cytomegalovirus initiates innate immune responses and restricts virus replication.

    Directory of Open Access Journals (Sweden)

    Arun Kapoor

    Full Text Available Nucleotide-binding oligomerization domain 2 (NOD2 is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease.

  10. Optical reprogramming of human somatic cells using ultrashort Bessel-shaped near-infrared femtosecond laser pulses

    Science.gov (United States)

    Uchugonova, Aisada; Breunig, Hans Georg; Batista, Ana; König, Karsten

    2015-11-01

    We report a virus-free optical approach to human cell reprogramming into induced pluripotent stem cells with low-power nanoporation using ultrashort Bessel-shaped laser pulses. Picojoule near-infrared sub-20 fs laser pulses at a high 85 MHz repetition frequency are employed to generate transient nanopores in the membrane of dermal fibroblasts for the introduction of four transcription factors to induce the reprogramming process. In contrast to conventional approaches which utilize retro- or lentiviruses to deliver genes or transcription factors into the host genome, the laser method is virus-free; hence, the risk of virus-induced cancer generation limiting clinical application is avoided.

  11. (including travel dates) Proposed itinerary

    Indian Academy of Sciences (India)

    Ashok

    31 July to 22 August 2012 (including travel dates). Proposed itinerary: Arrival in Bangalore on 1 August. 1-5 August: Bangalore, Karnataka. Suggested institutions: Indian Institute of Science, Bangalore. St Johns Medical College & Hospital, Bangalore. Jawaharlal Nehru Centre, Bangalore. 6-8 August: Chennai, TN.

  12. Theory including future not excluded

    DEFF Research Database (Denmark)

    Nagao, K.; Nielsen, H.B.

    2013-01-01

    We study a complex action theory (CAT) whose path runs over not only past but also future. We show that, if we regard a matrix element defined in terms of the future state at time T and the past state at time TA as an expectation value in the CAT, then we are allowed to have the Heisenberg equation......, Ehrenfest's theorem, and the conserved probability current density. In addition,we showthat the expectation value at the present time t of a future-included theory for large T - t and large t - T corresponds to that of a future-not-included theory with a proper inner product for large t - T. Hence, the CAT...

  13. Device including a contact detector

    DEFF Research Database (Denmark)

    2011-01-01

    arms (12) may extend from the supporting body in co-planar relationship with the first surface. The plurality of cantilever arms (12) may extend substantially parallel to each other and each of the plurality of cantilever arms (12) may include an electrical conductive tip for contacting the area......The present invention relates to a probe for determining an electrical property of an area of a surface of a test sample, the probe is intended to be in a specific orientation relative to the test sample. The probe may comprise a supporting body defining a first surface. A plurality of cantilever...... of the test sample by movement of the probe relative to the surface of the test sample into the specific orientation.; The probe may further comprise a contact detector (14) extending from the supporting body arranged so as to contact the surface of the test sample prior to any one of the plurality...

  14. Neoclassical transport including collisional nonlinearity.

    Science.gov (United States)

    Candy, J; Belli, E A

    2011-06-10

    In the standard δf theory of neoclassical transport, the zeroth-order (Maxwellian) solution is obtained analytically via the solution of a nonlinear equation. The first-order correction δf is subsequently computed as the solution of a linear, inhomogeneous equation that includes the linearized Fokker-Planck collision operator. This equation admits analytic solutions only in extreme asymptotic limits (banana, plateau, Pfirsch-Schlüter), and so must be solved numerically for realistic plasma parameters. Recently, numerical codes have appeared which attempt to compute the total distribution f more accurately than in the standard ordering by retaining some nonlinear terms related to finite-orbit width, while simultaneously reusing some form of the linearized collision operator. In this work we show that higher-order corrections to the distribution function may be unphysical if collisional nonlinearities are ignored.

  15. Imunofluorescência utilizando isolados brasileiros no diagnóstico sorológico de infecção por lentivírus em caprinos Immunofluorescence using Brazilian isolates for serological diagnosis of lentivirus infection in goats

    Directory of Open Access Journals (Sweden)

    Dilmara Reischak

    2002-01-01

    Full Text Available Os lentivírus de pequenos ruminantes (SRLV têm distribuição mundial e causam infecções persistentes em ovinos e caprinos. O objetivo deste trabalho foi desenvolver um teste de imunofluorescência indireta (IFA, utilizando isolados brasileiros de SRLV, para o diagnóstico sorológico de infecção por estes agentes em caprinos. A técnica de IFA foi comparada, quanto à sensibilidade e à especificidade, ao teste de AGID com antígeno do vírus Maedi-Visna WLC-1. Cultivos celulares secundários de membrana sinovial ovina infectadas com dois isolados de SRLV de origem caprina (CAEV Br/UFRGS-2 e CAEV Br/UFRGS-5 foram utilizados para o teste de IFA. Duzentas e trinta e nove amostras de soro caprino foram submetidas aos dois testes. O teste de AGID detectou 129 (53.9% amostras de soro caprino com anticorpos para SRLV. O teste de IFA detectou mais amostras reagentes, sendo que resultados diferentes foram observados de acordo com o isolado de SRLV empregado. Quando o isolado CAEV Br/UFRGS-2 foi utilizado como antígeno, 216 (90.3% amostras de soro caprino foram reagentes, enquanto que o isolado CAEV Br/UFRGS-5 detectou 213 (89.1% amostras de soro positivas. Não houve diferença estatisticamente significativa entre esses dois isolados. O teste de IFA desenvolvido teve sensibilidade de 94.6% e 96.9% e especificidade 14.5% e 20%, quando os isolados CAEV Br/UFRGS-2 e CAEV Br/UFRGS-5 foram usados como antígeno, respectivamente. O aprimoramento da técnica, assim como sua comparação com um teste mais sensível, ainda se fazem necessários. No entanto, os resultados demonstraram que a técnica de IFA, utilizando isolados brasileiros de SRLV como antígeno, apresenta potencial como um teste alternativo e complementar para o diagnóstico sorológico de infecção por estes agentes.Small ruminant lentiviruses (SRLV are distributed worldwide and cause persistent infections in sheep and goats. The purpose of this work was to develop an indirect

  16. The Human Factor in Innovation and Productivity Including an Analysis of Hearings on the Human Factor. Report by the Subcommittee on Science, Research and Technology, Transmitted to the Committee on Science and Technology, U.S. House of Representatives, Ninety-Seventh Congress, Second Session. Serial FF.

    Science.gov (United States)

    Congress of the U.S., Washington, DC. House Committee on Science and Technology.

    The House Committee on Science and Technology, Subcommittee on Science, Research and Technology, sponsored an American Association for the Advancement of Science seminar (July 28, 1981) and 6 days of hearings (September 9-17, 1981) on "The Human Factor in Innovation and Productivity." These hearings were designed to increase knowledge…

  17. Breeding of transgenic cattle for human coagulation factor IX by a combination of lentiviral system and cloning.

    Science.gov (United States)

    Monzani, P S; Sangalli, J R; De Bem, T H C; Bressan, F F; Fantinato-Neto, P; Pimentel, J R V; Birgel-Junior, E H; Fontes, A M; Covas, D T; Meirelles, F V

    2013-02-28

    Recombinant coagulation factor IX must be produced in mammalian cells because FIX synthesis involves translational modifications. Human cell culture-based expression of human coagulation factor IX (hFIX) is expensive, and large-scale production capacity is limited. Transgenic animals may greatly increase the yield of therapeutic proteins and reduce costs. In this study, we used a lentiviral system to obtain transgenic cells and somatic cell nuclear transfer (SCNT) to produce transgenic animals. Lentiviral vectors carrying hFIX driven by 3 bovine β-casein promoters were constructed. Bovine epithelial mammary cells were transduced by lentivirus, selected with blasticidin, plated on extracellular matrix, and induced by lactogenic hormones; promoter activity was evaluated by quantitative PCR. Transcriptional activity of the 5.335-kb promoter was 6-fold higher than the 3.392- and 4.279-kb promoters, which did not significantly differ. Transgenic bovine fibroblasts were transduced with lentivirus carrying the 5.335-kb promoter and used as donor cells for SCNT. Cloned transgenic embryo production yielded development rates of 28.4%, similar to previous reports on cloned non-transgenic embryos. The embryos were transferred to recipient cows (N = 21) and 2 births of cloned transgenic cattle were obtained. These results suggest combination of the lentiviral system and cloning may be a good strategy for production of transgenic cattle.

  18. MiR-9 is overexpressed in spontaneous canine osteosarcoma and promotes a metastatic phenotype including invasion and migration in osteoblasts and osteosarcoma cell lines

    International Nuclear Information System (INIS)

    Fenger, Joelle M.; Roberts, Ryan D.; Iwenofu, O. Hans; Bear, Misty D.; Zhang, Xiaoli; Couto, Jason I.; Modiano, Jaime F.; Kisseberth, William C.; London, Cheryl A.

    2016-01-01

    MicroRNAs (miRNAs) regulate the expression of networks of genes and their dysregulation is well documented in human malignancies; however, limited information exists regarding the impact of miRNAs on the development and progression of osteosarcoma (OS). Canine OS exhibits clinical and molecular features that closely resemble the corresponding human disease and it is considered a well-established spontaneous animal model to study OS biology. The purpose of this study was to investigate miRNA dysregulation in canine OS. We evaluated miRNA expression in primary canine OS tumors and normal canine osteoblast cells using the nanoString nCounter system. Quantitative PCR was used to validate the nanoString findings and to assess miR-9 expression in canine OS tumors, OS cell lines, and normal osteoblasts. Canine osteoblasts and OS cell lines were stably transduced with pre-miR-9 or anti-miR-9 lentiviral constructs to determine the consequences of miR-9 on cell proliferation, apoptosis, invasion and migration. Proteomic and gene expression profiling of normal canine osteoblasts with enforced miR-9 expression was performed using 2D-DIGE/tandem mass spectrometry and RNA sequencing and changes in protein and mRNA expression were validated with Western blotting and quantitative PCR. OS cell lines were transduced with gelsolin (GSN) shRNAs to investigate the impact of GSN knockdown on OS cell invasion. We identified a unique miRNA signature associated with primary canine OS and identified miR-9 as being significantly overexpressed in canine OS tumors and cell lines compared to normal osteoblasts. Additionally, high miR-9 expression was demonstrated in tumor-specific tissue obtained from primary OS tumors. In normal osteoblasts and OS cell lines transduced with miR-9 lentivirus, enhanced invasion and migration were observed, but miR-9 did not affect cell proliferation or apoptosis. Proteomic and transcriptional profiling of normal canine osteoblasts overexpressing miR-9 identified

  19. Inhibition of microtubules and dynein rescues human immunodeficiency virus type 1 from owl monkey TRIMCyp-mediated restriction in a cellular context-specific fashion.

    Science.gov (United States)

    Pawlica, Paulina; Dufour, Caroline; Berthoux, Lionel

    2015-04-01

    IFN-induced restriction factors can significantly affect the replicative capacity of retroviruses in mammals. TRIM5α (tripartite motif protein 5, isoform α) is a restriction factor that acts at early stages of the virus life cycle by intercepting and destabilizing incoming retroviral cores. Sensitivity to TRIM5α maps to the N-terminal domain of the retroviral capsid proteins. In several New World and Old World monkey species, independent events of retrotransposon-mediated insertion of the cyclophilin A (CypA)-coding sequence in the trim5 gene have given rise to TRIMCyp (also called TRIM5-CypA), a hybrid protein that is active against some lentiviruses in a species-specific fashion. In particular, TRIMCyp from the owl monkey (omkTRIMCyp) very efficiently inhibits human immunodeficiency virus type 1 (HIV-1). Previously, we showed that disrupting the integrity of microtubules (MTs) and of cytoplasmic dynein complexes partially rescued replication of retroviruses, including HIV-1, from restriction mediated by TRIM5α. Here, we showed that efficient restriction of HIV-1 by omkTRIMCyp was similarly dependent on the MT network and on dynein complexes, but in a context-dependent fashion. When omkTRIMCyp was expressed in human HeLa cells, restriction was partially counteracted by pharmacological agents targeting MTs or by small interfering RNA-mediated inhibition of dynein. The same drugs (nocodazole and paclitaxel) also rescued HIV-1 from restriction in cat CRFK cells, although to a lesser extent. Strikingly, neither nocodazole, paclitaxel nor depletion of the dynein heavy chain had a significant effect on the restriction of HIV-1 in an owl monkey cell line. These results suggested the existence of cell-specific functional interactions between MTs/dynein and TRIMCyp. © 2015 The Authors.

  20. The effect of delta-like 1 homologue on the proliferation and odontoblastic differentiation in human dental pulp stem cells.

    Science.gov (United States)

    Qi, Shengcai; Yan, Yanhong; Wen, Yue; Li, Jialiang; Wang, Jing; Chen, Fubo; Tang, Xiaoshan; Shang, Guangwei; Xu, Yuanzhi; Wang, Raorao

    2017-06-01

    This study aimed to investigate the functions of delta-like homologue 1 (DLK1) in the proliferation and differentiation of human dental pulp stem cells (hDPSCs). Immunohistochemical analysis was used to determine the expression of alkaline phosphatase (ALP), dentin sialophosphoprotein (DSPP), DLK1, NOTCH1 and p-ERK1/2 in the mouse first maxillary molar. Recombinant lentivirus was constructed to overexpress DLK1 stably in hDPSCs. The cell viability and proliferation of hDPSCs were examined by CCK8 and EdU incorporation assay respectively. The odontoblastic differentiation of hDPSCs was determined by detection of ALPase activity assay, ALP and alizarin red staining and the expression of mineralization-related genes including ALP, DSPP and dental matrix protein. The mRNA and protein levels of DLK1 and p-ERK1/2 protein expression were detected. ERK inhibitor was used to test the differentiation effect of DLK1 on hDPSCs. Delta-like homologue 1 was highly expressed on the odontoblasts and dental pulp cells on the first maxillary molar; the expression of p-ERK1/2 is similar with the DLK1 in the same process. The expression level of DLK1 increased significantly after the odontoblastic induction of hDPSCs. DLK1 overexpression increased the proliferation ability of hDPSCs and inhibited odontoblastic differentiation of hDPSCs. The protein level of p-ERK1/2 significantly increased in hDPSCs/dlk1-oe group. ERK signalling pathway inhibitor reversed the odontoblastic differentiation effects of DLK1 on hDPSCs. The proliferation of hDPSCs was promoted after DLK1 overexpression. DLK1 inhibited the odontoblastic differentiation of hDPSCs, which maybe through ERK signalling pathway. © 2017 John Wiley & Sons Ltd.

  1. Cisplatin induces protective autophagy through activation of BECN1 in human bladder cancer cells.

    Science.gov (United States)

    Lin, Ji-Fan; Lin, Yi-Chia; Tsai, Te-Fu; Chen, Hung-En; Chou, Kuang-Yu; Hwang, Thomas I-Sheng

    2017-01-01

    Cisplatin-based chemotherapy is the first line treatment for several cancers including bladder cancer (BC). Autophagy induction has been implied to contribute to cisplatin resistance in ovarian cancer; and a high basal level of autophagy has been demonstrated in human bladder tumors. Therefore, it is reasonable to speculate that autophagy may account for the failure of cisplatin single treatment in BC. This study investigated whether cisplatin induces autophagy and the mechanism involved using human BC cell lines. Human BC cells (5637 and T24) were used in this study. Cell viability was detected using water soluble tetrazolium-8 reagents. Autophagy induction was detected by monitoring the levels of light chain 3 (LC3)-II and p62 by Western blot, LC3-positive puncta formation by immunofluorescence, and direct observation of the autophagolysosome (AL) formation by transmission electron microscopy. Inhibitors including bafilomycin A1 (Baf A1), chloroquine (CQ), and shRNA-based lentivirus against autophagy-related genes (ATG7 and ATG12) were utilized. Apoptosis level was detected by caspase 3/7 activity and DNA fragmentation. Cisplatin decreased cell viability and induced apoptosis of 5637 and T24 cells in a dose-and time-dependent manner. The increased LC3-II accumulation, p62 clearance, the number of LC3-positive puncta, and ALs in cisplatin-treated cells suggested that cisplatin indeed induces autophagy. Inhibition of cisplatin-induced autophagy using Baf A1, CQ, or ATG7/ATG12 shRNAs significantly enhanced cytotoxicity of cisplatin toward BC cells. These results indicated that cisplatin induced protective autophagy which may contribute to the development of cisplatin resistance and resulted in treatment failure. Mechanistically, upregulation of beclin-1 (BECN1) was detected in cisplatin-treated cells, and knockdown of BECN1 using shRNA attenuated cisplatin-induced autophagy and subsequently enhanced cisplatin-induced apoptosis. Collectively, the study results

  2. Sphingosine 1-phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier

    Directory of Open Access Journals (Sweden)

    van Doorn Ruben

    2012-06-01

    Full Text Available Abstract Background The sphingosine 1-phosphate (S1P receptor modulator FTY720P (Gilenya® potently reduces relapse rate and lesion activity in the neuroinflammatory disorder multiple sclerosis. Although most of its efficacy has been shown to be related to immunosuppression through the induction of lymphopenia, it has been suggested that a number of its beneficial effects are related to altered endothelial and blood–brain barrier (BBB functionality. However, to date it remains unknown whether brain endothelial S1P receptors are involved in the maintenance of the function of the BBB thereby mediating immune quiescence of the brain. Here we demonstrate that the brain endothelial receptor S1P5 largely contributes to the maintenance of brain endothelial barrier function. Methods We analyzed the expression of S1P5 in human post-mortem tissues using immunohistochemistry. The function of S1P5 at the BBB was assessed in cultured human brain endothelial cells (ECs using agonists and lentivirus-mediated knockdown of S1P5. Subsequent analyses of different aspects of the brain EC barrier included the formation of a tight barrier, the expression of BBB proteins and markers of inflammation and monocyte transmigration. Results We show that activation of S1P5 on cultured human brain ECs by a selective agonist elicits enhanced barrier integrity and reduced transendothelial migration of monocytes in vitro. These results were corroborated by genetically silencing S1P5 in brain ECs. Interestingly, functional studies with these cells revealed that S1P5 strongly contributes to brain EC barrier function and underlies the expression of specific BBB endothelial characteristics such as tight junctions and permeability. In addition, S1P5 maintains the immunoquiescent state of brain ECs with low expression levels of leukocyte adhesion molecules and inflammatory chemokines and cytokines through lowering the activation of the transcription factor NFκB. Conclusion Our

  3. Feline Immunodeficiency Virus Evolutionarily Acquires Two Proteins, Vif and Protease, Capable of Antagonizing Feline APOBEC3.

    Science.gov (United States)

    Yoshikawa, Rokusuke; Takeuchi, Junko S; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Kimura, Yuichi; Ren, Fengrong; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

    2017-06-01

    The interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. Mammalian genes encode apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins, which act as intrinsic restriction factors against lentiviruses. To overcome APOBEC3-mediated antiviral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (Vif), and Vif degrades host APOBEC3 proteins via a ubiquitin/proteasome-dependent pathway. Although the Vif-APOBEC3 interaction and its evolutionary significance, particularly those of primate lentiviruses (including HIV) and primates (including humans), have been well investigated, those of nonprimate lentiviruses and nonprimates are poorly understood. Moreover, the factors that determine lentiviral pathogenicity remain unclear. Here, we focus on feline immunodeficiency virus (FIV), a pathogenic lentivirus in domestic cats, and the interaction between FIV Vif and feline APOBEC3 in terms of viral virulence and evolution. We reveal the significantly reduced diversity of FIV subtype B compared to that of other subtypes, which may associate with the low pathogenicity of this subtype. We also demonstrate that FIV subtype B Vif is less active with regard to feline APOBEC3 degradation. More intriguingly, we further reveal that FIV protease cleaves feline APOBEC3 in released virions. Taken together, our findings provide evidence that a lentivirus encodes two types of anti-APOBEC3 factors, Vif and viral protease. IMPORTANCE During the history of mammalian evolution, mammals coevolved with retroviruses, including lentiviruses. All pathogenic lentiviruses, excluding equine infectious anemia virus, have acquired the vif gene via evolution to combat APOBEC3 proteins, which are intrinsic restriction factors against exogenous lentiviruses. Here we demonstrate that FIV, a pathogenic lentivirus in domestic cats, antagonizes feline APOBEC3

  4. Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling

    Science.gov (United States)

    Wang, Linlin; Schulz, Thomas C.; Sherrer, Eric S.; Dauphin, Derek S.; Shin, Soojung; Nelson, Angelique M.; Ware, Carol B.; Zhan, Mei; Song, Chao-Zhong; Chen, Xiaoji; Brimble, Sandii N.; McLean, Amanda; Galeano, Maria J.; Uhl, Elizabeth W.; D'Amour, Kevin A.; Chesnut, Jonathan D.; Rao, Mahendra S.

    2007-01-01

    Despite progress in developing defined conditions for human embryonic stem cell (hESC) cultures, little is known about the cell-surface receptors that are activated under conditions supportive of hESC self-renewal. A simultaneous interrogation of 42 receptor tyrosine kinases (RTKs) in hESCs following stimulation with mouse embryonic fibroblast (MEF) conditioned medium (CM) revealed rapid and prominent tyrosine phosphorylation of insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R); less prominent tyrosine phosphorylation of epidermal growth factor receptor (EGFR) family members, including ERBB2 and ERBB3; and trace phosphorylation of fibroblast growth factor receptors. Intense IGF1R and IR phosphorylation occurred in the absence of MEF conditioning (NCM) and was attributable to high concentrations of insulin in the proprietary KnockOut Serum Replacer (KSR). Inhibition of IGF1R using a blocking antibody or lentivirus-delivered shRNA reduced hESC self-renewal and promoted differentiation, while disruption of ERBB2 signaling with the selective inhibitor AG825 severely inhibited hESC proliferation and promoted apoptosis. A simple defined medium containing an IGF1 analog, heregulin-1β (a ligand for ERBB2/ERBB3), fibroblast growth factor-2 (FGF2), and activin A supported long-term growth of multiple hESC lines. These studies identify previously unappreciated RTKs that support hESC proliferation and self-renewal, and provide a rationally designed medium for the growth and maintenance of pluripotent hESCs. PMID:17761519

  5. 7 CFR 1437.303 - Aquaculture, including ornamental fish.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Aquaculture, including ornamental fish. 1437.303... ASSISTANCE PROGRAM Determining Coverage Using Value § 1437.303 Aquaculture, including ornamental fish. (a... human consumption as determined by CCC. (2) Fish raised as feed for other fish that are consumed by...

  6. Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

    Directory of Open Access Journals (Sweden)

    Jakobsen Maria

    2011-02-01

    Full Text Available Abstract Background Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα, interleukin-12 (IL-12, and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs. Methods Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels. Results Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by

  7. Human Technology and Human Affects

    DEFF Research Database (Denmark)

    Fausing, Bent

    2009-01-01

    Human Technology and Human Affects  This year Samsung introduced a mobile phone with "Soul". It was made with a human touch and included itself a magical touch. Which function does technology and affects get in everyday aesthetics like this, its images and interactions included this presentation...... will ask and try to answer. The mobile phone and its devices are depicted as being able to make a unique human presence, interaction, and affect. The medium, the technology is a necessary helper to get towards this very special and lost humanity. Without the technology, no special humanity - soul....... The paper will investigate how technology, humanity, affects, and synaesthesia are presented and combined with examples from everyday aesthetics, e.g. early computer tv-commercial, net-commercial for mobile phones. Technology and affects point, is the conclusion, towards a forgotten pre-human and not he...

  8. Viral infection of human progenitor and liver-derived cells encapsulated in three-dimensional PEG-based hydrogel

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nam-Joon; Elazar, Menashe; Xiong, Anming; Glenn, Jeffrey S [Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, CCSR Building Room 3115A, 269 Campus Drive, Stanford, CA 94305 (United States); Lee, Wonjae [Mechanical Engineering, Stanford University, Stanford, CA 94305 (United States); Chiao, Eric; Baker, Julie [Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305 (United States); Frank, Curtis W, E-mail: jeffrey.glenn@stanford.ed, E-mail: curt.frank@stanford.ed [Department of Chemical Engineering, Stanford University, Stanford, CA 94305 (United States)

    2009-02-15

    We have studied the encapsulation of human progenitor cells into 3D PEG hydrogels. Replication-incompetent lentivirus promoter reporter vectors were found to efficiently detect the in vivo expression of human hepatic genes in hydrogel-encapsulated liver progenitor cells. Similarly, hydrogel-encapsulated cells could be efficiently infected with hepatitis C virus, and progeny infectious virus could be recovered from the media supernatants of the hydrogels. Provocatively, the diameters of these virus particles range from {approx}50 to 100 nm, while the calculated mesh size of the 8 k hydrogel is 44.6 +- 1.7 A. To reconcile how viral particles can penetrate the hydrogels to infect the encapsulated cells, we propose that microfractures/defects of the hydrogel result in a functional pore size of up to 20 fold greater than predicted by theoretical mesh calculations. These results suggest a new model of hydrogel structure, and have exciting implications for tissue engineering and hepatitis virus studies. (communication)

  9. Viral infection of human progenitor and liver-derived cells encapsulated in three-dimensional PEG-based hydrogel

    International Nuclear Information System (INIS)

    Cho, Nam-Joon; Elazar, Menashe; Xiong, Anming; Glenn, Jeffrey S; Lee, Wonjae; Chiao, Eric; Baker, Julie; Frank, Curtis W

    2009-01-01

    We have studied the encapsulation of human progenitor cells into 3D PEG hydrogels. Replication-incompetent lentivirus promoter reporter vectors were found to efficiently detect the in vivo expression of human hepatic genes in hydrogel-encapsulated liver progenitor cells. Similarly, hydrogel-encapsulated cells could be efficiently infected with hepatitis C virus, and progeny infectious virus could be recovered from the media supernatants of the hydrogels. Provocatively, the diameters of these virus particles range from ∼50 to 100 nm, while the calculated mesh size of the 8 k hydrogel is 44.6 ± 1.7 A. To reconcile how viral particles can penetrate the hydrogels to infect the encapsulated cells, we propose that microfractures/defects of the hydrogel result in a functional pore size of up to 20 fold greater than predicted by theoretical mesh calculations. These results suggest a new model of hydrogel structure, and have exciting implications for tissue engineering and hepatitis virus studies. (communication)

  10. Widening the adoption of workflows to include human and human-machine scientific processes

    Science.gov (United States)

    Salayandia, L.; Pinheiro da Silva, P.; Gates, A. Q.

    2010-12-01

    Scientific workflows capture knowledge in the form of technical recipes to access and manipulate data that help scientists manage and reuse established expertise to conduct their work. Libraries of scientific workflows are being created in particular fields, e.g., Bioinformatics, where combined with cyber-infrastructure environments that provide on-demand access to data and tools, result in powerful workbenches for scientists of those communities. The focus in these particular fields, however, has been more on automating rather than documenting scientific processes. As a result, technical barriers have impeded a wider adoption of scientific workflows by scientific communities that do not rely as heavily on cyber-infrastructure and computing environments. Semantic Abstract Workflows (SAWs) are introduced to widen the applicability of workflows as a tool to document scientific recipes or processes. SAWs intend to capture a scientists’ perspective about the process of how she or he would collect, filter, curate, and manipulate data to create the artifacts that are relevant to her/his work. In contrast, scientific workflows describe the process from the point of view of how technical methods and tools are used to conduct the work. By focusing on a higher level of abstraction that is closer to a scientist’s understanding, SAWs effectively capture the controlled vocabularies that reflect a particular scientific community, as well as the types of datasets and methods used in a particular domain. From there on, SAWs provide the flexibility to adapt to different environments to carry out the recipes or processes. These environments range from manual fieldwork to highly technical cyber-infrastructure environments, i.e., such as those already supported by scientific workflows. Two cases, one from Environmental Science and another from Geophysics, are presented as illustrative examples.

  11. Solid-state nuclear magnetic resonance (NMR) spectroscopy of human immunodeficiency virus gp41 protein that includes the fusion peptide: NMR detection of recombinant Fgp41 in inclusion bodies in whole bacterial cells and structural characterization of purified and membrane-associated Fgp41.

    Science.gov (United States)

    Vogel, Erica P; Curtis-Fisk, Jaime; Young, Kaitlin M; Weliky, David P

    2011-11-22

    Human immunodeficiency virus (HIV) infection of a host cell begins with fusion of the HIV and host cell membranes and is mediated by the gp41 protein, a single-pass integral membrane protein of HIV. The 175 N-terminal residues make up the ectodomain that lies outside the virus. This work describes the production and characterization of an ectodomain construct containing the 154 N-terminal gp41 residues, including the fusion peptide (FP) that binds to target cell membranes. The Fgp41 sequence was derived from one of the African clade A strains of HIV-1 that have been less studied than European/North American clade B strains. Fgp41 expression at a level of ~100 mg/L of culture was evidenced by an approach that included amino acid type (13)CO and (15)N labeling of recombinant protein and solid-state NMR (SSNMR) spectroscopy of lyophilized whole cells. The approach did not require any protein solubilization or purification and may be a general approach for detection of recombinant protein. The purified Fgp41 yield was ~5 mg/L of culture. SSNMR spectra of membrane-associated Fgp41 showed high helicity for the residues C-terminal of the FP. This was consistent with a "six-helix bundle" (SHB) structure that is the final gp41 state during membrane fusion. This observation and negligible Fgp41-induced vesicle fusion supported a function for SHB gp41 of membrane stabilization and fusion arrest. SSNMR spectra of residues in the membrane-associated FP provided evidence of a mixture of molecular populations with either helical or β-sheet FP conformation. These and earlier SSNMR data strongly support the existence of these populations in the SHB state of membrane-associated gp41. © 2011 American Chemical Society

  12. Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

    Directory of Open Access Journals (Sweden)

    Erik Corona

    Full Text Available Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS, providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

  13. Towards a general framework for including noise impacts in LCA

    NARCIS (Netherlands)

    Cucurachi, Stefano; Heijungs, Reinout; Ohlau, Katrin

    Purpose Several damages have been associated with the exposure of human beings to noise. These include auditory effects, i.e., hearing impairment, but also non-auditory physiological ones such as hypertension and ischemic heart disease, or psychological ones such as annoyance, depression, sleep

  14. 25 CFR 20.403 - What do protective services include?

    Science.gov (United States)

    2010-04-01

    ....403 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES FINANCIAL ASSISTANCE AND SOCIAL SERVICES PROGRAMS Services to Children, Elderly, and Families § 20.403 What do protective services include? Protective services provided to a child, family or elderly person will be documented in...

  15. Human Parvoviruses

    Science.gov (United States)

    Söderlund-Venermo, Maria; Young, Neal S.

    2016-01-01

    SUMMARY Parvovirus B19 (B19V) and human bocavirus 1 (HBoV1), members of the large Parvoviridae family, are human pathogens responsible for a variety of diseases. For B19V in particular, host features determine disease manifestations. These viruses are prevalent worldwide and are culturable in vitro, and serological and molecular assays are available but require careful interpretation of results. Additional human parvoviruses, including HBoV2 to -4, human parvovirus 4 (PARV4), and human bufavirus (BuV) are also reviewed. The full spectrum of parvovirus disease in humans has yet to be established. Candidate recombinant B19V vaccines have been developed but may not be commercially feasible. We review relevant features of the molecular and cellular biology of these viruses, and the human immune response that they elicit, which have allowed a deep understanding of pathophysiology. PMID:27806994

  16. 42 CFR 410.100 - Included services.

    Science.gov (United States)

    2010-10-01

    ... service; however, maintenance therapy itself is not covered as part of these services. (c) Occupational... increase respiratory function, such as graded activity services; these services include physiologic... rehabilitation plan of treatment, including physical therapy services, occupational therapy services, speech...

  17. Static, Lightweight Includes Resolution for PHP

    NARCIS (Netherlands)

    M.A. Hills (Mark); P. Klint (Paul); J.J. Vinju (Jurgen)

    2014-01-01

    htmlabstractDynamic languages include a number of features that are challenging to model properly in static analysis tools. In PHP, one of these features is the include expression, where an arbitrary expression provides the path of the file to include at runtime. In this paper we present two

  18. Article Including Environmental Barrier Coating System

    Science.gov (United States)

    Lee, Kang N. (Inventor)

    2015-01-01

    An enhanced environmental barrier coating for a silicon containing substrate. The enhanced barrier coating may include a bond coat doped with at least one of an alkali metal oxide and an alkali earth metal oxide. The enhanced barrier coating may include a composite mullite bond coat including BSAS and another distinct second phase oxide applied over said surface.

  19. Rare thoracic cancers, including peritoneum mesothelioma

    NARCIS (Netherlands)

    Siesling, Sabine; van der Zwan, Jan Maarten; Izarzugaza, Isabel; Jaal, Jana; Treasure, Tom; Foschi, Roberto; Ricardi, Umberto; Groen, Harry; Tavilla, Andrea; Ardanaz, Eva

    Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002,

  20. Rare thoracic cancers, including peritoneum mesothelioma

    NARCIS (Netherlands)

    Siesling, Sabine; Zwan, J.M.V.D.; Izarzugaza, I.; Jaal, J.; Treasure, T.; Foschi, R.; Ricardi, U.; Groen, H.; Tavilla, A.; Ardanaz, E.

    2012-01-01

    Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002,

  1. Effect and Mechanism of EGFL7 Downregulation in Human Osteosarcoma Cells on the Biological Function of Co-cultured HUVEC

    Directory of Open Access Journals (Sweden)

    Xia Li

    2018-03-01

    Full Text Available Background: Even though epidermal growth factor-like domain 7 is known to be overexpressed in osteosarcoma and is associated with poor clinical outcome, few reports are available regarding its mechanism. Aims: The objective of this study was to explore the effect and mechanism of downregulating epidermal growth factor-like domain 7 expression in a human osteosarcoma cell line on the biological function of co-cultured human umbilical vein endothelial cells. Study Design: Cell study. Methods: In the present study, human osteosarcoma cell lines U2OS, Saos-2, HOS, and MG63, and normal human osteoblasts were cultured in Dulbecco’s Modified Eagle Medium containing 10% fetal bovine serum and 1x antibiotics at 37 °C and 5% CO2 in an incubator. Of the four osteosarcoma cell lines, U2OS expresses the highest level of epidermal growth factor-like domain 7 mRNA as determined using quantitative reverse transcription polymerase chain reaction. With the knockdown of epidermal growth factor-like domain 7 in U2OS and human umbilical vein endothelial cells by lentivirus, the proliferation and apoptosis of U2OS and human umbilical vein endothelial cells were investigated using MTT and flow cytometry assays. After the co-culture of human umbilical vein endothelial cells and epidermal growth factor-like domain 7-knockdown U2OS, the in vitro effects on cell proliferation, apoptosis, adhesion, migration, and the angiogenic ability of human umbilical vein endothelial cells were detected using MTT, flow cytometry, Transwell, and tube formation assays, respectively. The expressions of phosphoinositide 3-kinase, phospho-Akt, total Akt, and vascular endothelial growth factor in human umbilical vein endothelial cells were detected using western blot assay. Results: Lentivirus with epidermal growth factor-like domain 7 shRNA could not significantly affect the proliferation and apoptosis of both U2OS and human umbilical vein endothelial cells, whereas the knockdown of

  2. Human evolution

    DEFF Research Database (Denmark)

    Llamas, Bastien; Willerslev, Eske; Orlando, Ludovic Antoine Alexandre

    2017-01-01

    The field of human ancient DNA (aDNA) has moved from mitochondrial sequencing that suffered from contamination and provided limited biological insights, to become a fully genomic discipline that is changing our conception of human history. Recent successes include the sequencing of extinct homini...

  3. Human Cloning

    National Research Council Canada - National Science Library

    Johnson, Judith A; Williams, Erin D

    2006-01-01

    .... Scientists in other labs, including Harvard University and the University of California at San Francisco, intend to produce cloned human embryos in order to derive stem cells for medical research...

  4. Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line.

    Directory of Open Access Journals (Sweden)

    Chao Niu

    Full Text Available Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD. We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies.

  5. Including environmental concerns in energy policies

    International Nuclear Information System (INIS)

    Potier, Michel

    2014-05-01

    In this article, the author comments the different impacts on the environment and risks related to energy, provided that all energies have an impact on the environment (renewable energies are generally cleaner than fossil energies) and these impacts can be on human health, ecosystems, buildings, crops, landscapes, and climate change. He comments the efforts made in the search for a higher energetic efficiency, and proposes an overview of the various available tools implemented by environmental policies in the energy sector: regulatory instruments, economic instruments, negotiated agreements, and informational instruments. He comments the implementation of an energetic taxing aimed at developing a greater respect of the environment

  6. Including Indigenous Minorities in Decision-Making

    DEFF Research Database (Denmark)

    Pristed Nielsen, Helene

    Based on theories of public sphere participation and deliberative democracy, this book presents empirical results from a study of experiences with including Aboriginal and Maori groups in political decision-making in respectively Western Australia and New Zealand......Based on theories of public sphere participation and deliberative democracy, this book presents empirical results from a study of experiences with including Aboriginal and Maori groups in political decision-making in respectively Western Australia and New Zealand...

  7. Gas storage materials, including hydrogen storage materials

    Science.gov (United States)

    Mohtadi, Rana F; Wicks, George G; Heung, Leung K; Nakamura, Kenji

    2013-02-19

    A material for the storage and release of gases comprises a plurality of hollow elements, each hollow element comprising a porous wall enclosing an interior cavity, the interior cavity including structures of a solid-state storage material. In particular examples, the storage material is a hydrogen storage material such as a solid state hydride. An improved method for forming such materials includes the solution diffusion of a storage material solution through a porous wall of a hollow element into an interior cavity.

  8. Distal radioulnar joint: functional anatomy, including pathomechanics.

    Science.gov (United States)

    Haugstvedt, J R; Langer, M F; Berger, R A

    2017-05-01

    The distal radioulnar joint allows the human to rotate the forearm to place the hand in a desired position to perform different tasks, without interfering with the grasping function of the hand. The ulna is the stable part of the forearm around which the radius rotates; the stability of the distal radioulnar joint is provided by the interaction between ligaments, muscles and bones. The stabilizing structures are the triangular fibrocartilage complex, the ulnocarpal ligament complex, the extensor carpi ulnaris tendon and tendon sheath, the pronator quadratus, the interosseous membrane and ligament, the bone itself and the joint capsule. The purpose of this review article is to present and illustrate the current understanding of the functional anatomy and pathomechanics of this joint.

  9. Humanized mouse models: Application to human diseases.

    Science.gov (United States)

    Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

    2018-05-01

    Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

  10. Electric Power Monthly, August 1990. [Glossary included

    Energy Technology Data Exchange (ETDEWEB)

    1990-11-29

    The Electric Power Monthly (EPM) presents monthly summaries of electric utility statistics at the national, Census division, and State level. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data includes generation by energy source (coal, oil, gas, hydroelectric, and nuclear); generation by region; consumption of fossil fuels for power generation; sales of electric power, cost data; and unusual occurrences. A glossary is included.

  11. Electrochemical cell structure including an ionomeric barrier

    Science.gov (United States)

    Lambert, Timothy N.; Hibbs, Michael

    2017-06-20

    An apparatus includes an electrochemical half-cell comprising: an electrolyte, an anode; and an ionomeric barrier positioned between the electrolyte and the anode. The anode may comprise a multi-electron vanadium phosphorous alloy, such as VP.sub.x, wherein x is 1-5. The electrochemical half-cell is configured to oxidize the vanadium and phosphorous alloy to release electrons. A method of mitigating corrosion in an electrochemical cell includes disposing an ionomeric barrier in a path of electrolyte or ion flow to an anode and mitigating anion accumulation on the surface of the anode.

  12. Isolators Including Main Spring Linear Guide Systems

    Science.gov (United States)

    Goold, Ryan (Inventor); Buchele, Paul (Inventor); Hindle, Timothy (Inventor); Ruebsamen, Dale Thomas (Inventor)

    2017-01-01

    Embodiments of isolators, such as three parameter isolators, including a main spring linear guide system are provided. In one embodiment, the isolator includes first and second opposing end portions, a main spring mechanically coupled between the first and second end portions, and a linear guide system extending from the first end portion, across the main spring, and toward the second end portion. The linear guide system expands and contracts in conjunction with deflection of the main spring along the working axis, while restricting displacement and rotation of the main spring along first and second axes orthogonal to the working axis.

  13. 28 CFR 20.32 - Includable offenses.

    Science.gov (United States)

    2010-07-01

    ... Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record... vehicular manslaughter, driving under the influence of drugs or liquor, and hit and run), when unaccompanied by a § 20.32(a) offense. These exclusions may not be applicable to criminal history records...

  14. Including Students with Visual Impairments: Softball

    Science.gov (United States)

    Brian, Ali; Haegele, Justin A.

    2014-01-01

    Research has shown that while students with visual impairments are likely to be included in general physical education programs, they may not be as active as their typically developing peers. This article provides ideas for equipment modifications and game-like progressions for one popular physical education unit, softball. The purpose of these…

  15. Extending flood damage assessment methodology to include ...

    African Journals Online (AJOL)

    Optimal and sustainable flood plain management, including flood control, can only be achieved when the impacts of flood control measures are considered for both the man-made and natural environments, and the sociological aspects are fully considered. Until now, methods/models developed to determine the influences ...

  16. BIOLOGIC AND ECONOMIC EFFECTS OF INCLUDING DIFFERENT ...

    African Journals Online (AJOL)

    The biologic and economic effects of including three agro-industrial by-products as ingredients in turkey poult diets were investigated using 48 turkey poults in a completely randomised design experiment. Diets were formulated to contain the three by-products – wheat offal, rice husk and palm kernel meal, each at 20% level ...

  17. Including Children Dependent on Ventilators in School.

    Science.gov (United States)

    Levine, Jack M.

    1996-01-01

    Guidelines for including ventilator-dependent children in school are offered, based on experience with six such students at a New York State school. Guidelines stress adherence to the medical management plan, the school-family partnership, roles of the social worker and psychologist, orientation, transportation, classroom issues, and steps toward…

  18. NATO Human View Architecture and Human Networks

    Science.gov (United States)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  19. Cisplatin induces protective autophagy through activation of BECN1 in human bladder cancer cells

    Directory of Open Access Journals (Sweden)

    Lin JF

    2017-05-01

    Full Text Available Ji-Fan Lin,1 Yi-Chia Lin,2 Te-Fu Tsai,2,3 Hung-En Chen,2 Kuang-Yu Chou,2,3 Thomas I-Sheng Hwang2–4 1Central Laboratory, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 2Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei, 3Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, 4Department of Urology, Taipei Medical University, Taipei, Taiwan Purpose: Cisplatin-based chemotherapy is the first line treatment for several cancers including bladder cancer (BC. Autophagy induction has been implied to contribute to cisplatin resistance in ovarian cancer; and a high basal level of autophagy has been demonstrated in human bladder tumors. Therefore, it is reasonable to speculate that autophagy may account for the failure of cisplatin single treatment in BC. This study investigated whether cisplatin induces autophagy and the mechanism involved using human BC cell lines.Materials and methods: Human BC cells (5637 and T24 were used in this study. Cell viability was detected using water soluble tetrazolium-8 reagents. Autophagy induction was detected by monitoring the levels of light chain 3 (LC3-II and p62 by Western blot, LC3-positive puncta formation by immunofluorescence, and direct observation of the autophagolysosome (AL formation by transmission electron microscopy. Inhibitors including bafilomycin A1 (Baf A1, chloroquine (CQ, and shRNA-based lentivirus against autophagy-related genes (ATG7 and ATG12 were utilized. Apoptosis level was detected by caspase 3/7 activity and DNA fragmentation.Results: Cisplatin decreased cell viability and induced apoptosis of 5637 and T24 cells in a dose- and time-dependent manner. The increased LC3-II accumulation, p62 clearance, the number of LC3-positive puncta, and ALs in cisplatin-treated cells suggested that cisplatin indeed induces autophagy. Inhibition of cisplatin-induced autophagy using Baf A1, CQ, or ATG7/ATG12 shRNAs significantly enhanced cytotoxicity of

  20. Photoactive devices including porphyrinoids with coordinating additives

    Science.gov (United States)

    Forrest, Stephen R; Zimmerman, Jeramy; Yu, Eric K; Thompson, Mark E; Trinh, Cong; Whited, Matthew; Diev, Vlacheslav

    2015-05-12

    Coordinating additives are included in porphyrinoid-based materials to promote intermolecular organization and improve one or more photoelectric characteristics of the materials. The coordinating additives are selected from fullerene compounds and organic compounds having free electron pairs. Combinations of different coordinating additives can be used to tailor the characteristic properties of such porphyrinoid-based materials, including porphyrin oligomers. Bidentate ligands are one type of coordinating additive that can form coordination bonds with a central metal ion of two different porphyrinoid compounds to promote porphyrinoid alignment and/or pi-stacking. The coordinating additives can shift the absorption spectrum of a photoactive material toward higher wavelengths, increase the external quantum efficiency of the material, or both.

  1. Electric power monthly, September 1990. [Glossary included

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-17

    The purpose of this report is to provide energy decision makers with accurate and timely information that may be used in forming various perspectives on electric issues. The power plants considered include coal, petroleum, natural gas, hydroelectric, and nuclear power plants. Data are presented for power generation, fuel consumption, fuel receipts and cost, sales of electricity, and unusual occurrences at power plants. Data are compared at the national, Census division, and state levels. 4 figs., 52 tabs. (CK)

  2. Nuclear reactor shield including magnesium oxide

    International Nuclear Information System (INIS)

    Rouse, C.A.; Simnad, M.T.

    1981-01-01

    An improvement is described for nuclear reactor shielding of a type used in reactor applications involving significant amounts of fast neutron flux. The reactor shielding includes means providing structural support, neutron moderator material, neutron absorber material and other components, wherein at least a portion of the neutron moderator material is magnesium in the form of magnesium oxide either alone or in combination with other moderator materials such as graphite and iron

  3. Model for safety reports including descriptive examples

    International Nuclear Information System (INIS)

    1995-12-01

    Several safety reports will be produced in the process of planning and constructing the system for disposal of high-level radioactive waste in Sweden. The present report gives a model, with detailed examples, of how these reports should be organized and what steps they should include. In the near future safety reports will deal with the encapsulation plant and the repository. Later reports will treat operation of the handling systems and the repository

  4. Jet-calculus approach including coherence effects

    International Nuclear Information System (INIS)

    Jones, L.M.; Migneron, R.; Narayanan, K.S.S.

    1987-01-01

    We show how integrodifferential equations typical of jet calculus can be combined with an averaging procedure to obtain jet-calculus-based results including the Mueller interference graphs. Results in longitudinal-momentum fraction x for physical quantities are higher at intermediate x and lower at large x than with the conventional ''incoherent'' jet calculus. These results resemble those of Marchesini and Webber, who used a Monte Carlo approach based on the same dynamics

  5. Human T-lymphotropic virus type-1 p30 alters cell cycle G2 regulation of T lymphocytes to enhance cell survival

    Directory of Open Access Journals (Sweden)

    Silverman Lee

    2007-07-01

    Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 causes adult T-cell leukemia/lymphoma and is linked to a number of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13 and p30, whose roles are still being defined in the virus life cycle and in HTLV-1 virus-host cell interactions. Proviral clones of HTLV-1 with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. p30 expressed exogenously differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and while acting as a repressor of many genes including Tax, in part by blocking tax/rex RNA nuclear export, selectively enhances key gene pathways involved in T-cell signaling/activation. Results Herein, we analyzed the role of p30 in cell cycle regulation. Jurkat T-cells transduced with a p30 expressing lentivirus vector accumulated in the G2-M phase of cell cycle. We then analyzed key proteins involved in G2-M checkpoint activation. p30 expression in Jurkat T-cells resulted in an increase in phosphorylation at serine 216 of nuclear cell division cycle 25C (Cdc25C, had enhanced checkpoint kinase 1 (Chk1 serine 345 phosphorylation, reduced expression of polo-like kinase 1 (PLK1, diminished phosphorylation of PLK1 at tyrosine 210 and reduced phosphorylation of Cdc25C at serine 198. Finally, primary human lymphocyte derived cell lines immortalized by a HTLV-1 proviral clone defective in p30 expression were more susceptible to camptothecin induced apoptosis. Collectively these data are consistent with a cell survival role of p30 against genotoxic insults to HTLV-1 infected lymphocytes. Conclusion Collectively, our data are the first to indicate that HTLV-1 p30 expression results in activation of the G2-M cell cycle checkpoint, events that would promote early viral spread and T

  6. [Renal patient's diet: Can fish be included?].

    Science.gov (United States)

    Castro González, M I; Maafs Rodríguez, A G; Galindo Gómez, C

    2012-01-01

    Medical and nutritional treatment for renal disease, now a major public health issue, is highly complicated. Nutritional therapy must seek to retard renal dysfunction, maintain an optimal nutritional status and prevent the development of underlying pathologies. To analyze ten fish species to identify those that, because of their low phosphorus content, high biological value protein and elevated n-3 fatty acids EPA and DHA, could be included in renal patient's diet. The following fish species (Litte tunny, Red drum, Spotted eagleray, Escolar, Swordfish, Big-scale pomfret, Cortez flounder, Largemouth blackbass, Periche mojarra, Florida Pompano) were analyzed according to the AOAC and Keller techniques to determine their protein, phosphorus, sodium, potassium, cholesterol, vitamins D(3) and E, and n-3 EPA+DHA content. These results were used to calculate relations between nutrients. The protein in the analyzed species ranged from 16.5 g/100 g of fillet (Largemouth black bass) to 27.2 g/100 g (Red drum); the lowest phosphorus value was 28.6 mg/100 g (Periche mojarra) and the highest 216.3 mg/100 g (Spotted eagle ray). 80% of the fish presented > 100 mg EPA + DHA in 100 g of fillet. By its Phosphorus/gProtein ratio, Escolar and Swordfish could not be included in the renal diet; Little tunny, Escolar, Big-scale pomfret, Largemouth black-bass, Periche mojarra and Florida Pompano presented a lower Phosphorus/EPA + DHA ratio. Florida pompano is the most recommended specie for renal patients, due to its optimal nutrient relations. However, all analyzed species, except Escolar and Swordfish, could be included in renal diets.

  7. MOS modeling hierarchy including radiation effects

    International Nuclear Information System (INIS)

    Alexander, D.R.; Turfler, R.M.

    1975-01-01

    A hierarchy of modeling procedures has been developed for MOS transistors, circuit blocks, and integrated circuits which include the effects of total dose radiation and photocurrent response. The models were developed for use with the SCEPTRE circuit analysis program, but the techniques are suitable for other modern computer aided analysis programs. The modeling hierarchy permits the designer or analyst to select the level of modeling complexity consistent with circuit size, parametric information, and accuracy requirements. Improvements have been made in the implementation of important second order effects in the transistor MOS model, in the definition of MOS building block models, and in the development of composite terminal models for MOS integrated circuits

  8. Drug delivery device including electrolytic pump

    KAUST Repository

    Foulds, Ian G.; Buttner, Ulrich; Yi, Ying

    2016-01-01

    Systems and methods are provided for a drug delivery device and use of the device for drug delivery. In various aspects, the drug delivery device combines a “solid drug in reservoir” (SDR) system with an electrolytic pump. In various aspects an improved electrolytic pump is provided including, in particular, an improved electrolytic pump for use with a drug delivery device, for example an implantable drug delivery device. A catalytic reformer can be incorporated in a periodically pulsed electrolytic pump to provide stable pumping performance and reduced actuation cycle.

  9. Drug delivery device including electrolytic pump

    KAUST Repository

    Foulds, Ian G.

    2016-03-31

    Systems and methods are provided for a drug delivery device and use of the device for drug delivery. In various aspects, the drug delivery device combines a “solid drug in reservoir” (SDR) system with an electrolytic pump. In various aspects an improved electrolytic pump is provided including, in particular, an improved electrolytic pump for use with a drug delivery device, for example an implantable drug delivery device. A catalytic reformer can be incorporated in a periodically pulsed electrolytic pump to provide stable pumping performance and reduced actuation cycle.

  10. The role of integrin-α5 in the proliferation and odontogenic differentiation of human dental pulp stem cells.

    Science.gov (United States)

    Cui, Li; Xu, Shuaimei; Ma, Dandan; Gao, Jie; Liu, Ying; Yue, Jing; Wu, Buling

    2014-02-01

    It has been reported that integrin-α5 (ITGA5) activity is related to cell proliferation, differentiation, migration, and organ development. However, the involvement of ITGA5 in the biological functions of human dental pulp stem cells (hDPSCs) has not been explored. The aim of this study was to investigate the role of ITGA5 in the proliferation and odontogenic differentiation of hDPSCs. We knocked down ITGA5 in hDPSCs using lentivirus-mediated ITGA5 short hairpin RNA (shRNA). Changes in the proliferation in hDPSCs infected with lentiviruses expressing ITGA5-specific shRNA or negative control shRNA were examined using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 5-ethynyl-2'-deoxyuridine labeling. Both ITGA5 knockdown cells and shMock cells were cultured in mineralization medium for 3 weeks, and the differentiation of cells was detected with alizarin red S staining. The expression of odontogenic differentiation-related molecular markers was assessed using real-time polymerase chain reaction and Western blot assays. The knockdown of ITGA5 decreased the proliferation capacity of hDPSCs. ITGA5 shRNA promoted odontogenic differentiation of hDPSCs with the enhanced formation of mineralized nodules. It also up-regulated the messenger RNA expression of multiple markers of odontogenesis and the expression of dentin sialophosphoprotein protein. These findings suggest that ITGA5 plays an important role in maintaining hDPSCs in a proliferative state. The inhibition of ITGA5 signaling promotes the odontogenic differentiation of hDPSCs. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  11. Energy principle with included boundary conditions

    International Nuclear Information System (INIS)

    Lehnert, B.

    1994-01-01

    Earlier comments by the author on the limitations of the classical form of the extended energy principle are supported by a complementary analysis on the potential energy change arising from free-boundary displacements of a magnetically confined plasma. In the final formulation of the extended principle, restricted displacements, satisfying pressure continuity by means of plasma volume currents in a thin boundary layer, are replaced by unrestricted (arbitrary) displacements which can give rise to induced surface currents. It is found that these currents contribute to the change in potential energy, and that their contribution is not taken into account by such a formulation. A general expression is further given for surface currents induced by arbitrary displacements. The expression is used to reformulate the energy principle for the class of displacements which satisfy all necessary boundary conditions, including that of the pressure balance. This makes a minimization procedure of the potential energy possible, for the class of all physically relevant test functions which include the constraints imposed by the boundary conditions. Such a procedure is also consistent with a corresponding variational calculus. (Author)

  12. Aerosol simulation including chemical and nuclear reactions

    International Nuclear Information System (INIS)

    Marwil, E.S.; Lemmon, E.C.

    1985-01-01

    The numerical simulation of aerosol transport, including the effects of chemical and nuclear reactions presents a challenging dynamic accounting problem. Particles of different sizes agglomerate and settle out due to various mechanisms, such as diffusion, diffusiophoresis, thermophoresis, gravitational settling, turbulent acceleration, and centrifugal acceleration. Particles also change size, due to the condensation and evaporation of materials on the particle. Heterogeneous chemical reactions occur at the interface between a particle and the suspending medium, or a surface and the gas in the aerosol. Homogeneous chemical reactions occur within the aersol suspending medium, within a particle, and on a surface. These reactions may include a phase change. Nuclear reactions occur in all locations. These spontaneous transmutations from one element form to another occur at greatly varying rates and may result in phase or chemical changes which complicate the accounting process. This paper presents an approach for inclusion of these effects on the transport of aerosols. The accounting system is very complex and results in a large set of stiff ordinary differential equations (ODEs). The techniques for numerical solution of these ODEs require special attention to achieve their solution in an efficient and affordable manner. 4 refs

  13. Addressing Stillbirth in India Must Include Men.

    Science.gov (United States)

    Roberts, Lisa; Montgomery, Susanne; Ganesh, Gayatri; Kaur, Harinder Pal; Singh, Ratan

    2017-07-01

    Millennium Development Goal 4, to reduce child mortality, can only be achieved by reducing stillbirths globally. A confluence of medical and sociocultural factors contribute to the high stillbirth rates in India. The psychosocial aftermath of stillbirth is a well-documented public health problem, though less is known of the experience for men, particularly outside of the Western context. Therefore, men's perceptions and knowledge regarding reproductive health, as well as maternal-child health are important. Key informant interviews (n = 5) were analyzed and 28 structured interviews were conducted using a survey based on qualitative themes. Qualitative themes included men's dual burden and right to medical and reproductive decision making power. Wives were discouraged from expressing grief and pushed to conceive again. If not successful, particularly if a son was not conceived, a second wife was considered a solution. Quantitative data revealed that men with a history of stillbirths had greater anxiety and depression, perceived less social support, but had more egalitarian views towards women than men without stillbirth experience. At the same time fathers of stillbirths were more likely to be emotionally or physically abusive. Predictors of mental health, attitudes towards women, and perceived support are discussed. Patriarchal societal values, son preference, deficient women's autonomy, and sex-selective abortion perpetuate the risk for future poor infant outcomes, including stillbirth, and compounds the already higher risk of stillbirth for males. Grief interventions should explore and take into account men's perceptions, attitudes, and behaviors towards reproductive decision making.

  14. Including gauge corrections to thermal leptogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Huetig, Janine

    2013-05-17

    This thesis provides the first approach of a systematic inclusion of gauge corrections to leading order to the ansatz of thermal leptogenesis. We have derived a complete expression for the integrated lepton number matrix including all resummations needed. For this purpose, a new class of diagram has been invented, namely the cylindrical diagram, which allows diverse investigations into the topic of leptogenesis such as the case of resonant leptogenesis. After a brief introduction of the topic of the baryon asymmetry in the universe and a discussion of its most promising solutions as well as their advantages and disadvantages, we have presented our framework of thermal leptogenesis. An effective model was described as well as the associated Feynman rules. The basis for using nonequilibrium quantum field theory has been built in chapter 3. At first, the main definitions have been presented for equilibrium thermal field theory, afterwards we have discussed the Kadanoff-Baym equations for systems out of equilibrium using the example of the Majorana neutrino. The equations have also been solved in the context of leptogenesis in chapter 4. Since gauge corrections play a crucial role throughout this thesis, we have also repeated the naive ansatz by replacing the free equilibrium propagator by propagators including thermal damping rates due to the Standard Model damping widths for lepton and Higgs fields. It is shown that this leads to a comparable result to the solutions of the Boltzmann equations for thermal leptogenesis. Thus it becomes obvious that Standard Model corrections are not negligible for thermal leptogenesis and therefore need to be included systematically from first principles. In order to achieve this we have started discussing the calculation of ladder rung diagrams for Majorana neutrinos using the HTL and the CTL approach in chapter 5. All gauge corrections are included in this framework and thus it has become the basis for the following considerations

  15. Including gauge corrections to thermal leptogenesis

    International Nuclear Information System (INIS)

    Huetig, Janine

    2013-01-01

    This thesis provides the first approach of a systematic inclusion of gauge corrections to leading order to the ansatz of thermal leptogenesis. We have derived a complete expression for the integrated lepton number matrix including all resummations needed. For this purpose, a new class of diagram has been invented, namely the cylindrical diagram, which allows diverse investigations into the topic of leptogenesis such as the case of resonant leptogenesis. After a brief introduction of the topic of the baryon asymmetry in the universe and a discussion of its most promising solutions as well as their advantages and disadvantages, we have presented our framework of thermal leptogenesis. An effective model was described as well as the associated Feynman rules. The basis for using nonequilibrium quantum field theory has been built in chapter 3. At first, the main definitions have been presented for equilibrium thermal field theory, afterwards we have discussed the Kadanoff-Baym equations for systems out of equilibrium using the example of the Majorana neutrino. The equations have also been solved in the context of leptogenesis in chapter 4. Since gauge corrections play a crucial role throughout this thesis, we have also repeated the naive ansatz by replacing the free equilibrium propagator by propagators including thermal damping rates due to the Standard Model damping widths for lepton and Higgs fields. It is shown that this leads to a comparable result to the solutions of the Boltzmann equations for thermal leptogenesis. Thus it becomes obvious that Standard Model corrections are not negligible for thermal leptogenesis and therefore need to be included systematically from first principles. In order to achieve this we have started discussing the calculation of ladder rung diagrams for Majorana neutrinos using the HTL and the CTL approach in chapter 5. All gauge corrections are included in this framework and thus it has become the basis for the following considerations

  16. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...... surgical techniques and better outcome after peripheral nerve injury. Decision making in peripheral nerve surgery continues to be a complex challenge, where the mechanism of injury, repeated clinical evaluation, neuroradiological and neurophysiological examination, and detailed knowledge of the peripheral...... nervous system response to injury are prerequisite to obtain the best possible outcome. Surgery continues to be the primary treatment modality for peripheral nerve tumors and advances in adjuvant oncological treatment has improved outcome after malignant peripheral nerve tumors. The present chapter...

  17. AMS at the ANU including biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Fifield, L K; Allan, G L; Cresswell, R G; Ophel, T R [Australian National Univ., Canberra, ACT (Australia); King, S J; Day, J P [Manchester Univ. (United Kingdom). Dept. of Chemistry

    1994-12-31

    An extensive accelerator mass spectrometry program has been conducted on the 14UD accelerator at the Australian National University since 1986. In the two years since the previous conference, the research program has expanded significantly to include biomedical applications of {sup 26}Al and studies of landform evolution using isotopes produced in situ in surface rocks by cosmic ray bombardment. The system is now used for the measurement of {sup 10}Be, {sup 14}C, {sup 26}Al, {sup 36}Cl, {sup 59}Ni and {sup 129}I, and research is being undertaken in hydrology, environmental geochemistry, archaeology and biomedicine. On the technical side, a new test system has permitted the successful off-line development of a high-intensity ion source. A new injection line to the 14UD has been established and the new source is now in position and providing beams to the accelerator. 4 refs.

  18. AMS at the ANU including biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Fifield, L.K.; Allan, G.L.; Cresswell, R.G.; Ophel, T.R. [Australian National Univ., Canberra, ACT (Australia); King, S.J.; Day, J.P. [Manchester Univ. (United Kingdom). Dept. of Chemistry

    1993-12-31

    An extensive accelerator mass spectrometry program has been conducted on the 14UD accelerator at the Australian National University since 1986. In the two years since the previous conference, the research program has expanded significantly to include biomedical applications of {sup 26}Al and studies of landform evolution using isotopes produced in situ in surface rocks by cosmic ray bombardment. The system is now used for the measurement of {sup 10}Be, {sup 14}C, {sup 26}Al, {sup 36}Cl, {sup 59}Ni and {sup 129}I, and research is being undertaken in hydrology, environmental geochemistry, archaeology and biomedicine. On the technical side, a new test system has permitted the successful off-line development of a high-intensity ion source. A new injection line to the 14UD has been established and the new source is now in position and providing beams to the accelerator. 4 refs.

  19. CERN Technical Training: LABVIEW courses include RADE

    CERN Multimedia

    HR Department

    2009-01-01

    The contents of the "LabView Basic I" and "LabView Intermediate II" courses have recently been changed to include, respectively, an introduction to and expert training in the Rapid Application Development Environment (RADE). RADE is a LabView-based application developed at CERN to integrate LabView in the accelerator and experiment control infrastructure. It is a suitable solution to developing expert tools, machine development analysis and independent test facilities. The course names have also been changed to "LabVIEW Basics I with RADE Introduction" and "LabVIEW Intermediate II with Advanced RADE Application". " LabVIEW Basics I with RADE Introduction" is designed for: Users preparing to develop applications using LabVIEW, or NI Developer Suite; users and technical managers evaluating LabVIEW or NI Developer Suite in purchasing decisions; users pursuing the Certified LabVIEW Developer certification. The course pr...

  20. CERN Technical Training: LABVIEW courses include RADE

    CERN Multimedia

    HR Department

    2009-01-01

    The contents of the "LabView Basic I" and "LabView Intermediate II" courses have recently been changed to include, respectively, an introduction to and expert training in the Rapid Application Development Environment (RADE). RADE is a LabView-based application developed at CERN to integrate LabView in the accelerator and experiment control infrastructure. It is a suitable solution to developing expert tools, machine development analysis and independent test facilities. The course names have also been changed to "LabVIEW Basics I with RADE Introduction" and "LabVIEW Intermediate II with Advanced RADE Application". " LabVIEW Basics I with RADE Introduction" is designed for: Users preparing to develop applications using LabVIEW, or NI Developer Suite; users and technical managers evaluating LabVIEW or NI Developer Suite in purchasing decisions; users pursuing the Certified LabVIEW Developer certification. The course prepares participants to develop test and measurement, da...

  1. CERN Technical Training: LABVIEW courses include RADE

    CERN Multimedia

    HR Department

    2009-01-01

    The contents of "LabView Basic I" and "LabView Intermediate II" trainings have been recently changed to include, respectively, an introduction and an expert training on the Rapid Application Development Environment (RADE). RADE is a LabView-based application developed at CERN to integrate LabView in the accelerator and experiment control infrastructure. It is a suitable solution to develop expert tools, machine development analysis and independent test facilities. The course names have also been changed to "LabVIEW Basics I with RADE Introduction" and "LabVIEW Intermediate II with Advanced RADE Application". " LabVIEW Basics I with RADE Introduction" is designed for: Users preparing to develop applications using LabVIEW, or NI Developer Suite; users and technical managers evaluating LabVIEW or NI Developer Suite in purchasing decisions; users pursuing the Certified LabVIEW Developer certification. The course prepare...

  2. Critical point anomalies include expansion shock waves

    Energy Technology Data Exchange (ETDEWEB)

    Nannan, N. R., E-mail: ryan.nannan@uvs.edu [Mechanical Engineering Discipline, Anton de Kom University of Suriname, Leysweg 86, PO Box 9212, Paramaribo, Suriname and Process and Energy Department, Delft University of Technology, Leeghwaterstraat 44, 2628 CA Delft (Netherlands); Guardone, A., E-mail: alberto.guardone@polimi.it [Department of Aerospace Science and Technology, Politecnico di Milano, Via La Masa 34, 20156 Milano (Italy); Colonna, P., E-mail: p.colonna@tudelft.nl [Propulsion and Power, Delft University of Technology, Kluyverweg 1, 2629 HS Delft (Netherlands)

    2014-02-15

    From first-principle fluid dynamics, complemented by a rigorous state equation accounting for critical anomalies, we discovered that expansion shock waves may occur in the vicinity of the liquid-vapor critical point in the two-phase region. Due to universality of near-critical thermodynamics, the result is valid for any common pure fluid in which molecular interactions are only short-range, namely, for so-called 3-dimensional Ising-like systems, and under the assumption of thermodynamic equilibrium. In addition to rarefaction shock waves, diverse non-classical effects are admissible, including composite compressive shock-fan-shock waves, due to the change of sign of the fundamental derivative of gasdynamics.

  3. CLIC expands to include the Southern Hemisphere

    CERN Multimedia

    Roberto Cantoni

    2010-01-01

    Australia has recently joined the CLIC collaboration: the enlargement will bring new expertise and resources to the project, and is especially welcome in the wake of CERN budget redistributions following the recent adoption of the Medium Term Plan.   The countries involved in CLIC collaboration With the signing of a Memorandum of Understanding on 26 August 2010, the ACAS network (Australian Collaboration for Accelerator Science) became the 40th member of in the multilateral CLIC collaboration making Australia the 22nd country to join the collaboration. “The new MoU was signed by the ACAS network, which includes the Australian Synchrotron and the University of Melbourne”, explains Jean-Pierre Delahaye, CLIC Study Leader. “Thanks to their expertise, the Australian institutes will contribute greatly to the CLIC damping rings and the two-beam test modules." Institutes from any country wishing to join the CLIC collaboration are invited to assume responsibility o...

  4. Should Broca's area include Brodmann area 47?

    Science.gov (United States)

    Ardila, Alfredo; Bernal, Byron; Rosselli, Monica

    2017-02-01

    Understanding brain organization of speech production has been a principal goal of neuroscience. Historically, brain speech production has been associated with so-called Broca’s area (Brodmann area –BA- 44 and 45), however, modern neuroimaging developments suggest speech production is associated with networks rather than with areas. The purpose of this paper was to analyze the connectivity of BA47 ( pars orbitalis) in relation to language . A meta-analysis was conducted to assess the language network in which BA47 is involved. The Brainmap database was used. Twenty papers corresponding to 29 experimental conditions with a total of 373 subjects were included. Our results suggest that BA47 participates in a “frontal language production system” (or extended Broca’s system). The BA47  connectivity found is also concordant with a minor role in language semantics. BA47 plays a central role in the language production system.

  5. Musculoskeletal ultrasound including definitions for ultrasonographic pathology

    DEFF Research Database (Denmark)

    Wakefield, RJ; Balint, PV; Szkudlarek, Marcin

    2005-01-01

    Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints...... in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US...... pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis....

  6. Grand unified models including extra Z bosons

    International Nuclear Information System (INIS)

    Li Tiezhong

    1989-01-01

    The grand unified theories (GUT) of the simple Lie groups including extra Z bosons are discussed. Under authors's hypothesis there are only SU 5+m SO 6+4n and E 6 groups. The general discussion of SU 5+m is given, then the SU 6 and SU 7 are considered. In SU 6 the 15+6 * +6 * fermion representations are used, which are not same as others in fermion content, Yukawa coupling and broken scales. A conception of clans of particles, which are not families, is suggested. These clans consist of extra Z bosons and the corresponding fermions of the scale. The all of fermions in the clans are down quarks except for the standard model which consists of Z bosons and 15 fermions, therefore, the spectrum of the hadrons which are composed of these down quarks are different from hadrons at present

  7. Including climate change in energy investment decisions

    International Nuclear Information System (INIS)

    Ybema, J.R.; Boonekamp, P.G.M.; Smit, J.T.J.

    1995-08-01

    To properly take climate change into account in the analysis of energy investment decisions, it is required to apply decision analysis methods that are capable of considering the specific characteristics of climate change (large uncertainties, long term horizon). Such decision analysis methods do exist. They can explicitly include evolving uncertainties, multi-stage decisions, cumulative effects and risk averse attitudes. Various methods are considered in this report and two of these methods have been selected: hedging calculations and sensitivity analysis. These methods are applied to illustrative examples, and its limitations are discussed. The examples are (1a) space heating and hot water for new houses from a private investor perspective and (1b) as example (1a) but from a government perspective, (2) electricity production with an integrated coal gasification combined cycle (ICGCC) with or without CO 2 removal, and (3) national energy strategy to hedge for climate change. 9 figs., 21 tabs., 42 refs., 1 appendix

  8. Education Program on Fossil Resources Including Coal

    Science.gov (United States)

    Usami, Masahiro

    Fossil fuels including coal play a key role as crucial energies in contributing to economic development in Asia. On the other hand, its limited quantity and the environmental problems causing from its usage have become a serious global issue and a countermeasure to solve such problems is very much demanded. Along with the pursuit of sustainable development, environmentally-friendly use of highly efficient fossil resources should be therefore, accompanied. Kyushu-university‧s sophisticated research through long years of accumulated experience on the fossil resources and environmental sectors together with the advanced large-scale commercial and empirical equipments will enable us to foster cooperative research and provide internship program for the future researchers. Then, this program is executed as a consignment business from the Ministry of Economy, Trade and Industry from 2007 fiscal year to 2009 fiscal year. The lecture that uses the textbooks developed by this program is scheduled to be started a course in fiscal year 2010.

  9. Human-machine interactions

    Science.gov (United States)

    Forsythe, J Chris [Sandia Park, NM; Xavier, Patrick G [Albuquerque, NM; Abbott, Robert G [Albuquerque, NM; Brannon, Nathan G [Albuquerque, NM; Bernard, Michael L [Tijeras, NM; Speed, Ann E [Albuquerque, NM

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  10. Analysis of Smart Composite Structures Including Debonding

    Science.gov (United States)

    Chattopadhyay, Aditi; Seeley, Charles E.

    1997-01-01

    Smart composite structures with distributed sensors and actuators have the capability to actively respond to a changing environment while offering significant weight savings and additional passive controllability through ply tailoring. Piezoelectric sensing and actuation of composite laminates is the most promising concept due to the static and dynamic control capabilities. Essential to the implementation of these smart composites are the development of accurate and efficient modeling techniques and experimental validation. This research addresses each of these important topics. A refined higher order theory is developed to model composite structures with surface bonded or embedded piezoelectric transducers. These transducers are used as both sensors and actuators for closed loop control. The theory accurately captures the transverse shear deformation through the thickness of the smart composite laminate while satisfying stress free boundary conditions on the free surfaces. The theory is extended to include the effect of debonding at the actuator-laminate interface. The developed analytical model is implemented using the finite element method utilizing an induced strain approach for computational efficiency. This allows general laminate geometries and boundary conditions to be analyzed. The state space control equations are developed to allow flexibility in the design of the control system. Circuit concepts are also discussed. Static and dynamic results of smart composite structures, obtained using the higher order theory, are correlated with available analytical data. Comparisons, including debonded laminates, are also made with a general purpose finite element code and available experimental data. Overall, very good agreement is observed. Convergence of the finite element implementation of the higher order theory is shown with exact solutions. Additional results demonstrate the utility of the developed theory to study piezoelectric actuation of composite

  11. Zγ production at NNLO including anomalous couplings

    Science.gov (United States)

    Campbell, John M.; Neumann, Tobias; Williams, Ciaran

    2017-11-01

    In this paper we present a next-to-next-to-leading order (NNLO) QCD calculation of the processes pp → l + l -γ and pp\\to ν \\overline{ν}γ that we have implemented in MCFM. Our calculation includes QCD corrections at NNLO both for the Standard Model (SM) and additionally in the presence of Zγγ and ZZγ anomalous couplings. We compare our implementation, obtained using the jettiness slicing approach, with a previous SM calculation and find broad agreement. Focusing on the sensitivity of our results to the slicing parameter, we show that using our setup we are able to compute NNLO cross sections with numerical uncertainties of about 0.1%, which is small compared to residual scale uncertainties of a few percent. We study potential improvements using two different jettiness definitions and the inclusion of power corrections. At √{s}=13 TeV we present phenomenological results and consider Zγ as a background to H → Zγ production. We find that, with typical cuts, the inclusion of NNLO corrections represents a small effect and loosens the extraction of limits on anomalous couplings by about 10%.

  12. Alternating phase focussing including space charge

    International Nuclear Information System (INIS)

    Cheng, W.H.; Gluckstern, R.L.

    1992-01-01

    Longitudinal stability can be obtained in a non-relativistic drift tube accelerator by traversing each gap as the rf accelerating field rises. However, the rising accelerating field leads to a transverse defocusing force which is usually overcome by magnetic focussing inside the drift tubes. The radio frequency quadrupole is one way of providing simultaneous longitudinal and transverse focusing without the use of magnets. One can also avoid the use of magnets by traversing alternate gaps between drift tubes as the field is rising and falling, thus providing an alternation of focussing and defocusing forces in both the longitudinal and transverse directions. The stable longitudinal phase space area is quite small, but recent efforts suggest that alternating phase focussing (APF) may permit low velocity acceleration of currents in the 100-300 ma range. This paper presents a study of the parameter space and a test of crude analytic predictions by adapting the code PARMILA, which includes space charge, to APF. 6 refs., 3 figs

  13. Probabilistic production simulation including CHP plants

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, H.V.; Palsson, H.; Ravn, H.F.

    1997-04-01

    A probabilistic production simulation method is presented for an energy system containing combined heat and power plants. The method permits incorporation of stochastic failures (forced outages) of the plants and is well suited for analysis of the dimensioning of the system, that is, for finding the appropriate types and capacities of production plants in relation to expansion planning. The method is in the tradition of similar approaches for the analysis of power systems, based on the load duration curve. The present method extends on this by considering a two-dimensional load duration curve where the two dimensions represent heat and power. The method permits the analysis of a combined heat and power system which includes all the basic relevant types of plants, viz., condensing plants, back pressure plants, extraction plants and heat plants. The focus of the method is on the situation where the heat side has priority. This implies that on the power side there may be imbalances between demand and production. The method permits quantification of the expected power overflow, the expected unserviced power demand, and the expected unserviced heat demand. It is shown that a discretization method as well as double Fourier series may be applied in algorithms based on the method. (au) 1 tab., 28 ills., 21 refs.

  14. Langevin simulations of QCD, including fermions

    International Nuclear Information System (INIS)

    Kronfeld, A.S.

    1986-02-01

    We encounter critical slow down in updating when xi/a -> infinite and in matrix inversion (needed to include fermions) when msub(q)a -> 0. A simulation that purports to solve QCD numerically will encounter these limits, so to face the challenge in the title of this workshop, we must cure the disease of critical slow down. Physically, this critical slow down is due to the reluctance of changes at short distances to propagate to large distances. Numerically, the stability of an algorithm at short wavelengths requires a (moderately) small step size; critical slow down occurs when the effective long wavelength step size becomes tiny. The remedy for this disease is an algorithm that propagates signals quickly throughout the system; i.e. one whose effective step size is not reduced for the long wavelength conponents of the fields. (Here the effective ''step size'' is essentially an inverse decorrelation time.) To do so one must resolve various wavelengths of the system and modify the dynamics (in CPU time) of the simulation so that all modes evolve at roughly the same rate. This can be achieved by introducing Fourier transforms. I show how to implement Fourier acceleration for Langevin updating and for conjugate gradient matrix inversion. The crucial feature of these algorithms that lends them to Fourier acceleration is that they update the lattice globally; hence the Fourier transforms are computed once per sweep rather than once per hit. (orig./HSI)

  15. SEEPAGE MODEL FOR PA INCLUDING DRIFT COLLAPSE

    International Nuclear Information System (INIS)

    C. Tsang

    2004-01-01

    The purpose of this report is to document the predictions and analyses performed using the seepage model for performance assessment (SMPA) for both the Topopah Spring middle nonlithophysal (Tptpmn) and lower lithophysal (Tptpll) lithostratigraphic units at Yucca Mountain, Nevada. Look-up tables of seepage flow rates into a drift (and their uncertainty) are generated by performing numerical simulations with the seepage model for many combinations of the three most important seepage-relevant parameters: the fracture permeability, the capillary-strength parameter 1/a, and the percolation flux. The percolation flux values chosen take into account flow focusing effects, which are evaluated based on a flow-focusing model. Moreover, multiple realizations of the underlying stochastic permeability field are conducted. Selected sensitivity studies are performed, including the effects of an alternative drift geometry representing a partially collapsed drift from an independent drift-degradation analysis (BSC 2004 [DIRS 166107]). The intended purpose of the seepage model is to provide results of drift-scale seepage rates under a series of parameters and scenarios in support of the Total System Performance Assessment for License Application (TSPA-LA). The SMPA is intended for the evaluation of drift-scale seepage rates under the full range of parameter values for three parameters found to be key (fracture permeability, the van Genuchten 1/a parameter, and percolation flux) and drift degradation shape scenarios in support of the TSPA-LA during the period of compliance for postclosure performance [Technical Work Plan for: Performance Assessment Unsaturated Zone (BSC 2002 [DIRS 160819], Section I-4-2-1)]. The flow-focusing model in the Topopah Spring welded (TSw) unit is intended to provide an estimate of flow focusing factors (FFFs) that (1) bridge the gap between the mountain-scale and drift-scale models, and (2) account for variability in local percolation flux due to

  16. Comparison of Human Sodium/Iodide Symporter (hNIS) Gene Expressions between Lentiviral and Adenoviral Vectors in Rat Mesenchymal Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, So Yeon; Lee, Won Woo; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Sung Jin; Lee, Heui Ran [Medical Research Center, Seoul National University, Seoul (Korea, Republic of)

    2008-10-15

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirusmediated delivery systems has not been reported. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and transduction efficiency of Rad-hNIS into rMSC evaluated by Rad-GFP was 19.1{+-}4.7%, 54.0{+-}6.4%, 85.7{+-}8.7%, and 98.4{+-}1.3% at MOI 1, 5, 20, and 100, respectively. The hNIS expressions in lenti-hNIS-rMSC or adeno-hNIS-rMSC were assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry and western blot analyses revealed that hNIS expressions in lenti-hNIS-rMSC were greater than those in adeno-hNIS-rMSC at MOI 20 but lower than at MOI 50. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (29,704{+-}6,659 picomole/10{sup 6} cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (6,168{+-}2,134 picomole/10{sup 6} cells). Despite lower amount of expressed protein, hNIS function in rMSC was greater by lentivirus than by adenovirus mediated expression. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative vector efficiency for transgene expression.

  17. Comparison of Human Sodium/Iodide Symporter (hNIS) Gene Expressions between Lentiviral and Adenoviral Vectors in Rat Mesenchymal Stem Cells

    International Nuclear Information System (INIS)

    Park, So Yeon; Lee, Won Woo; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun; Kim, Sung Jin; Lee, Heui Ran

    2008-01-01

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirusmediated delivery systems has not been reported. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and transduction efficiency of Rad-hNIS into rMSC evaluated by Rad-GFP was 19.1±4.7%, 54.0±6.4%, 85.7±8.7%, and 98.4±1.3% at MOI 1, 5, 20, and 100, respectively. The hNIS expressions in lenti-hNIS-rMSC or adeno-hNIS-rMSC were assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry and western blot analyses revealed that hNIS expressions in lenti-hNIS-rMSC were greater than those in adeno-hNIS-rMSC at MOI 20 but lower than at MOI 50. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (29,704±6,659 picomole/10 6 cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (6,168±2,134 picomole/10 6 cells). Despite lower amount of expressed protein, hNIS function in rMSC was greater by lentivirus than by adenovirus mediated expression. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative vector efficiency for transgene expression

  18. Comparison of human sodium iodide symporter (hNIS) gene expression between lentiviral and adenoviral vectors in rat mesenchymal stem cell

    International Nuclear Information System (INIS)

    Park, So Yeon; Lee, Won Woo; Kim, Sung Jin; Lee, Heui Ran; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun

    2007-01-01

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirus-mediated delivery systems has not been done. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated stably hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning the hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and Rad-hNIS transduced rMSC (adeno-hNIS-rMSC) was evaluated for the hNIS expression 48 hours post infection at MOI 1, 5, 20, 50, and 100. The hNIS expression in lenti-hNIS-rMSC or adeno-hNIS-rMSC was assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry using mono-clonal anti-hNIS antibody revealed that intensity of hNIS immunoreactivity in lenti-hNIS-rMSC was greater than that in adeno-hNIS-rMSC at MOl 20 but lower than that at MOl 50. Western blot analysis also showed that lenti-hNIS-rMSC was intermediate between adeno-hNIS-rMSCs at MOl 20 and 50 in hNIS expression. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (297046659 picomole/106 cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (61682134 picomole/106 cells). These results suggest that lentivirus mediated hNIS expression is greater in terms of hNIS function but lower in terms of hNIS protein amount than adenovirus mediated hNIS expression 48 hours post infection. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative viral efficiency of transgene expression

  19. 45 CFR 1308.11 - Eligibility criteria: Hearing impairment including deafness.

    Science.gov (United States)

    2010-10-01

    ... OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR... impairment including deafness. (a) A child is classified as deaf if a hearing impairment exists which is so... hearing loss can include impaired listening skills, delayed language development, and articulation...

  20. Special Section: Human Rights

    Science.gov (United States)

    Frydenlund, Knut; And Others

    1978-01-01

    Eleven articles examine human rights in Europe. Topics include unemployment, human rights legislation, role of the Council of Europe in promoting human rights, labor unions, migrant workers, human dignity in industralized societies, and international violence. Journal available from Council of Europe, Directorate of Press and Information, 67006…

  1. Complementation of Myelodysplastic Syndrome Clones with Lentivirus Expression Libraries

    Science.gov (United States)

    2013-01-01

    Description HRAS Homo sapiens v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS), transcript 1 CDC25C Homo sapiens cell division cycle 25...homolog C (CDC25C), transcript variant 1 MYC Homo sapiens v-myc myeloctomatosis viral oncogene homolog (avian) (MYC) MAP3K7 Homo sapiens mitogen...activated protein kinase kinase kinase 7 (MAP3K7) MAP3K8 Homo sapiens mitogen-activated protein kinase kinase kinase 8 (MAP3K8) SF3B1 Homo sapiens

  2. Evaluation of antivirals against corona- and lentiviruses in cell cultures

    NARCIS (Netherlands)

    Meer, F.J.U.M. van der

    2007-01-01

    Virus infections constitute a continuous health threat. As illustrated by the recent emergence of new - the SARS coronavirus - and the re-emergence of known viruses - influenza, ebola - this threat is certainly not yet decreasing. Rather, many conditions and considerations indicate that viruses will

  3. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    Science.gov (United States)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    The dilemma of designing an advanced undergraduate laboratory lies in the desire to teach and reinforce basic principles and techniques while at the same time exposing students to the excitement of research. We report here on a one-semester, project-based biochemistry laboratory that combines the best features of a cookbook approach (high success rate, achievement of defined goals) with those of an investigative, discovery-based approach (student involvement in the experimental design, excitement of real research). Individual modules may be selected and combined to meet the needs of different courses and different institutions. The central theme of this lab is protein purification and design. This laboratory accompanies the first semester of biochemistry (Structure and Function of Macromolecules, a course taken mainly by junior and senior chemistry and biological chemistry majors). The protein chosen as the object of study is the enzyme lysozyme, which is utilized in all projects. It is suitable for a student lab because it is easily and inexpensively obtained from egg white and is extremely stable, and its high isoelectric point (pI = 11) allows for efficient separation from other proteins by ion-exchange chromatography. Furthermore, a literature search conducted by the resourceful student reveals a wealth of information, since lysozyme has been the subject of numerous studies. It was the first enzyme whose structure was determined by crystallography (1). Hendrickson et al. (2) have previously described an intensive one-month laboratory course centered around lysozyme, although their emphasis is on protein stability rather than purification and engineering. Lysozyme continues to be the focus of much exciting new work on protein folding and dynamics, structure and activity (3 - 5). This lab course includes the following features: (i) reinforcement of basic techniques, such as preparation of buffers, simple enzyme kinetics, and absorption spectroscopy; (ii

  4. A historical reflection on the discovery of human retroviruses.

    Science.gov (United States)

    Vahlne, Anders

    2009-05-01

    The discovery of HIV-1 as the cause of AIDS was one of the major scientific achievements during the last century. Here the events leading to this discovery are reviewed with particular attention to priority and actual contributions by those involved. Since I would argue that discovering HIV was dependent on the previous discovery of the first human retrovirus HTLV-I, the history of this discovery is also re-examined. The first human retroviruses (HTLV-I) was first reported by Robert C. Gallo and coworkers in 1980 and reconfirmed by Yorio Hinuma and coworkers in 1981. These discoveries were in turn dependent on the previous discovery by Gallo and coworkers in 1976 of interleukin 2 or T-cell growth factor as it was called then. HTLV-II was described by Gallo's group in 1982. A human retrovirus distinct from HTLV-I and HTLV-II in that it was shown to have the morphology of a lentivirus was in my mind described for the first time by Luc Montagnier in an oral presentation at Cold Spring Harbor in September of 1983. This virus was isolated from a patient with lymphadenopathy using the protocol previously described for HTLV by Gallo. The first peer reviewed paper by Montagnier's group of such a retrovirus, isolated from two siblings of whom one with AIDS, appeared in Lancet in April of 1984. However, the proof that a new human retrovirus (HIV-1) was the cause of AIDS was first established in four publications by Gallo's group in the May 4th issue of Science in 1984.

  5. A historical reflection on the discovery of human retroviruses

    Directory of Open Access Journals (Sweden)

    Vahlne Anders

    2009-05-01

    Full Text Available Abstract The discovery of HIV-1 as the cause of AIDS was one of the major scientific achievements during the last century. Here the events leading to this discovery are reviewed with particular attention to priority and actual contributions by those involved. Since I would argue that discovering HIV was dependent on the previous discovery of the first human retrovirus HTLV-I, the history of this discovery is also re-examined. The first human retroviruses (HTLV-I was first reported by Robert C. Gallo and coworkers in 1980 and reconfirmed by Yorio Hinuma and coworkers in 1981. These discoveries were in turn dependent on the previous discovery by Gallo and coworkers in 1976 of interleukin 2 or T-cell growth factor as it was called then. HTLV-II was described by Gallo's group in 1982. A human retrovirus distinct from HTLV-I and HTLV-II in that it was shown to have the morphology of a lentivirus was in my mind described for the first time by Luc Montagnier in an oral presentation at Cold Spring Harbor in September of 1983. This virus was isolated from a patient with lymphadenopathy using the protocol previously described for HTLV by Gallo. The first peer reviewed paper by Montagnier's group of such a retrovirus, isolated from two siblings of whom one with AIDS, appeared in Lancet in April of 1984. However, the proof that a new human retrovirus (HIV-1 was the cause of AIDS was first established in four publications by Gallo's group in the May 4th issue of Science in 1984.

  6. Risk Factors for Breast Cancer, Including Occupational Exposures

    Directory of Open Access Journals (Sweden)

    Elisabete Weiderpass

    2011-03-01

    Full Text Available The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr. For breast cancer the following substances have been classified as “carcinogenic to humans” (Group 1: alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure. Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification “probably carcinogenic to humans” (Group 2A includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women.

  7. Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Deepak A Lamba

    2010-01-01

    Full Text Available Inherited and acquired retinal degenerations are frequent causes of visual impairment and photoreceptor cell replacement therapy may restore visual function to these individuals. To provide a source of new retinal neurons for cell based therapies, we developed methods to derive retinal progenitors from human ES cells.In this report we have used a similar method to direct induced pluripotent stem cells (iPS from human fibroblasts to a retinal progenitor fate, competent to generate photoreceptors. We also found we could purify the photoreceptors derived from the iPS cells using fluorescence activated cell sorting (FACS after labeling photoreceptors with a lentivirus driving GFP from the IRBP cis-regulatory sequences. Moreover, we found that when we transplanted the FACS purified iPSC derived photoreceptors, they were able to integrate into a normal mouse retina and express photoreceptor markers.This report provides evidence that enriched populations of human photoreceptors can be derived from iPS cells.

  8. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  9. Human cognition

    International Nuclear Information System (INIS)

    Norman, D.A.

    1982-01-01

    The study of human cognition encompasses the study of all mental phenomena, from the receipt and interpretation of sensory information to the final control of the motor system in the performance of action. The cognitive scientist examines all intermediary processes, including thought, decision making, and memory and including the effects of motivation, states of arousal and stress, the study of language, and the effects of social factors. The field therefore ranges over an enormous territory, covering all that is known or that should be known about human behavior. It is not possible to summarize the current state of knowledge about cognition with any great confidence that we know the correct answer about any aspect of the work. Nontheless, models provide good characterizations of certain aspects of the data and situations. Even if these models should prove to be incorrect, they do provide good approximate descriptions of people's behavior in some situations, and these approximations will still apply even when the underlying theories have changed. A quick description is provided of models within a number of areas of human cognition and skill and some general theoretical frameworks with which to view human cognition. The frameworks are qualitative descriptions that provide a way to view the development of more detailed, quantitative models and, most important, a way of thinking about human performance and skill

  10. Evaluating human genetic diversity

    National Research Council Canada - National Science Library

    This book assesses the scientific value and merit of research on human genetic differences--including a collection of DNA samples that represents the whole of human genetic diversity--and the ethical...

  11. Ionic liquids, electrolyte solutions including the ionic liquids, and energy storage devices including the ionic liquids

    Science.gov (United States)

    Gering, Kevin L.; Harrup, Mason K.; Rollins, Harry W.

    2015-12-08

    An ionic liquid including a phosphazene compound that has a plurality of phosphorus-nitrogen units and at least one pendant group bonded to each phosphorus atom of the plurality of phosphorus-nitrogen units. One pendant group of the at least one pendant group comprises a positively charged pendant group. Additional embodiments of ionic liquids are disclosed, as are electrolyte solutions and energy storage devices including the embodiments of the ionic liquid.

  12. Do pigeons prefer alternatives that include near-hit outcomes?

    Science.gov (United States)

    Stagner, Jessica P; Case, Jacob P; Sticklen, Mary F; Duncan, Amanda K; Zentall, Thomas R

    2015-07-01

    Pigeons show suboptimal choice on a gambling-like task similar to that shown by humans. Humans also show a preference for gambles in which there are near hits (losses that come close to winning). In the present research, we asked if pigeons would show a preference for alternatives with near-hit-like trials. In Experiment 1, we included an alternative that presented a near hit, in which a stimulus associated with reinforcement (a presumed conditioned reinforcer) changed to a stimulus associated with the absence of reinforcement (a presumed conditioned inhibitor). The pigeons tended to avoid this alternative. In Experiment 2, we varied the duration of the presumed conditioned reinforcer (2 vs. 8 s) that changed to a presumed conditioned inhibitor (8 vs. 2 s) and found that the longer the conditioned reinforcer was presented, the more the pigeons avoided it. In Experiment 3, the near-hit alternative involved an ambiguous stimulus for 8 s that changed to a presumed conditioned reinforcer (or a presumed conditioned inhibitor) for 2 s, but the pigeons still avoided it. In Experiment 4, we controlled for the duration of the conditioned reinforcer by presenting it first for 2 s followed by the ambiguous stimulus for 8 s. Once again, the pigeons avoided the alternative with the near-hit trials. In all 4 experiments, the pigeons tended to avoid alternatives that provided near-hit-like trials. We concluded that humans may be attracted to near-hit trials because near-hit trials give them the illusion of control, whereas this does not appear to be a factor for pigeons. (c) 2015 APA, all rights reserved).

  13. Human factor reliability program

    International Nuclear Information System (INIS)

    Knoblochova, L.

    2017-01-01

    The human factor's reliability program was at Slovenske elektrarne, a.s. (SE) nuclear power plants. introduced as one of the components Initiatives of Excellent Performance in 2011. The initiative's goal was to increase the reliability of both people and facilities, in response to 3 major areas of improvement - Need for improvement of the results, Troubleshooting support, Supporting the achievement of the company's goals. The human agent's reliability program is in practice included: - Tools to prevent human error; - Managerial observation and coaching; - Human factor analysis; -Quick information about the event with a human agent; -Human reliability timeline and performance indicators; - Basic, periodic and extraordinary training in human factor reliability(authors)

  14. Radiation and nuclear safety included in the environmental health programme

    International Nuclear Information System (INIS)

    Salomaa, S.

    1996-01-01

    Finland is currently preparing a national environmental health programme, the objective of which is to chart the main environmental health problems in Finland, to identify means for securing a healthy environment, and to draw up a practical action programme for preventing and rectifying problems pertaining to environmental health. Radiation and nuclear safety form an essential part of preventive health care. The action programme is based on decisions and programmes approved at the WHO Conference on the Environment and Health, held in Helsinki in June 1994. In addition to the state of the Finnish environment and the health of the Finnish population, the programme addresses the relevant international issues, in particular in areas adjacent to Finland. The Committee on Environmental Health is expected to complete its work by the end of the year. A wide range of representatives from various branches of administration have contributed to the preparation of the programme. Besides physical, biological and chemical factors, the environmental factors affecting health also include the physical environment and the psychological, social and aesthetic features of the environment. Similarly, environmental factors that have an impact on the health of present or future generations, on the essential preconditions of life and on the quality of life are investigated. The serious risk to nature caused by human actions is also considered as a potential risk to human health. (orig.)

  15. Catalyst support structure, catalyst including the structure, reactor including a catalyst, and methods of forming same

    Science.gov (United States)

    Van Norman, Staci A.; Aston, Victoria J.; Weimer, Alan W.

    2017-05-09

    Structures, catalysts, and reactors suitable for use for a variety of applications, including gas-to-liquid and coal-to-liquid processes and methods of forming the structures, catalysts, and reactors are disclosed. The catalyst material can be deposited onto an inner wall of a microtubular reactor and/or onto porous tungsten support structures using atomic layer deposition techniques.

  16. Tabhu: tools for antibody humanization.

    KAUST Repository

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna

    2014-01-01

    for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps of the humanization experiment protocol. AVAILABILITY: http

  17. The NDUFB6 subunit of the mitochondrial respiratory chain complex I is required for electron transfer activity: A proof of principle study on stable and controlled RNA interference in human cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Loublier, Sandrine; Bayot, Aurelien; Rak, Malgorzata; El-Khoury, Riyad; Benit, Paule [Inserm U676, Hopital Robert Debre, F-75019 Paris (France); Universite Paris 7, Faculte de medecine Denis Diderot, IFR02 Paris (France); Rustin, Pierre, E-mail: pierre.rustin@inserm.fr [Inserm U676, Hopital Robert Debre, F-75019 Paris (France); Universite Paris 7, Faculte de medecine Denis Diderot, IFR02 Paris (France)

    2011-10-22

    Highlights: {yields} NDUFB6 is required for activity of mitochondrial complex I in human cell lines. {yields} Lentivirus based RNA interference results in frequent off target insertions. {yields} Flp-In recombinase mediated miRNA insertion allows gene-specific extinction. -- Abstract: Molecular bases of inherited deficiencies of mitochondrial respiratory chain complex I are still unknown in a high proportion of patients. Among 45 subunits making up this large complex, more than half has unknown function(s). Understanding the function of these subunits would contribute to our knowledge on mitochondrial physiology but might also reveal that some of these subunits are not required for the catalytic activity of the complex. A direct consequence of this finding would be the reduction of the number of candidate genes to be sequenced in patients with decreased complex I activity. In this study, we tested two different methods to stably extinct complex I subunits in cultured cells. We first found that lentivirus-mediated shRNA expression frequently resulted in the unpredicted extinction of additional gene(s) beside targeted ones. This can be ascribed to uncontrolled genetic material insertions in the genome of the host cell. This approach thus appeared inappropriate to study unknown functions of a gene. Next, we found it possible to specifically extinct a CI subunit gene by direct insertion of a miR targeting CI subunits in a Flp site (HEK293 Flp-In cells). By using this strategy we unambiguously demonstrated that the NDUFB6 subunit is required for complex I activity, and defined conditions suitable to undertake a systematic and stable extinction of the different supernumerary subunits in human cells.

  18. The NDUFB6 subunit of the mitochondrial respiratory chain complex I is required for electron transfer activity: A proof of principle study on stable and controlled RNA interference in human cell lines

    International Nuclear Information System (INIS)

    Loublier, Sandrine; Bayot, Aurelien; Rak, Malgorzata; El-Khoury, Riyad; Benit, Paule; Rustin, Pierre

    2011-01-01

    Highlights: → NDUFB6 is required for activity of mitochondrial complex I in human cell lines. → Lentivirus based RNA interference results in frequent off target insertions. → Flp-In recombinase mediated miRNA insertion allows gene-specific extinction. -- Abstract: Molecular bases of inherited deficiencies of mitochondrial respiratory chain complex I are still unknown in a high proportion of patients. Among 45 subunits making up this large complex, more than half has unknown function(s). Understanding the function of these subunits would contribute to our knowledge on mitochondrial physiology but might also reveal that some of these subunits are not required for the catalytic activity of the complex. A direct consequence of this finding would be the reduction of the number of candidate genes to be sequenced in patients with decreased complex I activity. In this study, we tested two different methods to stably extinct complex I subunits in cultured cells. We first found that lentivirus-mediated shRNA expression frequently resulted in the unpredicted extinction of additional gene(s) beside targeted ones. This can be ascribed to uncontrolled genetic material insertions in the genome of the host cell. This approach thus appeared inappropriate to study unknown functions of a gene. Next, we found it possible to specifically extinct a CI subunit gene by direct insertion of a miR targeting CI subunits in a Flp site (HEK293 Flp-In cells). By using this strategy we unambiguously demonstrated that the NDUFB6 subunit is required for complex I activity, and defined conditions suitable to undertake a systematic and stable extinction of the different supernumerary subunits in human cells.

  19. Launch Lock Assemblies Including Axial Gap Amplification Devices and Spacecraft Isolation Systems Including the Same

    Science.gov (United States)

    Barber, Tim Daniel (Inventor); Hindle, Timothy (Inventor); Young, Ken (Inventor); Davis, Torey (Inventor)

    2014-01-01

    Embodiments of a launch lock assembly are provided, as are embodiments of a spacecraft isolation system including one or more launch lock assemblies. In one embodiment, the launch lock assembly includes first and second mount pieces, a releasable clamp device, and an axial gap amplification device. The releasable clamp device normally maintains the first and second mount pieces in clamped engagement; and, when actuated, releases the first and second mount pieces from clamped engagement to allow relative axial motion there between. The axial gap amplification device normally residing in a blocking position wherein the gap amplification device obstructs relative axial motion between the first and second mount pieces. The axial gap amplification device moves into a non-blocking position when the first and second mount pieces are released from clamped engagement to increase the range of axial motion between the first and second mount pieces.

  20. TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts.

    Science.gov (United States)

    Bernstein, Diana L; Le Lay, John E; Ruano, Elena G; Kaestner, Klaus H

    2015-05-01

    Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator-like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics.

  1. Electrolyte solutions including a phosphoranimine compound, and energy storage devices including same

    Science.gov (United States)

    Klaehn, John R.; Dufek, Eric J.; Rollins, Harry W.; Harrup, Mason K.; Gering, Kevin L.

    2017-09-12

    An electrolyte solution comprising at least one phosphoranimine compound and a metal salt. The at least one phosphoranimine compound comprises a compound of the chemical structure ##STR00001## where X is an organosilyl group or a tert-butyl group and each of R.sup.1, R.sup.2, and R.sup.3 is independently selected from the group consisting of an alkyl group, an aryl group, an alkoxy group, or an aryloxy group. An energy storage device including the electrolyte solution is also disclosed.

  2. A Human Rights Glossary.

    Science.gov (United States)

    Flowers, Nancy

    1998-01-01

    Presents a human rights glossary that includes definitions of basic terms, treaties, charters, and groups/organizations that have been featured in previous articles in this edition of "Update on Law-Related Education"; the human rights terms have been compiled as part of the celebration of the Universal Declaration of Human Rights…

  3. Variations in the ultrastructure of human nasal cilia including abnormalities found in retinitis pigmentosa.

    Science.gov (United States)

    Fox, B; Bull, T B; Arden, G B

    1980-01-01

    The electron microscopic structure of cilia from the inferior turbinate of the nose was studied in 12 adults, four with chronic sinusitis, one with allergic rhinitis, two with bronchiectasis, three with deviated nasal septum, and two normals. The changes are compared with those found in nasal cilia in 14 patients with retinitis pigmentosa. There were compound cilia in the seven cases with chronic sinusitis, allergic rhinitis, and bronchiectasis but, apart from this, the structure of the cilia was similar in all 12 cases. There were variations in the microtubular pattern in about 4% of cilia, dynein arms were not seen in 4%, and in the rest an average of 5-6 dynein arms were seen in each cilium. The orientation of the cilia was 0 to 90 degrees. In the retinitis pigmentosa patients there was a highly significant increase in cilial abnormalities. The establishment on a quantitative basis of the variations in normal structure of nasal cilila facilitated the recognition of an association between cilial abnormalities and retinitis pigmentosa and should help in the identification of associations that may exist between cilial abnormalities and other diseases. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 7 Fig. 8 PMID:7400333

  4. Variations in the ultrastructure of human nasal cilia including abnormalities found in retinitis pigmentosa.

    OpenAIRE

    Fox, B; Bull, T B; Arden, G B

    1980-01-01

    The electron microscopic structure of cilia from the inferior turbinate of the nose was studied in 12 adults, four with chronic sinusitis, one with allergic rhinitis, two with bronchiectasis, three with deviated nasal septum, and two normals. The changes are compared with those found in nasal cilia in 14 patients with retinitis pigmentosa. There were compound cilia in the seven cases with chronic sinusitis, allergic rhinitis, and bronchiectasis but, apart from this, the structure of the cilia...

  5. Update on the Human Broad Tapeworm (Genus Diphyllobothrium), Including Clinical Relevance

    Czech Academy of Sciences Publication Activity Database

    Scholz, Tomáš; García, H. H.; Kuchta, Roman; Wicht, B.

    2009-01-01

    Roč. 22, č. 1 (2009), s. 146-160 ISSN 0893-8512 R&D Projects: GA MŠk LC522; GA ČR GA524/04/0342; GA ČR GA524/08/0885 Institutional research plan: CEZ:AV0Z60220518 Keywords : Cestoda * D. latum * zoonosis Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 14.691, year: 2009

  6. Polybrene inhibits human mesenchymal stem cell proliferation during lentiviral transduction.

    Directory of Open Access Journals (Sweden)

    Paul Lin

    Full Text Available Human mesenchymal stem cells (hMSCs can be engineered to express specific genes, either for their use in cell-based therapies or to track them in vivo over long periods of time. To obtain long-term expression of these genes, a lentivirus- or retrovirus-mediated cell transduction is often used. However, given that the efficiency with these viruses is typically low in primary cells, additives such as polybrene are always used for efficient viral transduction. Unfortunately, as presented here, exposure to polybrene alone at commonly used concentratons (1-8 µg/mL negatively impacts hMSC proliferation in a dose-dependent manner as measured by CyQUANT, EdU incorporation, and cell cycle analysis. This inhibition of proliferation was observable in culture even 3 weeks after exposure. Culturing the cells in the presence of FGF-2, a potent mitogen, did not abrogate this negative effect of polybrene. In fact, the normally sharp increase in hMSC proliferation that occurs during the first days of exposure to FGF-2 was absent at 4 µg/mL or higher concentrations of polybrene. Similarly, the effect of stimulating cell proliferation under simulated hypoxic conditions was also decreased when cells were exposed to polybrene, though overall proliferation rates were higher. The negative influence of polybrene was, however, reduced when the cells were exposed to polybrene for a shorter period of time (6 hr vs 24 hr. Thus, careful evaluation should be done when using polybrene to aid in lentiviral transduction of human MSCs or other primary cells, especially when cell number is critical.

  7. Designing monitoring programs for chemicals of emerging concern in potable reuse ⋯ What to include and what not to include?

    KAUST Repository

    Drewes, Jorg; Anderson, Paul D.; Denslow, Nancy D.; Olivieri, Adam W.; Schlenk, Daniel K.; Snyder, Shane A.; Maruya, Keith

    2012-01-01

    This study discussed a proposed process to prioritize chemicals for reclaimed water monitoring programs, selection of analytical methods required for their quantification, toxicological relevance of chemicals of emerging concern regarding human health, and related issues. Given that thousands of chemicals are potentially present in reclaimed water and that information about those chemicals is rapidly evolving, a transparent, science-based framework was developed to guide prioritization of which compounds of emerging concern (CECs) should be included in reclaimed water monitoring programs. The recommended framework includes four steps: (1) compile environmental concentrations (e.g., measured environmental concentration or MEC) of CECs in the source water for reuse projects; (2) develop a monitoring trigger level (MTL) for each of these compounds (or groups thereof) based on toxicological relevance; (3) compare the environmental concentration (e.g., MEC) to the MTL; CECs with a MEC/MTL ratio greater than 1 should be prioritized for monitoring, compounds with a ratio less than '1' should only be considered if they represent viable treatment process performance indicators; and (4) screen the priority list to ensure that a commercially available robust analytical method is available for that compound. © IWA Publishing 2013.

  8. Designing monitoring programs for chemicals of emerging concern in potable reuse--what to include and what not to include?

    Science.gov (United States)

    Drewes, J E; Anderson, P; Denslow, N; Olivieri, A; Schlenk, D; Snyder, S A; Maruya, K A

    2013-01-01

    This study discussed a proposed process to prioritize chemicals for reclaimed water monitoring programs, selection of analytical methods required for their quantification, toxicological relevance of chemicals of emerging concern regarding human health, and related issues. Given that thousands of chemicals are potentially present in reclaimed water and that information about those chemicals is rapidly evolving, a transparent, science-based framework was developed to guide prioritization of which compounds of emerging concern (CECs) should be included in reclaimed water monitoring programs. The recommended framework includes four steps: (1) compile environmental concentrations (e.g., measured environmental concentration or MEC) of CECs in the source water for reuse projects; (2) develop a monitoring trigger level (MTL) for each of these compounds (or groups thereof) based on toxicological relevance; (3) compare the environmental concentration (e.g., MEC) to the MTL; CECs with a MEC/MTL ratio greater than 1 should be prioritized for monitoring, compounds with a ratio less than '1' should only be considered if they represent viable treatment process performance indicators; and (4) screen the priority list to ensure that a commercially available robust analytical method is available for that compound.

  9. Designing monitoring programs for chemicals of emerging concern in potable reuse ⋯ What to include and what not to include?

    KAUST Repository

    Drewes, Jorg

    2012-11-01

    This study discussed a proposed process to prioritize chemicals for reclaimed water monitoring programs, selection of analytical methods required for their quantification, toxicological relevance of chemicals of emerging concern regarding human health, and related issues. Given that thousands of chemicals are potentially present in reclaimed water and that information about those chemicals is rapidly evolving, a transparent, science-based framework was developed to guide prioritization of which compounds of emerging concern (CECs) should be included in reclaimed water monitoring programs. The recommended framework includes four steps: (1) compile environmental concentrations (e.g., measured environmental concentration or MEC) of CECs in the source water for reuse projects; (2) develop a monitoring trigger level (MTL) for each of these compounds (or groups thereof) based on toxicological relevance; (3) compare the environmental concentration (e.g., MEC) to the MTL; CECs with a MEC/MTL ratio greater than 1 should be prioritized for monitoring, compounds with a ratio less than \\'1\\' should only be considered if they represent viable treatment process performance indicators; and (4) screen the priority list to ensure that a commercially available robust analytical method is available for that compound. © IWA Publishing 2013.

  10. More Human than Human.

    Science.gov (United States)

    Lawrence, David

    2017-07-01

    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  11. The different expression profiles of microRNAs in elderly and young human dental pulp and the role of miR-433 in human dental pulp cells.

    Science.gov (United States)

    Wang, Kejing; Li, Li; Wu, Junjun; Qiu, Qin; Zhou, Fengjuan; Wu, Hongkun

    2015-03-01

    As a kind of endogenous noncoding small RNA, MicroRNA (miRNA) plays important roles of regulation to various physiological functions, while its affections on senescence of human dental pulp cell (HDPCs) are still unknown. Thus, we identified the senescence-associated miRNAs in HDPCs by microarray analysis, predicted their targets and regulatory signaling pathway by gene ontology and Kyoto encyclopedia of genes and genomes pathway database analysis. After validated, the senescence-associated miRNAs' expression level was up- and down-regulated using lentivirus package and cell transfection to find its role in HDPCs' morphology, proliferation, apoptosis, and mineralization. The results showed 27 miRNAs differentially expressed at least 1.5-fold, of which 16 were up-regulated and 11 down-regulated, the function of their targets was mainly focused on signal transduction, cell proliferation, apoptosis, and transcription regulation. According to the change fold, we speculated that miR-433 could be one of the vital senescence-associated miRNAs of HDPCs and found its target (GRB2), validated that miR-433 could negatively regulate GRB2 and the RAS-MAPK signaling pathway, leading to the decline of proliferation and mineralization ability of HDPCs and the acceleration of cell apoptosis, suggesting the regulation of miR-433 might be the potential target to promote repair and regeneration of HDPCs in the elderly. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Human papillomavirus molecular biology.

    Science.gov (United States)

    Harden, Mallory E; Munger, Karl

    Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Ergonomics in nuclear and human factors engineering

    International Nuclear Information System (INIS)

    Muench, E.; Schultheiss, G.F.

    1988-01-01

    The work situation including man-machine-relationships in nuclear power plants is described. The overview gives only a compact summary of some important ergonomic parameters, i.e. human body dimension, human load, human characteristics and human knowledge. (DG)

  14. Human-Robot Teams Informed by Human Performance Moderator Functions

    Science.gov (United States)

    2012-08-29

    performance factors that affect the ability of a human to drive at night, which includes the eyesight of the driver, the fatigue level of the driver...where human factors are factors that affect the performance of an individual. 7 for human interaction. For instance, they explain the various human... affecting trust in human-robot interaction. Human Factors 53(5), 517-527 (2001) 35. Hart, S. G. and Staveland, L. E. Development of NASA-TLX (Task

  15. Human transbodies to VP40 inhibit cellular egress of Ebola virus-like particles

    International Nuclear Information System (INIS)

    Teimoori, Salma; Seesuay, Watee; Jittavisutthikul, Surasak; Chaisri, Urai; Sookrung, Nitat; Densumite, Jaslan; Saelim, Nawannaporn; Chulanetra, Monrat; Maneewatch, Santi; Chaicumpa, Wanpen

    2016-01-01

    A direct acting anti-Ebola agent is needed. VP40, a conserved protein across Ebolavirus (EBOV) species has several pivotal roles in the virus life cycle. Inhibition of VP40 functions would lessen the virion integrity and interfere with the viral assembly, budding, and spread. In this study, cell penetrable human scFvs (HuscFvs) that bound to EBOV VP40 were produced by phage display technology. Gene sequences coding for VP40-bound-HuscFvs were subcloned from phagemids into protein expression plasmids downstream to a gene of cell penetrating peptide, i.e., nonaarginine (R9). By electron microscopy, transbodies from three clones effectively inhibited egress of the Ebola virus-like particles from human hepatic cells transduced with pseudo-typed-Lentivirus particles carrying EBOV VP40 and GP genes. Computerized simulation indicated that the effective HuscFvs bound to multiple basic residues in the cationic patch of VP40 C-terminal domain which are important in membrane-binding for viral matrix assembly and virus budding. The transbodies bound also to VP40 N-terminal domain and L domain peptide encompassed the PTAPPEY (WW binding) motif, suggesting that they might confer VP40 function inhibition through additional mechanism(s). The generated transbodies are worthwhile tested with authentic EBOV before developing to direct acting anti-Ebola agent for preclinical and clinical trials. - Highlights: • Cell penetrable human scFvs (transbodies) to Ebolavirus (EBOV) VP40 were produced. • The transbodies inhibited egress of EBOV-like particles (VLPs) from human hepatocytes. • They interacted with VP40 CTD basic residues important for plasma membrane binding. • And hence interfere with viral matrix assembly and viral progeny budding. • This is the first report on human antibodies that target intracellular EBOV VP40.

  16. Knockdown of ZFR suppresses cell proliferation and invasion of human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Xiaolan Zhao

    Full Text Available BACKGROUND: Zinc finger RNA binding protein (ZFR is involved in the regulation of growth and cancer development. However, little is known about ZFR function in pancreatic cancer. METHODS: Herein, to investigate whether ZFR is involved in tumor growth, Oncomine microarray data was firstly used to evaluate ZFR gene expression in human pancreatic tumors. Then short hairpin RNA (shRNA targeting ZFR was designed and delivered into PANC-1 pancreatic cancer cells to knock down ZFR expression. Cell viability, cell proliferation and cell cycle analysis after ZFR knockdown were determined by MTT, colony forming and FACS, respectively. In addition, cell migration and invasion were assessed using the Transwell system. RESULTS: The expression of ZFR was significantly higher in pancreatic tumors than normal pancreas tissues by Oncomine database analysis. Knockdown of ZFR by shRNA-expressing lentivirus significantly decreased the viability and invasion ability of pancreatic cancer cells. Moreover, FACS analysis showed that knockdown of ZFR in PANC-1 cells caused a significant cell cycle arrest at G0/G1 phase. Furthermore, knockdown of ZFR decreased the levels of CDK2, CDK4, CyclinA and CyclinD1 and enhanced the expression of p27, which has evidenced by qRT-PCR and Western blot analysis. CONCLUSIONS: Knockdown of ZFR might provide a novel alternative to targeted therapy of pancreatic cancer and deserves further investigation.

  17. Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses

    Directory of Open Access Journals (Sweden)

    Ryan P. McNamara

    2018-02-01

    Full Text Available Extracellular vesicles (EVs or exosomes have been implicated in the pathophysiology of infections and cancer. The negative regulatory factor (Nef encoded by simian immunodeficiency virus (SIV and human immunodeficiency virus (HIV plays a critical role in the progression to AIDS and impairs endosomal trafficking. Whether HIV-1 Nef can be loaded into EVs has been the subject of controversy, and nothing is known about the connection between SIV Nef and EVs. We find that both SIV and HIV-1 Nef proteins are present in affinity-purified EVs derived from cultured cells, as well as in EVs from SIV-infected macaques. Nef-positive EVs were functional, i.e., capable of membrane fusion and depositing their content into recipient cells. The EVs were able to transfer Nef into recipient cells. This suggests that Nef readily enters the exosome biogenesis pathway, whereas HIV virions are assembled at the plasma membrane. It suggests a novel mechanism by which lentiviruses can influence uninfected and uninfectable, i.e., CD4-negative, cells.

  18. ECONOMICS OF HUMAN RESOURCES

    Directory of Open Access Journals (Sweden)

    IOANA - JULIETA JOSAN

    2011-04-01

    Full Text Available The purpose of this paper is to analyze human resources in terms of quantitative and qualitative side with special focus on the human capital accumulation influence. The paper examines the human resources trough human capital accumulation in terms of modern theory of human resources, educational capital, health, unemployment and migration. The findings presented in this work are based on theoretical economy publications and data collected from research materials. Sources of information include: documents from organizations - the EUROSTAT, INSSE - studies from publications, books, periodicals, and the Internet. The paper describes and analyzes human resources characteristics, human resource capacities, social and economic benefits of human capital accumulation based on economy, and the government plans and policies on health, education and labor market.

  19. Identification of astrocytoma associated genes including cell surface markers

    International Nuclear Information System (INIS)

    Boon, Kathy; Edwards, Jennifer B; Eberhart, Charles G; Riggins, Gregory J

    2004-01-01

    Despite intense effort the treatment options for the invasive astrocytic tumors are still limited to surgery and radiation therapy, with chemotherapy showing little or no increase in survival. The generation of Serial Analysis of Gene Expression (SAGE) profiles is expected to aid in the identification of astrocytoma-associated genes and highly expressed cell surface genes as molecular therapeutic targets. SAGE tag counts can be easily added to public expression databases and quickly disseminated to research efforts worldwide. We generated and analyzed the SAGE transcription profiles of 25 primary grade II, III and IV astrocytomas [1]. These profiles were produced as part of the Cancer Genome Anatomy Project's SAGE Genie [2], and were used in an in silico search for candidate therapeutic targets by comparing astrocytoma to normal brain transcription. Real-time PCR and immunohistochemistry were used for the validation of selected candidate target genes in 2 independent sets of primary tumors. A restricted set of tumor-associated genes was identified for each grade that included genes not previously associated with astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase), with a high percentage of cell surface genes. Two genes with available antibodies, Aquaporin 1 and Topoisomerase 2A, showed protein expression consistent with transcript level predictions. This survey of transcription in malignant and normal brain tissues reveals a small subset of human genes that are activated in malignant astrocytomas. In addition to providing insights into pathway biology, we have revealed and quantified expression for a significant portion of cell surface and extra-cellular astrocytoma genes

  20. Are cultural values and beliefs included in U.S. based HIV interventions?

    OpenAIRE

    Wyatt, GE; Williams, JK; Gupta, A; Malebranche, D

    2012-01-01

    Objective: To determine the extent to which current United States based human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) prevention and risk reduction interventions address and include aspects of cultural beliefs in definitions, curricula, measures and related theories that may contradict current safer sex messages. Method: A comprehensive literature review was conducted to determine which published human immunodeficiency virus/acquired immune deficiency syndrome (H...

  1. Universal health coverage in 'One ASEAN': are migrants included?

    Science.gov (United States)

    Guinto, Ramon Lorenzo Luis R; Curran, Ufara Zuwasti; Suphanchaimat, Rapeepong; Pocock, Nicola S

    2015-01-01

    As the Association of South East Asian Nations (ASEAN) gears toward full regional integration by 2015, the cross-border mobility of workers and citizens at large is expected to further intensify in the coming years. While ASEAN member countries have already signed the Declaration on the Protection and Promotion of the Rights of Migrant Workers, the health rights of migrants still need to be addressed, especially with ongoing universal health coverage (UHC) reforms in most ASEAN countries. This paper seeks to examine the inclusion of migrants in the UHC systems of five ASEAN countries which exhibit diverse migration profiles and are currently undergoing varying stages of UHC development. A scoping review of current migration trends and policies as well as ongoing UHC developments and migrant inclusion in UHC in Indonesia, Malaysia, Philippines, Singapore, and Thailand was conducted. In general, all five countries, whether receiving or sending, have schemes that cover migrants to varying extents. Thailand even allows undocumented migrants to opt into its Compulsory Migrant Health Insurance scheme, while Malaysia and Singapore are still yet to consider including migrants in their government-run UHC systems. In terms of predominantly sending countries, the Philippines's social health insurance provides outbound migrants with portable insurance yet with limited benefits, while Indonesia still needs to strengthen the implementation of its compulsory migrant insurance which has a health insurance component. Overall, the five ASEAN countries continue to face implementation challenges, and will need to improve on their UHC design in order to ensure genuine inclusion of migrants, including undocumented migrants. However, such reforms will require strong political decisions from agencies outside the health sector that govern migration and labor policies. Furthermore, countries must engage in multilateral and bilateral dialogue as they redefine UHC beyond the basis of

  2. Center Innovation Fund: JSC CIF (also includes JSC IRAD) Program

    Data.gov (United States)

    National Aeronautics and Space Administration — JSC provides and applies its preeminent capabilities in science and technology to develop, operate, and integrate human exploration missions.  The Center...

  3. Human engineering

    International Nuclear Information System (INIS)

    Yang, Seong Hwan; Park, Bum; Gang, Yeong Sik; Gal, Won Mo; Baek, Seung Ryeol; Choe, Jeong Hwa; Kim, Dae Sung

    2006-07-01

    This book mentions human engineering, which deals with introduction of human engineering, Man-Machine system like system design, and analysis and evaluation of Man-Machine system, data processing and data input, display, system control of man, human mistake and reliability, human measurement and design of working place, human working, hand tool and manual material handling, condition of working circumstance, working management, working analysis, motion analysis working measurement, and working improvement and design in human engineering.

  4. Human intrusion: New ideas?

    International Nuclear Information System (INIS)

    Cooper, J.R.

    2002-01-01

    Inadvertent human intrusion has been an issue for the disposal of solid radioactive waste for many years. This paper discusses proposals for an approach for evaluating the radiological significance of human intrusion as put forward by ICRP with contribution from work at IAEA. The approach focuses on the consequences of the intrusion. Protective actions could, however, include steps to reduce the probability of human intrusion as well as the consequences. (author)

  5. Human reliability analysis

    International Nuclear Information System (INIS)

    Dougherty, E.M.; Fragola, J.R.

    1988-01-01

    The authors present a treatment of human reliability analysis incorporating an introduction to probabilistic risk assessment for nuclear power generating stations. They treat the subject according to the framework established for general systems theory. Draws upon reliability analysis, psychology, human factors engineering, and statistics, integrating elements of these fields within a systems framework. Provides a history of human reliability analysis, and includes examples of the application of the systems approach

  6. Linking Microbiota to Human Diseases

    DEFF Research Database (Denmark)

    Wu, Hao; Tremaroli, Valentina; Bäckhed, F

    2015-01-01

    The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2...

  7. Global Journal of Humanities

    African Journals Online (AJOL)

    Journal Homepage Image. Global Journal of Humanities is aimed at promoting reasearch in all areas of Humanities including philosophy, languages, linguistics, literature, history, fine/applied arts, theater arts, architecture, etc. Visit the Global Journal Series website here: http://www.globaljournalseries.com/ ...

  8. Human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2006-01-01

    Human rights reflect a determined effort to protect the dignity of each and every human being against abuse of power. This endeavour is as old as human history. What is relatively new is the international venture for the protection of human dignity through internationally accepted legal standards

  9. Human Reliability Program Overview

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  10. OAS :: Accountability :: Human Resources

    Science.gov (United States)

    OAS, including its organizational structure, each organizational unit's staffing, vacant posts, and a list of procurement notices for formal bids, links to the performance contract and travel control Plan Human Resources Organizational Structure Functions of each organizational unit Vacant Posts

  11. Human reliability

    International Nuclear Information System (INIS)

    Embrey, D.E.

    1987-01-01

    Concepts and techniques of human reliability have been developed and are used mostly in probabilistic risk assessment. For this, the major application of human reliability assessment has been to identify the human errors which have a significant effect on the overall safety of the system and to quantify the probability of their occurrence. Some of the major issues within human reliability studies are reviewed and it is shown how these are applied to the assessment of human failures in systems. This is done under the following headings; models of human performance used in human reliability assessment, the nature of human error, classification of errors in man-machine systems, practical aspects, human reliability modelling in complex situations, quantification and examination of human reliability, judgement based approaches, holistic techniques and decision analytic approaches. (UK)

  12. Philosophical foundations of human rights

    CERN Document Server

    Liao, Matthew S

    2015-01-01

    What makes something a human right? What is the relationship between the moral foundations of human rights and human rights law? What are the difficulties of appealing to human rights? This book offers the first comprehensive survey of current thinking on the philosophical foundations of human rights. Divided into four parts, this book focusses firstly on the moral grounds of human rights, for example in our dignity, agency, interests or needs. 'Secondly, it looks at the implications that different moral perspectives on human rights bear for human rights law and politics. Thirdly, it discusses specific and topical human rights including freedom of expression and religion, security, health and more controversial rights such as a human right to subsistence. The final part discusses nuanced critical and reformative views on human rights from feminist, Kantian and relativist perspectives among others. The essays represent new and canonical research by leading scholars in the field. Each part is comprised of a set...

  13. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, Des

    2009-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  14. 25 CFR 20.401 - What is included under Services to Children, Elderly, and Families?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false What is included under Services to Children, Elderly, and Families? 20.401 Section 20.401 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES FINANCIAL ASSISTANCE AND SOCIAL SERVICES PROGRAMS Services to Children, Elderly, and Families § 20.401 What...

  15. Enhanced UWB Radio Channel Model for Short-Range Communication Scenarios Including User Dynamics

    DEFF Research Database (Denmark)

    Kovacs, Istvan Zsolt; Nguyen, Tuan Hung; Eggers, Patrick Claus F.

    2005-01-01

    channel model represents an enhancement of the existing IEEE 802.15.3a/4a PAN channel model, where antenna and user-proximity effects are not included. Our investigations showed that significant variations of the received wideband power and time-delay signal clustering are possible due the human body...

  16. Dictionary of scientific units including dimensionless numbers and scales

    National Research Council Canada - National Science Library

    Jerrard, H.G; McNeill, D.B

    1992-01-01

    .... The text includes the most recently accepted values of all units. Several disciplines, which have in the past employed few scientific principles and the dictionary has been extended to include examples of these.

  17. Should Relational Aggression Be Included in DSM-V?

    Science.gov (United States)

    Keenan, Kate; Coyne, Claire; Lahey, Benjamin B.

    2008-01-01

    The study examines whether relational aggression should be included in DSM-V disruptive behavior disorders. The results conclude that some additional information is gathered from assessing relational aggression but not enough to be included in DSM-V.

  18. Partially ionized plasmas including the third symposium on uranium plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, M. [ed.

    1976-09-01

    Separate abstracts are included for 28 papers on electrically generated plasmas, fission generated plasmas, nuclear pumped lasers, gaseous fuel reactor research, and applications. Five papers have been previously abstracted and included in ERA.

  19. 48 CFR 536.213-371 - Bids that include options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Bids that include options... Contracting for Construction 536.213-371 Bids that include options. (a) Subject to the limitations in paragraph (c) of this section, you may include options in contracts if it is in the Government's interest...

  20. 29 CFR 780.616 - Operations included in raising livestock.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Operations included in raising livestock. 780.616 Section... Employment in Agriculture and Livestock Auction Operations Under the Section 13(b)(13) Exemption Requirements for Exemption § 780.616 Operations included in raising livestock. Raising livestock includes such...

  1. Human niche, human behaviour, human nature.

    Science.gov (United States)

    Fuentes, Agustin

    2017-10-06

    The concept of a 'human nature' or 'human natures' retains a central role in theorizing about the human experience. In Homo sapiens it is clear that we have a suite of capacities generated via our evolutionary past, and present, and a flexible capacity to create and sustain particular kinds of cultures and to be shaped by them. Regardless of whether we label these capacities 'human natures' or not, humans occupy a distinctive niche and an evolutionary approach to examining it is critical. At present we are faced with a few different narratives as to exactly what such an evolutionary approach entails. There is a need for a robust and dynamic theoretical toolkit in order to develop a richer, and more nuanced, understanding of the cognitively sophisticated genus Homo and the diverse sorts of niches humans constructed and occupied across the Pleistocene, Holocene, and into the Anthropocene. Here I review current evolutionary approaches to 'human nature', arguing that we benefit from re-framing our investigations via the concept of the human niche and in the context of the extended evolutionary synthesis (EES). While not a replacement of standard evolutionary approaches, this is an expansion and enhancement of our toolkit. I offer brief examples from human evolution in support of these assertions.

  2. The Human Cell Atlas.

    Science.gov (United States)

    Regev, Aviv; Teichmann, Sarah A; Lander, Eric S; Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir

    2017-12-05

    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

  3. Developing human technology curriculum

    Directory of Open Access Journals (Sweden)

    Teija Vainio

    2012-10-01

    Full Text Available During the past ten years expertise in human-computer interaction has shifted from humans interacting with desktop computers to individual human beings or groups of human beings interacting with embedded or mobile technology. Thus, humans are not only interacting with computers but with technology. Obviously, this shift should be reflected in how we educate human-technology interaction (HTI experts today and in the future. We tackle this educational challenge first by analysing current Master’s-level education in collaboration with two universities and second, discussing postgraduate education in the international context. As a result, we identified core studies that should be included in the HTI curriculum. Furthermore, we discuss some practical challenges and new directions for international HTI education.

  4. Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations.

    Science.gov (United States)

    Heringa, Minne B; Geraets, Liesbeth; van Eijkeren, Jan C H; Vandebriel, Rob J; de Jong, Wim H; Oomen, Agnes G

    2016-12-01

    Titanium dioxide white pigment consists of particles of various sizes, from which a fraction is in the nano range (food as additive E 171 as well as in other products, such as food supplements and toothpaste. Here, we assessed whether a human health risk can be expected from oral ingestion of these titanium dioxide nanoparticles (TiO 2 NPs), based on currently available information. Human health risks were assessed using two different approaches: Approach 1, based on intake, i.e. external doses, and Approach 2, based on internal organ concentrations using a kinetic model in order to account for accumulation over time (the preferred approach). Results showed that with Approach 1, a human health risk is not expected for effects in liver and spleen, but a human health risk cannot be excluded for effects on the ovaries. When based on organ concentrations by including the toxicokinetics of TiO 2 NPs (Approach 2), a potential risk for liver, ovaries and testes is found. This difference between the two approaches shows the importance of including toxicokinetic information. The currently estimated risk can be influenced by factors such as absorption, form of TiO 2 , particle fraction, particle size and physico-chemical properties in relation to toxicity, among others. Analysis of actual particle concentrations in human organs, as well as organ concentrations and effects in liver and the reproductive system after chronic exposure to well-characterized TiO 2 (NPs) in animals are recommended to refine this assessment.

  5. Testing and assessment strategies, including alternative and new approaches

    DEFF Research Database (Denmark)

    Meyer, Otto A.

    2003-01-01

    The object of toxicological testing is to predict possible adverse effect in humans when exposed to chemicals whether used as industrial chemicals, pharmaceuticals or pesticides. Animal models are predominantly used in identifying potential hazards of chemicals. The use of laboratory animals raises...... ethical concern. However, irrespective of animal welfare it is an important aspect of the discipline of toxicology that the primary object is human health. The ideal testing and assessment strategy is simple to use all the available test methods and preferably more in laboratory animal species from which...... uses and of the absence of health problems involved with their use. Thus, the regulatory toxicology is a cocktail of science and pragmatism added a crucial concern for animal welfare. Test methods are most often used in a testing sequence as bricks in a testing strategy. The main key driving forces...

  6. IRSN annual report 2012 - including Financial report 2012

    International Nuclear Information System (INIS)

    Schuler, Matthieu; Marchal, Valerie; Albert, Marc-Gerard; Baudry, Michel; Bigot, Marie-Pierre; Charron, Sylvie; Clavelle, Stephanie; Cousinou, Patrick; Deschamps, Patrice; Delattre, Aleth; Demeillers, Didier; Dumas, Agnes; Franquard, Dominique; Goudal, Bernard; Jalouneix, Jean; Laloi, Patrick; Monti, Pascale; Richer, Gerard; Rollinger, Francois; Rouyer, Veronique; Rutschkovsky, Nathalie; Scott De Martinville, Edouard; Tharaud, Christine; Verpeaux, Jean-luc; Jaunet, Camille; Hedouin, Jean-Christophe

    2013-01-01

    This annual report for the French nuclear safety and radiation protection Institute (IRSN) addresses its organizational aspects (highlights, figures illustrating the activity, organizational chart, councils and committees), proposes a summary of activities and presentation of the strategy (transparency and communication policy, promotion of a safety and radiation protection culture). The main part addresses the activities regarding safety, nuclear security and non-proliferation, radiation protection of the environment and in terms of human health, and emergency and post-accidental situations. The last part addresses issues of efficiency (property, health, safety, environmental protection and quality, and human resources). A financial report is also proposed and contains a management report, financial statements, and an appendix to annual accounts

  7. 76 FR 61741 - Bmc Software, Inc. Including On-Site Leased Workers From COMSYS ITS Including Remote Workers...

    Science.gov (United States)

    2011-10-05

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-74,540] Bmc Software, Inc... November 23, 2010, applicable to workers of BMC Software, Inc., including on-site leased workers from... BMC Software, inc., including on-site leased workers from Comsys ITS, and including remote workers...

  8. Prenatal Triclosan Exposure and Anthropometric Measures Including Anogenital Distance in Danish Infants

    DEFF Research Database (Denmark)

    Lassen, Tina Harmer; Frederiksen, Hanne; Kyhl, Henriette Boye

    2016-01-01

    , Swan SH, Main KM, Andersson AM, Lind DV, Husby S, Wohlfahrt-Veje C, Skakkebæk NE, Jensen TK. 2016. Prenatal triclosan exposure and anthropometric measures including anogenital distance in Danish infants. Environ Health Perspect 124:1261-1268; http://dx.doi.org/10.1289/ehp.1409637.......BACKGROUND: Triclosan (TCS) is widely used as an antibacterial agent in consumer products such as hand soap and toothpaste, and human exposure is widespread. TCS is suspected of having endocrine-disrupting properties, but few human studies have examined the developmental effects of prenatal TCS...

  9. On the use of risk-informed regulation including organizational factors

    International Nuclear Information System (INIS)

    Gibelli, S.M.O.; Alvarenga, M.A.B.

    1998-01-01

    Risk-Informed Regulation (RIR) can be applied by using Probabilistic Safety Assessment (PSA) as a basic tool. Traditionally, PSA methodology encompasses the calculation of failure probabilities of Structures, Systems and Components (SSCs) and direct associated human errors. However, there are indirect causes related to human failures, associated with Organizational Factors, which are normally not included in fault trees, that may influence plant risk evaluation. This paper discusses on possible applications of RIR and on Organizational Factors. It also presents a classification of Angra-1 NPP unresolved issues, aiming a future inclusion of these factors into a PSA calculation. (author)

  10. An African Perspective on Human Rights.

    Science.gov (United States)

    Shiman, David

    1992-01-01

    Presents a series of classroom activities comparing differing views of human rights in the United Nations Universal Declaration of Human Rights and the African Charter on Human and People's Rights. Includes excerpts from the African Charter on Human and People's Rights and the full text of the Universal Declaration of Human Rights. (CFR)

  11. Human Smuggling

    NARCIS (Netherlands)

    Siegel - Rozenblit, Dina; Zaitch, Damian

    2014-01-01

    Human smuggling is based on a consensus between smuggler, smuggled, and his/her family (which usually guarantees or effectuates payment). However, unauthorized immigrants are violating immigration laws and human smugglers are profiting from enabling illegal immigration. Both human smuggling and its

  12. 26 CFR 1.1013-1 - Property included in inventory.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Property included in inventory. 1.1013-1 Section... inventory. The basis of property required to be included in inventory is the last inventory value of such property in the hands of the taxpayer. The requirements with respect to the valuation of an inventory are...

  13. 31 CFR 103.51 - Dollars as including foreign currency.

    Science.gov (United States)

    2010-07-01

    ... RECORDKEEPING AND REPORTING OF CURRENCY AND FOREIGN TRANSACTIONS General Provisions § 103.51 Dollars as including foreign currency. Wherever in this part an amount is stated in dollars, it shall be deemed to mean... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Dollars as including foreign currency...

  14. Microfluidic devices and methods including porous polymer monoliths

    Science.gov (United States)

    Hatch, Anson V; Sommer, Gregory J; Singh, Anup K; Wang, Ying-Chih; Abhyankar, Vinay V

    2014-04-22

    Microfluidic devices and methods including porous polymer monoliths are described. Polymerization techniques may be used to generate porous polymer monoliths having pores defined by a liquid component of a fluid mixture. The fluid mixture may contain iniferters and the resulting porous polymer monolith may include surfaces terminated with iniferter species. Capture molecules may then be grafted to the monolith pores.

  15. Solar Energy Education. Reader, Part II. Sun story. [Includes glossary

    Energy Technology Data Exchange (ETDEWEB)

    1981-05-01

    Magazine articles which focus on the subject of solar energy are presented. The booklet prepared is the second of a four part series of the Solar Energy Reader. Excerpts from the magazines include the history of solar energy, mythology and tales, and selected poetry on the sun. A glossary of energy related terms is included. (BCS)

  16. A framework for including family health spillovers in economic evaluation

    NARCIS (Netherlands)

    H. Al-Janabi (Hareth); N.J.A. van Exel (Job); W.B.F. Brouwer (Werner); J. Coast (Joanna)

    2016-01-01

    textabstractHealth care interventions may affect the health of patients' family networks. It has been suggested that these health spillovers? should be included in economic evaluation, but there is not a systematic method for doing this. In this article, we develop a framework for including health

  17. Articles which include chevron film cooling holes, and related processes

    Science.gov (United States)

    Bunker, Ronald Scott; Lacy, Benjamin Paul

    2014-12-09

    An article is described, including an inner surface which can be exposed to a first fluid; an inlet; and an outer surface spaced from the inner surface, which can be exposed to a hotter second fluid. The article further includes at least one row or other pattern of passage holes. Each passage hole includes an inlet bore extending through the substrate from the inlet at the inner surface to a passage hole-exit proximate to the outer surface, with the inlet bore terminating in a chevron outlet adjacent the hole-exit. The chevron outlet includes a pair of wing troughs having a common surface region between them. The common surface region includes a valley which is adjacent the hole-exit; and a plateau adjacent the valley. The article can be an airfoil. Related methods for preparing the passage holes are also described.

  18. SORBS2 and TLR3 induce premature senescence in primary human fibroblasts and keratinocytes

    International Nuclear Information System (INIS)

    Liesenfeld, Melanie; Mosig, Sandy; Funke, Harald; Jansen, Lars; Runnebaum, Ingo B; Dürst, Matthias; Backsch, Claudia

    2013-01-01

    Genetic aberrations are required for the progression of HPV-induced cervical precancers. A prerequisite for clonal expansion of cancer cells is unlimited proliferative capacity. In a cell culture model for cervical carcinogenesis loss of genes located on chromosome 4q35→qter and chromosome 10p14-p15 were found to be associated with escape from senescence. Moreover, by LOH and I-FISH analyses a higher frequency of allele loss of these regions was also observed in cervical carcinomas as compared to CIN3. The aim of this study was to identify candidate senescence-related genes located on chromosome 4q35→qter and chromosome 10p14-p15 which may contribute to clonal expansion at the transition of CIN3 to cancer. Microarray expression analyses were used to identify candidate genes down-regulated in cervical carcinomas as compared to CIN3. In order to relate these genes with the process of senescence their respective cDNAs were overexpressed in HPV16-immortalized keratinocytes as well as in primary human fibroblasts and keratinocytes using lentivirus mediated gene transduction. Overall fifteen genes located on chromosome 4q35→qter and chromosome 10p14-p15 were identified. Ten of these genes could be validated in biopsies by RT-PCR. Of interest is the novel finding that SORBS2 and TLR3 can induce senescence in primary human fibroblasts and keratinocytes but not in HPV-immortalized cell lines. Intriguingly, the endogenous expression of both genes increases during finite passaging of primary keratinocytes in vitro. The relevance of the genes SORBS2 and TLR3 in the process of cellular senescence warrants further investigation. In ongoing experiments we are investigating whether this increase in gene expression is also characteristic of replicative senescence

  19. Human intrusion

    International Nuclear Information System (INIS)

    Hora, S.; Neill, R.; Williams, R.; Bauser, M.; Channell, J.

    1993-01-01

    This paper focused on the possible approaches to evaluating the impacts of human intrusion on nuclear waste disposal. Several major issues were reviewed. First, it was noted that human intrusion could be addressed either quantitatively through performance assessments or qualitatively through design requirements. Second, it was decided that it was impossible to construct a complete set of possible future human intrusion scenarios. Third, the question of when the effect of possible human intrusion should be considered, before or after site selection was reviewed. Finally, the time frame over which human intrusion should be considered was discussed

  20. Electric drive systems including smoothing capacitor cooling devices and systems

    Energy Technology Data Exchange (ETDEWEB)

    Dede, Ercan Mehmet; Zhou, Feng

    2017-02-28

    An electric drive system includes a smoothing capacitor including at least one terminal, a bus bar electrically coupled to the at least one terminal, a thermoelectric device including a first side and a second side positioned opposite the first side, where the first side is thermally coupled to at least one of the at least one terminal and the bus bar, and a cooling element thermally coupled to the second side of the thermoelectric device, where the cooling element dissipates heat from the thermoelectric device.

  1. Human Rights/Human Needs.

    Science.gov (United States)

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  2. Diabetes Nutrition: Including Sweets in Your Meal Plan

    Science.gov (United States)

    Diabetes nutrition: Including sweets in your meal plan Diabetes nutrition focuses on healthy foods, but sweets aren't necessarily ... your meal plan. By Mayo Clinic Staff Diabetes nutrition focuses on healthy foods. But you can eat ...

  3. Initiation devices, initiation systems including initiation devices and related methods

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, Michael A.; Condit, Reston A.; Rasmussen, Nikki; Wallace, Ronald S.

    2018-04-10

    Initiation devices may include at least one substrate, an initiation element positioned on a first side of the at least one substrate, and a spark gap electrically coupled to the initiation element and positioned on a second side of the at least one substrate. Initiation devices may include a plurality of substrates where at least one substrate of the plurality of substrates is electrically connected to at least one adjacent substrate of the plurality of substrates with at least one via extending through the at least one substrate. Initiation systems may include such initiation devices. Methods of igniting energetic materials include passing a current through a spark gap formed on at least one substrate of the initiation device, passing the current through at least one via formed through the at least one substrate, and passing the current through an explosive bridge wire of the initiation device.

  4. Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema

    Science.gov (United States)

    ... Submit Button NCHS Home Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema Recommend on Facebook ... Percent of visits to office-based physicians with COPD indicated on the medical record: 3.2% Source: ...

  5. [Brodmann Areas 8 and 9 Including the Frontal Eye Field].

    Science.gov (United States)

    Watanabe, Masataka

    2017-04-01

    Based on cytoarchitectonic analyses, Brodmann assigned numbers 8 and 9 to certain areas of the dorsal and medial prefrontal cortex (PFC) in humans and monkeys. Petrides and Pandya re-analyzed the cytoarchitectures of the human and monkey PFCs, and proposed slightly different brain maps for both species. They assigned numbers 8, 9 and 9/46 to the areas that were originally named areas 8 and 9. Areas 8 and 9 have both lateral and medial regions respectively. The lateral area 8 is important for conditional discrimination learning. The frontal eye field which occupies the most caudal region of area 8, is responsible for visual attention and control of eye movements. The lateral area 9 and area 9/46 are functionally similar to area 46 and play important roles in executive control. The dorsomedial prefrontal cortex (DMPFC) comprises the medial regions of areas 8 and 9 and is related to "Theory of Mind" and social cognition. The DMPFC is also known to show "default mode of brain activity" (i.e., more activity during rest than during cognitive task).

  6. Including estimates of the future in today's financial statements

    OpenAIRE

    Mary Barth

    2006-01-01

    This paper explains why the question is how, not if, today's financial statements should include estimates of the future. Including such estimates is not new, but their use is increasing. This increase results primarily because standard setters believe asset and liability measures that reflect current economic conditions and up-to-date expectations of the future will result in more useful information for making economic decisions, which is the objective of financial reporting. This is why sta...

  7. 75 FR 16513 - B&C Corporation, JR Engineering Division, Including B&C Distribution Center, Including On-Site...

    Science.gov (United States)

    2010-04-01

    ... Engineering Division, Including B&C Distribution Center, Including On-Site Leased Workers From B&C Services... occurred during the relevant time period at the B&C Distribution Center, Inc. of the B&C Corporation, JR Engineering Division, Barberton, Ohio. The B&C Distribution Center provides distribution and logistical...

  8. How Do Humans Perceive Emotion?

    Institute of Scientific and Technical Information of China (English)

    LI Wen

    2017-01-01

    Emotion carries crucial qualities of the human condition, representing one of the major challenges in artificial intelligence. Re-search in psychology and neuroscience in the past two to three decades has generated rich insights into the processes underlying human emotion. Cognition and emotion represent the two main pillars of the human psyche and human intelligence. While the hu-man cognitive system and cognitive brain has inspired and informed computer science and artificial intelligence, the future is ripe for the human emotion system to be integrated into artificial intelligence and robotic systems. Here, we review behavioral and neu-ral findings in human emotion perception, including facial emotion perception, olfactory emotion perception, multimodal emotion perception, and the time course of emotion perception. It is our hope that knowledge of how humans perceive emotion will help bring artificial intelligence strides closer to human intelligence.

  9. Human Problem Solving in 2012

    Science.gov (United States)

    Funke, Joachim

    2013-01-01

    This paper presents a bibliography of 263 references related to human problem solving, arranged by subject matter. The references were taken from PsycInfo and Academic Premier data-base. Journal papers, book chapters, and dissertations are included. The topics include human development, education, neuroscience, and research in applied settings. It…

  10. [Origin of sennosides in health teas including Malva leaves].

    Science.gov (United States)

    Kojima, T; Kishi, M; Sekita, S; Satake, M

    2001-06-01

    The aim of this study is to clarify whether sennosides are contained in the leaf of Malva verticillata L., and then to clarify the source of sennosides in health teas including malva leaves. The identification and determination of sennosides were performed with thin layer chromatography and high performance liquid chromatography. The leaf of Malva verticillata L. did not contain sennosides A or B and could be easily distinguished from senna leaf. Our previous report showed that sennosides are contained in weight-reducing herbal teas including malva leaves, and that senna leaf is a herbal component in some teas. Furthermore, in 10 samples of health tea including malva leaves that were bought last year, the smallest amount of sennosides was 6.1 mg/bag, and all health teas including malva leaves contained the leaf and midrib of senna. We suggest that sennosides A and B are not contained in the leaf of Malva verticillata L., and that the sennosides in health teas including malva leaves are not derived from malva leaf but from senna leaf.

  11. Latest animal models for anti-HIV drug discovery.

    Science.gov (United States)

    Sliva, Katja

    2015-02-01

    HIV research is limited by the fact that lentiviruses are highly species specific. The need for appropriate models to promote research has led to the development of many elaborate surrogate animal models. This review looks at the history of animal models for HIV research. Although natural animal lentivirus infections and chimeric viruses such as chimera between HIV and simian immunodeficiency virus and simian-tropic HIV are briefly discussed, the main focus is on small animal models, including the complex design of the 'humanized' mouse. The review also traces the historic evolution and milestones as well as depicting current models and future prospects for HIV research. HIV research is a complex and challenging task that is highly manpower-, money- and time-consuming. Besides factors such as hypervariability and latency, the lack of appropriate animal models that exhibit and recapitulate the entire infectious process of HIV, is one of the reasons behind the failure to eliminate the lentivirus from the human population. This obstacle has led to the exploitation and further development of many sophisticated surrogate animal models for HIV research. While there is no animal model that perfectly mirrors and mimics HIV infections in humans, there are a variety of host species and viruses that complement each other. Combining the insights from each model, and critically comparing the results obtained with data from human clinical trials should help expand our understanding of HIV pathogenesis and drive future drug development.

  12. A Cyber Security Risk Assessment of Hospital Infrastructure including TLS/SSL and other Threats

    OpenAIRE

    Millar, Stuart

    2016-01-01

    Cyber threats traditionally target governments, financial institutions and businesses. However, of growing concern is the threat to healthcare organizations. This study conducts a cyber security risk assessment of a theoretical hospital environment, to include TLS/SSL, which is an encryption protocol for network communications, plus other physical, logical and human threats. Despite significant budgets in the UK for the NHS, the spend on cyber security appears worryingly low and many hospital...

  13. Identification of Multiple Novel Viruses, Including a Parvovirus and a Hepevirus, in Feces of Red Foxes

    Science.gov (United States)

    van der Giessen, Joke; Haagmans, Bart L.; Osterhaus, Albert D. M. E.; Smits, Saskia L.

    2013-01-01

    Red foxes (Vulpes vulpes) are the most widespread members of the order of Carnivora. Since they often live in (peri)urban areas, they are a potential reservoir of viruses that transmit from wildlife to humans or domestic animals. Here we evaluated the fecal viral microbiome of 13 red foxes by random PCR in combination with next-generation sequencing. Various novel viruses, including a parvovirus, bocavirus, adeno-associated virus, hepevirus, astroviruses, and picobirnaviruses, were identified. PMID:23616657

  14. Spontaneous and radiation induced congenital malformations including their roles in miscarriages and stillbirths

    International Nuclear Information System (INIS)

    Martignoni, K.

    1990-01-01

    In the study described here an attempt was made to draw from a wide range of different sources data on the induction of congenital anomalies (malformations or defects existing at birth) by ionising and non-ionising rays during the various stages of gestation. This survey was chiefly based on findings in humans, results from animal experiments were solely included in cases where no suitable material was available for Man. (orig.) [de

  15. Expanding Health Technology Assessments to Include Effects on the Environment

    DEFF Research Database (Denmark)

    Marsh, Kevin; Ganz, Michael Lee; Hsu, John

    2016-01-01

    decision makers. Health care is an important and sizable sector of the economy that could warrant closer policy attention to its impact on the environment. Considerable work is needed to track decision makers' demands, augment the environmental evidence base, and develop robust methods for capturing......There is growing awareness of the impact of human activity on the climate and the need to stem this impact. Public health care decision makers from Sweden and the United Kingdom have started examining environmental impacts when assessing new technologies. This article considers the case...... and objectives extending beyond health care. Two types of challenges hinder this process. First, the nascent evidence base is insufficient to support the accurate comparison of technologies' environmental impacts. Second, cost-utility analysis, which is favored by many HTA agencies, could capture some...

  16. Human Integration Design Processes (HIDP)

    Science.gov (United States)

    Boyer, Jennifer

    2014-01-01

    The purpose of the Human Integration Design Processes (HIDP) document is to provide human-systems integration design processes, including methodologies and best practices that NASA has used to meet human systems and human rating requirements for developing crewed spacecraft. HIDP content is framed around human-centered design methodologies and processes in support of human-system integration requirements and human rating. NASA-STD-3001, Space Flight Human-System Standard, is a two-volume set of National Aeronautics and Space Administration (NASA) Agency-level standards established by the Office of the Chief Health and Medical Officer, directed at minimizing health and performance risks for flight crews in human space flight programs. Volume 1 of NASA-STD-3001, Crew Health, sets standards for fitness for duty, space flight permissible exposure limits, permissible outcome limits, levels of medical care, medical diagnosis, intervention, treatment and care, and countermeasures. Volume 2 of NASASTD- 3001, Human Factors, Habitability, and Environmental Health, focuses on human physical and cognitive capabilities and limitations and defines standards for spacecraft (including orbiters, habitats, and suits), internal environments, facilities, payloads, and related equipment, hardware, and software with which the crew interfaces during space operations. The NASA Procedural Requirements (NPR) 8705.2B, Human-Rating Requirements for Space Systems, specifies the Agency's human-rating processes, procedures, and requirements. The HIDP was written to share NASA's knowledge of processes directed toward achieving human certification of a spacecraft through implementation of human-systems integration requirements. Although the HIDP speaks directly to implementation of NASA-STD-3001 and NPR 8705.2B requirements, the human-centered design, evaluation, and design processes described in this document can be applied to any set of human-systems requirements and are independent of reference

  17. Classical mechanics including an introduction to the theory of elasticity

    CERN Document Server

    Hentschke, Reinhard

    2017-01-01

    This textbook teaches classical mechanics as one of the foundations of physics. It describes the mechanical stability and motion in physical systems ranging from the molecular to the galactic scale. Aside from the standard topics of mechanics in the physics curriculum, this book includes an introduction to the theory of elasticity and its use in selected modern engineering applications, e.g. dynamic mechanical analysis of viscoelastic materials. The text also covers many aspects of numerical mechanics, ranging from the solution of ordinary differential equations, including molecular dynamics simulation of many particle systems, to the finite element method. Attendant Mathematica programs or parts thereof are provided in conjunction with selected examples. Numerous links allow the reader to connect to related subjects and research topics. Among others this includes statistical mechanics (separate chapter), quantum mechanics, space flight, galactic dynamics, friction, and vibration spectroscopy. An introductory...

  18. Internet addiction neuroscientific approaches and therapeutical implications including smartphone addiction

    CERN Document Server

    Reuter, Martin

    2017-01-01

    The second edition of this successful book provides further and in-depth insight into theoretical models dealing with Internet addiction, as well as includes new therapeutical approaches. The editors also broach the emerging topic of smartphone addiction. This book combines a scholarly introduction with state-of-the-art research in the characterization of Internet addiction. It is intended for a broad audience including scientists, students and practitioners. The first part of the book contains an introduction to Internet addiction and their pathogenesis. The second part of the book is dedicated to an in-depth review of neuroscientific findings which cover studies using a variety of biological techniques including brain imaging and molecular genetics. The third part of the book focuses on therapeutic interventions for Internet addiction. The fourth part of the present book is an extension to the first edition and deals with a new emerging potential disorder related to Internet addiction – smartphone addicti...

  19. Ceramic substrate including thin film multilayer surface conductor

    Science.gov (United States)

    Wolf, Joseph Ambrose; Peterson, Kenneth A.

    2017-05-09

    A ceramic substrate comprises a plurality of ceramic sheets, a plurality of inner conductive layers, a plurality of vias, and an upper conductive layer. The ceramic sheets are stacked one on top of another and include a top ceramic sheet. The inner conductive layers include electrically conductive material that forms electrically conductive features on an upper surface of each ceramic sheet excluding the top ceramic sheet. The vias are formed in each of the ceramic sheets with each via being filled with electrically conductive material. The upper conductive layer includes electrically conductive material that forms electrically conductive features on an upper surface of the top ceramic sheet. The upper conductive layer is constructed from a stack of four sublayers. A first sublayer is formed from titanium. A second sublayer is formed from copper. A third sublayer is formed from platinum. A fourth sublayer is formed from gold.

  20. Tunable cavity resonator including a plurality of MEMS beams

    Science.gov (United States)

    Peroulis, Dimitrios; Fruehling, Adam; Small, Joshua Azariah; Liu, Xiaoguang; Irshad, Wasim; Arif, Muhammad Shoaib

    2015-10-20

    A tunable cavity resonator includes a substrate, a cap structure, and a tuning assembly. The cap structure extends from the substrate, and at least one of the substrate and the cap structure defines a resonator cavity. The tuning assembly is positioned at least partially within the resonator cavity. The tuning assembly includes a plurality of fixed-fixed MEMS beams configured for controllable movement relative to the substrate between an activated position and a deactivated position in order to tune a resonant frequency of the tunable cavity resonator.

  1. Meta-structure and tunable optical device including the same

    Science.gov (United States)

    Han, Seunghoon; Papadakis, Georgia Theano; Atwater, Harry

    2017-12-26

    A meta-structure and a tunable optical device including the same are provided. The meta-structure includes a plurality of metal layers spaced apart from one another, an active layer spaced apart from the plurality of metal layers and having a carrier concentration that is tuned according to an electric signal applied to the active layer and the plurality of metal layers, and a plurality of dielectric layers spaced apart from one another and each having one surface contacting a metal layer among the plurality of metal layers and another surface contacting the active layer.

  2. EC6 safety enhancement - including impact of Fukushima lessons learned

    Energy Technology Data Exchange (ETDEWEB)

    Yu, S.; Zemdegs, R.; Boyle, S.; Soulard, M., E-mail: stephen.yu@candu.com [Candu Energy Inc., Mississauga, Ontario (Canada)

    2012-09-15

    The Enhanced CANDU 6 (EC6) is the new Generation III CANDU reactor design that meets the most up to date regulatory requirements and customer expectations. EC6 builds on the proven high performance design inch as the Qinshan CANDU 6 units and has made improvements to safety and operational performance, and has incorporated extensive operational feedback including Fukushima. The Fukushima Dai-ichi March 11, 2011 event has demonstrated the importance of defence-in-depth considerations for beyond-design basis events, including severe accidents. The EC6 design is based on the defence-in-depth principles and provides further design features that address the lessons learned from Fukushima. (author)

  3. Solar Energy Education. Renewable energy: a background text. [Includes glossary

    Energy Technology Data Exchange (ETDEWEB)

    1985-01-01

    Some of the most common forms of renewable energy are presented in this textbook for students. The topics include solar energy, wind power hydroelectric power, biomass ocean thermal energy, and tidal and geothermal energy. The main emphasis of the text is on the sun and the solar energy that it yields. Discussions on the sun's composition and the relationship between the earth, sun and atmosphere are provided. Insolation, active and passive solar systems, and solar collectors are the subtopics included under solar energy. (BCS)

  4. Methods of producing adsorption media including a metal oxide

    Science.gov (United States)

    Mann, Nicholas R; Tranter, Troy J

    2014-03-04

    Methods of producing a metal oxide are disclosed. The method comprises dissolving a metal salt in a reaction solvent to form a metal salt/reaction solvent solution. The metal salt is converted to a metal oxide and a caustic solution is added to the metal oxide/reaction solvent solution to adjust the pH of the metal oxide/reaction solvent solution to less than approximately 7.0. The metal oxide is precipitated and recovered. A method of producing adsorption media including the metal oxide is also disclosed, as is a precursor of an active component including particles of a metal oxide.

  5. Calculation of Permeability inside the Basket including one Fuel Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Seung Hwan; Bang, Kyung Sik; Lee, Ju an; Choi, Woo Seok [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    In general, the porous media model and the effective thermal conductivity were used to simply the fuel assembly. The methods of calculating permeability were compared considering the flow inside a basket which includes a nuclear fuel. Detailed fuel assembly was a computational modeling and the flow characteristics were investigated. The flow inside the basket which included a fuel assembly is analyzed by CFD. As the height of the fuel assembly increases, the pressure drop linearly increased. The inertia resistance could be neglected. Three methods to calculate the permeability were compared. The permeability by the friction factor is 50% less than the permeability by wall shear stress and pressure drop.

  6. Environmental radioactivity in the North Atlantic region including the Faroe Islands and Greenland. 1990 and 1991

    International Nuclear Information System (INIS)

    Aarkrog, A.; Chen, Q.J.; Dahlgaard, H.; Hansen, H.; Nielsen, S.P.; Strandberg, M.; Buch, E.; Christensen, G.C.; Holm, E.

    1994-01-01

    Measurements of fallout radioactivity in the North Atlantic region including Faroe Islands and Greenland are reported. Strontium-90, cesium-137 and cesium-134 were determined in samples of precipitation, sea water, vegetation, various foodstuffs (including milk in the Faroes), and drinking water. Estimates are given of the mean contents of 90 Sr and 137 Cs in human diet in the Faroes and Greenland in 1990 and 1991. 99 Tc data on marine samples, in particular sea water from the Greenland Sea, are reported. (au) (77 tabs., 46 ills., 8 refs.)

  7. Environmental radioactivity in the North Atlantic region including the Faroe Islands and Greenland

    International Nuclear Information System (INIS)

    Aarkrog, A.; Chen, Q.J.; Dahlgaard, H.; Hansen, H.; Nielsen, S.P.; Buch, E.; Christensen, G.C.; Holm, E.

    1992-01-01

    Measurements of fallout radioactivity in the North Atlantic region including the Faroe Islands and Greenland are reported. Strontium-90, cesium-137 and cesium-134 were determined in samples of precipitation, sea water, vegetation, various foodstuffs (including milk in the Faroes), and drinking water. Estimates are given of the mean contents of 90 Sr and 137 Cs in human diet in the Faroes and Greenland in 1988 and 1989. 99 Tc data on marine samples, in particular sea water from the Greenland Sea, are reported. (au) (91 taps., 51 ills., 7 refs.)

  8. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  9. Hepatocyte nuclear factor 4A improves hepatic differentiation of immortalized adult human hepatocytes and improves liver function and survival.

    Science.gov (United States)

    Hang, Hua-Lian; Liu, Xin-Yu; Wang, Hai-Tian; Xu, Ning; Bian, Jian-Min; Zhang, Jian-Jun; Xia, Lei; Xia, Qiang

    2017-11-15

    Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH. Cells were analyzed for telomerase activity, proliferative capacity, hepatocyte markers, and tumorigenicity (c-myc) expression. Hepatocyte markers, hepatocellular functions, and morphology were studied in the HNF4A-overexpressing IHH. Hepatocyte markers and karyotype analysis were completed in the primary hepatocytes using shRNA knockdown of HNF4A. Nuclear translocation of β-catenin was assessed. Rat models of ALF were treated with encapsulated IHH or HNF4A-overexpressing IHH. A HNF4A-positive IHH line was established, which was non-tumorigenic and conserved properties of primary hepatocytes. HNF4A overexpression significantly enhanced mRNA levels of genes related to hepatic differentiation in IHH. Urea levels were increased by the overexpression of HNF4A, as measured 24h after ammonium chloride addition, similar to that of primary hepatocytes. Chromosomal abnormalities were observed in primary hepatocytes transfected with HNF4A shRNA. HNF4α overexpression could significantly promote β-catenin activation. Transplantation of HNF4A overexpressing IHH resulted in better liver function and survival of rats with ALF compared with IHH. HNF4A improved hepatic differentiation of IHH. Transplantation of HNF4A-overexpressing IHH could improve the liver function and survival in a rat model of ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 36 CFR 1254.94 - What must my request include?

    Science.gov (United States)

    2010-07-01

    ... includes the following elements: (1) Record group number or agency of origin or, for donated historical... volume in number of pages or cubic feet. (b) The estimated amount of time (work-days) that the microfilm... who would require training (see § 1254.108(b)). (c) The number and a description of the equipment that...

  11. 20 CFR 404.1013 - Included-excluded rule.

    Science.gov (United States)

    2010-04-01

    ... least one-half of your time in the pay period is in covered work. If you spend most of your time in a... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Included-excluded rule. 404.1013 Section 404.1013 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY...

  12. Including Critical Thinking and Problem Solving in Physical Education

    Science.gov (United States)

    Pill, Shane; SueSee, Brendan

    2017-01-01

    Many physical education curriculum frameworks include statements about the inclusion of critical inquiry processes and the development of creativity and problem-solving skills. The learning environment created by physical education can encourage or limit the application and development of the learners' cognitive resources for critical and creative…

  13. Modelling a linear PM motor including magnetic saturation

    NARCIS (Netherlands)

    Polinder, H.; Slootweg, J.G.; Compter, J.C.; Hoeijmakers, M.J.

    2002-01-01

    The use of linear permanent-magnet (PM) actuators increases in a wide variety of applications because of the high force density, robustness and accuracy. The paper describes the modelling of a linear PM motor applied in, for example, wafer steppers, including magnetic saturation. This is important

  14. Sexually transmitted infections, including HIV, in the Netherlands in 2006

    NARCIS (Netherlands)

    MG van Veen; FDH Koedijk; IVF van der Broek; ELM Op de Coul; IM de Boer; AI van Sighem; MAB van der Sande; soa-centra; Stichting HIV Monitoring; EPI/Cib

    2007-01-01

    The nationally covered low threshold STI centres offering STI care targeted at high risk groups, provide surveillance data to monitor national trends in STI, including HIV. In 2006, chlamydia remained the most commonly diagnosed bacterial STI in the Netherlands in the STI centres, in spite of

  15. 40 CFR 1502.14 - Alternatives including the proposed action.

    Science.gov (United States)

    2010-07-01

    ... impacts of the proposal and the alternatives in comparative form, thus sharply defining the issues and... action so that reviewers may evaluate their comparative merits. (c) Include reasonable alternatives not... identify such alternative in the final statement unless another law prohibits the expression of such a...

  16. 31 CFR 306.87 - Partnerships (including nominee partnerships).

    Science.gov (United States)

    2010-07-01

    ... (including nominee partnerships). An assignment of a security registered in the name of or assigned to a... appropriate for winding up partnership affairs. In those cases where assignments by or in behalf of all... dissolution. Upon voluntary dissolution, for any jurisdiction where a general partner may not act in winding...

  17. 10 CFR 905.11 - What must an IRP include?

    Science.gov (United States)

    2010-01-01

    ..., energy conservation and efficiency, cogeneration and district heating and cooling applications, and..., consumer preferences, environmental impacts, demand or energy impacts, implementation issues, revenue... 10 Energy 4 2010-01-01 2010-01-01 false What must an IRP include? 905.11 Section 905.11 Energy...

  18. Smart Antenna Skins, including Conformal Array, MMICs and Applications

    NARCIS (Netherlands)

    Bogaart, F.L.M. van den

    2000-01-01

    Low-cost technologies are presented for future space-borne and airborne SAR systems. These technologies include state-of-the art highly integrated circuits to miniaturise front-end, solutions to lower-cost interconnection technologies, new beamforming aspects and new architectures. The MMICs address

  19. LTRACK: Beam-transport calculation including wakefield effects

    International Nuclear Information System (INIS)

    Chan, K.C.D.; Cooper, R.K.

    1988-01-01

    LTRACK is a first-order beam-transport code that includes wakefield effects up to quadrupole modes. This paper will introduce the readers to this computer code by describing the history, the method of calculations, and a brief summary of the input/output information. Future plans for the code will also be described

  20. 30 CFR 250.1007 - What to include in applications.

    Science.gov (United States)

    2010-07-01

    ... features and other pertinent data including area, lease, and block designations; water depths; route...) submitted for a pipeline right-of-way shall bear a signed certificate upon its face by the engineer who made... additional design precautions you took to enable the pipeline to withstand the effects of water currents...

  1. cDNA encoding a polypeptide including a hevein sequence

    Energy Technology Data Exchange (ETDEWEB)

    Raikhel, N.V.; Broekaert, W.F.; Namhai Chua; Kush, A.

    1993-02-16

    A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1,018 nucleotides long and includes an open reading frame of 204 amino acids.

  2. Synthetic pulse radar including a microprocessor based controller

    International Nuclear Information System (INIS)

    Fowler, J.C.; Rubin, L.A.; Still, W.L.

    1980-01-01

    This invention relates to pulse radar detection of targets in extended media, including natural phenomena such as oil, coal and ore deposits within the earth. In particular, this invention relates to a pulse radar system employing a synthetic pulse formed from a fourier spectrum of frequencies generated and detected by a digitally controlled transmitter and receiver circuits

  3. Methodological challenges when doing research that includes ethnic minorities

    DEFF Research Database (Denmark)

    Morville, Anne-Le; Erlandsson, Lena-Karin

    2016-01-01

    minorities are included. Method: A thorough literature search yielded 21 articles obtained from the scientific databases PubMed, Cinahl, Web of Science and PsychInfo. Analysis followed Arksey and O’Malley’s framework for scoping reviews, applying content analysis. Results: The results showed methodological...

  4. Including patients’ perspectives in patient information leaflets: A polyocular approach

    DEFF Research Database (Denmark)

    Fage-Butler, Antoinette Mary

    2013-01-01

    Existing research reveals that patients’ perspectives are missing from mandatory patient information leaflets (PILs). At the same time, there is overwhelming consensus that they should be included in this genre, and a corresponding need for potential approaches to tackle this problem. This paper ...

  5. Prototype solar heating and cooling systems including potable hot water

    Science.gov (United States)

    1978-01-01

    Progress is reviewed in the development, delivery, and support of two prototype solar heating and cooling systems including potable hot water. The system consisted of the following subsystems: collector, auxiliary heating, potable hot water, storage, control, transport, and government-furnished site data acquisition.

  6. A Guide to Running a Recycling Project. [Includes Recycling Handbook].

    Science.gov (United States)

    Oregon Recycling Information and Organizing Network, Portland.

    This guide, designed for both students and adults, is intended for individuals who feel they might be interested in establishing a recycling depot. The guide includes such pertinent information as deciding how to set up a depot, markets and transportation, preparation of materials, where to place the depot and when to operate it, publicity and…

  7. Unsteady panel method for complex configurations including wake modeling

    CSIR Research Space (South Africa)

    Van Zyl, Lourens H

    2008-01-01

    Full Text Available implementations of the DLM are however not very versatile in terms of geometries that can be modeled. The ZONA6 code offers a versatile surface panel body model including a separated wake model, but uses a pressure panel method for lifting surfaces. This paper...

  8. Interviewing Objects: Including Educational Technologies as Qualitative Research Participants

    Science.gov (United States)

    Adams, Catherine A.; Thompson, Terrie Lynn

    2011-01-01

    This article argues the importance of including significant technologies-in-use as key qualitative research participants when studying today's digitally enhanced learning environments. We gather a set of eight heuristics to assist qualitative researchers in "interviewing" technologies-in-use (or other relevant objects), drawing on concrete…

  9. Towards ligand docking including explicit interface water molecules.

    Directory of Open Access Journals (Sweden)

    Gordon Lemmon

    Full Text Available Small molecule docking predicts the interaction of a small molecule ligand with a protein at atomic-detail accuracy including position and conformation the ligand but also conformational changes of the protein upon ligand binding. While successful in the majority of cases, docking algorithms including RosettaLigand fail in some cases to predict the correct protein/ligand complex structure. In this study we show that simultaneous docking of explicit interface water molecules greatly improves Rosetta's ability to distinguish correct from incorrect ligand poses. This result holds true for both protein-centric water docking wherein waters are located relative to the protein binding site and ligand-centric water docking wherein waters move with the ligand during docking. Protein-centric docking is used to model 99 HIV-1 protease/protease inhibitor structures. We find protease inhibitor placement improving at a ratio of 9:1 when one critical interface water molecule is included in the docking simulation. Ligand-centric docking is applied to 341 structures from the CSAR benchmark of diverse protein/ligand complexes [1]. Across this diverse dataset we see up to 56% recovery of failed docking studies, when waters are included in the docking simulation.

  10. 25 CFR 20.308 - What does earned income include?

    Science.gov (United States)

    2010-04-01

    ... self-employment, total profit from a business enterprise (i.e., gross receipts less expenses incurred in producing the goods or services). Business expenses do not include depreciation, personal business and entertainment expenses, personal transportation, capital equipment purchases, or principal...

  11. Visual Impairments, "Including Blindness." NICHCY Disability Fact Sheet #13

    Science.gov (United States)

    National Dissemination Center for Children with Disabilities, 2012

    2012-01-01

    Vision is one of the five senses. Being able to see gives tremendous access to learning about the world around--people's faces and the subtleties of expression, what different things look like and how big they are, and the physical environments, including approaching hazards. When a child has a visual impairment, it is cause for immediate…

  12. Truck Drivers And Risk Of STDs Including HIV

    Directory of Open Access Journals (Sweden)

    Bansal R.K

    1995-01-01

    Full Text Available Research Question: Whether long distance truck drivers are at a higher risk of contracting and transmitting STDs including HIV? Objectives: i To study the degree of knowledge of HIV and AIDS among long- distance truck drivers. ii Assess their sexual behaviour including condom use. iii Explore their prevailing social influences and substance abuse patterns. iv Explore their treatment seeking bahaviour as regards STDs. v Deduce their risk of contracting and transmitting STDs including HIV. Study Design: Cross- sectional interview. Setting: Transport Nagar, Indore (M.P Participants: 210 senior drivers (First drivers and 210 junior drivers (Second drivers. Study Variables: Extra-Marital sexual intercourse, condom usage, past and present history of STDs, treatment and counseling, substance abuse, social â€" cultural milieu. Outcome Variables: Risk of contraction of STDs. Statistical Analysis: Univariate analysis. Results: 94% of the drivers were totally ignorant about AIDS. 82.9% and 43.8 % of the senior and junior drivers had a history of extra- marital sex and of these only 2 regularly used condoms. 13.8% and 3.3 % of the senior and junior drivers had a past or present history suggestive of STD infection. Alcohol and Opium were regularly used by them. Conclusion: The studied drivers are at a high risk of contracting and transmitting STDs including HIV.

  13. Including Students with Severe Disabilities in General Education Settings.

    Science.gov (United States)

    Wisniewski, Lech; Alper, Sandra

    1994-01-01

    This paper presents five systematic phases for bringing about successful regular education inclusion of students with severe disabilities. Phases include develop networks within the community, assess school and community resources, review strategies for integration, install strategies that lead to integration, and develop a system of feedback and…

  14. Simple suggestions for including vertical physics in oil spill models

    International Nuclear Information System (INIS)

    D'Asaro, Eric; University of Washington, Seatle, WA

    2001-01-01

    Current models of oil spills include no vertical physics. They neglect the effect of vertical water motions on the transport and concentration of floating oil. Some simple ways to introduce vertical physics are suggested here. The major suggestion is to routinely measure the density stratification of the upper ocean during oil spills in order to develop a database on the effect of stratification. (Author)

  15. 27 CFR 53.181 - Further manufacture included.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Further manufacture... Further manufacture included. (a) In general. The payment of tax imposed by chapter 32 of the Code on the... of any use in further manufacture, or sale as part of a second manufactured article, described in...

  16. Fungi that Infect Humans.

    Science.gov (United States)

    Köhler, Julia R; Hube, Bernhard; Puccia, Rosana; Casadevall, Arturo; Perfect, John R

    2017-06-01

    Fungi must meet four criteria to infect humans: growth at human body temperatures, circumvention or penetration of surface barriers, lysis and absorption of tissue, and resistance to immune defenses, including elevated body temperatures. Morphogenesis between small round, detachable cells and long, connected cells is the mechanism by which fungi solve problems of locomotion around or through host barriers. Secretion of lytic enzymes, and uptake systems for the released nutrients, are necessary if a fungus is to nutritionally utilize human tissue. Last, the potent human immune system evolved in the interaction with potential fungal pathogens, so few fungi meet all four conditions for a healthy human host. Paradoxically, the advances of modern medicine have made millions of people newly susceptible to fungal infections by disrupting immune defenses. This article explores how different members of four fungal phyla use different strategies to fulfill the four criteria to infect humans: the Entomophthorales, the Mucorales, the Ascomycota, and the Basidiomycota. Unique traits confer human pathogenic potential on various important members of these phyla: pathogenic Onygenales comprising thermal dimorphs such as Histoplasma and Coccidioides ; the Cryptococcus spp. that infect immunocompromised as well as healthy humans; and important pathogens of immunocompromised patients- Candida , Pneumocystis , and Aspergillus spp. Also discussed are agents of neglected tropical diseases important in global health such as mycetoma and paracoccidiomycosis and common pathogens rarely implicated in serious illness such as dermatophytes. Commensalism is considered, as well as parasitism, in shaping genomes and physiological systems of hosts and fungi during evolution.

  17. The SMN1 common variant c.22 dupA in Chinese patients causes spinal muscular atrophy by nonsense-mediated mRNA decay in humans.

    Science.gov (United States)

    Bai, JinLi; Qu, YuJin; Cao, YanYan; Yang, Lan; Ge, Lin; Jin, YuWei; Wang, Hong; Song, Fang

    2018-02-20

    Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder that is mostly caused by homozygous deletion of the SMN1 gene. Approximately 5%-10% of SMA patients are believed to have SMN1 variants. c.22 dupA (p.Ser8lysfs*23) has been identified as the most frequent variant in the Chinese SMA population and to be associated with a severe phenotype. However, the exact molecular mechanism of the variant on the pathogenesis of SMA is unclear. We observed that SMN1 mRNA and the SMN protein in the peripheral blood cells of a patient with c.22 dupA were lower than those of controls. The aim of this study is to investigate whether nonsense-mediated mRNA decay (NMD) plays a role in the mechanism of the c.22 dupA variant of the SMN1 gene as it causes SMA. Two lymphoblasts cell lines from two patients (patient 1 and 2) with the c.22 dupA, and one dermal fibroblasts cell line from patient 2 were included in our study. Two-stage validation of the NMD mechanism was supplied. We first measured the changes in the transcript levels of the SMN1 gene by real-time quantitative PCR after immortalized B-lymphoblasts and dermal fibroblasts cells of the SMA patients were treated with inhibitors of the NMD pathway, including puromycin and cyclohemide. Next, lentivirus-mediated knockdown of the key NMD factor-Up-frameshift protein 1 (UPF1)-was performed in the fibroblasts cell line to further clarify whether the variant led to NMD, as UPF1 recognizes abnormally terminated transcripts as NMD substrates during translation. SC35 1.7-kb transcripts, a physiological NMD substrate was determined to be a NMD positive gene in our experiments. The two inhibitors resulted in a dramatic escalation of the levels of the full-length SMN1 (fl-SMN1) transcripts. Additionally, the SC35 1.7-kb mRNA levels were also increased, suggesting that NMD pathway is suppressed by the two inhibitors. For the 3 cell lines, the fold increase of the SMN1 transcript levels of cycloheximide ranged

  18. Including chemical-related impact categories in LCA on printed matter does it matter?

    DEFF Research Database (Denmark)

    Larsen, Henrik Fred; Hansen, Morten Søes; Hauschild, Michael Zwicky

    2004-01-01

    global warming, acidification and nutrification. The studies focus on energy consumption including the emissions and impact categories related to energy. The chemical-related impact categories comprising ecotoxicity and human toxicity are not included at all or only to a limited degree. In this paper we...... include these chemical-related impact categories by making use of some of the newest knowledge about emissions from the production at the printing industry combined with knowledge about the composition of the printing materials used during the production of offset printed matter. This paper is based...... printed matter produced on a fictitious sheet feed offset printing industry in Europe has been identified and shown in Figure 1 (light bars). „Ï The effect of including the chemical related impact categories is substantial as shown in Figure 1, e.g. the importance of paper is reduced from 67% to 31...

  19. The effects of human resource flexibility on human resources development

    Directory of Open Access Journals (Sweden)

    SeidMehdi Veise

    2014-08-01

    Full Text Available Human resources are the primary factor for development of competitiveness and innovation and reaching competitive advantage and they try to improve corporate capabilities through various characteristics such as value creation, scarcity and difficulty of imitation. This paper investigates the effect of human resource flexibility and its dimensions on human resource development and its dimensions. The survey was conducted using descriptive-correlation method that intended to describe how human resource flexibility was effective on human resource development. Questionnaire was tool of data collection. The statistical population included one hundred employees of the Electric Company in Ilam province, thus census method was used. Reliability of the questionnaire was measured via Cronbach's alpha equal to 0.96. The findings revealed that flexibility and its dimensions were effective on human resource development and dimensions of it. As a result, human resource flexibility should be considered for development of human resources and employees with the highest flexibility should be selected.

  20. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  1. Human kapital

    DEFF Research Database (Denmark)

    Grosen, Anders; Nielsen, Peder Harbjerg

    2007-01-01

    finansiel og human kapital. Den traditionelle rådgivnings snævre synsvinkel kan føre til forkerte investeringsråd. Der skal derfor opfordres til, at de finansielle virksomheder i tilrettelæggelsen af deres rådgivning af private kunder systematisk inddrager den humane kapitals størrelse og karakteristika i...

  2. Human trichuriasis

    DEFF Research Database (Denmark)

    Betson, Martha; Søe, Martin Jensen; Nejsum, Peter

    2015-01-01

    Human trichuriasis is a neglected tropical disease which affects hundreds of millions of people worldwide and is particularly prevalent among children living in areas where sanitation is poor. This review examines the current knowledge on the taxonomy, genetics and phylogeography of human Trichuris...

  3. Energy storage device including a redox-enhanced electrolyte

    Science.gov (United States)

    Stucky, Galen; Evanko, Brian; Parker, Nicholas; Vonlanthen, David; Auston, David; Boettcher, Shannon; Chun, Sang-Eun; Ji, Xiulei; Wang, Bao; Wang, Xingfeng; Chandrabose, Raghu Subash

    2017-08-08

    An electrical double layer capacitor (EDLC) energy storage device is provided that includes at least two electrodes and a redox-enhanced electrolyte including two redox couples such that there is a different one of the redox couples for each of the electrodes. When charged, the charge is stored in Faradaic reactions with the at least two redox couples in the electrolyte and in a double-layer capacitance of a porous carbon material that comprises at least one of the electrodes, and a self-discharge of the energy storage device is mitigated by at least one of electrostatic attraction, adsorption, physisorption, and chemisorption of a redox couple onto the porous carbon material.

  4. Progressive IRP Models for Power Resources Including EPP

    Directory of Open Access Journals (Sweden)

    Yiping Zhu

    2017-01-01

    Full Text Available In the view of optimizing regional power supply and demand, the paper makes effective planning scheduling of supply and demand side resources including energy efficiency power plant (EPP, to achieve the target of benefit, cost, and environmental constraints. In order to highlight the characteristics of different supply and demand resources in economic, environmental, and carbon constraints, three planning models with progressive constraints are constructed. Results of three models by the same example show that the best solutions to different models are different. The planning model including EPP has obvious advantages considering pollutant and carbon emission constraints, which confirms the advantages of low cost and emissions of EPP. The construction of progressive IRP models for power resources considering EPP has a certain reference value for guiding the planning and layout of EPP within other power resources and achieving cost and environmental objectives.

  5. 3D integrated HYDRA simulations of hohlraums including fill tubes

    Science.gov (United States)

    Marinak, M. M.; Milovich, J.; Hammel, B. A.; Macphee, A. G.; Smalyuk, V. A.; Kerbel, G. D.; Sepke, S.; Patel, M. V.

    2017-10-01

    Measurements of fill tube perturbations from hydro growth radiography (HGR) experiments on the National Ignition Facility show spoke perturbations in the ablator radiating from the base of the tube. These correspond to the shadow of the 10 μm diameter glass fill tube cast by hot spots at early time. We present 3D integrated HYDRA simulations of these experiments which include the fill tube. Meshing techniques are described which were employed to resolve the fill tube structure and associated perturbations in the simulations. We examine the extent to which the specific illumination geometry necessary to accommodate a backlighter in the HGR experiment contributes to the spoke pattern. Simulations presented include high resolution calculations run on the Trinity machine operated by the Alliance for Computing at Extreme Scale (ACES) partnership. This work was performed under the auspices of the Lawrence Livermore National Security, LLC, (LLNS) under Contract No. DE-AC52-07NA27344.

  6. Management of radioactive waste from reprocessing including disposal aspects

    International Nuclear Information System (INIS)

    Malherbe, J.

    1991-01-01

    Based on a hypothetical scenario including a reactor park of 20 GWe consisting of Pressurised-Water-Reactors with a resulting annual production of 600 tonnes of heavy metal of spent fuel, all aspects of management of resulting wastes are studied. Waste streams from reprocessing include gaseous and liquid effluents, and a number of solid conditioned waste types. Disposal of waste is supposed to be performed either in a near-surface engineered repository, as long as the content of alpha-emitting radionuclides is low enough, and in a deep geological granite formation. After having estimated quantities, cost and radiological consequences, the sensitivity of results to modification in reactor park size, burn-up and the introduction of mixed-oxide fuel (MOX) is evaluated

  7. Improving the strength of amalgams by including steel fibers

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, Calvin T. [Hendrix College, Conway, AR 72032 (United States); Van Hoose, James R. [Siemens, Orlando, FL 32826 (United States); McGill, Preston B. [Marshall Space Flight Center, EM20, Huntsville, AL 35812 (United States); Grugel, Richard N., E-mail: richard.n.grugel@nasa.gov [Marshall Space Flight Center, EM30, Huntsville, AL 35812 (United States)

    2012-05-30

    Highlights: Black-Right-Pointing-Pointer A room temperature liquid Ga-In alloy was successfully substituted for mercury. Black-Right-Pointing-Pointer Physically sound amalgams with included steel fibers can be made. Black-Right-Pointing-Pointer A small volume fraction inclusion of fibers increased strength by {approx}20%. - Abstract: Mercury amalgams, due to their material properties, are widely and successfully used in dental practice. They are, however, also well recognized as having poor tensile strength. With the possibility of expanding amalgam applications it is demonstrated that tensile strength can be increased some 20% by including a small amount of steel fibers. Furthermore, it is shown that mercury can be replaced with a room temperature liquid gallium-indium alloy. Processing, microstructures, and mechanical test results of these novel amalgams are presented and discussed in view of means to further improve their properties.

  8. Microfluidic System Simulation Including the Electro-Viscous Effect

    Science.gov (United States)

    Rojas, Eileen; Chen, C. P.; Majumdar, Alok

    2007-01-01

    This paper describes a practical approach using a general purpose lumped-parameter computer program, GFSSP (Generalized Fluid System Simulation Program) for calculating flow distribution in a network of micro-channels including electro-viscous effects due to the existence of electrical double layer (EDL). In this study, an empirical formulation for calculating an effective viscosity of ionic solutions based on dimensional analysis is described to account for surface charge and bulk fluid conductivity, which give rise to electro-viscous effect in microfluidics network. Two dimensional slit micro flow data was used to determine the model coefficients. Geometry effect is then included through a Poiseuille number correlation in GFSSP. The bi-power model was used to calculate flow distribution of isotropically etched straight channel and T-junction microflows involving ionic solutions. Performance of the proposed model is assessed against experimental test data.

  9. Including investment risk in large-scale power market models

    DEFF Research Database (Denmark)

    Lemming, Jørgen Kjærgaard; Meibom, P.

    2003-01-01

    Long-term energy market models can be used to examine investments in production technologies, however, with market liberalisation it is crucial that such models include investment risks and investor behaviour. This paper analyses how the effect of investment risk on production technology selection...... can be included in large-scale partial equilibrium models of the power market. The analyses are divided into a part about risk measures appropriate for power market investors and a more technical part about the combination of a risk-adjustment model and a partial-equilibrium model. To illustrate...... the analyses quantitatively, a framework based on an iterative interaction between the equilibrium model and a separate risk-adjustment module was constructed. To illustrate the features of the proposed modelling approach we examined how uncertainty in demand and variable costs affects the optimal choice...

  10. Suddenly included: cultural differences in experiencing re-inclusion.

    Science.gov (United States)

    Pfundmair, Michaela; Graupmann, Verena; Du, Hongfei; Frey, Dieter; Aydin, Nilüfer

    2015-03-01

    In the current research, we examined whether re-inclusion (i.e. the change from a previous state of exclusion to a new state of inclusion) was perceived differently by people with individualistic and collectivistic cultural backgrounds. Individualists (German and Austrian participants) but not collectivists (Chinese participants) experienced re-inclusion differently than continued inclusion: While collectivistic participants did not differentiate between both kinds of inclusion, individualistic participants showed reduced fulfilment of their psychological needs under re-inclusion compared to continued inclusion. The results moreover revealed that only participants from individualistic cultures expressed more feelings of exclusion when re-included than when continually included. These exclusionary feelings partially mediated the relationship between the different states of inclusion and basic need fulfilment. © 2014 International Union of Psychological Science.

  11. MODEL OF THE TOKAMAK EDGE DENSITY PEDESTAL INCLUDING DIFFUSIVE NEUTRALS

    International Nuclear Information System (INIS)

    BURRELL, K.H.

    2003-01-01

    OAK-B135 Several previous analytic models of the tokamak edge density pedestal have been based on diffusive transport of plasma plus free-streaming of neutrals. This latter neutral model includes only the effect of ionization and neglects charge exchange. The present work models the edge density pedestal using diffusive transport for both the plasma and the neutrals. In contrast to the free-streaming model, a diffusion model for the neutrals includes the effect of both charge exchange and ionization and is valid when charge exchange is the dominant interaction. Surprisingly, the functional forms for the electron and neutral density profiles from the present calculation are identical to the results of the previous analytic models. There are some differences in the detailed definition of various parameters in the solution. For experimentally relevant cases where ionization and charge exchange rate are comparable, both models predict approximately the same width for the edge density pedestal

  12. Positron scattering by atomic hydrogen including positronium formation

    International Nuclear Information System (INIS)

    Higgins, K.; Burke, P.G.

    1993-01-01

    Positron scattering by atomic hydrogen including positronium formation has been formulated using the R-matrix method and a general computer code written. Partial wave elastic and ground state positronium formation cross sections have been calculated for L ≤ 6 using a six-state approximation which includes the ground state and the 2s and 2p pseudostates of both hydrogen and positronium. The elastic scattering results obtained are in good agreement with those derived from a highly accurate calculation based upon the intermediate energy R-matrix approach. As in a previous coupled-channel static calculation, resonance effects are observed at intermediate energies in the S-wave positronium formation cross section. However, in the present results, the dominant resonance arises in the P-wave cross sections at an energy of 2.73 Ryd and with a width of 0.19 Ryd. (author)

  13. XFEL OSCILLATOR SIMULATION INCLUDING ANGLE-DEPENDENT CRYSTAL REFLECTIVITY

    International Nuclear Information System (INIS)

    Fawley, William; Lindberg, Ryan; Kim, K.-J.; Shvyd'ko, Yuri

    2010-01-01

    The oscillator package within the GINGER FEL simulation code has now been extended to include angle-dependent reflectivity properties of Bragg crystals. Previously, the package was modified to include frequencydependent reflectivity in order to model x-ray FEL oscillators from start-up from shot noise through to saturation. We present a summary of the algorithms used for modeling the crystal reflectivity and radiation propagation outside the undulator, discussing various numerical issues relevant to the domain of high Fresnel number and efficient Hankel transforms. We give some sample XFEL-O simulation results obtained with the angle-dependent reflectivity model, with particular attention directed to the longitudinal and transverse coherence of the radiation output.

  14. QCD Reggeon field theory for every day: Pomeron loops included

    International Nuclear Information System (INIS)

    Altinoluk, Tolga; Kovner, Alex; Peressutti, Javier; Lublinsky, Michael

    2009-01-01

    We derive the evolution equation for hadronic scattering amplitude at high energy. Our derivation includes the nonlinear effects of finite partonic density in the hadronic wave function as well as the effect of multiple scatterings for scattering on dense hadronic target. It thus includes Pomeron loops. It is based on the evolution of the hadronic wave function derived in /cite{foam}. The kernel of the evolution equation defines the second quantized Hamiltonian of the QCD Reggeon Field Theory, H RFT beyond the limits considered so far. The two previously known limits of the evolution: dilute target (JIMWLK limit) and dilute projectile (KLWMIJ limit) are recovered directly from our final result. The Hamiltonian H RFT is applicable for the evolution of scattering amplitude for arbitrarily dense hadronic projectiles/targets - from 'dipole-dipole' to 'nucleus-nucleus' scattering processes.

  15. The Physics of Semiconductors An Introduction Including Devices and Nanophysics

    CERN Document Server

    Grundmann, Marius

    2006-01-01

    The Physics of Semiconductors provides material for a comprehensive upper-level-undergrauate and graduate course on the subject, guiding readers to the point where they can choose a special topic and begin supervised research. The textbook provides a balance between essential aspects of solid-state and semiconductor physics, on the one hand, and the principles of various semiconductor devices and their applications in electronic and photonic devices, on the other. It highlights many practical aspects of semiconductors such as alloys, strain, heterostructures, nanostructures, that are necessary in modern semiconductor research but typically omitted in textbooks. For the interested reader some additional advanced topics are included, such as Bragg mirrors, resonators, polarized and magnetic semiconductors are included. Also supplied are explicit formulas for many results, to support better understanding. The Physics of Semiconductors requires little or no prior knowledge of solid-state physics and evolved from ...

  16. The role of chemical engineering in medicinal research including Alzheimer's.

    Science.gov (United States)

    Kontogeorgis, Georgios M

    2015-01-01

    Various disciplines of chemical engineering, especially thermodynamics and kinetics, play an important role in medicinal research and this has been particularly recognized during the last 10-15 years (von Stockar and van der Wielen, J Biotechnol 59:25, 1997; Prausnitz, Fluid Phase Equilib 53:439, 1989; Prausnitz, Pure Appl Chem 79:1435, 2007; Dey and Prausnitz, Ind Eng Chem Res 50:3, 2011; Prausnitz, J Chem Thermodynamics 35:21, 2003; Tsivintzelis et al. AIChE J 55:756, 2009). It is expected that during the twenty-first century chemical engineering and especially thermodynamics can contribute as significantly to the life sciences development as it has been done with the oil and gas and chemical sectors in the twentieth century. Moreover, it has during the recent years recognized that thermodynamics can help in understanding diseases like human cataract, sickle-cell anemia, Creuzfeldt-Jacob ("mad cow" disease), and Alzheimer's which are connected to "protein aggregation." Several articles in the Perspectives section of prominent chemical engineering journals have addressed this issue (Hall, AIChE J 54:1956, 2008; Vekilov, AIChE J 54:2508, 2008). This work reviews recent applications of thermodynamics (and other areas of chemical engineering) first in drug development and then in the understanding of the mechanism of Alzheimer's and similar diseases.

  17. Expanding Health Technology Assessments to Include Effects on the Environment.

    Science.gov (United States)

    Marsh, Kevin; Ganz, Michael L; Hsu, John; Strandberg-Larsen, Martin; Gonzalez, Raquel Palomino; Lund, Niels

    2016-01-01

    There is growing awareness of the impact of human activity on the climate and the need to stem this impact. Public health care decision makers from Sweden and the United Kingdom have started examining environmental impacts when assessing new technologies. This article considers the case for incorporating environmental impacts into the health technology assessment (HTA) process and discusses the associated challenges. Two arguments favor incorporating environmental impacts into HTA: 1) environmental changes could directly affect people's health and 2) policy decision makers have broad mandates and objectives extending beyond health care. Two types of challenges hinder this process. First, the nascent evidence base is insufficient to support the accurate comparison of technologies' environmental impacts. Second, cost-utility analysis, which is favored by many HTA agencies, could capture some of the value of environmental impacts, especially those generating health impacts, but might not be suitable for addressing broader concerns. Both cost-benefit and multicriteria decision analyses are potential methods for evaluating health and environmental outcomes, but are less familiar to health care decision makers. Health care is an important and sizable sector of the economy that could warrant closer policy attention to its impact on the environment. Considerable work is needed to track decision makers' demands, augment the environmental evidence base, and develop robust methods for capturing and incorporating environmental data as part of HTA. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  18. Importance of including cultural practices in ecological restoration.

    Science.gov (United States)

    Wehi, Priscilla M; Lord, Janice M

    2017-10-01

    Ecosystems worldwide have a long history of use and management by indigenous cultures. However, environmental degradation can reduce the availability of culturally important resources. Ecological restoration aims to repair damage to ecosystems caused by human activity, but it is unclear how often restoration projects incorporate the return of harvesting or traditional life patterns for indigenous communities. We examined the incorporation of cultural use of natural resources into ecological restoration in the context of a culturally important but protected New Zealand bird; among award-winning restoration projects in Australasia and worldwide; and in the peer-reviewed restoration ecology literature. Among New Zealand's culturally important bird species, differences in threat status and availability for hunting were large. These differences indicate the values of a colonizing culture can inhibit harvesting by indigenous people. In Australasia among award-winning ecological restoration projects, restored areas beyond aesthetic or recreational use, despite many projects encouraging community participation. Globally, restoration goals differed among regions. For example, in North America, projects were primarily conservation oriented, whereas in Asia and Africa projects frequently focused on restoring cultural harvesting. From 1995 to 2014, the restoration ecology literature contained few references to cultural values or use. We argue that restoration practitioners are missing a vital component for reassembling functional ecosystems. Inclusion of sustainably harvestable areas within restored landscapes may allow for the continuation of traditional practices that shaped ecosystems for millennia, and also aid project success by ensuring community support. © 2017 Society for Conservation Biology.

  19. Swarm Robotics with Circular Formation Motion Including Obstacles Avoidance

    Directory of Open Access Journals (Sweden)

    Nabil M. Hewahi

    2017-07-01

    Full Text Available The robots science has been developed over the past few years, where robots have become used to accomplish difficult, repetitive or accurate tasks, which are very hard for humans to carry out. In this paper, we propose an algorithm to control the motion of a swarm of robots and make them able to avoid obstacles. The proposed solution is based on forming the robots in circular fashion. A group set of robots consists of multiple groups of robots, each group of robots consists of robots forming a circular shape and each group set is a circular form of robots. The proposed algorithm is concerned with first locating the randomly generated robots in groups and secondly with the swarm robot motion and finally with the swarm obstacle avoidance and swarm reorganization after crossing the obstacle. The proposed algorithm has been simulated with five different obstacles with various numbers of randomly generated robots. The results show that the swarm in the circular form can deal with the obstacles very effectively by passing the obstacles smoothly. The proposed algorithm has been compared with flocking algorithm and it is shown that the circular formation algorithm does not need extensive computation after obstacle avoidance whereas the flocking algorithm needs extensive computation. In addition, the circular formation algorithm maintains every robot in its group after avoiding the obstacles whereas with flocking algorithm does not.

  20. A review of multiple stressor studies that include ionising radiation

    International Nuclear Information System (INIS)

    Vanhoudt, Nathalie; Vandenhove, Hildegarde; Real, Almudena; Bradshaw, Clare; Stark, Karolina

    2012-01-01

    Studies were reviewed that investigated the combined effects of ionising radiation and other stressors on non-human biota. The aim was to determine the state of research in this area of science, and determine if a review of the literature might permit a gross generalization as to whether the combined effects of multi-stressors and radiation are fundamentally additive, synergistic or antagonistic. A multiple stressor database was established for different organism groups. Information was collected on species, stressors applied and effects evaluated. Studies were mostly laboratory based and investigated two-component mixtures. Interactions declared positive occurred in 58% of the studies, while 26% found negative interactions. Interactions were dependent on dose/concentration, on organism's life stage and exposure time and differed among endpoints. Except for one study, none of the studies predicted combined effects following Concentration Addition or Independent Action, and hence, no justified conclusions can be made about synergism or antagonism. - This review on multiple stressor studies involving radiation, highlights that most experimental designs used did not allow to deduce the nature of the interactive effects.

  1. Smart Farming: Including Rights Holders for Responsible Agricultural Innovation

    OpenAIRE

    Kelly Bronson

    2018-01-01

    This article draws on the literature of responsible innovation to suggest concrete processes for including rights holders in the “smart” agricultural revolution. It first draws upon historical agricultural research in Canada to highlight how productivist values drove seed innovations with particular consequences for the distribution of power in the food system. Next, the article uses document analysis to suggest that a similar value framework is motivating public investment in smart farming i...

  2. Aggregated Demand Modelling Including Distributed Generation, Storage and Demand Response

    OpenAIRE

    Marzooghi, Hesamoddin; Hill, David J.; Verbic, Gregor

    2014-01-01

    It is anticipated that penetration of renewable energy sources (RESs) in power systems will increase further in the next decades mainly due to environmental issues. In the long term of several decades, which we refer to in terms of the future grid (FG), balancing between supply and demand will become dependent on demand actions including demand response (DR) and energy storage. So far, FG feasibility studies have not considered these new demand-side developments for modelling future demand. I...

  3. Stochastic modelling of two-phase flows including phase change

    International Nuclear Information System (INIS)

    Hurisse, O.; Minier, J.P.

    2011-01-01

    Stochastic modelling has already been developed and applied for single-phase flows and incompressible two-phase flows. In this article, we propose an extension of this modelling approach to two-phase flows including phase change (e.g. for steam-water flows). Two aspects are emphasised: a stochastic model accounting for phase transition and a modelling constraint which arises from volume conservation. To illustrate the whole approach, some remarks are eventually proposed for two-fluid models. (authors)

  4. Production, control and utilization of radioisotopes including radiopharmaceuticals

    International Nuclear Information System (INIS)

    Muenze, R.

    1985-05-01

    From April 29th to May 5th, 1984 27 participants from 21 developing countries stayed within an IAEA Study Tour ('Production, Control and Utilization of Radioisotopes including Radiopharmaceuticals') in the GDR. In the CINR, Rossendorf the reactor, the cyclotron, the technological centre as well as the animal test laboratory were visited. The participants were made familiar by 10 papers with the development, production and control of radiopharmaceuticals in the CINR, Rossendorf. (author)

  5. Reliability evaluation of containments including soil-structure interaction

    International Nuclear Information System (INIS)

    Pires, J.; Hwang, H.; Reich, M.

    1985-12-01

    Soil-structure interaction effects on the reliability assessment of containment structures are examined. The probability-based method for reliability evaluation of nuclear structures developed at Brookhaven National Laboratory is extended to include soil-structure interaction effects. In this method, reliability of structures is expressed in terms of limit state probabilities. Furthermore, random vibration theory is utilized to calculate limit state probabilities under random seismic loads. Earthquake ground motion is modeled by a segment of a zero-mean, stationary, filtered Gaussian white noise random process, represented by its power spectrum. All possible seismic hazards at a site, represented by a hazard curve, are also included in the analysis. The soil-foundation system is represented by a rigid surface foundation on an elastic halfspace. Random and other uncertainties in the strength properties of the structure, in the stiffness and internal damping of the soil, are also included in the analysis. Finally, a realistic reinforced concrete containment is analyzed to demonstrate the application of the method. For this containment, the soil-structure interaction effects on; (1) limit state probabilities, (2) structural fragility curves, (3) floor response spectra with probabilistic content, and (4) correlation coefficients for total acceleration response at specified structural locations, are examined in detail. 25 refs., 21 figs., 12 tabs

  6. Electrolytes including fluorinated solvents for use in electrochemical cells

    Science.gov (United States)

    Tikhonov, Konstantin; Yip, Ka Ki; Lin, Tzu-Yuan

    2015-07-07

    Provided are electrochemical cells and electrolytes used to build such cells. The electrolytes include ion-supplying salts and fluorinated solvents capable of maintaining single phase solutions with the salts at between about -30.degree. C. to about 80.degree. C. The fluorinated solvents, such as fluorinated carbonates, fluorinated esters, and fluorinated esters, are less flammable than their non-fluorinated counterparts and increase safety characteristics of cells containing these solvents. The amount of fluorinated solvents in electrolytes may be between about 30% and 80% by weight not accounting weight of the salts. Fluorinated salts, such as fluoroalkyl-substituted LiPF.sub.6, fluoroalkyl-substituted LiBF.sub.4 salts, linear and cyclic imide salts as well as methide salts including fluorinated alkyl groups, may be used due to their solubility in the fluorinated solvents. In some embodiments, the electrolyte may also include a flame retardant, such as a phosphazene or, more specifically, a cyclic phosphazene and/or one or more ionic liquids.

  7. A Framework for Including Family Health Spillovers in Economic Evaluation.

    Science.gov (United States)

    Al-Janabi, Hareth; van Exel, Job; Brouwer, Werner; Coast, Joanna

    2016-02-01

    Health care interventions may affect the health of patients' family networks. It has been suggested that these "health spillovers" should be included in economic evaluation, but there is not a systematic method for doing this. In this article, we develop a framework for including health spillovers in economic evaluation. We focus on extra-welfarist economic evaluations where the objective is to maximize health benefits from a health care budget (the "health care perspective"). Our framework involves adapting the conventional cost-effectiveness decision rule to include 2 multiplier effects to internalize the spillover effects. These multiplier effects express the ratio of total health effects (for patients and their family networks) to patient health effects. One multiplier effect is specified for health benefit generated from providing a new intervention, one for health benefit displaced by funding this intervention. We show that using multiplier effects to internalize health spillovers could change the optimal funding decisions and generate additional health benefits to society. © The Author(s) 2015.

  8. Essential role of RAB27A in determining constitutive human skin color.

    Directory of Open Access Journals (Sweden)

    Yasuko Yoshida-Amano

    Full Text Available Human skin color is predominantly determined by melanin produced in melanosomes within melanocytes and subsequently distributed to keratinocytes. There are many studies that have proposed mechanisms underlying ethnic skin color variations, whereas the processes involved from melanin synthesis in melanocytes to the transfer of melanosomes to keratinocytes are common among humans. Apart from the activities in the melanogenic rate-limiting enzyme, tyrosinase, in melanocytes and the amounts and distribution patterns of melanosomes in keratinocytes, the abilities of the actin-associated factors in charge of melanosome transport within melanocytes also regulate pigmentation. Mutations in genes encoding melanosome transport-related molecules, such as MYO5A, RAB27A and SLAC-2A, have been reported to cause a human pigmentary disease known as Griscelli syndrome, which is associated with diluted skin and hair color. Thus we hypothesized that process might play a role in modulating skin color variations. To address that hypothesis, the correlations of expression of RAB27A and its specific effector, SLAC2-A, to melanogenic ability were evaluated in comparison with tyrosinase, using human melanocytes derived from 19 individuals of varying skin types. Following the finding of the highest correlation in RAB27A expression to the melanogenic ability, darkly-pigmented melanocytes with significantly higher RAB27A expression were found to transfer significantly more melanosomes to keratinocytes than lightly-pigmented melanocytes in co-culture and in human skin substitutes (HSSs in vivo, resulting in darker skin color in concert with the difference observed in African-descent and Caucasian skins. Additionally, RAB27A knockdown by a lentivirus-derived shRNA in melanocytes concomitantly demonstrated a significantly reduced number of transferred melanosomes to keratinocytes in co-culture and a significantly diminished epidermal melanin content skin color intensity (

  9. The COG database: an updated version includes eukaryotes

    Directory of Open Access Journals (Sweden)

    Sverdlov Alexander V

    2003-09-01

    Full Text Available Abstract Background The availability of multiple, essentially complete genome sequences of prokaryotes and eukaryotes spurred both the demand and the opportunity for the construction of an evolutionary classification of genes from these genomes. Such a classification system based on orthologous relationships between genes appears to be a natural framework for comparative genomics and should facilitate both functional annotation of genomes and large-scale evolutionary studies. Results We describe here a major update of the previously developed system for delineation of Clusters of Orthologous Groups of proteins (COGs from the sequenced genomes of prokaryotes and unicellular eukaryotes and the construction of clusters of predicted orthologs for 7 eukaryotic genomes, which we named KOGs after eukaryotic orthologous groups. The COG collection currently consists of 138,458 proteins, which form 4873 COGs and comprise 75% of the 185,505 (predicted proteins encoded in 66 genomes of unicellular organisms. The eukaryotic orthologous groups (KOGs include proteins from 7 eukaryotic genomes: three animals (the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and Homo sapiens, one plant, Arabidopsis thaliana, two fungi (Saccharomyces cerevisiae and Schizosaccharomyces pombe, and the intracellular microsporidian parasite Encephalitozoon cuniculi. The current KOG set consists of 4852 clusters of orthologs, which include 59,838 proteins, or ~54% of the analyzed eukaryotic 110,655 gene products. Compared to the coverage of the prokaryotic genomes with COGs, a considerably smaller fraction of eukaryotic genes could be included into the KOGs; addition of new eukaryotic genomes is expected to result in substantial increase in the coverage of eukaryotic genomes with KOGs. Examination of the phyletic patterns of KOGs reveals a conserved core represented in all analyzed species and consisting of ~20% of the KOG set. This conserved portion of the

  10. Extracellular Signal-Regulated Kinase 5 is Required for Low-Concentration H2O2-Induced Angiogenesis of Human Umbilical Vein Endothelial Cells.

    Science.gov (United States)

    Jiang, Shan; Zhang, Dongxin; Huang, Hong; Lei, Yonghong; Han, Yan; Han, Weidong

    2017-01-01

    Background . The aim of this study was to assess the effects of low concentrations of H 2 O 2 on angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro and explore the underlying mechanisms. Methods . HUVECs were cultured and stimulated with different concentrations of H 2 O 2 . Flow cytometric analysis was used to select an optimal concentration of H 2 O 2 for the following experiments. Cell proliferation, migration, and tubule formation were evaluated by Cell Counting Kit-8 (CCK-8) assays, scratch wound assays, and Matrigel tubule formation assays, respectively. For gain and loss of function studies, constitutively active MEK5 (CA-MEK5) and ERK5 shRNA lentiviruses were used to activate or knock down extracellular signal-regulated kinase 5 (ERK5). Results . We found that low concentrations of H 2 O 2 promoted HUVECs proliferation, migration, and tubule formation. ERK5 in HUVECs was significantly activated by H 2 O 2 . Enhanced ERK5 activity significantly amplified the proangiogenic effects of H 2 O 2 ; in contrast, ERK5 knock-down abrogated the effects of H 2 O 2 . Conclusions . Our results confirmed that low concentrations of H 2 O 2 promoted HUVECs angiogenesis in vitro, and ERK5 is an essential mediator of this process. Therefore, ERK5 may be a potential therapeutic target for promoting angiogenesis and improving graft survival.

  11. Kruppel-like factor 2 inhibit the angiogenesis of cultured human liver sinusoidal endothelial cells through the ERK1/2 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Xiao-Qing, E-mail: zeng.xiaoqing@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Li, Na, E-mail: Linala.2009@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Pan, Du-Yi, E-mail: lasikesmi@hotmail.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Miao, Qing, E-mail: sadsadvenus@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Ma, Gui-Fen, E-mail: ma.guifen@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Liu, Yi-Mei, E-mail: liuyimei1988@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Tseng, Yu-Jen, E-mail: dianatseng14@gmail.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Li, Feng, E-mail: li.feng2@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Xu, Li-Li, E-mail: xu.lili3@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Shi-Yao, E-mail: chen.shiyao@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Institute of Endoscopic Research of Zhongshan Hospital, Fudan University, Shanghai (China)

    2015-09-04

    Kruppel-like factor 2 (KLF2) is a crucial anti-angiogenic factor. However, its precise role in hepatic angiogenesis induced by liver sinusoidal endothelial cells (LSECs) remain unclear. This study was aimed to evaluate the effect of KLF2 on angiogenesis of LSECs and to explore the corresponding mechanism. Cultured human LSECs were infected with different lentiviruses to overexpress or suppress KLF2 expression. The CCK-8 assay, transwell migration assay and tube formation test, were used to investigate the roles of KLF2 in the proliferation, migration and vessel tube formation of LSECs, respectively. The expression and phosphorylation of ERK1/2 were detected by western blot. We discovered that the up-regulation of KLF2 expression dramatically inhibited proliferation, migration and tube formation in treated LSECs. Correspondingly, down-regulation of KLF2 expression significantly promoted proliferation, migration and tube formation in treated LSECs. Additionally, KLF2 inhibited the phosphorylation of ERK1/2 pathway, followed by the function of KLF2 in the angiogenesis of LSECs disrupted. In conclusion, KLF2 suppressed the angiogenesis of LSECs through inhibition of cell proliferation, migration, and vessel tube formation. These functions of KLF2 may be mediated through the ERK1/2 signaling pathway. - Highlights: • Overexpression of KLF2 inhibits the proliferation and migration of LSECs. • Overexpression of KLF2 inhibits the angiogenesis of LSECs. • ERK1/2 signaling pathway involved in the anti-angiogenic process of KLF2 on LSECs.

  12. Global anthropogenic emissions of particulate matter including black carbon

    Science.gov (United States)

    Klimont, Zbigniew; Kupiainen, Kaarle; Heyes, Chris; Purohit, Pallav; Cofala, Janusz; Rafaj, Peter; Borken-Kleefeld, Jens; Schöpp, Wolfgang

    2017-07-01

    This paper presents a comprehensive assessment of historical (1990-2010) global anthropogenic particulate matter (PM) emissions including the consistent and harmonized calculation of mass-based size distribution (PM1, PM2. 5, PM10), as well as primary carbonaceous aerosols including black carbon (BC) and organic carbon (OC). The estimates were developed with the integrated assessment model GAINS, where source- and region-specific technology characteristics are explicitly included. This assessment includes a number of previously unaccounted or often misallocated emission sources, i.e. kerosene lamps, gas flaring, diesel generators, refuse burning; some of them were reported in the past for selected regions or in the context of a particular pollutant or sector but not included as part of a total estimate. Spatially, emissions were calculated for 172 source regions (as well as international shipping), presented for 25 global regions, and allocated to 0.5° × 0.5° longitude-latitude grids. No independent estimates of emissions from forest fires and savannah burning are provided and neither windblown dust nor unpaved roads emissions are included. We estimate that global emissions of PM have not changed significantly between 1990 and 2010, showing a strong decoupling from the global increase in energy consumption and, consequently, CO2 emissions, but there are significantly different regional trends, with a particularly strong increase in East Asia and Africa and a strong decline in Europe, North America, and the Pacific region. This in turn resulted in important changes in the spatial pattern of PM burden, e.g. European, North American, and Pacific contributions to global emissions dropped from nearly 30 % in 1990 to well below 15 % in 2010, while Asia's contribution grew from just over 50 % to nearly two-thirds of the global total in 2010. For all PM species considered, Asian sources represented over 60 % of the global anthropogenic total, and residential combustion

  13. Global anthropogenic emissions of particulate matter including black carbon

    Directory of Open Access Journals (Sweden)

    Z. Klimont

    2017-07-01

    Full Text Available This paper presents a comprehensive assessment of historical (1990–2010 global anthropogenic particulate matter (PM emissions including the consistent and harmonized calculation of mass-based size distribution (PM1, PM2. 5, PM10, as well as primary carbonaceous aerosols including black carbon (BC and organic carbon (OC. The estimates were developed with the integrated assessment model GAINS, where source- and region-specific technology characteristics are explicitly included. This assessment includes a number of previously unaccounted or often misallocated emission sources, i.e. kerosene lamps, gas flaring, diesel generators, refuse burning; some of them were reported in the past for selected regions or in the context of a particular pollutant or sector but not included as part of a total estimate. Spatially, emissions were calculated for 172 source regions (as well as international shipping, presented for 25 global regions, and allocated to 0.5°  ×  0.5° longitude–latitude grids. No independent estimates of emissions from forest fires and savannah burning are provided and neither windblown dust nor unpaved roads emissions are included. We estimate that global emissions of PM have not changed significantly between 1990 and 2010, showing a strong decoupling from the global increase in energy consumption and, consequently, CO2 emissions, but there are significantly different regional trends, with a particularly strong increase in East Asia and Africa and a strong decline in Europe, North America, and the Pacific region. This in turn resulted in important changes in the spatial pattern of PM burden, e.g. European, North American, and Pacific contributions to global emissions dropped from nearly 30 % in 1990 to well below 15 % in 2010, while Asia's contribution grew from just over 50 % to nearly two-thirds of the global total in 2010. For all PM species considered, Asian sources represented over 60 % of the global

  14. Are cultural values and beliefs included in U.S. based HIV interventions?

    Science.gov (United States)

    Wyatt, Gail E; Williams, John K; Gupta, Arpana; Malebranche, Dominique

    2012-11-01

    To determine the extent to which current United States based human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) prevention and risk reduction interventions address and include aspects of cultural beliefs in definitions, curricula, measures and related theories that may contradict current safer sex messages. A comprehensive literature review was conducted to determine which published human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) prevention and risk reduction interventions incorporated aspects of cultural beliefs. This review of 166 human immunodeficiency virus (HIV) prevention and risk reduction interventions, published between 1988 and 2010, identified 34 interventions that varied in cultural definitions and the integration of cultural concepts. human immunodeficiency virus (HIV) interventions need to move beyond targeting specific populations based upon race/ethnicity, gender, sexual, drug and/or risk behaviors and incorporate cultural beliefs and experiences pertinent to an individual's risk. Theory based interventions that incorporate cultural beliefs within a contextual framework are needed if prevention and risk reduction messages are to reach targeted at risk populations. Implications for the lack of uniformity of cultural definitions, measures and related theories are discussed and recommendations are made to ensure that cultural beliefs are acknowledged for their potential conflict with safer sex skills and practices. Copyright © 2011. Published by Elsevier Inc.

  15. Integrated Environmental Modelling: Human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  16. 42 CFR 137.275 - May Self-Governance Tribes include IHS construction programs in a construction project agreement...

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false May Self-Governance Tribes include IHS construction... OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Purpose and Scope § 137.275 May Self-Governance Tribes include IHS construction programs in a construction project agreement or in a funding...

  17. Including policy and management in socio-hydrology models: initial conceptualizations

    Science.gov (United States)

    Hermans, Leon; Korbee, Dorien

    2017-04-01

    Socio-hydrology studies the interactions in coupled human-water systems. So far, the use of dynamic models that capture the direct feedback between societal and hydrological systems has been dominant. What has not yet been included with any particular emphasis, is the policy or management layer, which is a central element in for instance integrated water resources management (IWRM) or adaptive delta management (ADM). Studying the direct interactions between human-water systems generates knowledges that eventually helps influence these interactions in ways that may ensure better outcomes - for society and for the health and sustainability of water systems. This influence sometimes occurs through spontaneous emergence, uncoordinated by societal agents - private sector, citizens, consumers, water users. However, the term 'management' in IWRM and ADM also implies an additional coordinated attempt through various public actors. This contribution is a call to include the policy and management dimension more prominently into the research focus of the socio-hydrology field, and offers first conceptual variables that should be considered in attempts to include this policy or management layer in socio-hydrology models. This is done by drawing on existing frameworks to study policy processes throughout both planning and implementation phases. These include frameworks such as the advocacy coalition framework, collective learning and policy arrangements, which all emphasis longer-term dynamics and feedbacks between actor coalitions in strategic planning and implementation processes. A case about longter-term dynamics in the management of the Haringvliet in the Netherlands is used to illustrate the paper.

  18. Beyond the classic thermoneutral zone: Including thermal comfort.

    Science.gov (United States)

    Kingma, Boris Rm; Frijns, Arjan Jh; Schellen, Lisje; van Marken Lichtenbelt, Wouter D

    2014-01-01

    The thermoneutral zone is defined as the range of ambient temperatures where the body can maintain its core temperature solely through regulating dry heat loss, i.e., skin blood flow. A living body can only maintain its core temperature when heat production and heat loss are balanced. That means that heat transport from body core to skin must equal heat transport from skin to the environment. This study focuses on what combinations of core and skin temperature satisfy the biophysical requirements of being in the thermoneutral zone for humans. Moreover, consequences are considered of changes in insulation and adding restrictions such as thermal comfort (i.e. driver for thermal behavior). A biophysical model was developed that calculates heat transport within a body, taking into account metabolic heat production, tissue insulation, and heat distribution by blood flow and equates that to heat loss to the environment, considering skin temperature, ambient temperature and other physical parameters. The biophysical analysis shows that the steady-state ambient temperature range associated with the thermoneutral zone does not guarantee that the body is in thermal balance at basal metabolic rate per se. Instead, depending on the combination of core temperature, mean skin temperature and ambient temperature, the body may require significant increases in heat production or heat loss to maintain stable core temperature. Therefore, the definition of the thermoneutral zone might need to be reformulated. Furthermore, after adding restrictions on skin temperature for thermal comfort, the ambient temperature range associated with thermal comfort is smaller than the thermoneutral zone. This, assuming animals seek thermal comfort, suggests that thermal behavior may be initiated already before the boundaries of the thermoneutral zone are reached.

  19. Managing human performance

    International Nuclear Information System (INIS)

    Strucic, M.; Kavsek, D.

    2004-01-01

    Human performance remains a significant factor for management attention not only from a reactor safety perspective, but also from a financial one. Recent significant events analysis shows that human errors are still dominant causes and contributors to them. An analysis of significant events in nuclear industry occurred through 15-years period revealed that three of four significant events were triggered by human error, although the number of events have dropped by more than a factor of four. A number of human performance breakdowns occurred in the application of errorprevention techniques. These included a lack of pre-job briefs, inadequate turnover of tasks, ineffective use of peer checking, inadequate procedure adherence, and failure to apply a questioning attitude when unexpected changes were encountered in the task. Attempts by the industry to improve human performance have traditionally focused at the worker level. However, human error occurs within the context of the organization, which can either foster or resist human error. The greatest room for improvement lies not only in the continued improvement of front-line worker performance but more so in the identification and elimination of weaknesses in the organizational and managerial domains that contributes to worker performance at the job site. Based on mentioned analysis, other industrial sources and own operating experience, NPP Krsko is paying more attention to improve human performance among own as well as contractor workers. Through series of programs and activities, such as Reactivity Management Program, Safety Culture Program, Self-assessment Program, Corrective Action Program, Plant Performance Monitoring Program, developed in last few years, and through new procedures, written guides and publications, training and management efforts, number of human errors is going to be reduced. Involvement of higher levels of NPP Krsko organization in promotion and use of Human Performance techniques is

  20. Phenotypes in defined genotypes including siblings with Usher syndrome.

    Science.gov (United States)

    Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Andréasson, Sten

    2011-06-01

    To characterize visual function in defined genotypes including siblings with Usher syndrome. Thirteen patients with phenotypically different subtypes of Usher syndrome, including 3 families with affected siblings, were selected. Genetic analysis and ophthalmological examinations including visual fields, full-field electroretinography (ERG), multifocal electroretinography (mf ERG), and optical coherence tomography (OCT) were assessed. The patients' degree of visual handicap was evaluated by a questionnaire (ADL). Twelve of thirteen patients were genotyped as Usher 1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz flickering light response revealed remaining cone function. In 3 of the patients with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp distinction between the area with reduced function and the central area with remaining macular function and normal peak time. OCT demonstrated loss of foveal depression with distortion of the foveal architecture in the macula in all patients. The foveal thickness ranged from 159 to 384 µm and was not correlated to retinal function. Three siblings shared the same mutation for Usher 2C but in contrast to previous reports regarding this genotype, 1 of them diverged in phenotype with substantially normal visual fields, almost normal OCT and mf ERG findings, and only moderately reduced rod and cone function according to ERG. Evaluation of visual function comprising both the severity of the rod cone degeneration and the function in the macular region confirm phenotypical heterogeneity within siblings and between different genotypes of Usher syndrome.

  1. Developing HYDMN code to include the transient of MNSR

    International Nuclear Information System (INIS)

    Al-Barhoum, M.

    2000-11-01

    A description of the programs added to HYDMN code (a code for thermal-hydraulic steady state of MNSR) to include the transient of the same MNSR is presented. The code asks the initial conditions for the power (in k W) and the cold initial core inlet temperature (in degrees centigrade). A time-dependent study of the coolant inlet and outlet temperature, its speed, pool and tank temperatures is done for MNSR in general and for the Syrian MNSR in particular. The study solves the differential equations taken from reference (1) by using some numerical methods found in reference (3). The code becomes this way independent of any external information source. (Author)

  2. Modification of SKYSHINE-III to include cask array shadowing

    Energy Technology Data Exchange (ETDEWEB)

    Hertel, N.E. [Georgia Institute of Technology, Atlanta, GA (United States); Pfeifer, H.J. [NAC International, Norcross, GA (United States); Napolitano, D.G. [NISYS Corporation, Duluth, GA (United States)

    2000-03-01

    The NAC International version of SKYSHINE-III has been expanded to represent the radiation emissions from ISFSI (Interim Spent Fuel Storage Installations) dry storage casks using surface source descriptions. In addition, this modification includes a shadow shielding algorithm of the casks in the array. The resultant code is a flexible design tool which can be used to rapidly assess the impact of various cask loadings and arrangements. An example of its use in calculating dose rates for a 10x8 cask array is presented. (author)

  3. Composite material including nanocrystals and methods of making

    Science.gov (United States)

    Bawendi, Moungi G.; Sundar, Vikram C.

    2010-04-06

    Temperature-sensing compositions can include an inorganic material, such as a semiconductor nanocrystal. The nanocrystal can be a dependable and accurate indicator of temperature. The intensity of emission of the nanocrystal varies with temperature and can be highly sensitive to surface temperature. The nanocrystals can be processed with a binder to form a matrix, which can be varied by altering the chemical nature of the surface of the nanocrystal. A nanocrystal with a compatibilizing outer layer can be incorporated into a coating formulation and retain its temperature sensitive emissive properties.

  4. Endoscopic Management of Vascular Sinonasal Tumors, Including Angiofibroma.

    Science.gov (United States)

    Snyderman, Carl H; Pant, Harshita

    2016-06-01

    The greatest challenge in the surgical treatment of angiofibromas is dealing with the hypervascularity of these tumors. Staging systems that take into account the vascularity of the tumor may be more prognostic. A variety of treatment strategies are used to deal with the vascularity of angiofibromas, including preoperative embolization, segmentation of the tumor into vascular territories, use of hemostatic tools, and staging of surgery. Even large angiofibromas with intracranial extension and residual vascularity can be successfully managed by a skull base team using endoscopic techniques. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Solution of neutron slowing down equation including multiple inelastic scattering

    International Nuclear Information System (INIS)

    El-Wakil, S.A.; Saad, A.E.

    1977-01-01

    The present work is devoted the presentation of an analytical method for the calculation of elastically and inelastically slowed down neutrons in an infinite non absorbing homogeneous medium. On the basis of the Central limit theory (CLT) and the integral transform technique the slowing down equation including inelastic scattering in terms of the Green function of elastic scattering is solved. The Green function is decomposed according to the number of collisions. A formula for the flux at any lethargy O (u) after any number of collisions is derived. An equation for the asymptotic flux is also obtained

  6. cDNA encoding a polypeptide including a hevein sequence

    Energy Technology Data Exchange (ETDEWEB)

    Raikhel, Natasha V. (Okemos, MI); Broekaert, Willem F. (Dilbeek, BE); Chua, Nam-Hai (Scarsdale, NY); Kush, Anil (New York, NY)

    1993-02-16

    A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1018 nucleotides long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a pu GOVERNMENT RIGHTS This application was funded under Department of Energy Contract DE-AC02-76ER01338. The U.S. Government has certain rights under this application and any patent issuing thereon.

  7. Smart Farming: Including Rights Holders for Responsible Agricultural Innovation

    Directory of Open Access Journals (Sweden)

    Kelly Bronson

    2018-02-01

    Full Text Available This article draws on the literature of responsible innovation to suggest concrete processes for including rights holders in the “smart” agricultural revolution. It first draws upon historical agricultural research in Canada to highlight how productivist values drove seed innovations with particular consequences for the distribution of power in the food system. Next, the article uses document analysis to suggest that a similar value framework is motivating public investment in smart farming innovations. The article is of interest to smart farming’s decision makers (from farmers to governance actors and a broader audience – anyone interested in engendering equity through innovation-led societal transitions.

  8. Clinton administration budget includes mixed bag for science

    Science.gov (United States)

    Showstack, Randy

    The $1,766 trillion federal budget proposal that the Clinton Administration rolled out on February 1—which promises to protect Social Security and Medicare and work within mandated budget caps—generally provides favorable news for federally funded science research and development.Within the 17% ($592 billion) of the federal budget earmarked for discretionary spending, the Administration's budget proposal increases funding for nondefense research and development for the seventh year in a row. This includes increased funding for a number of science accounts and money for a series of new science initiatives.

  9. The epigenetic regulation of SOX9 by miR-145 in human chondrosarcoma.

    Science.gov (United States)

    Mak, Isabella W Y; Singh, Shalini; Turcotte, Robert; Ghert, Michelle

    2015-01-01

    Chondrosarcoma is the most common primary bone malignancy in the adult population with a high rate of pulmonary metastasis. Chondrosarcoma is managed with surgical excision as the tumors do not respond well to conventional chemotherapy or radiation therapy. Thus, there exists a dire need to develop systemic treatment options to target chondrosarcoma cells for metastatic spread. We hypothesized that the expression of miR-145 is low in chondrosarcoma, leading to decreased transcriptional control of SOX9 (the master regulator of chondrogenesis), and downstream activation of the transcription factor ETV5. We have previously shown that ETV5 activates MMP-2 expression in chondrosarcoma, which in turn increases local bone matrix resorption. In this study, we confirm high expression of SOX9 in human chondrosarcoma using real-time PCR, Western blotting, and immunofluorescence. An ETV5 promoter-reporter plasmid was transfected into chondrosarcoma cells to determine if SOX9 directly regulates the expression of ETV5. Co-transfection of the ETV5 promoter-plasmid with SOX9 lentivirus significantly increased the luciferase activity derived from the ETV5 promoter, from which the regulatory relationship between SOX9 and ETV5 is established. MiR-145 was found to be down-regulated in chondrosarcoma cell lines, patient samples, and further confirmed with a public sarcoma database. After stable miR-145 lentiviral transfection, the subsequent mRNA expression levels of SOX9, ETV5, and MMP-2 were significantly decreased in chondrosarcoma cells. The results generated by this study may have important clinical significance in the treatment of patients with chondrosarcoma in that targeted miRNA may have the potential to downregulate the upstream activators of proteases such as MMP-2. © 2014 Wiley Periodicals, Inc.

  10. [Knockdown of ATG5 enhances the sensitivity of human renal carcinoma cells to sunitinib].

    Science.gov (United States)

    Li, Peng; Han, Qi; Tang, Ming; Zhang, Keqin

    2017-03-01

    Objective To investigate the expression levels of autophagy-related gene 5 (ATG5) and microtubule-associated protein 1 light chain 3 (LC3) and their effects on sunitinib resistance in human renal carcinoma cells. Methods After clinic-pathologic feature and survival analysis, 99 renal clear cell carcinoma tissues with different histological grades were used to detect the expression of ATG5 and LC3 by immunohistochemistry. Renal carcinoma cell line A-498 was infected with lentivirus-mediated ATG5 shRNA. Western blot analysis was performed to confirm the efficiency of ATG5 knockdown. Proliferation rate of A-498 cells in control group and ATG5 low expression group was determined by flow cytometry. Finally, the survival rate was detected by MTT assay after A-498 cells were treated with different concentrations of sunitinib. Results The expression levels of ATG5 and LC3 in renal clear cell carcinoma tissues were significantly higher than those in para-tumor tissues. The expression levels of ATG5 and LC3 were associated with classification, histological grade, TNM stage and survival rate, rather than gender, age, location, tumor size. Compared with the control group, the protein expressions of ATG5 and LC3 significantly decreased in A-498 cells with ATG5 low expression. The cell proliferation rate in ATG5 downregulation group was lower than that in the control group. Compared with control group, the survival rate in ATG5 low expression group were significantly reduced in a dose-dependent manner after sunitinib treatment. Conclusion Autophagy is active in renal clear cell carcinoma, and the drug sensitivity to sunitinib in renal cancer cells can be enhanced by the downregulation of ATG5.

  11. Effectiveness of human factors simulator

    International Nuclear Information System (INIS)

    Moragas, F.

    2015-01-01

    En 2011, ANAV started the exploitation of the Human Factors Simulator installed in TECNATOM Training Center located in L'Hospital de L'Infant Tarragona. AVAN's Strategic Plan includes the Action Plan for the improvement of human behavior. The plan includes improving the efficiency of the efficiency of the human factors simulator. It is proposed to improve the efficiency into two different terms: winning effectiveness in modeling behaviors, and interweaving the activities in the simulator with the actual strategy of promoting Safety culture and human behaviour. (Author)

  12. TOOLS TO INCLUDE BLIND STUDENTS IN SCHOOL BUILDING PERFORMANCE ASSESSMENTS

    Directory of Open Access Journals (Sweden)

    Tania Pietzschke Abate

    2016-05-01

    Full Text Available This article discusses the design of data collection instruments that include the opinions of blind students, in accordance with the principles of Universal Design (UD. The aim of this study is to understand the importance of adapting data collection instruments for the inclusion of disabled persons in field research in Architecture and Design, among other fields. The data collection instruments developed were a play interview with a tactile map and a 3D survey with the use of tactile models. These instruments sought to assess the school environment experienced by blind students. The study involved students from the early years of a school for the blind who had not yet mastered the Braille system. The participation of these students was evaluated. A multidisciplinary team consisting of architects, designers, educators, and psychologists lent support to the study. The results showed that the data collection instruments adapted to blind students were successful in making the group of authors examine questions regarding UD. An analysis of the participatory phase showed that the limitations resulting from blindness determine the specificities in the adaptation and implementation process of the instruments in schools. Practical recommendations for future studies related to instruments in the UD thematic are presented. This approach is in line with the global trend of including disabled persons in society based on these users’ opinions concerning what was designed by architects and designers.

  13. Kabuki syndrome: expanding the phenotype to include microphthalmia and anophthalmia.

    Science.gov (United States)

    McVeigh, Terri P; Banka, Siddharth; Reardon, William

    2015-10-01

    Kabuki syndrome is a rare genetic malformation syndrome that is characterized by distinct facies, structural defects and intellectual disability. Kabuki syndrome may be caused by mutations in one of two histone methyltransferase genes: KMT2D and KDM6A. We describe a male child of nonconsanguineous Irish parents presenting with multiple malformations, including bilateral extreme microphthalmia; cleft palate; congenital diaphragmatic hernia; duplex kidney; as well as facial features of Kabuki syndrome, including interrupted eyebrows and lower lid ectropion. A de-novo germline mutation in KMT2D was identified. Whole-exome sequencing failed to reveal mutations in any of the known microphthalmia/anopthalmia genes. We also identified four other patients with Kabuki syndrome and microphthalmia. We postulate that Kabuki syndrome may produce this type of ocular phenotype as a result of extensive interaction between KMT2D, WAR complex proteins and PAXIP1. Children presenting with microphthalmia/anophthalmia should be examined closely for other signs of Kabuki syndrome, especially at an age where the facial gestalt might be less readily appreciable.

  14. Proposal to Include Electrical Energy in the Industrial Return Statistics

    CERN Document Server

    2003-01-01

    At its 108th session on the 20 June 1997, the Council approved the Report of the Finance Committee Working Group on the Review of CERN Purchasing Policy and Procedures. Among other topics, the report recommended the inclusion of utility supplies in the calculation of the return statistics as soon as the relevant markets were deregulated, without reaching a consensus on the exact method of calculation. At its 296th meeting on the 18 June 2003, the Finance Committee approved a proposal to award a contract for the supply of electrical energy (CERN/FC/4693). The purpose of the proposal in this document is to clarify the way electrical energy will be included in future calculations of the return statistics. The Finance Committee is invited: 1. to agree that the full cost to CERN of electrical energy (excluding the cost of transport) be included in the Industrial Service return statistics; 2. to recommend that the Council approves the corresponding amendment to the Financial Rules set out in section 2 of this docum...

  15. Exclusive queueing model including the choice of service windows

    Science.gov (United States)

    Tanaka, Masahiro; Yanagisawa, Daichi; Nishinari, Katsuhiro

    2018-01-01

    In a queueing system involving multiple service windows, choice behavior is a significant concern. This paper incorporates the choice of service windows into a queueing model with a floor represented by discrete cells. We contrived a logit-based choice algorithm for agents considering the numbers of agents and the distances to all service windows. Simulations were conducted with various parameters of agent choice preference for these two elements and for different floor configurations, including the floor length and the number of service windows. We investigated the model from the viewpoint of transit times and entrance block rates. The influences of the parameters on these factors were surveyed in detail and we determined that there are optimum floor lengths that minimize the transit times. In addition, we observed that the transit times were determined almost entirely by the entrance block rates. The results of the presented model are relevant to understanding queueing systems including the choice of service windows and can be employed to optimize facility design and floor management.

  16. Impact of a pain protocol including hypnosis in major burns.

    Science.gov (United States)

    Berger, Mette M; Davadant, Maryse; Marin, Christian; Wasserfallen, Jean-Blaise; Pinget, Christophe; Maravic, Philippe; Koch, Nathalie; Raffoul, Wassim; Chiolero, René L

    2010-08-01

    Pain is a major issue after burns even when large doses of opioids are prescribed. The study focused on the impact of a pain protocol using hypnosis on pain intensity, anxiety, clinical course, and costs. All patients admitted to the ICU, aged >18 years, with an ICU stay >24h, accepting to try hypnosis, and treated according to standardized pain protocol were included. Pain was scaled on the Visual Analog Scale (VAS) (mean of daily multiple recordings), and basal and procedural opioid doses were recorded. Clinical outcome and economical data were retrieved from hospital charts and information system, respectively. Treated patients were matched with controls for sex, age, and the burned surface area. Forty patients were admitted from 2006 to 2007: 17 met exclusion criteria, leaving 23 patients, who were matched with 23 historical controls. Altogether patients were 36+/-14 years old and burned 27+/-15%BSA. The first hypnosis session was performed after a median of 9 days. The protocol resulted in the early delivery of higher opioid doses/24h (ppatient. A pain protocol including hypnosis reduced pain intensity, improved opioid efficiency, reduced anxiety, improved wound outcome while reducing costs. The protocol guided use of opioids improved patient care without side effects, while hypnosis had significant psychological benefits.

  17. Study on 'Tannix' an absorbent for heavy metals including uranium

    International Nuclear Information System (INIS)

    Nakamura, Yasuo

    1997-01-01

    To treat radioactive wastes including uranium and transuranic elements such as plutonium, americium etc., development of an absorbent which can be used to absorb and isolate these elements without producing secondary wastes after treatment was attempted. And an absorbent has been successfully developed by polymerizing tannin, a natural product. It is known that tannin binds heavy metals including uranium resulting to produce their precipitates. There are some reports suggesting its absorption ability for uranium. However, tannin has not been used to isolate a heavy metal from a solution because it is soluble in water. Here, insolubilization of tannin was attempted and a manufacturing method for a gelatinized insoluble tannin named as ''Tannix'' was established. Wattle tannin extracted from Mimosa pudica produced in Africa was dissolved in an alkaline solution and gelatinized by heating after the addition of formalin. Thus obtained insoluble tannin was used after crushing and sieving. This product, ''Tannix'' was able to absorb more than 99% of uranium in the waste. And the absorbed Tannin could be degraded by incineration even at a low temperature, leaving only uranium, but not producing any secondary product. (M.N.)

  18. Global Analysis of Solar Neutrino Oscillations Including SNO CC Measurement

    CERN Document Server

    Bahcall, J N; Peña-Garay, C; Bahcall, John N; Peña-Garay, Carlos

    2001-01-01

    For active and sterile neutrinos, we present the globally allowed solutions for two neutrino oscillations. We include the SNO CC measurement and all other relevant solar neutrino and reactor data. Five active neutrino oscillation solutions (LMA, LOW, SMA, VAC, and Just So2) are currently allowed at 3 sigma; three sterile neutrino solutions (Just So2, SMA, and VAC) are allowed at 3 sigma. The goodness of fit is satisfactory for all eight solutions. We also investigate the robustness of the allowed solutions by carrying out global analyses with and without: 1) imposing solar model constraints on the 8B neutrino flux, 2) including the Super-Kamiokande spectral energy distribution and day-night data, 3) using an enhanced CC cross section for deuterium (due to radiative corrections), and 4) a optimistic, hypothetical reduction by a factor of three of the error of the SNO CC rate. For every analysis strategy used in this paper, the most favored solutions all involve large mixing angles: LMA, LOW, or VAC. The favore...

  19. Numerical optimization of conical flow waveriders including detailed viscous effects

    Science.gov (United States)

    Bowcutt, Kevin G.; Anderson, John D., Jr.; Capriotti, Diego

    1987-01-01

    A family of optimized hypersonic waveriders is generated and studied wherein detailed viscous effects are included within the optimization process itself. This is in contrast to previous optimized waverider work, wherein purely inviscid flow is used to obtain the waverider shapes. For the present waveriders, the undersurface is a streamsurface of an inviscid conical flowfield, the upper surface is a streamsurface of the inviscid flow over a tapered cylinder (calculated by the axisymmetric method of characteristics), and the viscous effects are treated by integral solutions of the boundary layer equations. Transition from laminar to turbulent flow is included within the viscous calculations. The optimization is carried out using a nonlinear simplex method. The resulting family of viscous hypersonic waveriders yields predicted high values of lift/drag, high enough to break the L/D barrier based on experience with other hypersonic configurations. Moreover, the numerical optimization process for the viscous waveriders results in distinctly different shapes compared to previous work with inviscid-designed waveriders. Also, the fine details of the viscous solution, such as how the shear stress is distributed over the surface, and the location of transition, are crucial to the details of the resulting waverider geometry. Finally, the moment coefficient variations and heat transfer distributions associated with the viscous optimized waveriders are studied.

  20. Control rod calibration including the rod coupling effect

    International Nuclear Information System (INIS)

    Szilard, R.; Nelson, G.W.

    1984-01-01

    In a reactor containing more than one control rod, which includes all reactors licensed in the United States, there will be a 'coupling' or 'shadowing' of control rod flux at the location of a control rod as a result of the flux depression caused by another control rod. It was decided to investigate this phenomenon further, and eventually to put calibration table data or formulae in a small computer in the control room, so once could insert the positions of the three control rods and receive the excess reactivity without referring to separate tables. For this to be accomplished, a 'three control- rod reactivity function' would be used which would include the flux coupling between the rods. The function is design and measured data was fitted into it to determine the calibration constants. The input data for fitting the trial functions consisted of 254 data points, each consisting of the position of the reg, shim, and transient rods, and the total excess reactivity. (About 200 of these points were 'critical balance points', that is the rod positions for which reactor was critical, and the remainder were determined by positive period measurements.) Although this may be unrealistic from a physical viewpoint, the function derived gave a very accurate recalculation of the input data, and thus would faithfully give the excess reactivity for any possible combination of the locations of the three control rods. The next step, incorporation of the three-rod function into the minicomputer, will be pursued in the summer and fall of 1984